2025 ADA 糖尿病医学诊疗标准

规范内分泌与代谢· 糖尿病 · 2025

Authors

Keywords

Mandeep Bajaj, MBBS, President, Medicine & Science Patti Urbanski, MEd, RD, President, Heath Care & Education

Abstract

T]he simple word Care may suffice to express [the journal's] philosophical mission. The new journal is designed to promote better patient care by serving the expanded needs of all health professionals committed to the care of patients with diabetes. As such, the American Diabetes Association views Diabetes Care as a reaffirmation of Francis Weld Peabody's contention that "the secret of the care of the patient is in caring for the patient.

# Introduction and Methodology

Introduction and Methodology

Diabetes is a complex, chronic condition requiring continuous medical care with comprehensive risk-reduction strategies beyond glycemic management. Ongoing diabetes self-management education and support are critical to empowering people, preventing acute complications, and reducing the risk of long-term complications. Significant evidence exists that supports a range of interventions to improve diabetes outcomes.

The American Diabetes Association (ADA) "Standards of Care in Diabetes," referred to here as the Standards of Care, serves as a comprehensive resource to clinicians, researchers, policy makers, and other stakeholders. It outlines key elements of diabetes care, sets treatment goals, and provides tools to assess care quality, all aimed at improving diabetes care and outcomes across diverse populations.

The ADA Professional Practice Committee (PPC) updates the Standards of Care annually and includes discussion of emerging clinical considerations in the text, and as evidence evolves, clinical guidance is added to the recommendations in the Standards of Care. The Standards of Care is a "living" document where important updates are published online should the PPC determine that new evidence or regulatory changes (e.g., drug or technology approvals, label changes) merit immediate inclusion. More information on the "Living Standards" can be found on the ADA professional website DiabetesPro at professional.diabetes.org/ standards-of-care/living-standards-update. The Standards of Care supersedes all previously published ADA statements-and the recommendations therein-on clinical topics within the purview of the Standards of Care; while still containing valuable analysis, ADA statements should not be considered the current position of the ADA. The Standards of Care receives annual review and approval by the ADA Board of Directors and is reviewed by the ADA scientific team and clinical leadership. The Standards of Care also undergoes external peer review annually.

# SCOPE OF THE GUIDELINES

SCOPE OF THE GUIDELINES

The recommendations in the Standards of Care include screening, diagnostic, and therapeutic actions that are scientifically proved or known based on expert clinical practice or believed to favorably affect health outcomes of people with diabetes. They also cover the prevention, screening, diagnosis, and management of diabetesassociated complications and comorbidities. The recommendations encompass care throughout the life span for youth (children aged birth to 11 years and adolescents aged 12-17 years), adults (aged 18-64 years), and older adults (aged $65 years). The recommendations cover the management of type 1 diabetes, type 2 diabetes, gestational diabetes mellitus, and other types of diabetes and/or hyperglycemic conditions.

The Standards of Care does not provide comprehensive treatment plans for complications associated with diabetes, such as diabetic retinopathy or diabetic foot ulcers, but offers guidance on how and when to screen for diabetes complications, management of complications in the primary care and diabetes care settings, and referral to specialists as appropriate. Similarly, regarding the psychosocial and behavioral health factors often associated with diabetes and that can affect diabetes care, the Standards of Care provides guidance on how and when to screen, management in the primary care and diabetes care settings, and referral but does not provide comprehensive management plans for conditions that require specialized care, such as mental illness.

INTENDED AUDIENCE

The intended audience for the Standards of Care includes primary care physicians, endocrinologists, nurse practitioners, physician associates/assistants, pharmacists, registered dietitian nutritionists, diabetes care and education specialists, and all members of the diabetes care team. The Standards of Care also provides guidance to specialists caring for people with diabetes and its multitude of complications, such as cardiologists, nephrologists, emergency physicians, internists, pediatricians, psychologists, neurologists, ophthalmologists, and podiatrists. Additionally, these recommendations help payors, policy makers, researchers, research funding organizations, and advocacy groups to align their policies and resources and deliver optimal care for people living with diabetes.

The ADA strives to improve and update the Standards of Care to ensure that clinicians, health plans, and policy makers can continue to rely on it as the most authoritative source for current guidelines for diabetes care. The Standards of Care recommendations are not intended to preclude clinical judgment. They must be applied in the context of excellent clinical care, with adjustments for individual preferences, comorbidities, and other patient factors. For more detailed information about the management of diabetes, please refer to Medical Management of Type 1 Diabetes (1) and Medical Management of Type 2 Diabetes (2).

METHODOLOGY AND PROCEDURE

The Standards of Care includes discussion of evidence and clinical practice recommendations intended to optimize care for people with diabetes by assisting health care professionals and individuals in making shared decisions about diabetes care. The recommendations are informed by a systematic review of evidence and an assessment of the benefits and risks of alternative care options.

Professional Practice Committee

The PPC of the ADA is responsible for the Standards of Care content. The PPC is an interprofessional expert committee comprising physicians, nurse practitioners, pharmacists, diabetes care and education specialists, registered dietitian nutritionists, behavioral health scientists, and others who have expertise in a range of areas including but not limited to adult and pediatric endocrinology, epidemiology, public health, behavioral health, cardiovascular risk management, microvascular complications, nephrology, neurology, ophthalmology, podiatry, clinical pharmacology, preconception and pregnancy care, weight management and diabetes prevention, and use of technology in diabetes management. Each year, ADA conducts a national call for applications to recruit members of the PPC. Appointment to the PPC is based on excellence in clinical practice and research, with attention to appropriate representation of members based on considerations including but not limited to demographic, geographic, work setting, or identity characteristics (e.g., gender, race and ethnicity, ability level). A PPC chair or co-chairs are appointed by the ADA (N.A.E. and R.G.M. are co-chairs for the 2025 Standards of Care) and oversee the committee. In addition to the PPC members, several professionals serve as designated subject matter experts to support the PPC in the development of specific content areas of the Standards of Care. While designated subject matter experts assist with content development, only PPC members formally vote on Standards of Care recommendations for final approval.

Additionally, several organizations have endorsed specific sections of the 2025 Standards of Care. The American College of Cardiology (ACC) reviewed and approved Section 10, "Cardiovascular Disease and Risk Management." The American Society for Bone and Mineral Research reviewed and approved the "Bone Health" subsection in Section 4, "Comprehensive Medical Evaluation and Assessment of Comorbidities." The Obesity Society reviewed and approved Section 8, "Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes." New to the 2025 Standards of Care, the American Geriatrics Society reviewed and approved Section 13, "Older Adults."

Each section of the Standards of Care is reviewed annually and updated with the latest evidence-based recommendations by a subcommittee. The subcommittees perform systematic literature reviews and identify and summarize the scientific evidence. An information specialist with knowledge and experience in literature searching (a librarian) is consulted as necessary. A guideline methodologist (R.R.B. for the 2025 Standards of Care) with expertise and training in evidence-based medicine and guideline development methodology oversees all methodological aspects of the development of the Standards of Care and serves as a statistical analyst.

Disclosure and Duality of Interest Management

All members of the expert panel (the PPC members and subject matter experts) and ADA scientific team are required to comply with the ADA policy on duality of interest, which requires disclosure of any financial, intellectual, or other interests that might be construed as constituting an actual, potential, or apparent conflict, regardless of relevancy to the guideline topic. For transparency, ADA requires full disclosure of all relationships.

Full disclosure statements from all committee members are solicited and reviewed during the appointment process. Disclosures are then updated throughout the guideline development process (specifically before the start of every meeting), and disclosure statements are submitted by every Standards of Care contributor upon submission of the updated Standards of Care section. Members are required to disclose conflicts for a time frame that includes 1 year prior to initiation of the committee appointment process until publication of that year's Standards of Care. Potential dualities of interest are evaluated by a designated review panel and, if necessary, the Legal Affairs Division of the ADA. The duality of interest assessment is based on the relative weight of the financial relationship (i.e., the monetary amount) and the relevance of the relationship (i.e., the degree to which an independent observer might reasonably interpret an association as related to the topic or recommendation of consideration). In addition, the ADA adheres to section 7 of the Council of Medical Specialty Societies "Code for Interactions with Companies" (3) . The duality of interest review panel also ensures the majority of the PPC and the PPC chair or co-chairs are without potential conflict relevant to the subject area. Furthermore, the PPC chair or co-chairs are required to remain unconflicted for 1 year after the publication of the Standards of Care. Members of the committee who disclose a potential duality of interest pertinent to any specific recommendation are prohibited from participating in discussions related to those recommendations and their votes are excluded. No expert panel members were employees of any pharmaceutical or medical device company during the development of the 2025 Standards of Care. Members of the PPC, their employers, and their disclosed potential dualities of interest are listed in the section "Disclosures: Standards of Care in Diabetes-2025."

Evidence Review

The Standards of Care subcommittee for each section creates an initial list of relevant clinical questions that is reviewed and discussed by the expert panel. In consultation with a systematic review expert and librarian, each subcommittee devises and executes systematic literature searches. For the 2025 Standards of Care, PubMed, Medline, and EMBASE were searched for the time periods of 1 June 2023 to 19 July 2024. Searches are limited to studies published in English. Subcommittee members also manually search journals, reference lists of conference proceedings, and regulatory agency websites. All potentially relevant citations are then subjected to a full-text review. In consultation with the methodologist, the subcommittees prepare the evidence summaries and grading for each section of the Standards of Care. All PPC members discuss and review the evidence summaries and make revisions as appropriate. The final evidence summaries are then deliberated on by the PPC, and the recommendations that will appear in the Standards of Care are drafted.

Grading of Evidence and Recommendation Development

A grading system (Table 1 ) developed by the ADA and modeled after existing methods is used to clarify and codify the evidence that forms the basis for the recommendations in the Standards of Care. All recommendations in the Standards of Care are critical to comprehensive care regardless of rating. ADA recommendations are assigned ratings of A, B, or C, depending on the quality of the evidence in support of the recommendation. Expert opinion E is a separate category for recommendations in which there is no evidence from clinical trials, clinical trials may be impractical, or there is conflicting evidence. Recommendations assigned an E level of evidence are informed by key opinion leaders in diabetes (members of the PPC and external subject matter experts) and cover important elements of clinical care. All Standards of Care recommendations receive a rating for the strength of the evidence and not for the strength of the recommendation. Recommendations with A-level evidence are based on large, well-designed randomized controlled trials or well-done meta-analyses of randomized controlled trials. Generally, these recommendations have the best chance of improving outcomes when applied to the population for which they are appropriate. Recommendations with lower levels of evidence may be equally important but are not as well supported.

Of course, published evidence is only one component of clinical decision-making.

Clinicians care for people, not populations; guidelines must always be interpreted with the individual person in mind. Individual circumstances, such as comorbid and coexisting diseases, age, education, disability, and, above all, the values and preferences of the person with diabetes, must be considered and may lead to different treatment goals and strategies. Furthermore, conventional evidence hierarchies, such as the one adapted by the ADA, may miss nuances important in diabetes care. For example, although there is excellent evidence from clinical trials supporting the importance of achieving multiple risk factor control, the optimal way to achieve this result is less clear. It is difficult to assess each component of such a complex intervention.

Evidence to Recommendations

All accumulated evidence was reviewed and discussed by all PPC members and external subject matter experts during multiple virtual meetings and a 2-day inperson meeting in Arlington, Virginia, in July 2024. Standards of Care recommendations were updated based on the newly acquired evidence, and each recommendation was voted on by the PPC, with 80% consensus required for any recommendation to be approved.

Revision Process

Public comment is particularly important in the development of clinical practice recommendations; it promotes transparency and provides key stakeholders, including people with diabetes and their caregivers, the opportunity to identify and address gaps in care.The ADA holds a year-long public comment period requesting feedback on the Standards of Care. The PPC reviews compiled feedback from the public in preparation for the annual update but considers more pressing updates throughout the year, which may be published as "living" Standards updates. Feedback from the larger clinical community and general public was invaluable for the revision of the 2024 Standards of Care. Readers who wish to comment on the 2025 Standards of Care are invited to do so at professional.diabetes.org/SOC.

Feedback for the Standards of Care is also obtained from external peer reviewers. The Standards of Care is reviewed by ADA clinical leadership and scientific and medical team and is approved by the ADA Board of Directors, which includes health care Table 1 -ADA evidence-grading system for "Standards of Care in Diabetes"

Level of evidence Description

A Clear evidence from well-conducted, generalizable randomized controlled trials that are adequately powered, including: • Evidence from a well-conducted multicenter trial • Evidence from a meta-analysis that incorporated quality ratings in the analysis Supportive evidence from well-conducted randomized controlled trials that are adequately powered, including: • Evidence from a well-conducted trial at one or more institutions • Evidence from a meta-analysis that incorporated quality ratings in the analysis B Supportive evidence from well-conducted cohort studies, including:

• Evidence from a well-conducted prospective cohort study or registry • Evidence from a well-conducted meta-analysis of cohort studies Supportive evidence from a well-conducted case-control study

C

Supportive evidence from poorly controlled or uncontrolled studies, including:

• Evidence from randomized clinical trials with one or more major or three or more minor methodological flaws that could invalidate the results • Evidence from observational studies with high potential for bias (such as case series with comparison with historical controls) • Evidence from case series or case reports Conflicting evidence with the weight of evidence supporting the recommendation

E

Expert consensus or clinical experience diabetesjournals.org/care Introduction and Methodology professionals, scientists, and other stakeholders. The ACC performs an independent external peer review, and the ACC provides endorsement of Section 10, "Cardiovascular Disease and Risk Management." In addition, the American Society for Bone and Mineral Research provides endorsement for the "Bone Health" subsection of Section 4, "Comprehensive Medical Evaluation and Assessment of Comorbidities," The Obesity Society provides endorsement for Section 8, "Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes," and the American Geriatrics Society provides endorsement for Section 13, "Older Adults." Feedback received from every stakeholder is adequately addressed by the committee, and the final version is approved by all parties prior to publication.

The ADA adheres to the Council of Medical Specialty Societies revised "CMSS Principles for the Development of Specialty Society Clinical Guidelines" (4).

ADA STANDARDS, STATEMENTS, REPORTS, AND REVIEWS

The ADA has been actively involved in developing and disseminating diabetes care clinical practice recommendations and related documents for more than 35 years. The ADA Standards of Care is an essential resource for health care professionals caring for people with diabetes. ADA Statements, Consensus Reports, and Scientific Reviews support the recommendations included in the Standards of Care.

Standards of Care

The annual Standards of Care supplement to Diabetes Care contains the official ADA position, is authored by the ADA, and provides all of the ADA's current clinical practice recommendations.

ADA Statement

An ADA statement is an official ADA point of view or position that does not contain clinical practice recommendations and may be issued on advocacy, policy, economic, or medical issues related to diabetes. ADA statements undergo a formal review process, including external peer review and review by the appropriate ADA national committee, ADA clinical leadership, ADA scientific team, and, as warranted, the ADA Board of Directors.

Consensus Report

An ADA consensus report is a document on a particular topic that is authored by a technical expert panel under the auspices of ADA. The document does not reflect the official ADA position but rather represents the panel's collective analysis, evaluation, and expert opinion. The primary objective of a consensus report is to provide clarity and insight on a medical or scientific matter related to diabetes for which the evidence is contradictory, emerging, or incomplete. The report also aims to highlight evidence gaps and to propose avenues for future research. Consensus reports undergo a formal review process, including external peer review and review by the ADA PPC and ADA scientific team, for publication.

Scientific Review

A scientific review is a balanced review and analysis of the literature on a scientific or medical topic related to diabetes. A scientific review is not an ADA position and does not contain clinical practice recommendations but is produced under the auspices of the ADA by invited experts. The scientific review may provide a scientific rationale for clinical practice recommendations in the Standards of Care. The category may also include task force and expert committee reports. The field of diabetes care is rapidly changing as new research, technology, and treatments that can improve the health and well-being of people with diabetes continue to emerge. With annual updates since 1989, the American Diabetes Association has long been a leader in producing guidelines that capture the most current state of the field.

Summary of Revisions

The 2025 "Standards of Care in Diabetes" has continued to incorporate person-first and inclusive language. Efforts were made to consistently apply terminology that empowers people with diabetes and recognizes the individual at the center of diabetes care.

Although levels of evidence for several recommendations have been updated, these changes are not outlined below where the clinical recommendation has remained the same. That is, changes in evidence level from, for example, E to C, are not noted below. The 2025 Standards of Care contains, in addition to many minor changes that clarify recommendations or reflect new evidence, more substantive revisions detailed below.

SECTION CHANGES

Endorsements

For the second consecutive year, the "Bone Heath" subsection in Section 4, "Comprehensive Medical Evaluation and Assessment of Comorbidities," received endorsement from the American Society for Bone and Mineral Research and Section 8, "Obesity and Weight Management for the Prevention of Type 2 Diabetes," received endorsement from The Obesity Society. For the seventh consecutive year, Section 10, "Cardiovascular Disease and Risk Management," received endorsement from the American College of Cardiology. For the first time, Section 13, "Older Adults," received endorsement from the American Geriatrics Society.

Section 1. Improving Care and Promoting Health in Populations (https://doi.org/10.2337/dc25-S001) Recommendation 1.1 was expanded to include people at risk for diabetes in addition to those with diabetes.

Recommendation 1.2 was revised to include, in addition to the Chronic Care Model, other evidence-based care delivery models and frameworks that have been demonstrated to improve diabetes care delivery and health outcomes. These include the Patient-Centered Medical Home model, Accountable Care Organizations, and value-based payment models and are discussed in the text.

Recommendation 1.5 was added to emphasize the importance of quality improvement initiatives and interprofessional teams for supporting sustainable and scalable process changes that improve quality of care and health outcomes. Implementation concepts were added throughout the section to provide actionable guidance on how to implement and sustain interventions that improve care delivery and population health.

Recommendation 1.6 was added to emphasize the importance of assessing and addressing disparities in diabetes care and health outcomes.The text includes actionable guidance on measuring health disparities and engaging interprofessional teams and community partners to address them.

Recommendation 1.7 was revised to emphasize the importance of screening for and addressing multiple social determinants of health that impact diabetes management, health outcomes, and quality of life.

The narrative text now includes an expanded discussion of cost and affordability considerations as well as health disparities and social determinants of health.

Table 1 .1 was added to highlight the importance of engaging an interprofessional team approach to person-centered care for people with diabetes across the life span.

Section 2. Diagnosis and Classification of Diabetes

(https://doi.org/10.2337/dc25-S002) Table 2 .3 was added to provide considerations related to the use and interpretation of laboratory measurement of glucose and A1C.

The "Classification" subsection has been updated to provide a pragmatic approach to management of individuals who have features of both type 1 and type 2 diabetes.

In the "Type 1 Diabetes" subsection, Recommendation 2.7 was added to emphasize the importance of antibody-based screening for presymptomatic type 1 diabetes in individuals with a family history of type 1 diabetes or otherwise known elevated genetic risk. The associated text was also updated and expanded to reflect these changes.

The "Gestational Diabetes Mellitus" subsection was completely updated to facilitate understanding and implementation of the current various approaches to screening for and diagnosis of gestational diabetes mellitus (GDM) .

The text in various other subsections, including those that discuss diabetes and immune checkpoint inhibitors, the role of the gut microbiome in diabetes risk, and monogenic diabetes, was updated.

Section 3. Prevention or Delay of Diabetes and Associated Comorbidities

(https://doi.org/10.2337/dc25-S003) In the "Lifestyle Behavior Change for Type 2 Diabetes Prevention" subsection, text pertaining to sleep health in relation to risk of type 2 diabetes was added. This addition highlights sleep as a central component in the management of prediabetes and type 2 diabetes, placing it on a level playing field with other lifestyle behaviors (e.g., physical activity and eating patterns).

In the "Pharmacologic Interventions to Delay Type 2 Diabetes" subsection, the text on the proposed use of vitamin D therapy to prevent type 2 diabetes was extensively updated. The text related to longterm metformin therapy and associated vitamin B12 deficiency was also updated.

The language in Recommendation 3.15 was strengthened to facilitate discussion with selected individuals aged $8 years with stage 2 type 1 diabetes about the role of teplizumab-mzwv infusion to delay the onset of symptomatic type 1 diabetes (stage 3).

Section 4. Comprehensive Medical Evaluation and Assessment of Comorbidities

(https://doi.org/10.2337/dc25-S004) Language in Fig. 4 .1 was updated, and Table 4 .1 was modified to include changes made throughout Section 4.

Recommendation 4.3 was changed to include assessment for glycemic status and previous treatment at the initial visit and follow-up visits as appropriate.

Table 4 .2 was amended to include essential components for assessment, planning, and referral as appropriate.

Changes were made in the "Immunizations" subsection to reflect updates for COVID-19, pneumococcal pneumonia, influenza, and respiratory syncytial virus. Table 4 .3 was revised to include important vaccination updates.

Recommendation 4.6 was modified to specify initial and repeat screening for autoimmune thyroid disease.

Recommendation 4.10 was updated to specify avoiding medications with known association with higher fracture risk. Recommendation 4.12 was revised to include the recommended intake of calcium for people with diabetes. Recommendation 4.13 was updated to specify when antiresorptive medications and osteoanabolic agents should be considered.

Table 4 .4 was updated to specify when bone mineral density testing should be performed.

A new subsection, "Dental Care," was added and includes two new recommendations. Recommendation 4.15 was added to state people with diabetes should be referred for a dental exam at least once per year. Recommendation 4.16 was added to state that efforts between medical and dental teams should be coordinated so that glucose-lowering medications can be appropriately adjusted prior to and in the post-dental procedure period as needed.

Figure 10 .5 was added to illustrate recommendations for screening for asymptomatic and undiagnosed cardiovascular disease, and Fig. 10 .6 was added to provide an overview of recommendations for the prevention of the development of symptomatic heart failure in people with diabetes.

Section 11. Chronic Kidney Disease and Risk Management (https://doi.org/10.2337/dc25-S011) Recommendation 11.3 was amended for clarity about optimizing blood pressure management goals.

Recommendation 11.4a was revised to clarify that ACE inhibitors or ARBs should be titrated to the maximally tolerated dose to prevent the progression of CKD and reduce cardiovascular events in nonpregnant individuals with diabetes and hypertension.

Recommendation 11.4b was modified to specify appropriate monitoring for increased serum creatinine levels, serum potassium levels, and hypokalemia when ACE inhibitors, ARBs, or mineralocorticoid receptor antagonists are used.

Recommendation 11.5b was updated to state that for people with type 2 diabetes and CKD, a GLP-1 RA with demonstrated benefit in this population should be used to reduce cardiovascular risk and kidney disease progression. Recommendation 11.6 was added to state that potentially harmful antihypertensive medications in pregnancy should be avoided in sexually active individuals of childbearing potential not using reliable contraception and to switch to options considered safer prior to conception and during pregnancy.

Recommendation 11.7 was updated to specify reducing urinary albumin by $30% to slow progression of CKD.

Recommendation 11.8 was updated to specify protein goals for individuals with stage 3 or higher CKD and those who are treated with dialysis.

Table 11 .1 was added to include reasons to consider non-diabetes-related kidney diseases in a person with CKD and diabetes, and Table 11 .3 was added to include suggestions for interventions that lower albuminuria. Section 12. Retinopathy, Neuropathy, and Foot Care (https://doi.org/10.2337/dc25-S012) Recommendation 12.5 was updated to specify involvement of an ophthalmologist for more frequent examinations if retinopathy is progressing or sight threatening.

Recommendation 12.8 wording was changed to reflect that a dilated eye exam should be performed before and in the first trimester, rather than one or the other.

Recommendation 12.19 was modified to include additional screening criteria for symptoms and signs of autonomic neuropathy.

Recommendation 12.22 was updated to recommend against opioid use for neuropathic pain treatment due to the potential for adverse events, and the narrative text was updated to expand on this.

A short discussion on the role of weight management and neuropathy was added to the narrative text.

Recommendation 12.24 was updated to include the Ipswich touch test as an option for neurological assessment.

Recommendation 12.29 was expanded to include the importance of smoke cessation and referral for counseling for individuals who smoke and have a prior history of lower-extremity complications, loss of protective sensation, structural abnormalities, or PAD.

Increasing role of surgery in diabetic foot management was added to the narrative text of foot care section.

Section 13. Older Adults (https://doi.org/10.2337/dc25-S013) The 4Ms framework of age-friendly health systems (Mentation, Medications, Mobility, and What Matters Most) as it applies to diabetes management in older adults was introduced and illustrated in the new Fig. 13 .1.

Recommendation 13.8a was modified to include time in range and time below range in addition to A1C treatment goals for older adults who are otherwise healthy with few and stable chronic conditions and intact cognitive functional status.

Recommendation 13.8b was modified to include time in range and time below range in addition to A1C treatment goals for older adults who have intermediate or complex health who are clinically heterogeneous with variable life expectancy.

Table 13 .1 was modified to include a column on reasonable CGM goals for each health status category.

In the "Treatment" section, the appropriate selection and use of SGLT2 inhibitors in older adults was expanded. Section 14. Children and Adolescents (https://doi.org/10.2337/dc25-S014) Recommendation 14.4 in the "Type 1 Diabetes" section was added to emphasize key nutrition principles. Recommendation 14.10 was altered to emphasize limits on sedentary activity. Recommendation 14.21 was changed to state that insulin pumps should be offered to anyone with type 1 diabetes who can use the devices safely. Recommendation 14.24 was modified to remove lack of access as a reason for less stringent A1C goals. Recommendation 14.26 was altered to include weight gain as a balancing measure for more stringent A1C goals. Recommendation 14.36 was changed to exclude secondary causes of hypertension. Recommendation 14.41 was updated to include the use of age-approved statins.

Recommendation 14.50 was modified to state that screening should be repeated at a minimum of 2-year intervals or more frequently if screening is normal and BMI is increasing. Recommendation 14.57 was revised to include the key nutritional principles and provide specific examples of healthy food choices and what foods should be avoided.

Recommendation 14.60 was changed to recommend an A1C goal of < 6.5% ( < 48 mmol/mol) for most children and adolescents with type 2 diabetes who have a low risk of hypoglycemia and a higher risk of complications.

Recommendation 14.65 was revised to change the terminology from "hyperglycemic hyperosmolar nonketotic syndrome" to "hyperglycemic hyperosmolar state" and include intravenous fluid as the initial step to treat severe hyperglycemia (blood glucose $600 mg/dL) once the diagnosis is confirmed.

The narrative was updated to reinforce the benefits and safety of GLP-1 RAs in decreasing A1C, weight, blood pressure, and insulin dose reduction. Figure 14 .1 was updated to reflect the revision in this recommendation.

Recommendation 14.73 was modified to reflect that excluding secondary hypertension is an essential step in hypertension management.

Recommendation 14.104 was revised to state that vaping and electronic cigarettes are both discouraged.

Recommendation 14.105 in the "Substance Use in Pediatric Diabetes" section was added to state that all youth with diabetes should be advised not to use cannabis recreationally in any form. Recommendation 14.108 was modified to encourage pediatric diabetes specialists to partner with youth with diabetes and their caregivers to engage in shared decision-making.

Tables 14.1A and 14.1B were modified to include changes made throughout Section 14.

Section 15. Management of Diabetes in Pregnancy

(https://doi.org/10.2337/dc25-S015) Section 15 was restructured to discuss the care of pregnant individuals with type 1 diabetes, type 2 diabetes, and GDM in all sections and to discuss aspects of management in each relevant subsection (e.g., preconception care and pharmacotherapy); consequently, the order of appearance of some of the recommendations changed. Recommendation 15.7 wording was changed to reflect that a dilated eye exam should be performed before and in the first trimester, rather than one or the other.

Table 15 .1 was updated with a folic acid supplement recommendation of 400-800 mg/day and clarification for which checklist items are only for individuals with preexisting diabetes and not for individuals with prediabetes or a history of GDM, and specific immunizations were omitted and referenced.

In Recommendation 15.10, the benefits of CGM use in type 1 diabetes and pregnancy were clarified, and an addition of its potential to be beneficial in other types of diabetes in pregnancy was added.

Recommendation 15.12 no longer states that CGM metrics should not be used as a substitute for blood glucose monitoring; the recommendation now states that CGM may be used in conjunction with blood glucose monitoring to achieve glycemic goals.

Glucose goals for preexisting diabetes, GDM treated with insulin, and GDM not treated with insulin are consolidated into a new Table 15 .2.

"Management of Gestational Diabetes Mellitus" and "Management of Preexisting Type 1 Diabetes and Type 2 Diabetes Pregnancy" were merged into one subsection, titled "Management of Diabetes in Pregnancy," which includes all aspects of management for all types of diabetes (e.g., nutrition, physical activity, and pharmacotherapy).

Recommendation 15.14 provides more clarification on the recommended eating pattern in pregnancy.

Insulin recommendations that were previously split into separate recommendations for preexisting diabetes and GDM were merged.

There are two new recommendations regarding AID use in type 1 diabetes and pregnancy. Recommendation 15.19 states that AID systems are recommended if the system has a pregnancy-specific glucose goal. Recommendation 15.20 states that AID systems may be considered for select individuals with an experienced health care team if the system does not have a pregnancy-specific glucose goal or algorithm.

Recommendation 15.21 provides more clarification for why metformin and glyburide should not be first-line agents for management of diabetes in pregnancy.

The narrative for subsection "Physical Activity" includes recommended activity levels for pregnancy, as these pertain to individuals with any type of diabetes in pregnancy.

The "Insulin" subsection includes information on different insulin delivery modalities used during labor and delivery or postpartum.

The recommendation to explicitly measure blood pressure during pregnancy is now mentioned in the narrative of the "Preeclampsia and Aspirin" subsection per the recent guidelines of the U.S. Preventive Services Task Force.

Recommendation 15.25 was split into two recommendations. Recommendation 15.25a provides more examples of potentially harmful medications in pregnancy. Recommendation 15.25b recommends that lipid-lowering medications be avoided in most circumstances in pregnancy but that statins may be considered for use in high-risk individuals (such as those with prior ASCVD and familial hypercholesterolemia) when benefits outweigh risks. The narrative discusses Recommendation 15.25b in more detail and includes discussion of studies of pravastatin use in pregnancy.

Section 16. Diabetes Care in the Hospital (https://doi.org/10.2337/dc25-S016) Diabetes care in the hospital stresses identification and treatment of dysglycemia and provides glycemic goals. For the treatment of persistent hyperglycemia starting at a threshold of $180 mg/dL ($10.0 mmol/L), Recommendation 16.4a was amended to reflect that insulin should be initiated or intensified for the majority of critically ill individuals, and Recommendation 16.4b was added to state that insulin and/or other glucose-lowering therapies should be initiated or intensified for the majority of noncritically ill individuals.

Recommendation 16.5a was updated to state that a glycemic goal of 140-180 mg/dL (7.8-10.0 mmol/L) is recommended for most critically ill individuals, but more stringent individualized glycemic goals may be appropriate if they can be achieved without significant hypoglycemia. Recommendation 16.5b was updated to recommend a glycemic goal of 100-180 mg/dL (5.6-10.0 mmol/L) for most noncritically ill individuals if it can be achieved without significant hypoglycemia.

Recommendation 16.7 was amended for clarity on the use of insulin pump or AID continuation and their use in people with diabetes who are hospitalized, when clinically appropriate.

Recommendation 16.8a was added to state that continuous intravenous insulin infusion is recommended for achieving glycemic goals and avoiding hypoglycemia in critically ill individuals.

The language regarding a hypoglycemia management surveillance protocol for health systems was updated for clarity in Recommendation 16.12.

Guidance regarding use of GLP-1 RA and dual GIP and GLP-1 RA medications in the perioperative setting and regarding instructions in preparation for procedures or surgery has been added to the narrative text.

Recommendations 16.14 and 16.15 were added for DKA and HHS management; transition to maintenance subcutaneous insulin administration and discharge planning were added. Additionally, the newly added Fig. 16 .1 includes treatment pathways for DKA and HHS.

Section 17. Diabetes Advocacy (https://doi.org/10.2337/dc25-S017) The subsections "Diabetes Care in the School Setting" and "Diabetes and Driving" were updated with information from recently published advocacy statements. The subsection "Diabetes Management in Detention Facilities" was added with information from a recently published advocacy statement. The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

DIABETES AND POPULATION HEALTH

Recommendations 1.1 Ensure treatment decisions are timely, rely on evidence-based guidelines, capture key elements within the social determinants of health, and are made collaboratively with people with or at risk for diabetes and caregivers based on individual preferences, prognoses, comorbidities, and informed financial considerations. B 1.2 Align approaches to diabetes management with evidence-based care models. These models emphasize person-centered team care, integrated longterm treatment approaches to diabetes and comorbidities, and ongoing collaborative communication and goal setting between all team members and with people with diabetes. A 1.3 Care systems should facilitate in-person and virtual team-based care, include those knowledgeable and experienced in diabetes management as part of the team, and utilize patient registries, decision support tools, proactive care planning, and community involvement to meet needs of individuals with diabetes. B 1.4 Assess diabetes management, risk factors, and complications (Table 4 .1) using reliable and relevant data metrics to improve processes of care and health outcomes, with attention to care costs, individual preferences and goals for care, and treatment burden. B 1.5 Health systems should adopt a culture of quality improvement, implement benchmarking programs, and engage interprofessional teams to support sustainable and scalable process changes to improve quality of care and health outcomes. A Population health is defined as "the health outcomes of a group of individuals, including the distribution of health outcomes within the group" (1) . These outcomes can be measured in terms of health indicators (mortality, morbidity, and functional status), disease epidemiology (incidence and prevalence), and behavioral and metabolic factors (physical activity, nutrition, A1C, time in range, etc.) (1) . Clinical practice recommendations are tools for health care professionals who seek to improve health across populations; however, for optimal outcomes, diabetes care must also be individualized for each person with diabetes and for each person's context, as well as across the life span. Thus, efforts to improve population health will require a combination of policy-level, system-level, and person-level approaches. With such an integrated approach in mind, the American Diabetes Association (ADA) highlights the importance of person-centered care, defined as care that considers an individual's comorbidities and prognoses; is respectful of and responsive to individual preferences, needs, and values; and ensures that the individual's values guide all clinical decisions (2) . Social determinants of health (SDOH)-factors often beyond an individual's direct control and potentially representing lifelong risks-play a significant role in both clinical and psychosocial outcomes. To improve health, support overall well-being, and eliminate disparities, it is crucial to address these determinants, particularly for individuals from racial and ethnic minority communities, underserved geographic areas (rural or urban), and those facing socioeconomic barriers to care and health (3) . This section discusses the current state of diabetes and diabetes care in the U.S. and provides guidance for health care professionals as well as health systems, community partners, payors, and policymakers on improving the delivery of diabetes care to improve the health of all people at risk for or living with diabetes.

To provide actionable guidance for improving the care for and health outcomes of people with and at risk for diabetes, this section examines care delivery and payment models demonstrated to support high-quality, evidence-based care; offers guidance on practical strategies for system-level improvement; and discusses opportunities to expand access to health care and diabetes self-management education and support (DSMES) through telehealth, mobile platforms, interprofessional team care, and engagement of community-based care partners and resources.

As SDOH have a central role in diabetes burden, management, and outcomes, the subsection TAILORING TREATMENT FOR SOCIAL CON- TEXT discusses the importance of screening individuals for SDOH, advises on strategies to identify disparities in diabetes management and outcomes experienced by at-risk populations, and offers actionable guidance for addressing SDOH and health disparities at the individual and population levels.

State of Diabetes Care

The proportion of people with diabetes who achieve recommended A1C, blood pressure, and LDL cholesterol levels has fluctuated over the years, with some improvement over time (4, 5) . In 2015-2018 (the most recent time period with population-level data available), just 50.5% of U.S. community-dwelling adults with diabetes achieved A1C < 7% and 75.4% achieved A1C < 8% (5) . The goal blood pressure of < 130/80 mmHg was achieved by just 47.7% of adults with diabetes, while 70.4% achieved blood pressure < 140/90 mmHg (5) . Lipid goals, defined in these studies as non-HDL cholesterol < 130 mg/dL, was achieved by 55.7% of adults with diabetes, and all three risk factors were treated to goal in just 22.2% (5) . Importantly, many people who did not attain A1C, blood pressure, and lipid goals were not receiving any or adequate pharmacotherapy for glycemic, hypertension, and dyslipidemia management, respectively, which underscores the urgent need for care delivery systems and structural facilitators (i.e., health and public health policies and payment models) that enable timely and equitable delivery of evidencebased care and address diabetes prevention and treatment in communities (5) . Many segments of the population, such as children, young adults, and individuals with complex health needs, financial or other social hardships, and/or limited English proficiency, as well as individuals in groups that have been historically marginalized, face particular challenges to diabetes management (6) (7) (8) . A U.S. populationbased study based on National Health and Nutrition Examination Survey (NHANES) data showed that younger people with diabetes, Mexican American people, non-Hispanic Black people, those with a lower level of educational attainment, and those who are underinsured are most likely to be undertreated, particularly for glycemic management (5) .

Gaps and disparities in diabetes management and outcomes are also prevalent among youth with diabetes in the U.S. Data from SEARCH for Diabetes in Youth (SEARCH), a population-based registry network of five centers across five U.S. states, showed that in 2014-2019, mean A1C was 9.1% (SD 2.0) among youth and young adults with type 1 diabetes and 8.9% (SD 2.9) in youth and young adults with type 2 diabetes; these values increased from 8.5% (SD 1.5) and 8.4% (SD 2.8), respectively, in 2002-2007 (9) . In youth and young adults with type 1 diabetes, identifying as a non-Hispanic Black person or a Native American person (compared with identifying as a non-Hispanic White person), being younger, not being treated with insulin pump therapy, and having low annual household income were associated with a higher A1C level (9) . Data from the T1D Exchange Quality Improvement Collaborative (T1DX-QI), a learning health network of pediatric and adult centers across the U.S., revealed that between 2016 and 2018, mean A1C was 8.1% (65 mmol/mol) among children with type 1 diabetes 5 years of age and 9.3% (78 mmol/mol) among children 15-18 years of age. Only 17% of youth under 18 years of age with type 1 diabetes achieved the recommended A1C goal of < 7.5% ( < 58 mmol/mol), and A1C levels for non-Hispanic Black youth were higher than those for non-Hispanic or Hispanic White youth-a disparity that persisted after adjustment for socioeconomic status (10) .

Diabetes and its associated health complications pose a significant financial hardship to individuals and society. It is estimated that the annual cost of diagnosed diabetes in the U.S. in 2022 was $413 billion, including $307 billion in direct health care costs and $106 billion in reduced productivity (11) . After adjusting for inflation, the economic costs of diabetes increased by 7% between 2017 and 2022 and by 35% between 2012 and 2022 (11) . This is attributed to both the increased prevalence of diabetes and the higher cost per person with diabetes. People living with diabetes also face financial hardship, which is correlated with higher A1C, diabetes distress, and depressive symptoms (12) .

The growing gaps in diabetes care quality and outcomes, the high and rising costs of diabetes care across the U.S., and the disparities experienced by individuals from racial and ethnic minoritized backgrounds and those facing socioeconomic barriers to care call for urgent, substantial, and multisectoral system-level improvements to care delivery (13) .

Evidence-Based Care Models to Improve Population Health

A major barrier to optimal and comprehensive diabetes care is a delivery system that is often fragmented, lacks clinical information capabilities, is not appropriately incentivized and funded, does not adequately engage people with diabetes and the communities where they live, and is poorly designed for the coordinated and longitudinal delivery of chronic care (14) . Several models have been demonstrated to improve aspects of diabetes care delivery and health outcomes.

The Chronic Care Model (CCM) is a commonly used framework for describing diabetes care programs (15) . It includes six core elements to optimize the care of people with chronic disease: 1. Delivery system design (moving from a reactive to a proactive care delivery system where planned visits are coordinated through a team-based approach) 2. Self-management support 3. Decision support, particularly at the point of care during a clinical encounter (basing care on evidence-based, effective care guidelines) 4. Clinical information systems (using registries that can provide personspecific and population-based support to the care team) 5. Community resources and policies (identifying or developing resources to support healthy lifestyles) 6. Health systems (to create a qualityoriented culture)

Randomized controlled trials of CCM interventions have shown that while interventions vary, programs that include core components of the CCM decrease A1C (mean difference -0.21% [95% CI -0.30 to -0.13], P < 0.001 compared with usual care), with greater improvements seen among adults with higher baseline A1C and with interventions that include four or more CCM elements (16) . CCM-aligned programs also improved blood pressure levels and processes of diabetes care (e.g., screening for complications of diabetes), though there was no impact on cholesterol levels, tobacco use, or weight (17) . Multiple studies have examined individual components of the CCM with respect to diabetes management and have found inconsistent levels of benefit with case management, teambased care, use of electronic patient registries, clinician education, clinician and patient reminders, and patient education and promotion of individual self-management (18) . The inconsistencies in findings may be driven by heterogeneity of interventions, settings, and evaluation strategies. Collaborative, interprofessional teams, which can bring together multiple disciplines within the health care system, payors, and community partners, are best suited to provide care for people with chronic conditions such as diabetes and to facilitate individuals' self-management (Table 1 .1) (19) (20) (21) (22) (23) (24) (25) . The care team, which centers around the person with diabetes, should avoid therapeutic inertia and prioritize timely and appropriate intensification of behavior change (nutrition and physical activity), pharmacologic therapy, and/or social and financial support systems for individuals who have not achieved recommended metabolic goals or are experiencing high burden of treatment.

Initiatives such as the Patient-Centered Medical Home (PCMH) model can improve health outcomes by fostering comprehensive primary care and offering new opportunities for team-based chronic disease management (26) (27) (28) . Accountable Care Organizations (ACOs), a primary carecentered delivery and payment model, can support the implementation of the CCM and ultimately improve diabetesrelated metrics in participating organizations (29) . The Accountable Health Communities Model was introduced to support identifying and addressing health-related social needs to improve disease management and health outcomes (30) ; early evidence showed reduction in emergency department use among Medicare and Medicaid beneficiaries, but diabetes-specific metrics were not examined, and program effectiveness has been limited by scarcity of resources to meet identified healthrelated social needs (31) . Alternative Payment Models (APMs) have had mixed effects on diabetes care delivery and outcomes, with higher-risk APMs (i.e., models with greater financial risk assumed by the provider, such as capitated payment models) generally associated with greater improvements in diabetes care processes than lower-risk APMs (32) . Value-based payment models are hypothesized to better support the implementation and sustainability of innovative care delivery models seeking to improve population health (26, 33) , though evidence for currently available value-based insurance designs is limited (32) .

Telehealth

Telehealth uses digital tools like video conferencing, mobile apps, and remote monitoring to deliver a range of health services remotely, including clinical care, education, and administrative support. Telemedicine, a subset of telehealth, focuses specifically on remote clinical care, such as diagnosis, treatment, and consultations through real-timecommunication. Increased access to and effective use of telehealth services, alongside in-person care, can enhance timely access to diabetes care and DSMES services for individuals with diabetes (34) (35) (36) (37) (38) .

Telehealth should be used to complement but not replace in-person visits for optimal glycemic management (39, 40) . Increasingly, evidence suggests that various telehealth modalities may facilitate reducing A1C in people with type 2 diabetes compared with usual care or in addition to usual care (41) , and findings suggest that telemedicine is a safe method of delivering care for people with type 1 diabetes in rural areas (42) . For rural populations or those with limited physical access to health care, telehealth has a growing body of evidence for its effectiveness, particularly with regard to glycemic management as measured by A1C (43) (44) (45) (46) . In addition, evidence supports the effectiveness of telehealth in hypertension and dyslipidemia interventions (47) . Interactive strategies that facilitate communication between health care professionals and people with diabetes, including the use of web-based portals or text messaging and those that incorporate medication adjustment, appear to be effective in improving outcomes (44, 48) . Telehealth and other virtual environments can be used to offer diabetes self-management education and clinical support and remove geographic and transportation barriers for individuals living in underresourced areas or with disabilities (49) . Telehealth resources can also have a role in improving diabetes management in children and adolescents with type 1 diabetes (50) and addressing SDOH in young adults with diabetes (51) . Optimally leveraging telehealth to improve diabetes management requires anticipating and addressing barriers posed by cost, capacity, and resources (including broadband internet access) of people with diabetes and the existing clinical infrastructure into which telehealth approaches are being integrated (52) .

Strategies for System-Level Improvement

Optimal diabetes management requires a systematic approach and coordinated team of health care professionals working in an environment where personcentered, high-quality care is a priority (8, 17, 53, 54) . While many diabetes care processes and access to technologies have improved nationally in the past decade, the overall quality of care for people with diabetes remains suboptimal (5) . Efforts to increase the quality of diabetes care include providing care that is concordant with evidence-based guidelines (54) , expanding the role of teams to implement more intensive disease management strategies (19) , tracking medication-taking behavior (55) , redesigning care processes (56) , implementing electronic health record (EHR) population health tools (57) , empowering and educating people with diabetes (58) , reducing financial barriers (59) , leveraging telehealth to improve access to care (43) , assessing and addressing psychosocial issues (60, 61) , and engaging community resources and public policies that support healthy lifestyles (62) . The National Diabetes Education Program maintains an online resource (cdc.gov/diabetes/php/toolkits/index. html) to help health care professionals design and implement more effective health care delivery systems for people with diabetes. Given the pluralistic needs of people with diabetes and that the challenges they experience (complex insulin treatment plans, new technologies, changes in capacity for self-management, etc.) vary over the course of disease management and life span, engagement of an interprofessional team with complementary expertise is essential (20) .

Behaviors and Well-being

Successful diabetes care also requires a systematic approach to supporting the behavior-change efforts of people with diabetes. High-quality DSMES has been shown to improve a person's self-management, satisfaction, and glycemic outcomes (see Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes," for a detailed review of the evidence supporting DSMES). National DSMES standards call for an integrated approach that includes clinical content and skills, behavioral strategies (goal setting, problem-solving, etc.), and engagement with psychosocial concerns (61) . Increasingly, such support is available through online or mobile platforms that can support user access and effectiveness. These curricula should be tailored to the needs of their intended populations, including addressing the "digital divide," i.e., access to the technology required for implementation (46, 63) .

Cost Considerations for Medication-Taking Behaviors

The cost of diabetes medications and devices is an ongoing barrier to achieving glycemic goals. Based on a national survey conducted in 2021, 18.6% of U.S. adults with type 1 diabetes and 15.8% of adults with insulin-treated type 2 diabetes reported rationing (i.e., skipping, taking less, and/or delaying) their insulin to save money (64) . Insulin underuse due to cost has been termed "cost-related medication nonadherence" (here referred to as cost-related barriers to medication use).

The ADA Insulin Access and Affordability Working Group has recommended system-level approaches to address this issue, including concepts such as costsharing for insured people with diabetes based on the lowest price available, a list price for insulins that closely reflects the net price, and health plans that ensure people with diabetes can access insulin without undue administrative burden or excessive cost (65) . In 2021, the Centers for Medicare & Medicaid Services (CMS) launched the Part D Senior Savings Model (66) , which requires participating plans to cover insulins with a $35 maximum monthly out-of-pocket payment. In 2022, 43% of stand-alone Part D plan enrollees and 60% of Medicare Advantage Part D plan enrollees participated in the Senior Savings Model (67) . Most recently, the Inflation Reduction Act of 2022 capped out-of-pocket payments for insulin at $35 per insulin per month for all Medicare beneficiaries. A patchwork of solutions has also been introduced for individuals with commercial insurance and those without health insurance. Over the past 5 years, 25 states and the District of Columbia have capped out-of-pocket expenditures for insulin in select state-regulated commercial health plans (68) . Between 2023 and 2024, three major insulin manufacturers similarly lowered the price of insulin to $35 per month in select circumstances (69) . These programs may help reduce the financial hardship of diabetes management, though many are challenging to navigate, not all people with diabetes can benefit, and costs for insulin delivery and glucose monitoring remain high. Thus, all people with diabetes should be screened for financial hardship of treatment, cost-related barriers to medication use, and rationing of other essential services due to medical costs (70) .

The cost of medications (not only insulin) influences prescribing patterns and medication use because of the financial strain on the person with diabetes and the lack of secondary payor support (public and private insurance) for effective approved glucose-lowering, cardiovascular and kidney disease risk-reducing, and weight management therapies. There is robust evidence of disparities in the use of evidence-based therapies among individuals from racial and ethnic minoritized backgrounds, those with lower income levels, those living in rural areas, and those with limited insurance coverage (4, (71) (72) (73) (74) (75) (76) (77) (78) (79) (80) . Financial barriers remain a major source of health disparities, and costs should be a focus of treatment goals and clinical decisions (81) . (See TAILORING TREATMENT FOR SOCIAL CONTEXT.) Reduction in cost-related barriers to medication use is associated with better health outcomes and quality of life (82) .

Access to Care

Recommendation 4.17 was updated to reflect that an assessment for disability should be performed at the initial visit and an assessment for decline in function should be performed at each subsequent visit. Recommendation 4.18 was modified to include inquiring about sexual health in men and to screen with a morning serum total testosterone if symptoms and/or signs of hypogonadism are present. Recommendation 4.19 was added to specifically state that men with diabetes or prediabetes should be screened for erectile dysfunction, and new text was added on erectile dysfunction.

A new subsection, "Female Sexual Dysfunction," was added and includes two new recommendations. Recommendation 4.20 states that health care professionals should inquire about sexual health, particularly in women who experience depression and/or anxiety and those with recurrent urinary tract infections. Recommendation 4.21 was added to state that health care professionals should screen for symptoms and/or signs of genitourinary syndrome of menopause.

The terminology for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) was updated to metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunctionassociated steatohepatitis (MASH), respectively. This updated nomenclature was incorporated throughout the section.

Recommendation 4.22a was revised to specify when to screen for the risk of having or developing cirrhosis related to MASH using the calculated fibrosis-4 index (FIB-4).

Recommendation 4.23 was amended to state that adults with type 2 diabetes or prediabetes and a FIB-4 > 1.3 should have additional risk stratification performed. Recommendation 4.24 was revised to state that individuals with a higher risk for significant liver fibrosis should be referred to a gastroenterologist or hepatologist.

Recommendation 4.25 was revised to include an interprofessional team approach when promoting weight loss, particularly with a structured nutrition plan and physical activity program for cardiometabolic benefits and histological improvement.

Recommendation 4.26 was revised to include a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide 1 (GLP-1) receptor agonist (RA) with potential benefits in MASH as an adjunctive therapy to lifestyle interventions for weight loss in adults with type 2 diabetes, MASLD, and overweight or obesity.

Recommendation 4.27a was revised to state that in adults with type 2 diabetes and biopsy-proven MASH or those at high risk for liver fibrosis, use of pioglitazone or a GLP-1 RA or a dual GIP and GLP-1 RA is preferred for glycemic management due to potential beneficial effects on MASH. Recommendation 4.27b was added to state that combination therapy with pioglitazone and a GLP-1 RA can be considered for treatment of hyperglycemia in adults with type 2 diabetes with biopsyproven MASH or those at high risk of liver fibrosis because of potential beneficial effects of such a combination on MASH.

Recommendation 4.28 was added to state that treatment with a thyroid hormone receptor-b agonist in adults with type 2 diabetes or prediabetes with MASLD with moderate (F2) or advanced (F3) liver fibrosis may be considered and that the individual should be referred to a gastroenterologist or hepatologist with expertise in MASLD management for the initiation and monitoring of this therapy.

Recommendation 4.29 was added to emphasize that treatment initiation and monitoring should be individualized and within the context of an interprofessional team for MASLD and MASH management. (https://doi.org/10.2337/dc25-S005) In the "Diabetes Self-Management Education and Support" subsection, Recommendation 5.1 was updated to emphasize that all people with diabetes should be advised to participate in diabetes selfmanagement education and support (DSMES) rather than being just encouraged to participate. Recommendation 5.2 was updated to clarify when to provide DSMES. Recommendation 5.3 was revised to be more succinct and action-oriented, placing emphasis on routine assessment of key goals of DSMES.

Recommendation 5.4 was added to emphasize the importance of screening for behavioral health concerns at the same time points as evaluating the need for DSMES.

Language in Recommendation 5.5 was updated to state that DSMES should be culturally appropriate and responsive to individual preferences, needs, and values. Recommendation 5.6 was updated to reflect the now-common practice of remote-delivery of DSMES and reimbursement for remotely delivered modalities. Recommendation 5.9 was updated to reinforce the importance of screening for and including social determinants of health in guiding the design and delivery of DSMES.

In the "Medical Nutrition Therapy" subsection, Recommendation 5.12 was updated to emphasize the importance of providing treatment based on nutrition, physical activity, and behavioral therapy for individuals with overweight or obesity, aiming for at least 3-7% weight loss.

Recommendation 5.14 on eating patterns now has revised verbiage to include processed foods, lean proteins, and nondairy alternatives.

Recommendation 5.16 was updated to include actionable language and clarity regarding the use of dietary supplements for glycemic benefits.

Recommendations 5.17 and 5.18 were updated to have revised and actionable language, respectively. Recommendation 5.19 was updated to use actionable language.

Recommendation 5.20 was revised to recommend limiting sodium as clinically appropriate, which can be done, in part, by limiting consumption of processed foods.

Recommendation 5.21 was modified to recommend water over nutritive and nonnutritive sweetened beverages, and Recommendation 5.22 was added to state that nonnutritive sweeteners can be used instead of sugar-sweetened products in moderation and for short term to reduce overall calorie and carbohydrate intake.

Recommendation 5.23 was added to emphasize the screening for malnutrition, especially for those who have undergone metabolic surgery and for those being treated with weight management pharmacological therapies.

Recommendation 5.25 was revised to use actionable language.

Recommendation 5.26 was added to address the issue of sodium-glucose cotransporter (SGLT) inhibition being associated with ketoacidosis under certain conditions. It provides guidance on awareness, prevention, risk mitigation, and dietary adjustments.

Recommendation 5.29 was added to encourage intake of plant-based proteins and fiber, and Recommendation 5.31 was added to encourage limiting foods high in saturated fats to reduce cardiovascular disease risk.

Two new recommendations were added for religious fasting. Recommendation 5.32 states to use the Diabetes and Ramadan International Alliance comprehensive prefasting risk assessment for risk stratification of people with diabetes prior to engaging in religious fasting. Recommendation 5.33 was created to provide guidance to health care professionals caring for people with diabetes who participate in religious fasting.

Additionally, newly added Fig. 5 .1 illustrates differences and similarities between religious and intermittent fasting for people with diabetes. Table 5 .4 includes a risk calculation and suggested risk score for people with diabetes who seek to fast during Ramadan, and Table 5 .5 includes information about medication changes during fasting.

In the "Physical Activity" subsection, Recommendation 5.34 was updated to include a statement about limiting the amount of time spent sedentary, which includes recreational screen time.

Recommendation 5.38 was modified to state that prolonged sitting should be interrupted at least every 30 min for glycemic benefits.

Recommendation 5.39 was added to counsel adults and youth receiving weight management pharmacotherapy or metabolic surgery to meet physical activity recommendations. The accompanying text addresses the concern of sarcopenic obesity with use of incretin therapies and metabolic surgery.

In the "Smoking Cessation: Tobacco, E-cigarettes, and Cannabis" subsection, Recommendation 5.42 was added to advise people with type 1 diabetes and those with other forms of diabetes at risk for diabetic ketoacidosis (DKA) to not use recreational cannabis in any form due to the risk of cannabis hyperemesis syndrome. The accompanying text describes cannabis hyperemesis syndrome and its diagnostic criteria. Recommendation 5.43 in "Supporting Positive Health Behaviors" was updated to include health-related quality of life as an outcome when using behavioral health strategies to support self-management and healthy behaviors.

Recommendation 5.45 in "Psychosocial Care" was revised to state the specific psychosocial concerns health care professionals should screen for including diabetes distress, depression, anxiety, fear of hypoglycemia, and disordered eating behaviors. Recommendation 5.48 in "Diabetes Distress" was updated to recommend the frequency of at least annual screening for diabetes distress in people with diabetes, caregivers, and family members. Recommendation 5.49 in "Anxiety" was updated to recommend screening for anxiety, which is in accordance with the U.S. Preventive Services Task Force recommendation for screening for anxiety.

Recommendation 5.50 in "Anxiety" was added to include a recommendation for screening for fear of hypoglycemia in people with diabetes at risk for hypoglycemia or fear of hypoglycemia. Recommendation 5.51 in "Depression" was modified to have more actionable language for the importance of depression rescreening.

Recommendation 5.54 in "Disordered Eating Behavior" was updated to recommend screening for disordered or disrupted eating using validated screening measures.

The accompanying text describes the disordered or disrupted eating behaviors commonly reported in people with diabetes.

Tables 5.7 and 5.8 were added to illustrate psychosocial concerns and their association with diabetes-related outcomes in adults with type 1 and type 2 diabetes, respectively. Section 6. Glycemic Goals and Hypoglycemia (https://doi.org/10.2337/dc25-S006) Recommendation 6.12 was added to promote routine screening for fear of hypoglycemia in individuals at risk for hypoglycemia.

A new subsection entitled "Hyperglycemic Crises: Diagnosis, Management, and Prevention" was added to cover the epidemiology, diagnostic criteria, and outpatient prevention of DKA and the hyperglycemic hyperosmolar state (HHS).

New recommendations on routine assessment of history of DKA and HHS (recommendation 6.20) and providing structured prevention education (Recommendation 6.21) in the outpatient setting were added. Tables 6 .9 and 6.10 were added and include risk factors for hyperglycemic crises as well as clinical presentation of DKA and HHS in people with diabetes, respectively. Figure 6 .2 was revised to provide a specific and actionable approach to selecting individual glycemic goals, accounting for health status and other person-and treatment-specific factors favoring more or less stringent goals.

Section 7. Diabetes Technology (https://doi.org/10.2337/dc25-S007) Recommendation 7.8 was modified to emphasize consideration for starting diabetes technology early, even at diagnosis. Recommendation 7.9 was added to emphasize that reports for all continuous glucose monitoring (CGM) devices, connected insulin devices, and continuous subcutaneous insulin infusion and automated insulin delivery (AID) systems should be standardized with at a minimum the ambulatory glucose profile and weekly summary. In addition, there should be options for raw data or daily and weekly reports available to the health care professionals.

Recommendation 7.14 was modified to make the clinician aware of potential interference of medications and other substances on glucose levels measured by blood glucose meters.

Table 7 .2 was modified to include the various potential substances or medical conditions that may affect glucose levels when measured by blood glucose meters.

Table 7 .3 was modified to include the description of over-the-counter CGM devices.

Recommendation 7.15 was modified to support the use of real-time CGM (rtCGM) and intermittently scanned CGM (isCGM) for youth and adults with diabetes (type 1 or type 2) on any type of insulin therapy based on the most recent literature. Recommendation 7.16 was added to consider the use of rtCGM or isCGM in adults with type 2 diabetes on glucoselowering agents other than insulin to achieve and maintain individualized glycemic goals.

Recommendation 7.18 was modified to align with Section 15, "Management of Diabetes in Pregnancy," and reflect the update of CGM benefits in type 1 diabetes and pregnancy and other types of diabetes in pregnancy.

The text on CGM was expanded to include the updated sensors integrated with AID systems and to update the most recent literature evidence supporting the benefits of CGM in individuals with type 2 diabetes on glucose-lowering agents other than insulin from clinical trials and realworld studies. Furthermore, the CGM section was expanded to include the need to standardize any diabetes technology device reports and to provide clinicians not only with single page summaries but also with access to detailed reports and even raw data from devices, especially those reporting insulin dose modifications, such as AID systems.

The text on insulin pumps and AID systems was greatly expanded to discuss the features of the various AID systems and their data from pivotal trials and real-world studies in type 1 and type 2 diabetes. Recommendation 7.29 was modified to include provision of support and diabetes management advice in people with diabetes using open-source closed-loop systems.

The text for open-source closed-loop systems was also expanded to include the most recent published evidence on the safety and effectiveness of these systems in people with type 1 diabetes. Recommendation 7.30 was expanded to include the benefits of combining technology with online or virtual coaching to improve glycemic outcomes in individuals with diabetes and prediabetes.

Recommendation 7.32 was refined to emphasize the importance of continuing the use of insulin pumps or AID in people with diabetes while hospitalized when clinically appropriate and with confirmatory point-of-care blood glucose measurements for insulin dose adjustments and hypoglycemia assessment and treatment. The use of these devices in the inpatient setting should be contingent on the availability of infrastructure support and institutional diabetes technology protocols. (https://doi.org/10.2337/dc25-S008) Recommendation 8.2a was updated to clarify that additional measurements of body fat distribution are warranted if BMI is indeterminant. Recommendation 8.2b was revised to recommend monitoring of obesity-related anthropometric measurements at least every 3 months during active weight management treatment.

Discussion of weight stigma and bias toward people living in larger bodies was added to the text. Recommendation 8.11 was enhanced to reflect the importance of continued monitoring, support, and interventions for individuals who have achieved weight loss goals to support the maintenance of these goals long term.

Recommendation 8.18 was added to recommend screening for malnutrition for people with diabetes and obesity who have lost significant weight. Recommendation 8.19 was added to recommend continuing weight management pharmacotherapy, as indicated, beyond reaching weight loss goals to maintain health benefits and avoid weight regain and worsening of cardiometabolic abnormalities that often result from sudden discontinuation of weight management pharmacotherapy.

Recommendation 8.25 was revised to emphasize use of a CGM device to improve safety in individuals with postmetabolic surgery hypoglycemia.

Updated Tables 8.1 and 8.2 provide detailed information on the efficacy, common side effects, safety considerations, and costs of approved weight management pharmacotherapy options.

Discussion of medication cost and access barriers was added to the text, including suggestions to members of the interprofessional diabetes care team on mitigating financial barriers.

Section 9. Pharmacologic Approaches to Glycemic Treatment (https://doi.org/10.2337/dc25-S009) This section was reorganized and expanded with two new subsections: 1) a subsection titled "Additional Recommendations for All Individuals With Diabetes" that includes new recommendations as well as recommendations previously listed with those for individuals with type 1 or type 2 diabetes if pertinent to individuals regardless of their type of diabetes, and 2) a subsection titled "Special Circumstances and Populations."

Figure 9 .1 was revised for clarity, and a general statement was added to Table 9 .1 on dose adjustments when using AID systems.

The subsection on insulin administration technique was expanded to address inhaled insulin and use of insulin bolus patches.

Recommendation 9.8 was revised to emphasize the importance of selecting glucose-lowering medications that provide sufficient effectiveness and achieve and maintain multiple treatment goals simultaneously, including improving cardiovascular, kidney, weight, and other relevant outcomes, reducing hypoglycemia risk, and considering cost, access, risk for adverse reactions, and individual preferences.

Recommendations were revised to explicitly advise on choice of pharmacotherapy for individuals with type 2 diabetes and established or high risk of atherosclerotic cardiovascular disease (ASCVD) (Recommendation 9.10), heart failure (Recommendation 9.11), and chronic kidney disease (CKD) (Recommendation 9.12) to improve health outcomes for individuals with these conditions irrespective of A1C. Recommendation 9.12 was added to recommend use of GLP-1 RA with demonstrated benefits in individuals with type 2 diabetes, symptomatic heart failure with preserved ejection fraction, and obesity. Recommendation 9.13 was revised to recommend use of either SGLT2 inhibitor or GLP-1 RA with demonstrated benefits in individuals with type 2 diabetes and CKD.

Recommendations 9.15 and 9.16 were added to recommend treatment of individuals with type 2 diabetes and MASLD or MASH with GLP-1 RA, dual GIP and GLP-1 RA, pioglitazone, or a combination of GLP-1 RA and pioglitazone based on the staging of liver disease risk and need for weight management.

Figure 9 .3 and the text discussing choice of glucose-lowering therapy in adults with type 2 diabetes were extensively revised to facilitate evidence-based selection of glucose-lowering therapies based on individualized treatment goals. Considerations of glucose-lowering medication effects on MASLD and MASH were added to Fig. 9 .3. Table 9 .2 was simplified and revised to better highlight important considerations when choosing medications for lowering glucose in type 2 diabetes. Recommendation 9.20 was clarified to recommend reassessing the need for and/or dose of medications with higher hypoglycemia risk (i.e., sulfonylureas, meglitinides, and insulin) when initiating a new glucoselowering medication to minimize the risk of hypoglycemia and treatment burden.

Recommendation 9.21 was added to advise against concurrent use of a dipeptidyl peptidase 4 inhibitor with a GLP-1 RA due to lack of additional glucose lowering beyond that of a GLP-1 RA alone. Recommendation 9.24 was clarified by specifying that a GLP-1 RA or a dual GIP and GLP-1 RA is preferred to insulin in adults with type 2 diabetes only in the absence of evidence of insulin deficiency.

Text in the "Basal Insulin" section was revised to provide guidance on switching between different basal insulin formulations.

Figure 9 .4 was revised for clarity, and the list of options for prandial insulin was expanded.

Recommendation 9.27 was revised to remove consideration of basal insulin doses exceeding 0.5 units/kg/day as evidence of overbasalization. Instead, signs of overbasalization including significant bedtime-to-morning or postprandial-topreprandial glucose differential, occurrences of hypoglycemia (aware or unaware), and high glycemic variability should be used.

Tables 9.3 and 9.4 were updated with glucose-lowering medication and insulin costs as of 1 July 2024, and an expanded discussion on medication costs and affordability was added to the text.

In the new subsection "Special Circumstances and Populations," Recommendations 9.31a, 9.31b, and 9.31c were added to advise on actions to take when medications are not available (such as medication shortages); Recommendations 9.32a and 9.32b were added to address care considerations for individuals of childbearing potential; and Recommendation 9.33 was added to provide guidance on mitigating risk of ketoacidosis when individuals at risk for ketoacidosis or who follow a ketogenic eating pattern are treated with SGLT inhibition. Additional text in this subsection discusses considerations for glucoselowering pharmacotherapy for individuals with diabetes secondary to chemotherapy and with other types of diabetes (i.e., pancreatogenic diabetes, cystic fibrosisrelated diabetes, posttransplant diabetes, maturity-onset diabetes of the young, and neonatal diabetes).

Section 10. Cardiovascular Disease and Risk Management (https://doi.org/10.2337/dc25-S010) Recommendation 10.1 was updated with details on the frequency of recommended blood pressure monitoring.

Figure 10 .2 was updated to provide clarity on medication classes for the treatment of confirmed hypertension in nonpregnant people with diabetes.

Recommendation 10.12 was modified to specify appropriate monitoring for increased serum creatinine levels, serum potassium levels, and hypokalemia when ACE inhibitors, angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists are used.

Recommendation 10.13 was added to specify hypertension treatment options that should be avoided during pregnancy and in sexually active individuals of childbearing potential not using reliable contraception.

Recommendation 10.26 was added to recommend that in most cases lipidlowering agents should be discontinued prior to conception and avoided in sexually active individuals of childbearing potential not using reliable contraception, unless the benefits may outweigh the risk.

Figures 10.3 and 10.4 were added to illustrate recommendations for primary prevention and secondary prevention of ASCVD, respectively, in people with diabetes using cholesterol-lowering therapy.

Triglyceride thresholds were updated in Recommendations 10.31 and 10. 32 .

The criteria for coronary artery disease investigations in Recommendation 10.39b were revised to include signs or symptoms of cardiac or associated vascular disease or electrocardiogram abnormalities.

Recommendation 10.41 was modified to include screening for peripheral artery disease (PAD) with ankle-brachial index testing in asymptomatic people with diabetes aged $65 years, microvascular disease in any location, or foot complications or any end-organ damage from diabetes if a PAD diagnosis would change management. PAD screening should also be considered in individuals with diabetes duration $10 years and high cardiovascular risk.

For individuals with type 2 diabetes, obesity, and symptomatic heart failure with preserved ejection fraction, Recommendation 10.46d was added to recommend treatment with a GLP-1 RA with demonstrated benefit in this population to reduce heart failure-related symptoms, reduce physical limitations, and improve exercise function.

The Affordable Care Act and Medicaid expansion have increased access to care for many individuals with diabetes, emphasizing the protection of people with preexisting conditions, health promotion, and disease prevention (83) . In fact, health insurance coverage increased from 84.7% in 2009 to 90. 1% in 2016 for adults with diabetes aged 18-64 years. As of early 2022, more than 35 million people in the U.S. were enrolled in some form of Affordable Care Act-related health insurance (84) . Coverage for those aged $65 years remained nearly universal (85) . People with diabetes who have either private or public insurance coverage are more likely to meet quality indicators for diabetes care (86) . However, even individuals with insurance coverage can experience financial barriers to care, particularly if enrolled in high-deductible health plans. In 2021, 28% of individuals with employersponsored health plans were enrolled in high-deductible health plans (87) . Such plans are increasing in popularity; by 2023, 51% of private industry employees had the option to enroll in a high-deductible health plan, although only 36% had access to health savings accounts, which can offset some of the out-of-pocket costs incurred with high-deductible plans (88) . Switching to a high-deductible health plan has been shown to increase financial hardship among people with diabetes (89), decrease and delay screening for retinopathy (90) , decrease blood pressure and A1C monitoring (90) , and increase the risks of experiencing both acute (severe hypoglycemia, hyperglycemic crises) (91) and chronic (myocardial infarction, stroke, hospitalization for heart failure, kidney failure, lower-extremity complications, proliferative retinopathy, and blindness) (92) diabetes complications. Insurance coverage and formulary design influence treatment decisions; it is essential that payors cover evidence-based diabetes care with minimal cost sharing by the person with diabetes. Health care teams should also discuss insurance coverage and financial barriers to care with all individuals with diabetes and pursue therapeutic strategies that minimize financial hardship.

Access to primary and specialty care is also essential for people with diabetes. While most adults with diabetes have access to a primary care clinician (a 2016 nationally representative population-based study found that 88% of adults with diabetes saw a primary care clinician in the prior year) (93) , fewer have access to specialty endocrinology/ diabetes care (94) . A study of Medicare beneficiaries found that just 33% of older adults with type 1 diabetes, 14% of adults with type 2 diabetes and history of severe hypoglycemia, and 9% of other adults with type 2 diabetes saw an endocrinologist in 2019 (94) . Racial and ethnic minoritized individuals, those with low income, those living in rural areas, and those residing in a longterm care facility were less likely to receive endocrinology care. Improving health outcomes for people with diabetes will therefore require improving availability of and access to primary and specialty services necessary to meet the full range of their health care needs (Table 1 .1).

Quality Improvement

A recent Cochrane systematic review concluded that quality improvement (QI) can significantly improve outcomes for people with diabetes (18) . As mandated by the Affordable Care Act, the Agency for Healthcare Research and Quality developed a National Quality Strategy based on three aims: improving the health of populations, improving overall quality and the personal experience of care, and reducing per capita cost (95) . QI methods have been documented to improve diabetes device uptake, increase screening for psychosocial care, and reduce inequities in access to diabetes technologies (96) (97) (98) (99) . Information and guidance specific to quality improvement and practice transformation for diabetes care are available from the National Institute of Diabetes and Digestive and Kidney Diseases guidance on diabetes care and quality (100) .

A successful QI team should include a clinical champion, administrative leader, QI/data specialist, and an individual living with or impacted by diabetes. Using patient registries and EHRs, health systems can evaluate the quality of diabetes care being delivered, benchmark metrics, and perform intervention cycles as part of QI strategies (13, 57, 101) . QI can also be used as an effective strategy to support application of clinical practice recommendations by health care professionals.

In addition to QI approaches, other strategies that simultaneously improve the quality of care and potentially reduce costs are gaining momentum and include reimbursement structures that, in contrast to visit-based billing, reward the provision of appropriate and highquality care to achieve metabolic goals (102) ; value-based payments; and incentives that accommodate personalized care goals (8, 103) . See EVIDENCE-BASED CARE MODELS TO IMPROVE POPULATION HEALTH, above, for more information.

TAILORING TREATMENT FOR SOCIAL CONTEXT

Recommendations 1. 6 Health systems should assess and address disparities in diabetes care and health outcomes (e.g., by stratifying clinical quality data by factors such as insurance status, race, ethnicity, preferred language for health care discussions, disability, and other social determinants of health). C (104) 1.7 During clinical encounters, assess for social determinants of health, including food insecurity, A housing insecurity, financial barriers, health insurance and health care access, environmental and neighborhood factors, and social capital/social community support, B to inform treatment decisions, with referral to appropriate local community resources. 1.8 Provide people with diabetes additional self-management support from lay health coaches, navigators, or community health workers when available. A 1.9 Consider the involvement of community health workers to support management of diabetes and cardiovascular risk factors, especially in underserved communities and health care systems. B Health inequities related to diabetes and its complications are well documented, are heavily influenced by SDOH, and have been associated with greater risk for developing diabetes, higher disease prevalence, and worse diabetes-related outcomes (104) (105) (106) . SDOH are defined as the economic, environmental, political, and social conditions in which people live and are responsible for a major part of health inequality worldwide (107) . Greater exposure to adverse SDOH over the life course results in poor health (108) . Interventions to address SDOH can improve diabetes-related outcomes (104, 109) . Using clinical quality data to identify inequities and opportunities for improvement is valuable for health care professionals, health systems, payors, policymakers, and people with diabetes (110) . The Joint Commission requires that all accredited organizations in its ambulatory health care, behavioral health care and human services, critical access hospital, and hospital accreditation programs collect race and ethnicity information and implement specific steps to reduce health care disparities. The Joint Commission specifically requires that organizations designate an individual or individuals) to lead efforts to reduce health care disparities, assess health-related social needs and provide information on community resources to meet these needs, identify health care disparities by stratifying quality and safety data using sociodemographic characteristics, develop an action plan to address health care disparities, work to actively reduce health care disparities, and inform key stakeholders about progress to reduce health care disparities (111) . The CMS Framework for Health Equity similarly prioritizes collection, reporting, and analysis of standardized individual-level demographic (including race, ethnicity, language, gender identity, sex, sexual orientation, and disability status) and SDOH data as well as assessing for and addressing disparities through improved access to culturally tailored services, team-based care, and community resources (112) . Quality measures assessing SDOH screening and intervention have been introduced by the National Committee for Quality Assurance (focused on food, housing, and transportation insecurity) (113) and CMS (focused on food, housing, and transportation insecurity, utility difficulties, and interpersonal safety) (114) .

Outside of SDOH, there are several contributors to inequities, including bias, institutional practices, and systemic factors (115) (116) (117) . The ADA recognizes the association between interpersonal, social, and environmental factors and the prevention and treatment of diabetes and has issued a call for research that seeks to better understand how social determinants influence behaviors and how the relationships between these variables might be modified for enhancing the prevention and management of diabetes (104) . While a comprehensive strategy to reduce diabetes-related health disparities in populations is yet to be formally studied, general recommendations from other chronic disease management and prevention models can be drawn upon to inform system-level strategies in diabetes (118) . For example, the National Academy of Medicine has published a framework for educating health care professionals on the importance of SDOH (119) . Furthermore, there are resources available for the inclusion of standardized sociodemographic variables in EHRs to facilitate the measurement of health disparities and the impact of interventions designed to reduce those disparities (95, 119, 120) .

SDOH are not consistently recognized and often go undiscussed-and are ultimately not addressed-during the clinical encounter (106) . Among people with chronic illnesses, two-thirds of those who reported not taking medications as prescribed due to cost-related barriers never shared this information with their physician (121) . A study using data from the National Health Interview Survey (NHIS) (106) found that half of adults with diabetes reported financial stress and about 20% reported food insecurity. Studies of both type 1 diabetes and type 2 diabetes have noted an association of one or more adverse SDOH with health care utilization and poor diabetes outcomes among individuals with diabetes (121, 122) . It is therefore important for people with diabetes to be screened for SDOH during clinical encounters and be referred to appropriate clinical and community resources to address these needs (Table 1 .1). Furthermore, health systems may benefit from compiling an inventory of such resources to facilitate referrals at the point of care. Policies and payment models that support addressing SDOH, both within and outside the health care setting, are needed to ensure that these efforts are both feasible and sustainable. One example of a statewide payment model that incentivizes value-based care, addressing SDOH and funding community-based health care professionals, is the Maryland Total Cost of Care Model, although it is currently limited by a narrow focus on preventing diabetes and does not consider diabetes care quality or health outcomes in people with diabetes (110, 123) .

Another population in which such issues must be considered is older adults, for whom social difficulties may further impair quality of life and increase the risk of functional dependency (124) (see Section 13, "Older Adults," for a detailed discussion of social considerations in older adults).

Creating system-level mechanisms to screen for SDOH may help overcome structural barriers and communication gaps between people with diabetes and health care professionals (106, 125) . A number of studies have proven the effectiveness of identifying SDOH by using validated screening tools (126) . In addition, brief, validated screening tools for some SDOH exist and could facilitate discussion around factors that significantly impact treatment during the clinical encounter.

Food Insecurity

Food insecurity is a household-level economic and social condition of limited or uncertain access to adequate food (127) . In 2022, almost 13% of Americans were food insecure (127) , and food insecurity is associated with increased risk of type 2 diabetes and higher-than-recommended glycemia (128, 129) . The rate is disproportionately higher among some groups that have been historically marginalized, low-income households, and households headed by single mothers. Additionally, those facing food insecurity have lower engagement in self-care behaviors and medication use, have higher rates of depression and diabetes distress, and have worse glycemic management compared with individuals who are food secure (128, 129) . Older adults with food insecurity are more likely to have emergency department visits and hospitalizations compared with older adults who do not report food insecurity (130) . Risk for food insecurity can be assessed with a validated two-item screening tool (131) that includes the following statements: 1) "Within the past 12 months, we worried whether our food would run out before we got money to buy more" and 2) "Within the past 12 months the food we bought just didn't last, and we didn't have money to get more." Interventions such as food prescription programs are considered promising to address food insecurity by integrating community resources into primary care settings and directly dealing with food deserts in underserved communities (132) .

In those with diabetes and food insecurity, the priority is mitigating the increased risk for severe hyperglycemia and hypoglycemia (133, 134) . The reasons for the increased risk of hyperglycemia can include the consumption of inexpensive carbohydrate-rich processed foods, binge eating, financial constraints to filling diabetes medication prescriptions, anxiety and depression, and poor sleep, all contributing to hyperglycemia and poor diabetes self-care behaviors. Hypoglycemia can occur due to inadequate or inconsistent carbohydrate consumption following the administration of sulfonylurea or insulin. Health care professionals should consider these factors when making treatment decisions for people with food insecurity and seek local resources to help people with diabetes and their family members obtain nutritious food more regularly (135) .

Housing Insecurity

Housing insecurity has been shown to be directly associated with a person's ability to maintain their diabetes self-management (136) . Housing insecurity often accompanies other barriers that challenge diabetes self-management. Food insecurity, lack of insurance, cognitive impairment, behavioral health concerns, and low literacy and numeracy skills are also factors (135) . The prevalence of diabetes among people experiencing housing insecurity is estimated to be around 8% (137) . Additionally, people with diabetes and housing insecurity need secure places to keep their diabetes medications and supplies as well as refrigerator access to safely store insulin. The risk for housing insecurity can be ascertained using a brief risk assessment tool developed and validated for use among veterans (138) . Given the potential challenges, health care professionals who care for housing-insecure individuals should be familiar with resources to support these individuals or have access to social workers who can facilitate stable housing as a way to improve diabetes care (139) .

Refugee, Migrant, and Seasonal Agricultural Workers

Refugee status, like having a diabetes diagnosis, is an independent risk factor for cardiovascular disease (140) . In areas undergoing humanitarian crises, refugees are at greater risk for obstacles to achieving optimal chronic disease management, but unfortunately there are few quality investigations into the particular situations of refugees with diabetes. There have been efforts to develop models of care specifically aimed at improving the health of refugee populations, but more work is needed to demonstrate effectiveness of those care models and approaches (141) .

Migrant and seasonal agricultural workers likely have a higher risk of type 2 diabetes than the general population. While migrant farmworker-specific data are lacking, most agricultural workers in the U.S. are Latino, a population with a high rate of type 2 diabetes. In addition, living in severe poverty brings with it food insecurity, high chronic stress, and an increased risk of diabetes; there is also an association between the exposure to certain pesticides and the incidence of diabetes (142) .

Data from the Department of Labor indicate that there are approximately 2.18 million agricultural workers in the U.S. (143) . These agricultural workers often travel throughout the country seasonally (144) , although less so than in past decades. According to 2022 health center data, 175 health centers across the U.S. reported providing care to 843,071 adult migrant farmworkers, and 91,839 had encounters for diabetes (142) . In a 2023 report on the National Agricultural Workers Survey, age-adjusted self-reported diabetes prevalence was 13.51% (95% CI 10.0-17.1) among migrant farmworkers and 10.8% (95% CI 9.0-12.6) among nonmigrant farmworkers (142) .

Migrant farmworkers and other agricultural workers encounter numerous and overlapping barriers to receiving care. Migration, which might occur as frequently as every few weeks for some, disrupts care. Common barriers to adequate diabetes care include those related to cost, culture, language, literacy, transportation, geographic distance, food access, long work hours, unfamiliarity with new communities, the complexity of the U.S. health care system, and limited access to various other resources like medications and DSMES (144) . Without regular care, farmworkers with diabetes can experience severe and often expensive complications that incur morbidity and mortality and affect quality of life. Nontraditional care delivery models, including mobile integrated health and telehealth, should be leveraged to improve access to high-quality care.

Health care professionals need to be attuned to the working and living conditions of people with diabetes. For example, if a farmworker with diabetes presents for care, appropriate referrals should be initiated to social workers and community resources, as available, to assist with removing barriers to care.

Language Barriers

Health systems and health care professionals caring for those with limited English proficiency should develop or offer educational programs and materials in culturally appropriate languages. Professional language assistance (i.e., interpreters) should be provided to individuals with limited English proficiency and/or other communication needs at no cost to them (145) . Use of untrained interpreters, including family members, should be avoided when possible, as this can result in confusing or inaccurate conveyance of information. Accompanying written materials should be in the language appropriate for the individual being supported and at a reading level that is not overly complicated-typically this is defined as a sixthgrade reading level. The National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care (National CLAS Standards) provide guidance on how health care professionals can reduce language barriers by improving their cultural competency, addressing health literacy, and ensuring communication with professional language assistance (145) . In addition, the National CLAS Standards website offers several resources and materials that can be used to improve the quality of care delivery to individuals with limited English proficiency (145) .

Health Literacy and Numeracy

Health literacy is the degree to which individuals can obtain, process, and understand basic health information and services needed to make appropriate decisions (146, 147) . Health literacy is strongly associated with individuals engaging in complex disease management and self-care (148) . Approximately 9 out of 10 American adults are estimated to have limited or low health literacy (146, 149) . Clinicians and diabetes care and education specialists should provide easy-to-understand information and reduce unnecessary complexity when developing care plans. Interventions addressing low health literacy in populations with diabetes seem effective in improving diabetes outcomes, including ones focusing primarily on education, self-care training, or disease management. Combining easily adapted materials with formal diabetes education demonstrates effectiveness on clinical and behavioral outcomes in populations with low literacy (150) . However, more research is needed to establish the most effective strategies for enhancing retention and application of diabetes knowledge among various populations of people with diabetes (148, 151) .

Health numeracy is also essential in diabetes prevention and management. Health numeracy requires primary numeric skills, applied health numeracy, and interpretive health numeracy, which is especially important for people using diabetes technologies like insulin pumps (152) . An emotional component also affects a person's ability to understand concepts of risk, probability, and communication of scientific evidence (153) . People with prediabetes or diabetes often need to perform numeric tasks such as interpreting food labels and blood glucose levels to make treatment decisions. Thus, both health literacy and numeracy are necessary for enabling effective communication between people with diabetes and health professionals, arriving at a treatment plan, and making diabetes self-management task decisions. If people with diabetes appear not to understand concepts associated with treatment decisions, both can be assessed using standardized screening measures (154) . Adjunctive education and support may be indicated if limited health literacy and numeracy are barriers to optimal care decisions (60) .

Social Capital and Community Support

Social capital, which comprises community and personal network instrumental support, promotes better health, whereas lack of social support is associated with poorer health outcomes in individuals with diabetes (104) . Of particular concern are the SDOH, including, among others, racism and discrimination (155) . These factors are rarely addressed in routine clinical practice but may be underlying reasons for adverse health outcomes and lower engagement in beneficial self-care behaviors and medication use. Optimally identifying and leveraging community resources are core components of chronic care management (15) .

Health care community linkages are receiving increasing attention from the American Medical Association, the Agency for Healthcare Research and Quality, and others to promote the translation of clinical recommendations for nutrition and physical activity in real-world settings (156) . Community health workers (CHWs) (157) , community paramedics (158) , peer supporters (159, 160) , and lay leaders (161) may assist in the delivery of DSMES services (119, 162) , particularly in underserved communities. The American Public Health Association defines a CHW as a "frontline public health worker who is a trusted member of and/or has an unusually close understanding of the community served" (163) . CHWs can be part of an evidencebased strategy to improve the management of diabetes and cardiovascular risk factors in underserved communities and health care systems (164) . The CHW scope of practice in areas such as outreach and communication, advocacy, social support, basic health education, referrals to community clinics, and other services has successfully provided social and primary preventive services to underserved populations in rural and hard-to-reach communities. Even though CHWs' core competencies are not clinical in nature, in some circumstances, clinicians may delegate limited clinical tasks to CHWs. If such is the case, these tasks must always be performed under the direct supervision of the delegating health professional and following state health care laws and statutes (165, 166) . Community paramedics are advanced paramedics with training in chronic disease monitoring and education, medication management, care coordination, and SDOH in addition to their emergency medical services expertise. While their scope of practice varies across states, community paramedics can engage and support people living with diabetes under the direction of a medical director by delivering diabetes education, assisting with medication management, performing health assessments and wound care, and connecting people with diabetes and care partners with clinical and community resources (158) .

SUMMARY

Improving individual and population health for people with and at risk for diabetes requires engagement of and collaboration between people with diabetes and their caregivers, interprofessional health care teams, health systems, community partners, payors, policymakers, and public health agencies. This section provides guidance to facilitate implementation of evidence-based diabetes care recommendations that are discussed in the Standards of Care with the goal of improving health, eliminating health disparities, and reducing the impact of diabetes and its complications on individuals and society. The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Diabetes mellitus is a group of metabolic disorders of carbohydrate metabolism in which glucose is both underutilized as an energy source and overproduced due to inappropriate gluconeogenesis and glycogenolysis, resulting in hyperglycemia (1) . Diabetes can be diagnosed by demonstrating increased concentrations of glucose in venous plasma or increased A1C in the blood. Diabetes is classified conventionally into several clinical categories (e.g., type 1 or type 2 diabetes, gestational diabetes mellitus, and other specific types derived from other causes, such as monogenic diabetes, exocrine pancreatic disorders, and high-risk medications) (2) .

DIAGNOSTIC TESTS FOR DIABETES

Diabetes may be diagnosed based on A1C or plasma glucose criteria. Plasma glucose criteria include either the fasting plasma glucose (FPG), 2-h plasma glucose (2-h PG) during a 75-g oral glucose tolerance test (OGTT), or random glucose accompanied by classic hyperglycemic symptoms (e.g., polyuria, polydipsia, and unexplained weight loss) or hyperglycemic crises (i.e., diabetic ketoacidosis [DKA] and/or hyperglycemic hyperosmolar state [HHS] ) (Table 2 .1). populations and individuals. FPG, 2-h PG, and A1C reflect different aspects of glucose metabolism, and diagnostic cut points for the different tests will identify groups with incomplete concordance (3) . Compared with FPG and A1C cut points, the 2-h PG value diagnoses more people with prediabetes and diabetes (4) . Moreover, the efficacy of interventions for primary prevention of type 2 diabetes (i.e., preventing conversion of prediabetes to type 2 diabetes) has been demonstrated mainly among individuals with prediabetes who have impaired glucose tolerance (IGT) with or without elevated fasting glucose, not for individuals with isolated impaired fasting glucose (IFG) or for those with prediabetes defined by A1C criteria (5) (6) (7) (8) .

The same tests may be used to screen for and diagnose diabetes and to detect individuals with prediabetes (9) (Table 2 .1 and Table 2 .2). Diabetes may be identified anywhere along the spectrum of clinical scenarios-in seemingly low-risk individuals who happen to have glucose testing, in individuals screened based on diabetes risk assessment, and in symptomatic individuals. There is presently insufficient evidence to support the use of continuous glucose monitoring (CGM) for screening or diagnosis of prediabetes or diabetes. For additional details on the evidence used to establish the criteria for the diagnosis of diabetes or prediabetes, see the American Diabetes Association (ADA) position statement "Diagnosis and Classification of Diabetes Mellitus" (2) and other reports (1, 3, 10, 11) .

Use of Fasting Plasma Glucose or 2-Hour Plasma Glucose for Screening and Diagnosis of Diabetes

In the less common clinical scenario where a person has classic hyperglycemic symptoms (e.g., polyuria, polydipsia, unexplained weight loss) or presents with hyperglycemic crisis, measurement of random plasma glucose is sufficient to diagnose diabetes (symptoms of hyperglycemia or hyperglycemic crisis plus random plasma glucose $200 mg/dL [$11.1 mmol/L]). In these cases, knowing the plasma glucose level is critical because, in addition to confirming that symptoms are due to diabetes, it will inform management decisions. Health care professionals may also want to know the A1C to determine the chronicity of hyperglycemia. However, in an individual without symptoms, FPG or 2-h PG can be used for screening and diagnosis of diabetes. In nonpregnant individuals, FPG (or A1C) is typically preferred for routine screening due to the ease of administration (Table 2 .3); however, the 2-h PG (OGTT) testing protocol diagnoses more diabetes than the other two tests and is preferentially recommended for screening for some conditions (e.g., cystic fibrosis-related diabetes or posttransplantation diabetes mellitus). In the absence of classic hyperglycemic symptoms, repeat testing is required to confirm the diagnosis regardless of the test used (see CONFIRMING THE DIAGNOSIS, below).

An advantage of glucose testing is that these assays are inexpensive and widely available. Disadvantages include the high diurnal variation in glucose and fasting requirement. Individuals may have difficulty fasting for the full 8-h period or may misreport their fasting status (Table 2 .3). Recent physical activity, illness, or acute stress can affect glucose concentrations. Glycolysis is also an important and underrecognized concern with glucose testing. Glucose concentrations will be falsely low if samples are not handled properly and promptly prior to analysis (1) .

People should follow a mixed eating pattern with at least 150 g of carbohydrates on the 3 days prior to OGTT (12) (13) (14) . Antecedent carbohydrate restriction in the days prior to OGTT can falsely elevate postchallenge glucose levels, potentially resulting in a false-positive OGTT (12) .

Use of A1C for Screening and Diagnosis of Diabetes

2.2a

The A1C test should be performed using a method that is certified by the National Glycohemoglobin Standardization Program (NGSP) as The A1C test should be performed using a method that is certified by the National Glycohemoglobin Standardization Program (NGSP) (ngsp.org) and standardized or traceable to the Diabetes Control and Complications Trial (DCCT) reference assay. Outside the U.S., some assays are NGSP certified but many more are International Federation of Clinical Chemistry (IFCC) certified (a similarly stringent process) (1) . Point-of-care A1C assays may be NGSP certified and cleared by the U.S. Food and Drug Administration (FDA) for use in monitoring glycemic management in people with diabetes in both Clinical Laboratory Improvement Amendments (CLIA)regulated and CLIA-waived settings. FDAapproved point-of-care A1C testing can be used in laboratories or sites that are CLIA certified, are inspected, and meet the CLIA quality standards. These standards include specified personnel requirements (including documented annual competency assessments) and participation three times per year in an approved proficiency testing program (15) (16) (17) (18) .

A1C has several advantages compared with FPG and OGTT, including greater convenience (fasting is not required), greater preanalytical stability, and fewer day-today perturbations during stress, changes in nutrition, or illness. However, it should be noted that there is lower sensitivity of A1C at the designated cut point compared with that of 2-h PG as well as limited access in some parts of the world (Table 2 .3).

A1C reflects glucose bound to hemoglobin over the life span of the erythrocyte (120 days) and is thus a "weighted" average that is more heavily affected by recent blood glucose exposure. This means that clinically meaningful changes in A1C can be seen in < 120 days. A1C is an indirect measure of glucose exposure, and factors that affect hemoglobin concentrations or erythrocyte turnover can affect A1C (e.g., thalassemia or folate deficiency) (Table 2 .3). A1C may not be a suitable diagnostic test in people with anemia, people treated with erythropoietin, or people undergoing hemodialysis or HIV treatment (1, 19, 20) . Some hemoglobin variants can interfere with A1C test results, but this depends on the specific assay. For individuals with a hemoglobin variant but normal red blood cell turnover, such as those with the sickle cell trait, an A1C assay without interference from hemoglobin variants should be used. An updated list of A1C assays with interferences is available at ngsp .org/interf.asp. Another genetic variant, X-linked glucose-6-phosphate dehydrogenase G202A, carried by 11% of African American individuals in the U.S., is associated with a decrease in A1C of about 0.8% in homozygous men and 0.7% in homozygous women compared with levels in individuals without the variant (21) .

There is controversy regarding racial differences in A1C. Studies have found that African American individuals have slightly higher A1C levels than non-Hispanic White or Hispanic people (22) (23) (24) (25) . The glucoseindependent racial difference in A1C is small (0.3 percentage points) and may reflect genetic differences in hemoglobin or red cell turnover that vary by ancestry. There is an emerging understanding of the genetic determinants of A1C (21) , but the field lacks adequate genetic data in diverse populations (26, 27) . While some genetic variants might be more common in certain race or ancestry groups, it is important that we do not use race or ancestry as proxies for poorly understood genetic differences. Reassuringly, studies have shown that the association of A1C with risk for complications appears to be similar in African American and non-Hispanic White populations (28) .

Confirming the Diagnosis

Unless there is a clear clinical diagnosis (e.g., individual with classic symptoms of hyperglycemia or hyperglycemic crisis and random plasma glucose $200 mg/dL [$11.1 mmol/L]), confirmation is necessary to establish the diagnosis. This can be accomplished by two abnormal screening test results, measured either at the same time (29) or at two different time points.

If using samples at two different time points, it is recommended that the second test, which may be either a repeat of the initial test or a different test, be performed in a timely manner. For example, if the A1C is 7.0% (53 mmol/mol) and a repeat result is 6.8% (51 mmol/mol), the diagnosis of diabetes is confirmed. Two different tests (such as A1C and FPG) both having results above the diagnostic threshold when collected at the same time or at two different time points would also confirm the diagnosis. On the other hand, if an individual has discordant results from two different tests, then the test result that is above the diagnostic cut point should be repeated, with careful consideration of factors that may affect measured A1C or glucose levels. The diagnosis is made based on the confirmatory screening test. For example, if an individual meets the diabetes criterion of A1C (two results $6.5% [$48 mmol/mol]) but not FPG ( < 126 mg/dL [ < 7.0 mmol/L]), that person should nevertheless be considered to have diabetes.

If individuals have test results near the margins of the diagnostic threshold, the health care professional should educate the individual about the onset of possible hyperglycemic symptoms and repeat the test in 3-6 months.

Consistent and substantial discordance between glucose values and A1C test results should prompt additional follow-up to determine the underlying reason for the discrepancy (including evaluation for the possibility of a problem or interference with either test) and whether it has clinical implications for the individual (Table 2 .3). In addition, consider other biomarkers, such as fructosamine and glycated albumin, which are alternative measures of chronic hyperglycemia that are approved for clinical use for monitoring glycemic management in people with diabetes. 1. Type 1 diabetes (due to autoimmune b-cell destruction, usually leading to absolute insulin deficiency, including latent autoimmune diabetes in adults) 2. Type 2 diabetes (due to a nonautoimmune progressive loss of adequate b-cell insulin secretion, frequently on the background of insulin resistance) 3. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes, diseases of the exocrine pancreas, and drug-or chemical-induced diabetes 4. Gestational diabetes mellitus (diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation or other types of diabetes occurring throughout pregnancy, such as type 1 diabetes).

Type 1 diabetes and type 2 diabetes are heterogeneous diseases in which clinical presentation and disease progression may vary considerably. Classification is important for determining personalized therapy, but some individuals cannot be clearly classified as having type 1 or type 2 diabetes at the time of diagnosis. The traditional paradigms of type 2 diabetes having onset only in adults and type 1 diabetes having onset only in children are not accurate, as both diseases occur in all age-groups. Children with type 1 diabetes often present with the hallmark symptoms of polyuria/polydipsia, and approximately half present with DKA (30) (31) (32) . The onset of type 1 diabetes may be more variable in adults; they may not present with the classic symptoms seen in children and may progress to insulin replacement more slowly (33) (34) (35) .

The features most useful in determination of type 1 diabetes include younger age at diagnosis ( < 35 years) with lower BMI ( < 25 kg/m 2 ), unintentional weight loss, ketoacidosis, and plasma glucose > 360 mg/dL ( > 20 mmol/L) at presentation (36) (Fig. 2 .

1).

Other features classically associated with type 1 diabetes, such as ketosis without acidosis, osmotic symptoms, family history, or a history of autoimmune diseases, are weak discriminators. Occasionally, people with type 2 diabetes may present with DKA (37) , particularly members of certain racial, ethnic, and ancestral groups (e.g., African American and Hispanic/Latino

Flowchart for investigation of suspected type 1 diabetes in newly diagnosed adults, based on data from White European populations

.1-Flowchart for investigation of suspected type 1 diabetes in newly diagnosed adults, based on data from White European populations. 1 No single clinical feature confirms type 1 diabetes in isolation. 2 Glutamic acid decarboxylase (GAD) should be the primary antibody measured and, if negative, should be followed by islet tyrosine phosphatase 2 (IA-2) and/or zinc transporter 8 (ZnT8) where these tests are available. In individuals who have not been treated with insulin, antibodies against insulin may also be useful. In those diagnosed at < 35 years of age who have no clinical features of type 2 diabetes or monogenic diabetes, a negative result does not change the diagnosis of type 1 diabetes, since 5-10% of people with type 1 diabetes do not have antibodies. 3 Monogenic diabetes is suggested by the presence of one or more of the following features: A1C < 58 mmol/mol ( < 7.5%) at diagnosis, one parent with diabetes, features of a specific monogenic cause (e.g., renal cysts, partial lipodystrophy, maternally inherited deafness, and severe insulin resistance in the absence of obesity), and monogenic diabetes prediction model probability > 5% (diabetesgenes.org/exeter-diabetes-app/ModyCalculator). 4 A C-peptide test is only indicated in people receiving insulin treatment. A random sample (with concurrent glucose) within 5 h of eating can replace a formal C-peptide stimulation test in the context of classification. If the result is $600 pmol/L ($1.8 ng/mL), the circumstances of testing do not matter. If the result is < 600 pmol/L ( < 1.8 ng/mL) and the concurrent glucose is < 4 mmol/L ( < 70 mg/dL) or the person may have been fasting, consider repeating the test. Results showing very low levels (e.g., < 80 pmol/L [ < 0.24 ng/mL]) do not need to be repeated. Where a person is insulin treated, C-peptide must be measured prior to insulin discontinuation to exclude severe insulin deficiency. Do not test C-peptide within 2 weeks of a hyperglycemic emergency. 5 Features of type 2 diabetes include increased BMI ($25 kg/m 2 ), absence of weight loss, absence of ketoacidosis, and less marked hyperglycemia. Less discriminatory features include non-White ethnicity, family history, longer duration and milder severity of symptoms prior to presentation, features of metabolic syndrome, and absence of a family history of autoimmunity. 6 If genetic testing does not confirm monogenic diabetes, the classification is unclear and a clinical decision should be made about treatment. 7 Type 2 diabetes should be strongly considered in older individuals. In some cases, investigation for pancreatic or other types of diabetes may be appropriate. 8 A person with possible type 1 diabetes who is not treated with insulin will require careful monitoring and education so that insulin can be rapidly initiated in the event of glycemic deterioration. 9 C-peptide values 200-600 pmol/L (0.6-1.8 ng/mL) are usually consistent with type 1 diabetes or maturity-onset diabetes of the young but may occur in insulin-treated type 2 diabetes, particularly in people with normal or low BMI or after long duration. Reprinted and adapted from Holt et al. (36) .

and that misdiagnosis is common and can occur in 40% of adults with new type 1 diabetes (e.g., adults with type 1 diabetes misdiagnosed as having type 2 diabetes). In comparison, individuals with maturity-onset diabetes of the young (MODY) may be misdiagnosed as having type 1 diabetes (36) . Although difficulties in distinguishing diabetes type may occur in all age-groups at onset, the diagnosis generally becomes more obvious over time in people with b-cell deficiency as the degree of b-cell deficiency becomes clear (Fig. 2 .1). One useful clinical tool for distinguishing diabetes type is the AABBCC approach: Age (e.g., for individuals < 35 years old, consider type 1 diabetes); Autoimmunity (e.g., personal or family history of autoimmune disease or polyglandular autoimmune syndromes); Body habitus (e.g., BMI < 25 kg/m 2 ); Background (e.g., family history of type 1 diabetes); Control (preferred term is "goal," i.e., the inability to achieve glycemic goals on noninsulin therapies); and Comorbidities (e.g., treatment with immune checkpoint inhibitors for cancer can cause acute autoimmune type 1 diabetes) (36) .

In both type 1 and type 2 diabetes, genetic and environmental factors can result in the progressive loss of b-cell mass and/or function that manifests clinically as hyperglycemia. Once hyperglycemia occurs, people with all forms of diabetes are at risk for developing the same chronic complications, although rates of progression may differ. The identification of individualized therapies for diabetes in the future will be informed by better characterization of the many paths to b-cell demise or dysfunction (38) . Across the globe, many groups are working on combining clinical, pathophysiological, and genetic characteristics to more precisely define the subsets of diabetes that are currently clustered into the type 1 diabetes versus type 2 diabetes nomenclature with the goal of optimizing personalized treatment approaches (39) . A diagnosis of type 1 diabetes does not preclude also having features classically associated with type 2 diabetes (e.g., insulin resistance, obesity, and other metabolic abnormalities), and until more precise subsets are used in clinical practice, it may be appropriate to categorize such an individual as having features of both type 1 and type 2 diabetes to facilitate access to appropriate treatment (e.g., glucagon-like peptide 1 receptor agonist [GLP-1 RA] or sodium-glucose cotransporter 2 [SGLT2] inhibitor therapies for potential weight and other cardiometabolic benefits) and monitoring systems.

Characterization of the underlying pathophysiology is more precisely developed in type 1 diabetes than in type 2 diabetes. It is clear from prospective studies that the persistent presence of two or more islet autoantibodies is a near-certain predictor of clinical diabetes (40) . In at-risk cohorts followed from birth or a very young age, seroconversion rarely occurs before 6 months of age and there is a peak in seroconversion between 9 and 24 months of age (41) (42) (43) . The rate of progression is dependent on the age at first detection of an autoantibody, number of autoantibodies, autoantibody specificity, and autoantibody titer. Glucose and A1C levels may rise well before the clinical onset of diabetes (e.g., changes in FPG and 2-h PG can occur about 6 months before diagnosis) (44) , making diagnosis feasible under ideal situations of serial monitoring of individuals at high risk of type 1 diabetes before the onset of DKA. Three distinct stages of type 1 diabetes have been defined (Table 2 .4) and serve as a framework for research and regulatory decision-making (38, 45) .

There is debate as to whether slowly progressive autoimmune diabetes with an adult onset should be termed latent autoimmune diabetes in adults (LADA) or type 1 diabetes. The clinical priority with detection of LADA is awareness that slow autoimmune b-cell destruction can occur in adults, leading to a long duration of marginal insulin secretory capacity. For this classification, all forms of diabetes mediated by autoimmune b-cell destruction independent of age of onset are included under the rubric of type 1 diabetes. Use of the term LADA is common and acceptable in clinical practice and has the practical impact of heightening awareness of a population of adults likely to have progressive autoimmune b-cell destruction (46) , thus accelerating insulin initiation prior to deterioration of glucose management or development of DKA (34, 47) . At the same time, there is evidence that application of only a single imperfect autoantibody test for determining LADA classification may lead to misclassification of some individuals with type 2 diabetes. Diagnostic accuracy may be improved by using higher-specificity tests, using confirmatory testing for other autoantibodies, and restricting testing to those with clinical features suggestive of autoimmune diabetes (48) .

The paths to b-cell demise and dysfunction are less well defined in type 2 diabetes, but deficient b-cell insulin secretion, frequently in the setting of insulin resistance, appears to be the common denominator. Type 2 diabetes is associated with insulin secretory defects related to genetic predisposition, epigenetic changes, inflammation, and metabolic stress. Future classification schemes for diabetes will likely focus on the pathophysiology of the underlying b-cell dysfunction (38, (49) (50) (51) (52) .

TYPE 1 DIABETES

Recommendations 2.6 Screening for presymptomatic type 1 diabetes may be done by detection of autoantibodies to insulin, glutamic acid decarboxylase (GAD), islet antigen 2 (IA-2), or zinc transporter 8 (ZnT8). B 2.7 Autoantibody-based screening for presymptomatic type 1 diabetes should be offered to those with a family history of type 1 diabetes or otherwise known elevated genetic risk. B 2.8 Having multiple confirmed islet autoantibodies is a risk factor for clinical diabetes. Testing for dysglycemia may be used to further forecast near-term risk (Table 2 .4). When multiple islet autoantibodies are identified, referral to a specialized center for further evaluation and/or consideration of a clinical trial or approved therapy to potentially delay development of clinical diabetes should be considered. B 2.9 Standardized islet autoantibody tests are recommended for classification of diabetes in adults who have phenotypic risk factors that overlap with those for type 1 diabetes (e.g., younger age at diagnosis, unintentional weight loss, ketoacidosis, or short time to insulin treatment). E autoimmune destruction of the pancreatic b-cells. Autoimmune markers include islet cell autoantibodies and autoantibodies to glutamic acid decarboxylase (GAD) (such as GAD65), insulin, the tyrosine phosphatases islet antigen 2 (IA-2) and IA-2b, and zinc transporter 8 (ZnT8). Numerous clinical studies are being conducted to test various methods of preventing or delaying type 1 diabetes in those with evidence of islet autoimmunity (trialnet.org/ our-research/prevention-studies) (40-42, 47,53,54) . The disease has strong HLA associations, with linkage to the DQB1 and DRB1 haplotypes, and genetic screening has been used in some research studies to identify high-risk populations. Specific alleles in these genes can be either predisposing (e.g., DRB1*0301-DQB1*0201 [DR3-DQ2] and DRB1*0401-DQB1*0302 [DR4-DQ8] ) or protective (e.g., DRB1*1501 and DQA1*0102-DQB1*0602). Stage 1 of type 1 diabetes is defined by the presence of two or more of these autoantibodies and normoglycemia (Table 2 .4). At stage 1, the 5-year risk of developing symptomatic type 1 diabetes is 44% overall but varies considerably based on number, titer, and specificity of autoantibodies as well as age of seroconversion and genetic risk (45) . Stage 2 includes individuals with multiple islet autoantibodies and dysglycemia not yet diagnostic of diabetes (dysglycemia can be defined by one or more criteria as outlined in Table 2 .4). At stage 2 of the disease, there is 60% risk by 2 years and 75% risk within 5 years of developing a clinical diagnosis of type 1 diabetes (55, 56) . A consensus guidance provides expert recommendations on what should be monitored and how often these factors should be monitored in individuals with presymptomatic type 1 diabetes (57) .

The rate of b-cell destruction is quite variable, being rapid in some individuals (particularly but not exclusively in infants and children) and slow in others (mainly but not exclusively adults) (44, 58) . Children and adolescents often present with DKA as the first manifestation of the disease, and rates in the U.S. have increased over the past 20 years (30) (31) (32) . Others have modest fasting hyperglycemia that can rapidly change to severe hyperglycemia and/or DKA with infection or other stress. Adults may retain sufficient b-cell function to prevent DKA for many years; such individuals may have remission characterized by decreased insulin needs for months or years, eventually become dependent on insulin for survival, and are at risk for DKA (33-35, 59,60) . At this later stage of the disease, there is little or no insulin secretion, as manifested by low or undetectable levels of plasma C-peptide. Immune-mediated diabetes is the most common form of diabetes in childhood and adolescence, but it can occur at any age. Autoimmune destruction of b-cells has multiple genetic factors and is also related to environmental factors that are still poorly defined. Although individuals did not classically have obesity when they presented with type 1 diabetes, obesity is increasingly common in the general population; as such, obesity should not preclude testing for type 1 diabetes. People with type 1 diabetes are also prone to other autoimmune disorders, such as Hashimoto thyroiditis, Graves disease, celiac disease, Addison disease, vitiligo, autoimmune hepatitis, myasthenia gravis, and pernicious anemia (see Section 4, "Comprehensive Medical Evaluation and Assessment of Comorbidities"). Type 1 diabetes can be associated with monogenic polyglandular autoimmune syndromes, including immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome, which is an early-onset systemic autoimmune, genetic disorder caused by mutation of the forkhead box protein 3 (FOXP3) gene, and another disorder caused by the autoimmune regulator (AIRE) gene mutation (61, 62) .

Introduction of immunotherapy, specifically checkpoint inhibitors, for cancer treatment has led to unexpected adverse events, including immune system activation precipitating autoimmune disease. Fulminant onset of type 1 diabetes can occur, with DKA and low or undetectable levels of C-peptide as a marker of endogenous b-cell function (63) (64) (65) . Fewer than half of these individuals have autoantibodies that are seen in type 1 diabetes, supporting alternate pathobiology. This immune-related adverse event occurs in just under 1% of checkpoint inhibitortreated individuals but most commonly occurs with agents that block the programmed cell death protein 1/programmed cell death ligand 1 pathway alone or in combination with other checkpoint inhibitors (66) . To date, the majority of immune checkpoint inhibitor-related cases of type 1 diabetes occur in people with high-risk HLA susceptibility haplotype for type 1 diabetes; however, people with either a neutral or typically protective • Islet autoantibodies (usually multiple)

• Dysglycemia:

8 IFG: FPG 100-125 mg/dL (5.6-6.9 mmol/L) or 8 IGT: 2-h PG 140-199 mg/dL (7.8-11.0 mmol/L) or 8 A1C 5.7-6.4% (39-47 mmol/mol) or $10% increase in A1C

• Autoantibodies may become absent • Diabetes by standard criteria Adapted from Skyler et al. (38) . FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; 2-h PG, 2-h plasma glucose. Alternative additional stage 2 diagnostic criteria of 30-, 60-, or 90-min plasma glucose on oral glucose tolerance test $200 mg/dL ($11.1 mmol/L) and confirmatory testing in those aged $18 years have been used in clinical trials (84) . Dysglycemia can be defined by one or more criteria as outlined in the table.

HLA haplotype for type 1 diabetes can also develop checkpoint inhibitor-associated type 1 diabetes (67) . To date, risk cannot be predicted by family history or autoantibodies, so all health care professionals administering these medications or caring for people who have a history of current or past exposure to these agents should be mindful of this adverse effect and educate and monitor individuals appropriately.

A number of viruses have been associated with type 1 diabetes, including enteroviruses such as Coxsackievirus B. During the coronavirus disease 2019 (COVID- 19) pandemic, numbers of cases of hyperglycemia, DKA, and new diabetes increased, suggesting that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a trigger for or can unmask type 1 diabetes (68) . Possible mechanisms of b-cell damage include virus-triggered b-cell death, immune-mediated loss of pancreatic b-cells, and damage to b-cells because of infection of surrounding exocrine cells. The cytokine storm associated with COVID-19 infection is a highly inflammatory state that could also contribute. To better characterize and understand the pathogenesis of new-onset COVID-19related diabetes, a global registry, CoviDIAB, has been established (69) .

Idiopathic Type 1 Diabetes Some forms of type 1 diabetes have no known etiologies. Individuals have permanent insulinopenia and are prone to DKA but have no evidence of b-cell autoimmunity. However, only a minority of people with type 1 diabetes fall into this category.

Screening for Type 1 Diabetes Risk

The incidence and prevalence of type 1 diabetes are increasing (70) . People with type 1 diabetes often present with acute symptoms of diabetes and markedly elevated blood glucose levels, and 25-50% are diagnosed with life-threatening DKA (30) (31) (32) . Family history of type 1 diabetes increases the risk of developing type 1 diabetes compared with the general population, but the majority, 90%, of individuals who develop type 1 diabetes do not have a known relative with the disease. Multiple studies indicate that measuring islet autoantibodies in relatives of those with type 1 diabetes (45) , in children from the general population (71, 72) , or in children from the general population with high genetic risk (73) can identify many individuals who will develop type 1 diabetes. A study reported the risk of progression to type 1 diabetes from the time of seroconversion to autoantibody positivity in three pediatric cohorts from Finland, Germany, and the U.S. Of the 585 children who developed more than two autoantibodies, nearly 70% developed type 1 diabetes within 10 years and 84% within 15 years (40) . These findings are highly significant, because while the German group was recruited from offspring of parents with type 1 diabetes, the Finnish and American groups were recruited from the general population. Remarkably, the findings in all three groups were the same, suggesting that the same sequence of events led to clinical disease in both "sporadic" and familial cases of type 1 diabetes. Indeed, the risk of type 1 diabetes increases as the number of relevant autoantibodies detected increases (53, 74, 75) . In The Environmental Determinants of Diabetes in the Young (TEDDY) study, type 1 diabetes developed in 21% of 363 subjects with at least one autoantibody at 3 years of age (76) . Such testing, coupled with education about diabetes symptoms and close follow-up, has been shown to enable earlier diagnosis and to prevent DKA (77, 78) . In several cohort studies, up to 50% of children with only a single autoantibody revert to being islet autoantibody negative during follow-up (79, 80) . Therefore, it is recommended that the first autoantibody-positive test be confirmed with a second test within 3 months, preferably in a laboratory that meets the performance standards set by the Islet Autoantibody Standardization Program (IASP) (57) .

Type 1 diabetes genetic risk scores have been used in newborn screening to identify those at risk for future presentation of the disease. In a simulation using one such genetic risk score, the majority of those who would go on to develop type 1 diabetes, > 77%, could be identified within just 10% of the general population, identifying a subset who may most benefit from autoantibody testing (81) . As many genetic risk studies have been performed in populations of European ancestry and discriminatory ability may differ in those of different ancestry, more large case-control cohorts from non-European populations are still needed (82) .

Screening programs are available in Europe (e.g., Fr1da and gppad.org), Australia (e.g., type1screen.org), and the U.S. (e.g., trialnet.org, askhealth.org, and cascadekids.org). General population-based screening programs may offer broader testing where high-quality, validated assays and resources for appropriate follow-up of results are available, with several countries considering making such testing part of standard care. In 2023, Italy introduced nationwide screening for type 1 diabetes and celiac disease in the general population aged 1-17 years (83) . Individuals who test autoantibody positive should be provided with or referred for counseling about the risk of developing diabetes, diabetes symptoms, and DKA prevention and should be given consideration for referral to a specialized center for further evaluation and/or consideration of a clinical trial or approved therapy to potentially delay development of clinical diabetes (84) .

PREDIABETES AND TYPE 2 DIABETES

Recommendations 2.10 Screening for risk of prediabetes and type 2 diabetes with an assessment of risk factors or validated risk calculator should be done in asymptomatic adults. B 2.11a Testing for prediabetes or type 2 diabetes in asymptomatic people should be considered in adults of any age with overweight or obesity who have one or more risk factors (Table 2 .5). B 2.11b For all other people, screening should begin at age 35 years. B 2.11c In people without prediabetes or diabetes after screening, repeat screening recommended at a minimum of 3-year intervals is reasonable, sooner with symptoms or change in risk (e.g., weight gain). C 2.12 To screen for prediabetes and type 2 diabetes, FPG, 2-h PG during 75-g OGTT, and A1C are each appropriate (Table 2 .1 and Table 2 .2). B 2.13 When using OGTT as a screening tool for prediabetes or diabetes, adequate carbohydrate intake (at least 150 g/day) should be assured for 3 days prior to testing. E 2.14 Risk-based screening for prediabetes or type 2 diabetes should be considered after the onset of puberty or after 10 years of age, whichever occurs earlier, in children and adolescents with overweight (BMI $85th percentile) or obesity (BMI $95th percentile) and who have one or more risk factors for diabetes. (See Table 2 .6 for evidence grading of risk factors.) B 2.15a Consider screening people for prediabetes or diabetes if they are on certain medications, such as glucocorticoids, statins, thiazide diuretics, some HIV medications, and secondgeneration antipsychotic medications, as these agents are known to increase the risk of these conditions. C

2.15b

In people who are prescribed second-generation antipsychotic medications, screen for prediabetes and diabetes at baseline and repeat 12-16 weeks after medication initiation or sooner, if clinically indicated, and annually thereafter. B 2.16 People with HIV should be screened for diabetes and prediabetes with an FPG test before starting antiretroviral therapy, at the time of switching antiretroviral therapy, and 3-6 months after starting or switching antiretroviral therapy. If initial screening results are normal, FPG should be checked annually. E Prediabetes Prediabetes is the term used for individuals whose glucose or A1C levels do not meet the criteria for diabetes yet have abnormal carbohydrate metabolism that results in elevated glucose levels (dysglycemia) intermediate between normoglycemia and diabetes (28, 85) . People with prediabetes are defined by the presence of IFG and/or IGT and/or A1C 5.7-6.4% (39-47 mmol/mol) (Table 2 .2). As prediabetes is an intermediate state between normoglycemia and diabetes, it is a significant risk factor for progression to diabetes as well as cardiovascular disease and several other cardiometabolic outcomes. Criteria for screening for diabetes or prediabetes in asymptomatic adults are outlined in Table 2 .5. Prediabetes is associated with obesity (especially abdominal or visceral obesity), dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension. The presence of prediabetes should prompt comprehensive screening for cardiovascular risk factors.

Diagnosis of Prediabetes

IFG is defined as FPG levels from 100 to 125 mg/dL (from 5.6 to 6.9 mmol/L) (78, 84) and IGT as 2-h PG levels during 75-g OGTT from 140 to 199 mg/dL (from 7.8 to 11.0 mmol/L) (10) . It should be noted that the World Health Organization and a number of diabetes organizations define the IFG lower limit at 110 mg/dL (6.1 mmol/L). The ADA also initially endorsed this IFG lower limit in 1997 (10) . However, in 2003 the ADA adopted the new range of 100-125 mg/dL (5.6-6.9 mmol/L) to better define IFG so that the population risk of developing diabetes with IFG would be similar to that with IGT (11) .

As with the glucose measures, several prospective studies that used A1C to predict the progression to diabetes demonstrated a strong, continuous curvilinear association between A1C and subsequent diabetes. In a systematic review of 44,203 individuals from 16 cohort studies with a follow-up interval averaging 5.6 years (range 2.8-12 years), those with A1C between 5.5% and 6.0% (between 37 and 42 mmol/mol) had a substantially increased risk of diabetes (5-year incidence from 9% to 25%). Those with an A1C range of 6.0-6.5% (42-48 mmol/mol) had a 5-year risk of developing diabetes between 25% and 50% and a relative risk 20 times higher than that with A1C of 5.0% (31 mmol/mol) (86) . In a community-based study of African American and non-Hispanic White adults without diabetes, baseline A1C was a stronger predictor of subsequent diabetes and cardiovascular events than fasting glucose (87) . Other analyses suggest that A1C of 5.7% (39 mmol/mol) or higher is associated with a diabetes risk similar to that of the high-risk participants in the Diabetes Prevention Program (DPP) (88) , and A1C at baseline was a strong predictor of the development of glucose-defined diabetes during the DPP and its follow-up (7) . An A1C range of 5.7-6.4% (39-47 mmol/mol) identifies a group of individuals at high risk for diabetes and cardiovascular outcomes. These individuals should be informed of their increased risk for diabetes and cardiovascular disease and counseled about effective strategies to lower their risks (see Section 3, "Prevention or Delay of Diabetes and Associated Comorbidities"). Similar to glucose measurements, the continuum of risk is continuous and curvilinear: as A1C rises, the diabetes risk rises disproportionately (86) . Aggressive interventions and vigilant follow-up should be pursued for those considered at very high risk (e.g., those with A1C > 6.0% [ > 42 mmol/mol] and individuals with both IFG and IGT).

Table 2 .5 outlines the criteria for screening for prediabetes. The ADA risk test is an additional option (i.e., an awareness tool for the layperson and the health care professional) for assessment to determine the appropriateness of screening for diabetes or prediabetes in asymptomatic adults (Fig. 2 .2) (diabetes.org/diabetes-risk-test). For additional background regarding risk factors and screening for prediabetes, see screening and testing for prediabetes and type 2 diabetes in asymptomatic adults and screening and testing for prediabetes and type 2 diabetes in children and adolescents, below. For details regarding individuals with prediabetes most likely to benefit from a formal behavioral or lifestyle intervention, see Section 3, "Prevention or Delay of Diabetes and Associated Comorbidities."

Type 2 Diabetes

Type 2 diabetes accounts for 90-95% of all diabetes. This form encompasses individuals who generally have relative (rather than absolute) insulin deficiency and have insulin resistance (i.e., decreased biological responses to insulin).

There are various causes of type 2 diabetes. Although the specific etiologies are not known, individuals do not have any of the other known causes of diabetes. Most, but not all, people with type 2 diabetes have overweight or obesity. Excess weight itself causes some degree of insulin resistance. Individuals who do not have obesity or overweight by traditional weight criteria may have an increased percentage of body fat distributed predominantly in the abdominal region, including sites involved in metabolic dysfunctionassociated steatotic liver disease (MASLD) and/or ectopic sites (e.g., skeletal muscle).

DKA seldom occurs spontaneously in type 2 diabetes (30) ; when seen, it usually arises in individuals who are insulinopenic and already treated with insulin (e.g., missed or inadequate doses); in people with ketosis-prone type 2 diabetes; in association with the stress of another illness such as infection (e.g., or myocardial infarction; in association with illicit drug use (e.g., cocaine); in association with certain social determinants of health; or with the use of certain medications such as glucocorticoids, second-generation antipsychotics, or SGLT2 inhibitors (89, 90) . HHS is more typically associated with type 2 diabetes (existing or new diagnosis) and is characterized by severe hyperglycemia, hyperosmolality, and dehydration in the absence of significant ketoacidosis. People with diabetes can also have mixed clinical features of both DKA and HHS (30) .

Type 2 diabetes frequently goes undiagnosed for many years, because hyperglycemia develops gradually and, at earlier stages, is often not severe enough for the individual to notice the classic diabetes symptoms caused by hyperglycemia, such as dehydration or unintentional weight loss. Nevertheless, even undiagnosed people with diabetes are at increased risk of developing macrovascular and microvascular complications.

People with type 2 diabetes early in the disease course may have insulin levels that appear normal or elevated, yet the failure to normalize blood glucose reflects a relative defect in glucose-stimulated insulin secretion that is insufficient to compensate for insulin resistance. Insulin resistance may improve with weight reduction, physical activity, and/or pharmacologic treatment of hyperglycemia but is seldom restored to normal. Recent interventions with intensive nutritional changes and exercise, newer pharmacological agents (e.g., GLP-1 RAs), or surgical weight loss can lead to diabetes remission (91-94) (see Section 8, "Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes").

The risk of developing type 2 diabetes increases with age, obesity, and lack of physical activity (95, 96) . It occurs more frequently in individuals with prediabetes, prior gestational diabetes mellitus, or polycystic ovary syndrome. It is also more common in people with hypertension or dyslipidemia and in certain racial, ethnic, and ancestral subgroups (Table 2 .5). It is often associated with a strong genetic predisposition or family history in firstdegree relatives (more so than type 1 diabetes). However, the genetics of type 2 diabetes are poorly understood and under intense investigation in this era of precision medicine (50) . The composition of the gut microbiome may also affect the likelihood of developing type 2 diabetes (97) . In adults without traditional risk factors for type 2 diabetes and/or of younger age, consider islet autoantibody testing (e.g., GAD autoantibodies) to exclude the diagnosis of type 1 diabetes (36) (Fig. 2 .1).

Screening and Testing for Prediabetes and Type 2 Diabetes in Asymptomatic Adults

Screening for prediabetes and type 2 diabetes risk through a targeted assessment of risk factors (Table 2 .5) or with an assessment tool, such as the ADA risk test (Fig. 2 .2) (diabetes.org/diabetes-risk-test), is recommended to guide health care professionals on whether performing a diagnostic test (Table 2 .1) is appropriate. Prediabetes and type 2 diabetes meet criteria for conditions in which early detection via screening is appropriate. Both conditions are common and impose significant clinical and public health burdens. There is often a long presymptomatic phase before the diagnosis of type 2 diabetes. Simple tests to detect preclinical disease are readily available (98) . The duration of glycemic burden is a strong predictor of adverse outcomes. There are effective interventions that prevent progression from prediabetes to diabetes. It is important to individualize the risk-tobenefit ratio of formal intervention for people with prediabetes and consider person-centered goals. Risk models have explored the benefit, in general finding higher benefit of intervention in those at highest risk (99) Yes (1 point) No (0 points)

5. Have you ever been diagnosed with high blood pressure?

Yes (1 point) No (0 points)

6. Are you physically active?

Yes (0 points) No (1 point)

7. What is your weight category?

See chart at right.

If you scored 5 or higher:

You are at increased risk for having type 2 diabetes. (100) .

In that report, progression from prediabetes to diabetes augmented risk of complications.

Despite the numerous benefits of screening and early diagnosis for prediabetes or diabetes, unfortunately many people in the U.S. and globally either remain undiagnosed or are diagnosed late, when complications have already arisen.

Additional considerations regarding testing for type 2 diabetes and prediabetes in asymptomatic individuals are described below.

Age

Age is a major risk factor for diabetes. Testing should begin at no later than age 35 years for all people (103) . Screening should be considered in adults of any age with overweight or obesity and one or more risk factors for diabetes.

Medications

Certain medications, such as glucocorticoids, statins (104) , thiazide diuretics, some HIV medications (19) , and secondgeneration antipsychotic medications (105) , should be considered when deciding whether to screen for prediabetes or diabetes, as these medications are known to increase the risks of these conditions.

For example, people taking secondgeneration antipsychotic medications require greater monitoring because of an increase in risk of type 2 diabetes associated with this medication (105) . There is a range of effects on metabolic parameters (e.g., hyperglycemia, dyslipidemia, and weight gain) across second-generation antipsychotic medications. People treated with these agents should be screened for prediabetes or diabetes at baseline, rescreened 12-16 weeks after medication initiation, and screened annually thereafter (105) . Repeat testing can occur sooner if clinically warranted.

People With HIV People with HIV are at higher risk for developing prediabetes and diabetes. In addition, some antiretroviral (ARV) therapies may further increase the risk. Therefore, a screening protocol for prediabetes and type 2 diabetes is recommended (106) . As the A1C test may underestimate glycemia in people with HIV, plasma glucose criteria are preferred to diagnose prediabetes and diabetes (20) .

Diabetes risk is increased with certain protease inhibitors (PIs) and nucleoside/ nucleotide reverse transcriptase inhibitors (NRTIs). New-onset diabetes is estimated to occur in more than 5% of individuals infected with HIV on PIs, whereas more than 15% may have prediabetes (107) . PIs are associated with insulin resistance and may also lead to apoptosis of pancreatic b-cells. NRTIs also affect fat distribution (both lipohypertrophy and lipoatrophy), which is associated with insulin resistance. For people with HIV and ARV-associated hyperglycemia, it may be appropriate to consider discontinuing the problematic ARV agents if safe and effective alternatives are available (108) . Before making ARV substitutions, carefully consider the possible effect on HIV virological control and the potential adverse effects of new ARV agents. In some cases, antihyperglycemic agents may still be necessary.

Testing Interval

The appropriate interval between screening tests is not known (109) . The rationale for the 3-year interval is that with this interval, the number of false-positive tests that require confirmatory testing will be reduced, and individuals with false-negative tests will be retested before substantial time elapses and complications develop (109) . In especially high-risk individuals such as those with previous values nearer to the diabetes diagnostic cut point, shorter intervals between screenings may be useful.

Community Screening

Ideally, screening should be carried out within a health care setting (including appropriately resourced pharmacies) because of the need for follow-up and treatment. Community screening outside a health care setting is generally not recommended because people with positive tests may not seek, or have access to, appropriate follow-up testing and care. However, in specific situations where an adequate referral system is established beforehand for positive tests, community screening may be considered. Community screening may also be poorly targeted; i.e., it may fail to reach the groups most at risk and inappropriately test those at very low risk or even those who have already been diagnosed (110) .

Screening in Dental Practices

Because of the bidirectional relationship between periodontal disease and diabetes, the utility of screening in a dental setting and referral to primary care as a means to improve the diagnosis of prediabetes and diabetes has been explored (111, 112) . For example, one study estimated that 30% of individuals $30 years of age seen in general dental practices (including both people with and without periodontal disease) had newly diagnosed dysglycemia (112) . Further research is needed to demonstrate the feasibility, effectiveness, and cost-effectiveness of screening in this setting. For additional background on oral health in relation to prediabetes and type 2 diabetes, see Section 4, "Comprehensive Medical Evaluation and Assessment of Comorbidities."

Screening and Testing for Prediabetes and Type 2 Diabetes in Children and Adolescents

The epidemiologic studies that formed the basis for the recommendations to use A1C and plasma glucose criteria to diagnose prediabetes and diabetes included only adult populations (113) . However, ADA clinical guidance concluded that A1C, FPG, or 2-h PG also could be used to test for prediabetes or type 2 diabetes in children and adolescents (114) .

In the last decade, the incidence and prevalence of type 2 diabetes in children and adolescents has increased dramatically, especially in certain high-risk racial, ethnic, and ancestral subgroups (115) . See Table 2 .6 for recommendations on risk-based screening for type 2 diabetes or prediabetes in asymptomatic children and adolescents in a clinical setting (114) . See Table 2 .1 and Table 2 .2 for the criteria for the diagnosis of diabetes and prediabetes, respectively, that apply to children, adolescents, and adults. See Section 14, "Children and Adolescents," for additional information on type 2 diabetes in children and adolescents.

PANCREATIC DIABETES OR DIABETES IN THE CONTEXT OF DISEASE OF THE EXOCRINE PANCREAS

Recommendation 2.17 Screen people for diabetes within 3-6 months following an episode of acute pancreatitis and annually thereafter. Screening for diabetes is recommended annually for people with chronic pancreatitis. E Pancreatic diabetes (also termed pancreatogenic diabetes or type 3c diabetes) includes both structural (e.g., destruction or removal of normal pancreatic tissue) and functional loss of glucose-normalizing insulin secretion in the context of exocrine pancreatic dysfunction and is commonly misdiagnosed as type 2 diabetes. The diverse set of etiologies includes pancreatitis (acute and chronic pancreatic inflammation and associated fibrosis leading to loss of functional exocrine and endocrine pancreatic function), trauma or pancreatectomy, neoplasia, cystic fibrosis (addressed later in this section), hemochromatosis, fibrocalculous pancreatopathy, rare genetic disorders, and idiopathic forms (2); as such, pancreatic diabetes is the preferred umbrella term (116) .

Acute (even a single bout) and chronic pancreatitis can lead to postpancreatitis diabetes mellitus (117) . A distinguishing feature is concurrent pancreatic exocrine insufficiency (consider screening individuals with acute and chronic pancreatitis for exocrine pancreatic insufficiency by measuring fecal elastase), pathological pancreatic imaging (endoscopic ultrasound, MRI, and computed tomography), and absence of type 1 diabetes-associated autoimmunity (118) (119) (120) (121) (122) . There is loss of both insulin and glucagon secretion and often higher-than-expected insulin requirements. Risk for microvascular complications appears to be similar to that of other forms of diabetes.

For people with pancreatitis and diabetes, therapy should be advanced if A1C goals are not met. Glucose-lowering therapies potentially associated with increased risk of pancreatitis (i.e., incretinbased therapies) should be avoided. Early initiation of insulin therapy should be considered. In the context of pancreatectomy, islet autotransplantation can be considered for selected individuals with medically refractory chronic pancreatitis in specialized centers to preserve endogenous islet function and insulin secretion (123, 124) . In some cases, autotransplant can lead to insulin independence. In others, it may decrease insulin requirements (125) . (127) . The relevance of CFRD is highlighted by its association with increased morbidity, mortality, and patient burden. Diabetes in this population, compared with individuals with type 1 or type 2 diabetes, is associated with worse nutritional status, more severe inflammatory lung disease, and greater mortality. Insulin insufficiency is the primary defect in CFRD. Genetically determined b-cell function and insulin resistance associated with infection and inflammation may also contribute to the development of CFRD.

Milder abnormalities of glucose tolerance are even more common and occur at earlier ages than CFRD. Whether individuals with IGT should be treated with insulin replacement has not currently been determined. Although screening for diabetes before the age of 10 years can identify risk for progression to CFRD in those with abnormal glucose tolerance, no benefit has been established with respect to weight, height, BMI, or lung function. OGTT is the recommended screening test for CFRD. Not unexpectedly, annual OGTTs are perceived as burdensome, and engagement in current CFRD screening guidelines is poor, with only 30% of adults with cystic fibrosis having annual OGTTs (128) . A1C is not recommended for screening due to low sensitivity; however, a value of $6.5% ($48 mmol/mol) is consistent with a diagnosis of CFRD and reduces patient screening burden (129) (130) (131) . Regardless of age, weight loss or failure of expected weight gain is a risk for CFRD and should prompt screening (129, 130) . The Cystic Fibrosis Foundation Patient Registry (132) evaluated 3,553 people with cystic fibrosis and identified 445 (13%) with CFRD. Early diagnosis and treatment of CFRD was associated with preservation of lung function. The European Cystic Fibrosis Society Patient Registry reported an increase in CFRD with age (10% increase per decade), genotype, decreased lung function, and female sex (133) . CGM or HOMA of b-cell function (134) may be more sensitive than OGTT to detect risk for progression to CFRD; however, evidence linking these results to long-term outcomes is lacking, and these tests are not recommended for screening outside the research setting (127) . There is inadequate evidence presently to alter CFRD screening based on use of highly effective CFTR modulator therapy, which uses small-molecule compounds that directly correct the basic defect of the CFTR channel and restore channel function (127) .

CFRD mortality has significantly decreased over time, and the gap in mortality between people with cystic fibrosis with and without diabetes has considerably narrowed (135) . There are limited clinical trial data on optimal therapy for CFRD. People with CFRD should be treated with insulin to attain individualized glycemic goals. See Section 9, "Pharmacologic Approaches to Glycemic Treatment," for further information.

Additional resources for the clinical management of CFRD can be found in the position statement "Clinical Care Guidelines for Cystic Fibrosis-Related Diabetes" (136) and in the International Society for Pediatric and Adolescent Diabetes (ISPAD) 2022 clinical practice consensus guidelines (127) . (137) . New-onset diabetes after transplantation (NODAT) is one such designation that describes individuals who develop new-onset diabetes following transplant. NODAT excludes people with pretransplant diabetes that was undiagnosed as well as posttransplant hyperglycemia that resolves by the time of discharge (138) . Another term, posttransplantation diabetes mellitus (PTDM) (138, 139) , describes the presence of diabetes in the posttransplant setting irrespective of the timing of diabetes onset (140) . The clinical importance of PTDM lies in its impact as a significant risk factor for cardiovascular disease and chronic kidney disease in solid-organ transplantation (137) .

Hyperglycemia is very common during the early posttransplant period, with 90% of kidney allograft recipients exhibiting hyperglycemia in the first few weeks following transplant (138, 139, 141, 142) . In most cases, such stress-or steroidinduced hyperglycemia resolves by the time of discharge (142, 143) . Although the use of immunosuppressive therapies is a major contributor to the development of PTDM, the risks of transplant rejection outweigh the risks of PTDM, and the role of the diabetes health care professional is to treat hyperglycemia appropriately regardless of the type of immunosuppression (138) . Risk factors for PTDM include both general diabetes risks (such as age, family history of diabetes, and obesity) and transplant-specific factors, such as use of immunosuppressant agents (144) (145) (146) . Whereas posttransplantation hyperglycemia is an important risk factor for subsequent PTDM, a formal diagnosis of PTDM is optimally made once the individual is stable on maintenance immunosuppression (usually at least 45 days) and in the absence of acute infection (138, (142) (143) (144) 147) .

The OGTT is recommended for the diagnosis of PTDM (1 year posttransplant) (138, 139, 148) . However, screening people with FPG and/or A1C can identify high-risk individuals who require further assessment and may reduce the number of overall OGTTs required.

Few randomized controlled studies have reported on the short-and long-term use of antihyperglycemic agents in the setting of PTDM (144, 149, 150) . Most studies have reported that transplant individuals with hyperglycemia and PTDM after transplantation have higher rates of rejection, infection, and rehospitalization (142, 144, 151) . Insulin therapy is the agent of choice for the management of hyperglycemia and diabetes in the hospital setting and can be continued postdischarge. Noninsulin glucose-lowering therapies can also be used for long-term management. The choice of agent is usually made based on the side effect profile of the medication, possible interactions with the individual's immunosuppression plan, and potential cardiovascular and renal benefits in individuals with PTDM (144) . See Section 9, "Pharmacologic Approaches to Glycemic Treatment," for further information.

MONOGENIC DIABETES SYNDROMES

Recommendations

2.24a

Regardless of current age, all people diagnosed with diabetes in the first 6 months of life should have genetic testing for neonatal diabetes. B 2.24b Children and young adults who do not have typical characteristics of type 1 or type 2 diabetes and family history of diabetes in successive generations (suggestive of an autosomal dominant pattern of inheritance) should have genetic testing for maturityonset diabetes of the young (MODY). B 2.24c In both instances, consultation with a center specializing in diabetes genetics is recommended to understand the significance of genetic mutations and how best to approach further evaluation, treatment, and genetic counseling. E Monogenic defects that cause b-cell dysfunction (e.g., neonatal diabetes and MODY) or insulin resistance syndromes (e.g., monogenic lipodystrophies) are present in a small fraction of people with diabetes ( < 5%) (152) . Table 2 .7 describes the most common causes of monogenic diabetes. For a comprehensive list of causes, see Genetic Diagnosis of Endocrine Disorders (153) and ISPAD 2022 clinical practice consensus guidelines (152) .

Diagnosis of Monogenic Diabetes

The diagnosis of monogenic diabetes should be considered in children and adults diagnosed with diabetes in early adulthood with the following findings: (36) . Correct diagnosis has critical implications, because 30-50% of people with K ATP -related neonatal diabetes will exhibit improved blood glucose levels when treated with high-dose oral sulfonylureas instead of insulin. Insulin gene (INS) mutations are the second most common cause of permanent neonatal diabetes, with insulin therapy being the preferred treatment strategy.

Maturity-Onset Diabetes of the Young

MODY is frequently characterized by onset of hyperglycemia at an early age (classically before age 25 years, although diagnosis may occur at older ages). MODY is characterized by impaired insulin secretion with minimal or no defects in insulin action (in the absence of coexistent obesity). It is inherited in an autosomal dominant pattern with abnormalities in at least 14 genes on different chromosomes identified to date (152) . The most commonly reported forms are GCK-MODY (MODY2), HNF1A-MODY (MODY3), and HNF4A-MODY (MODY1).

Correct diagnosis of monogenic forms of diabetes is critical because people who have them may be incorrectly diagnosed with type 1 or type 2 diabetes, leading to suboptimal, even potentially harmful, treatment plans and delays in diagnosing other family members (152) . A diagnosis of MODY should be considered in individuals who have atypical diabetes and multiple family members with diabetes not characteristic of type 1 or type 2 diabetes (155-162) (Fig. 2 .1). In most cases, the presence of autoantibodies for type 1 diabetes precludes further testing for monogenic diabetes, but the presence of autoantibodies in people with monogenic diabetes has been reported. Individuals in whom monogenic diabetes is suspected should have genetic testing. Genetic screening (i.e., next-generation sequencing) is increasingly available and cost-effective (152) . Consultation with a center specializing in diabetes genetics is recommended to understand the significance of genetic mutations and how best to approach further evaluation, treatment, and genetic counseling. Genetic counseling is recommended to ensure that affected individuals understand the patterns of inheritance and the importance of a correct diagnosis and to address comprehensive cardiovascular risk.

A diagnosis of one of the three most common forms of MODY, HNF1A-MODY, GCK-MODY, and HNF4A-MODY, allows for more cost-effective personalized therapy (i.e., no therapy for GCK-MODY and sulfonylureas as first-line therapy for HNF1A-MODY and HNF4A-MODY). See Section 9, "Pharmacologic Approaches to Glycemic Strong racial and ethnic disparities exist in the prevalence of undiagnosed diabetes. Therefore, early screening provides an initial step to identify these health disparities so that they can begin to address them (169-172). Diagnostic criteria for identifying undiagnosed diabetes in early pregnancy are the same as those used in nonpregnant individuals (Table 2 .1). Individuals found to have diabetes should be classified as having diabetes complicating pregnancy (most often type 2 diabetes, rarely type 1 diabetes or monogenic diabetes) and managed accordingly. Early abnormal glucose metabolism, defined as a fasting glucose threshold of 110 mg/dL (6.1 mmol/L) or an A1C of 5.9% (41 mmol/mol), may identify individuals who are at higher risk of adverse pregnancy and neonatal outcomes (preeclampsia, macrosomia, shoulder dystocia, and perinatal death), are at high risk of a later GDM diagnosis, and are more likely to need insulin treatment (174-176). An A1C threshold of 5.7% (39 mmol/L) has not been shown to be associated with adverse perinatal outcomes (177,178).

If early screenings for undiagnosed diabetes or early abnormal glucose metabolism were negative, individuals should be rescreened for GDM between 24 and 28 weeks of gestation and individuals not previously screened should be screened for GDM at the same time point (see Section 15, "Management of Diabetes in Pregnancy"). The GDM diagnostic criteria for the 75-g OGTT from the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) and the GDM screening and diagnostic criteria with the two-step approach were not derived from data in the first half of pregnancy and should not be used for early screening (179) . Most randomized controlled trials of treatment of early abnormal glucose metabolism have been underpowered for outcomes. One randomized controlled trial performed at 17 centers administered early screening (mean 15.6 ± 2.5 weeks) for GDM with a 75-g OGTT. Individuals who met World Health Organization criteria for GDM were randomized to receive early treatment or a repeat OGTT at 24-28 weeks (with deferred treatment if indicated). The first primary outcome measure was an adverse neonatal composite outcome including birth < 37 weeks, birth weight $4.5 kg, birth trauma, neonatal respiratory distress within 24 h of birth, phototherapy, stillbirth neonatal death, or shoulder dystocia. Early GDM treatment resulted in a modest improvement in the composite adverse neonatal outcome (24.9% early treatment vs. 30.5% control treatment, relative risk 0.82 [0.68-0.98]), although this was driven primarily by differences in rates of neonatal respiratory distress between groups that included neonates requiring $4 h of supplemental oxygen who may not have required a higher level of respiratory care. There was also a suggestion of more benefit (per prespecified subgroup analyses) among individuals who had the OGTT at < 14 weeks and among those with OGTT glycemic values in higher ranges (180) . Therefore, the benefits of treatment of early abnormal glucose metabolism remain uncertain. Nutrition counseling and periodic testing of glucose levels weekly to identify individuals with high glucose levels are suggested. Testing frequency may proceed to daily, and treatment may be intensified, if the FPG is predominantly > 110 mg/dL ( > 6.1 mmol/L) prior to 18 weeks of gestation.

Both the FPG and A1C are low-cost tests. An advantage of the A1C test is its convenience, as it can be added to the prenatal laboratories and does not require an early-morning fasting appointment. Disadvantages include inaccuracies in the presence of increased red blood cell turnover and hemoglobinopathies (usually reads lower) and higher values with anemia and reduced red blood cell turnover (181) . A1C is not reliable for screening for GDM or for preexisting diabetes at 15 weeks of gestation or later in part from the higher red blood cell turnover in pregnancy but also from the unknown diabetes status prior to pregnancy, which could help distinguish new-onset diabetes from preexisting diabetes.

GDM is often indicative of underlying b-cell dysfunction (182) , which confers marked increased risk for later development of glucose intolerance and diabetes in the mother after delivery (183) (184) (185) . As effective prevention interventions are available (186, 187) , individuals diagnosed with GDM should receive lifelong screening for prediabetes to allow interventions to reduce diabetes risk and for type 2 diabetes to allow treatment at the earliest possible time (188) .

Diagnosis

GDM carries risks for the mother, fetus, and neonate. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study (189) , a large-scale multinational cohort study completed by more than 23,000 pregnant individuals, demonstrated that risk of adverse maternal, fetal, and neonatal outcomes continuously increased as a function of maternal glycemia at 24-28 weeks of gestation, even within ranges previously considered normal for pregnancy. For most complications, there was no threshold for risk. These results have led to careful reconsideration of the diagnostic criteria for GDM.

GDM diagnosis (Table 2 .8) can be accomplished with either of two strategies:

1. The "one-step" 75-g OGTT derived from the IADPSG criteria, or 2. The older "two-step" approach with a 50-g (nonfasting) screen followed by a 100-g OGTT for those who screen positive based on the work of Carpenter-Coustan's interpretation of the older O'Sullivan and Mahan (190) criteria.

Different diagnostic criteria will identify different degrees of maternal hyperglycemia and maternal/fetal risk, leading experts to debate optimal strategies for the diagnosis of GDM.

One-Step Strategy

The IADPSG examined data from the HAPO study and defined diagnostic cut points for GDM as the average fasting, 1-h, and 2-h PG values during a 75-g OGTT in individuals at 24-28 weeks of gestation, wherein the cut points were those at which odds for adverse outcomes reached 1.75 times the estimated odds. This one-step strategy was anticipated to significantly increase the incidence of GDM (from 5-6% to 15-20%), primarily because only one abnormal value, not two, became sufficient to make the diagnosis (191) . Many regional studies have seen a roughly one-to threefold increase in GDM cases using the IADPSG criteria (192) . A study of pregnancy OGTTs with glucose levels blinded to caregivers found that 11 years after their pregnancies, individuals who would have been diagnosed with GDM by the one-step approach, as compared with those without GDM, were at 3.4-fold higher risk of developing prediabetes and type 2 diabetes and had children with a higher risk of obesity and increased body fat, suggesting that the group identified as having GDM by the one-step approach would benefit from the increased screening for diabetes and prediabetes after pregnancy (193) . The ADA recommends the IADPSG diagnostic criteria to optimize gestational outcomes, because these criteria are the only ones based on pregnancy outcomes rather than end points such as prediction of subsequent maternal diabetes. Expected benefits of using IADPSG criteria for offspring are inferred from intervention trials focusing on individuals with lower levels of hyperglycemia than those identified using older GDM diagnostic criteria. Those trials found modest benefits, including reduced rates of largefor-gestational-age births and preeclampsia (194, 195) . Of note, 80-90% of participants being treated for mild GDM in these two randomized controlled trials could be managed with lifestyle therapy alone. The OGTT glucose cutoffs in these two trials overlapped the thresholds recommended by the IADPSG, and in one trial (195) , the 2-h PG threshold (140 mg/dL [7.8 mmol/L]) was lower than the cutoff recommended by the IADPSG (153 mg/dL [8.5 mmol/L] ).

No randomized controlled trials of treating versus not treating GDM diagnosed by (204) . †ACOG notes that one elevated value can be used for diagnosis (204) .

diabetesjournals.org/care Diagnosis and Classification of Diabetes different criteria have been published to date. However, a randomized trial of testing for GDM at 24-28 weeks of gestation by the one-step method using IADPSG criteria versus the two-step method by Carpenter-Coustan criteria identified twice as many individuals with GDM using the one-step method. Despite treating more individuals for GDM using the one-step method, there was no difference in pregnancy and perinatal complications (196) , though concerns were raised about sample size estimates and unanticipated suboptimal engagement with the screening and treatment protocol. For example, in the two-step group, 165 participants not counted as having GDM were treated for isolated elevated FPG > 95 mg/dL ( > 5.3 mmol/L) (197) .

The one-step method identifies longterm risks of maternal prediabetes and diabetes as well as offspring glucose intolerance and adiposity. Post hoc GDM in individuals diagnosed with this method in the HAPO cohort was associated with higher prevalence of IGT; higher 30-min, 1-h, and 2-h glucose levels during the OGTT; and reduced insulin sensitivity and oral disposition index in their offspring at 10-14 years of age compared with offspring of mothers without GDM. Associations of mother's fasting, 1-h, and 2-h values on the 75-g OGTT were continuous with a comprehensive panel of offspring metabolic outcomes (198, 199) . HAPO Follow-up Study (HAPO FUS) data demonstrate that neonatal adiposity and fetal hyperinsulinemia (cord C-peptide), both higher across the continuum of maternal hyperglycemia, are mediators of childhood body fat (200) .

Data are lacking on how the treatment of mother's hyperglycemia in pregnancy affects her offspring's risk for obesity, diabetes, and other metabolic disorders (201, 202) . Additional well-designed clinical studies are needed to determine the optimal intensity of monitoring and treatment of individuals with GDM diagnosed by the one-step strategy.

Two-Step Strategy

In 2013, the NIH convened a consensus development conference to consider diagnostic criteria for diagnosing GDM (203) . The 15-member panel had representatives from obstetrics and gynecology, maternal-fetal medicine, pediatrics, diabetes research, biostatistics, and other related fields. The panel recommended continuing a two-step approach to screening that used a 1-h 50-g glucose loading test (GLT) followed by a 3-h 100-g OGTT for those who screened positive. The American College of Obstetricians and Gynecologists (ACOG) recommends any of the commonly used thresholds of 130, 135, or 140 mg/dL for the 1-h 50-g GLT (204) . A 2021 U.S. Preventive Services Task Force systematic review concluded that onestep versus two-step screening is associated with increased likelihood of GDM (11.5% vs. 4.9%) but without improved health outcomes (205) . The use of A1C at 24-28 weeks of gestation as a screening test for GDM does not function as well as the GLT (206) .

Importantly, the NIH panel noted the lack of clinical trial data demonstrating the benefits of the one-step strategy and the potential negative consequences of identifying a large group of individuals with GDM, including medicalization of pregnancy with increased health care utilization and costs. Moreover, screening with a 50-g GLT does not require fasting and therefore is easier to accomplish for many individuals. Treatment of higherthreshold maternal hyperglycemia, as identified by the two-step approach, reduces rates of neonatal macrosomia, large-forgestational-age births (207) , and shoulder dystocia without increasing small-forgestational-age births. ACOG currently supports the two-step approach but notes that one elevated value, as opposed to two, may be used for the diagnosis of GDM (204) . If this approach is implemented, the incidence of GDM will likely increase markedly. ACOG recommends either of two sets of diagnostic thresholds for the 3-h 100-g OGTT Carpenter-Coustan or National Diabetes Data Group (208, 209) . Each is based on different mathematical conversions of the original recommended thresholds by O'Sullivan and Mahan (190) , which used whole blood and nonenzymatic methods for glucose determination. A secondary analysis of data from a randomized clinical trial of identification and treatment of mild GDM (210) demonstrated that treatment was similarly beneficial in people meeting only the lower thresholds per Carpenter-Coustan (208) and in those meeting only the higher thresholds per National Diabetes Data Group (209) . If the two-step approach is used, it would appear advantageous to use the Carpenter-Coustan lower diagnostic thresholds, as shown in step 2 in Table 2 .8.

Future Considerations

Data exist to support each strategy, as demonstrated by conflicting recommendations by expert groups. A systematic review of economic evaluations of GDM screening found that the one-step method identified more cases of GDM and was more likely to be cost-effective than the two-step method (211) . The decision of which strategy to implement must therefore be made based on the relative values placed on factors that have yet to be measured (e.g., willingness to change practice based on correlation studies rather than intervention trial results, available infrastructure, and importance of cost considerations).

The IADPSG criteria (one-step strategy) have been adopted internationally as the preferred approach. Data that compare population-wide outcomes with one-step versus two-step approaches have been inconsistent to date (196, (212) (213) (214) . Pregnancies complicated by GDM per the IADPSG criteria, but not recognized as such, have outcomes comparable to pregnancies with diagnosed GDM by the more stringent two-step criteria (215, 216) . There remains strong consensus that establishing a uniform approach to diagnosing GDM will benefit people with GDM, caregivers, and policymakers. Longer-term outcome studies are currently underway. Three distinct stages of type 1 diabetes have been defined, with symptomatic type 1 diabetes being stage 3 (Table 2 .4). In individuals at risk for developing clinical type 1 diabetes, younger age of seroconversion (particularly under age 3 years), the total number of diabetesrelated autoantibodies (1), and the development of autoantibodies against islet antigen 2 (IA-2) have been associated with a more rapid progression to clinical type 1 diabetes. While continuous glucose monitoring can predict progression to overt diabetes in children with autoantibodies (2), OGTT-based metrics appear to be better at predicting progression compared with continuous glucose monitoring (3) . The decision to perform an OGTT may depend on such factors as eligibility and interest for stage-specific treatments, participation in clinical research, availability, and the burden of testing. A consensus guidance provides expert recommendations on what should be monitored and how often in people with presymptomatic type 1 diabetes (4). Several major randomized controlled trials, including the Diabetes Prevention Program (DPP) trial ( 5 ), the Finnish Diabetes Prevention Study (DPS) (6) , and the Da Qing Diabetes Prevention Study (Da Qing study) (7) , demonstrate that lifestyle/behavioral intervention with an individualized reduced-calorie meal plan is highly effective in preventing or delaying type 2 diabetes and improving other cardiometabolic risk factors (such as blood pressure, lipids, and inflammation) (8) . The strongest evidence for diabetes prevention in the U.S. comes from the DPP trial (5) . The DPP demonstrated that intensive lifestyle intervention could reduce the risk of incident type 2 diabetes by 58% over 3 years. Follow-up of three large trials of lifestyle intervention for diabetes prevention showed sustained reduction in the risk of progression to type 2 diabetes: 39% reduction at 30 years in the Da Qing study (9) , 43% reduction at 7 years in the Finnish DPS (6) , and 34% reduction at 10 years (10) and 27% reduction at 15 years (11) in the U.S. Diabetes Prevention Program Outcomes Study (DPPOS).

The DPP lifestyle intervention was a goal-based intervention. All participants were given the same weight loss and physical activity goals, but individualization was permitted to achieve the goals (12) . The two major goals of the DPP intensive lifestyle intervention were to achieve and maintain a minimum of 7% weight loss and to partake in 150 min of moderate-intensity physical activity per week, such as brisk walking. Although weight loss was the most important factor in reducing the risk of incident diabetes, achieving the behavioral goal of at least 150 min of physical activity per week, even without achieving the weight loss goal, reduced the incidence of type 2 diabetes by 44% (13) .

The 7% weight loss goal was selected because it was feasible to achieve and maintain and likely to lessen the risk of developing diabetes (as well as improve other cardiometabolic risk factors). Participants were encouraged to achieve the $7% weight loss during the first 6 months of the intervention. Further analysis suggests higher benefit for prevention of diabetes with at least 7-10% weight loss with lifestyle interventions (13) . The recommended pace of weight loss was 1-2 lb/week. Calorie goals were calculated by estimating the daily calories needed to maintain the participant's initial weight and subtracting 500-1,000 calories/day (depending on initial body weight). The initial focus of the nutrition intervention was on reducing total fat rather than calories. After several weeks, the concepts of calorie balance and the need to restrict calories and fat were introduced (12) .

The goal for physical activity was selected to approximate at least 700 kcal/week expenditure from physical activity. For ease of translation, this goal was described as at least 150 min of moderate-intensity physical activity per week, similar in intensity to brisk walking. Participants were encouraged to distribute their activity throughout the week with a minimum frequency of three times per week and at least 10 min per session. A maximum of 75 min of strength training could be applied toward the total 150 min/week physical activity goal (12) .

To implement the weight loss and physical activity goals, the DPP used an individual model of treatment rather than a group-based approach. This choice was based on a desire to intervene before participants had the possibility of developing diabetes or losing interest in the program. The individual approach also allowed for the tailoring of interventions to reflect the diversity of the population (12) .

The DPP intervention was administered as a structured core curriculum followed by a flexible maintenance program of individual counseling, group sessions, motivational campaigns, and restart opportunities. The 16-session core curriculum was completed within the first 24 weeks of the program. It included sessions on lowering calories, increasing physical activity, self-monitoring, maintaining healthy lifestyle behaviors (such as how to choose healthy food options when eating out), and guidance on managing psychological, social, and motivational challenges (12) .

While the DPP interventions were successful in preventing or delaying the onset of type 2 diabetes, long-term effects on clinically meaningful events (microvascular and macrovascular disease) have not been established (14) . However, there is potential benefit without the risk of harm with these interventions.

Nutrition

Nutrition counseling for weight loss in the DPP lifestyle intervention arm included a reduction of total fat and calories (5, 12, 13) . However, evidence suggests that there is not an ideal percentage of calories from carbohydrate, protein, and fat for all people to prevent diabetes; therefore, macronutrient distribution should be based on an individualized assessment of current eating patterns, preferences, and metabolic goals (15) . Based on other trials, a variety of eating patterns (15, 16) may also be appropriate for individuals with prediabetes (15) , including Mediterranean-style and low-carbohydrate eating plans (17) (18) (19) . Observational studies have also shown that vegetarian, plant-based (may include some animal products), and Dietary Approaches to Stop Hypertension (DASH) eating patterns are associated with a lower risk of developing type 2 diabetes (20) (21) (22) (23) . Evidence suggests that the overall quality of food consumed (as measured by the Healthy Eating Index, Alternative Healthy Eating Index, and DASH score), with an emphasis on whole grains, legumes, nuts, fruits, and vegetables and minimal refined and processed foods, is also associated with a lower risk of type 2 diabetes (22, 24, 25) . As is the case for those with diabetes, individualized medical nutrition therapy (see Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes," for more detailed information) is effective in lowering A1C in individuals diagnosed with prediabetes (26) .

Physical Activity

Moderate-intensity physical activity, such as brisk walking for 150 min/week, has shown beneficial effects in those with prediabetes (5) . Similarly, moderate-intensity physical activity has been shown to improve insulin sensitivity and reduce abdominal fat in children and young adults (27, 28) . Health care professionals are encouraged to promote a DPP-style program to all individuals who have been identified to be at an increased risk of type 2 diabetes. In addition to aerobic activity, a physical activity plan designed to prevent diabetes may include resistance training (12, 29) . Breaking up prolonged sedentary time may also be encouraged, as it lowers postprandial glucose levels (30) . The effects of physical activity appear to extend to the prevention of gestational diabetes mellitus (GDM) (31) .

Sleep Characteristics Associated With Increased Risk of Type 2 Diabetes

Sleep occupies approximately one-third of the day for most people and modulates a variety of metabolic, endocrine, and cardiovascular processes (32) . The latest ADA-EASD consensus report on management of hyperglycemia highlights sleep as a central component in the management of prediabetes and type 2 diabetes, placing it, for the first time, on the same level as other lifestyle behaviors (e.g., physical activity and nutrition) (33) . Sleep can be characterized using three key constructs: quantity, quality, and timing (i.e., chronotype). There is now established evidence for a U-shaped association between sleep duration and type 2 diabetes incidence, with the nadir typically occurring at 7 h per day, with short (typically defined as < 6 h) and long (typically defined as > 9 h) sleep duration having up to a 50% increase in the risk of type 2 diabetes, including progression from prediabetes (33) . Sleep quality has recently been defined as "an individual's self-satisfaction with all aspects of the sleep experience" (34, 35) . Poor sleep quality was associated with a 40-84% increased risk of developing type 2 diabetes in a meta-analysis (36) . Chronotype preference has been linked with many chronic diseases, including type 2 diabetes. For example, for those with a preference for evenings (i.e., going to bed late and getting up late), there was a 2.5-fold higher odds ratio for type 2 diabetes than for those with a preference for mornings (i.e., going to bed early and getting up early), independent of sleep duration and sleep sufficiency (37) .

Delivery and Dissemination of Lifestyle Behavior Change for Diabetes Prevention

Because the intensive lifestyle intervention in the DPP was effective in preventing type 2 diabetes among those at high risk for the disease and lifestyle behavior change programs for diabetes prevention were shown to be cost-effective, broader efforts to disseminate scalable lifestyle behavior change programs for diabetes prevention with coverage by third-party payors ensued (38) (39) (40) (41) (42) . Group delivery of DPP content in community or primary care settings has demonstrated the potential to reduce overall program costs while still producing weight loss and diabetes risk reduction (43, 44) .

The Centers for Disease Control and Prevention (CDC) developed the National Diabetes Prevention Program (National DPP), a resource designed to bring such evidencebased lifestyle change programs for preventing type 2 diabetes to communities (cdc.gov/diabetes-prevention). This online resource includes locations of CDC-recognized diabetes prevention lifestyle change programs (cdc.gov/diabetes/prevention/ find-a-program.html). To be eligible for this program, individuals must have a BMI in the overweight range and be at risk for diabetes based on laboratory testing, a previous diagnosis of GDM, or a positive risk test (cdc.gov/prediabetes/ risktest/). During the first 4 years of implementation of the CDC's National DPP, 36% achieved the 5% weight loss goal (45) . The CDC has also developed the Diabetes Prevention Impact Tool Kit (nccd. cdc.gov/toolkit/diabetesimpact) to help organizations assess the economics of providing or covering the National DPP (46) . To expand preventive services using a cost-effective model, the Centers for Medicare & Medicaid Services expanded Medicare reimbursement coverage for the National DPP to organizations recognized by the CDC that become Medicare suppliers for this service (innovation.cms. gov/innovation-models/medicare-diabetesprevention-program). The locations of Medicare DPPs are available online at innovation.cms.gov/innovation-models/ medicare-diabetes-prevention-program/ mdpp-map. To qualify for Medicare coverage, individuals must have BMI > 25 kg/m 2 (or BMI > 23 kg/m 2 if selfidentified as Asian) and glycemic testing consistent with prediabetes in the last year. Medicaid DPP is also expanding on a state-by-state basis.

While CDC-recognized behavioral counseling programs, including Medicare DPP services, have met minimum quality standards and are reimbursed by many payors, lower retention rates have been reported for younger adults and racial and ethnic minoritized populations (47) . Therefore, other programs and modalities of behavioral counseling for diabetes prevention may also be appropriate and efficacious based on individual preferences and availability. The use of community health workers to support DPP-like interventions has been shown to be effective and cost-effective (48,49) (see Section 1, "Improving Care and Promoting Health in Populations," for more information). The use of community health workers may facilitate the adoption of behavior changes for diabetes prevention while bridging barriers related to social determinants of health. However, coverage by third-party payors remains limited. Counseling by a registered dietitian/ nutritionist (RDN) has been shown to help individuals with prediabetes improve eating habits, increase physical activity, and achieve 7-10% weight loss (15, (50) (51) (52) . Individualized medical nutrition therapy (see Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes," for more detailed information) is also effective in improving glycemia in individuals diagnosed with prediabetes (26, 50) . Furthermore, trials involving medical nutrition therapy for adults with prediabetes found significant reductions in weight, waist circumference, and glycemia (23, 26) . Individuals with prediabetes can benefit from referral to an RDN for individualized medical nutrition therapy upon diagnosis and at regular intervals throughout their treatment plan (51, 53) . Other health care professionals, such as pharmacists and diabetes care and education specialists, may also be considered for diabetes prevention efforts (53, 54) .

Technology-assisted programs may effectively deliver a DPP-like intervention (55) (56) (57) (58) . A digital diabetes prevention program improved cardiovascular risk at 4 months but not at 12 months (59) . Such technology-assisted programs may deliver content through smartphones, web-based applications, and telehealth and may be an acceptable and efficacious option to bridge barriers, particularly for individuals with low income and/or in rural locations; however, not all technology-assisted programs are effective (55, (60) (61) (62) . The CDC Diabetes Prevention Recognition Program (DPRP) (cdc.gov/diabetes/prevention/requirementsrecognition.htm) certifies technologyassisted modalities as effective vehicles for DPP-based interventions; such programs must use an approved curriculum, include interaction with a coach, and attain the DPP outcomes of participation, physical activity reporting, and weight loss. Health care professionals should consider referring adults with prediabetes to certified technology-assisted programs.

PHARMACOLOGIC INTERVENTIONS TO DELAY TYPE 2 DIABETES

Hepatitis B

Compared with the general population, people with type 1 or type 2 diabetes have higher rates of hepatitis. Because of the higher likelihood of transmission of the disease, hepatitis B vaccine is recommended for adults with diabetes aged < 60 years. For adults aged $60 years, hepatitis B vaccine may be administered at the discretion of the treating clinician based on the person's likelihood of acquiring hepatitis B infection (19) .

Influenza

Influenza is a common, preventable infectious disease associated with high mortality and morbidity in vulnerable populations, including youth, older adults, and people with chronic diseases. Influenza vaccination in people with diabetes has been found to significantly reduce influenza and diabetesrelated hospital admissions (20) . In people with diabetes, the influenza vaccine has been associated with lower risk of all-cause mortality, cardiovascular mortality, and cardiovascular events (21) . Given the benefits of the annual influenza vaccination, it is recommended for all individuals $6 months of age who do not have a contraindication. The live attenuated influenza vaccine, which is delivered by nasal spray, is an option for people who are 2-49 years of age and are not pregnant, but people with chronic conditions such as diabetes are cautioned against taking the live attenuated influenza vaccine and are instead recommended to receive the inactive or recombinant influenza vaccination. As of the 2024-2025 season, all influenza vaccines offered in the U.S. are trivalent (22) .

Pneumococcal Pneumonia

Like influenza, pneumococcal pneumonia is a common, preventable disease. People with diabetes are at increased risk for pneumococcal infection and have been reported to have a high risk of hospitalization and death, with a mortality rate as high as 50% (23) . All people with diabetes should receive one of the CDC-recommended pneumococcal vaccines (24) . See details in Table 4 .3. (25) .

ASSESSMENT OF COMORBIDITIES

Besides assessing diabetes-related complications, clinicians and people with diabetes need to be aware of common comorbidities that affect people with diabetes and that may complicate management (26) (27) (28) .

Diabetes comorbidities are conditions that affect people with diabetes more often than age-matched people without diabetes. This section discusses many of the common comorbidities observed in people with diabetes but is not necessarily inclusive of all the conditions that have been reported. A low-trauma hip/pelvis, vertebral, or forearm fracture in people aged $65 years is diagnostic for osteoporosis independent of BMD and is one of the strongest risk factors for subsequent fractures, especially in the first 1-2 years after a fracture (37, 38) . Osteoporotic hip fractures are associated with significant morbidity, mortality, and societal costs (39) . It is estimated that 20% of individuals do not survive to 1 year after hip fracture, while 60% do not regain their prior functionality, living with permanent disability (40) .

Hip fractures in people with diabetes are associated with higher risk of mortality (28% in women and 57% in men), longer recovery, and delayed healing (41) compared with individuals without diabetes.

Epidemiology and Risk Factors

Age-specific fracture risk is significantly increased in people with type 1 or type 2 diabetes in both sexes, with a 34% increase in fracture risk compared with those without diabetes (42) .

Type 1 Diabetes. Fracture risk in people with type 1 diabetes is increased by 4.35 times for hip fractures, 1.83 times for upper limb fractures, and 1.97 times for ankle fractures (43) . Fractures occur even at young ages, 10-15 years earlier than they do in people without diabetes, and are less frequent at the vertebral level. Type 1 diabetes is often associated with low bone mass, although BMD underestimates the high risk of fracture observed in young individuals (43) . Risk of fracture is increased in people with type 1 diabetes with microvascular complications or neuropathy (41) ‡May also need to be checked after initiation or dose changes of medications that affect these laboratory values (i.e., diabetes medications, blood pressure medications, cholesterol medications, or thyroid medications). ^In people without dyslipidemia and not on cholesterol-lowering therapy, testing may be less frequent. §May be needed more frequently in people with diabetes with known chronic kidney disease or with changes in medications that affect kidney function and serum potassium (see Table 11 .2). jjIn people with presence of gastrointestinal symptoms, signs, laboratory manifestations, or clinical suspicion suggestive of celiac disease.

higher than in it is in individuals without diabetes (42, (45) (46) (47) . According to a metaanalysis that included 15 studies, people with type 2 diabetes had a 35% higher incidence of vertebral fractures, causing increased risk of mortality (HR 2.11 [95% CI 1.72-2.59]) (48) . Fracture risk is also increased in the upper limbs and ankle. However, bone loss is accelerated, and low BMD remains an independent risk factor for fractures (49, 50) .

Glycemic management significantly impacts fracture risk in people with diabetes. A meta-analysis revealed an 8% increased fracture risk per 1% rise in A1C level (RR 1.08 [95% CI 1.03-1.14]) (51) . Poor glycemic management (A1C > 9%) over 2 years in individuals with type 2 diabetes correlated with a 29% heightened fracture risk (52) . Notably, this risk was higher among White individuals than in other racial groups. Hypoglycemia also escalated the risk of fractures at the hip and other skeletal sites (RR 1.52 [95% CI 1.23-1.88]) (51) . A Japanese study echoed these findings, showing a fracture risk increase (hazard ratio [HR] 2.24 [95% CI 1.56-3.21] ) with severe hypoglycemia episodes (53) .

Longer disease duration further elevates fracture risk (54) ; data indicate individuals who have had type 2 diabetes for > 10 years face significantly higher fracture risks, which are largely attributed to ensuing microvascular and macrovascular damage affecting the skeleton. Additionally, high fracture risk is seen in people with cardiovascular disease (CVD), nephropathy, retinopathy, neuropathy, poor physical function, and frequent falls (55) (56) (57) .

Certain glucose-lowering medications also factor into fracture risk. Studies have reported increased fracture incidences in women using thiazolidinediones (TZD), with the risk doubling with 1-2 years of TZD use compared with placebo or other glucose-lowering medications (HR 2.23 [95% CI 1.65-3.01]) (58, 59) Type 2 Diabetes. People with type 2 diabetes have 5-10% higher BMD than people without diabetes, although they present with lower bone strength, impaired bone microarchitecture, and accelerated bone loss (49, (62) (63) (64) . A T-score adjustment of À0.5 has been proposed to improve fracture prediction by dual-energy X-ray absorptiometry (DXA). For example, a T-score #-2.0 should be interpreted as equivalent to -2.5 in a person without diabetes (50) . Notably, the Fracture Risk Assessment Tool (FRAX), although useful, does not factor in type 2 diabetes; an inclusion of the condition is estimated to mirror the effect of either a 10-year age increase or a 0.5 SD reduction in BMD T-score (65) . Fracture risk was higher in large observational studies in participants with diabetes compared with those without diabetes for a given T-score and age or for a given FRAX score (50) . One method to potentially improve fracture risk prediction for people with type 2 diabetes involves using the FRAX "rheumatoid arthritis" input as a proxy for diabetes risk (66, 67) . Additionally, performance of FRAX can be improved by using 1) trabecular bone score adjustment, 2) lowering femoral neck T-score input by 0.5 SD, or 3) increasing the age by 10 years (66) . Growing evidence suggests that fracture risk prediction is enhanced by use of trabecular bone score (65, 66) , although such studies are not available for 4 .4). Reassessment is recommended every 2-3 years (65), depending on the screening evaluation and the presence of additional risk factors, although the evidence on how frequently DXA should be repeated is less robust. According to the European Association for the Study of Obesity (EASO), DXA should be performed every 2 years in subjects undergoing bariatric-metabolic surgery.

DXA-assisted vertebral fracture assessment is a convenient and low-cost method to assess vertebral fractures, although traditional lateral thoracic/lumbar spine X-ray is still considered the gold standard (68) . MRI or computed tomography imaging studies performed for other purposes should be analyzed for presence of vertebral fractures as well as chest X-rays in hospitalized individuals. Bone turnover markers are commonly used in clinical practice to monitor bone formation and bone resorption, although they are suppressed in people with diabetes and have not been shown to predict fracture risk (69) .

Type 1 Diabetes. Because hip fracture risk in type 1 diabetes starts to increase after the age of 50, clinicians may consider assessing BMD after the 5th decade of life (43) . In people with type 1 diabetes, BMD underestimates fracture risk, but studies do not address the extent of underestimation of fracture risk.

According to the International Society for Pediatric and Adolescent Diabetes (ISPAD), regular assessment of bone health using bone densitometry in youth with type 1 diabetes is still controversial and not recommended, but it may be considered in association with celiac disease (70) .

Management

Appropriate glycemic management and minimizing hypoglycemic episodes are crucial for bone health in people with diabetes. Individuals with prolonged disease, microvascular and macrovascular complications, or frequent hypoglycemic episodes face higher fracture risks and fall risks due to factors like poor vision, neuropathy, sarcopenia, and impaired gait. Health care professionals should advocate moderate physical activity to enhance muscle health, gait coordination, and balance as part of fracture preventive strategies (56, 57, 71) .

Aerobic and weight-bearing exercise should be recommended to counteract the potential negative effect of weight loss on bone; specific guidelines have been published for older adults with type 2 diabetes (72) .

Osteoporosis and fracture prevention are first based on measures applied to the general population. All people with diabetes should receive an adequate daily intake of proteins, calcium, and vitamin D, stop smoking, and have regular physical activity (73) (74) (75) .

Intake of calcium should reflect the age-specific recommendations for the general population and should be obtained through diet and/or oral supplements (76) .

The optimal level of 25-hydroxyvitamin D is a matter of controversy (77) , although serum levels 20-30 ng/mL are generally thought to be sufficient (78) .

The safe upper limit is also a matter of debate, and there is substantial disagreement over whether to treat to a specified serum level. In the U.S., the recommended daily allowance of vitamin D is 600 IU for people aged 51-70 years and 800 IU for people aged > 70 years (78) . In clinical practice, this dose of supplement may not be sufficient to reach recommended serum levels of vitamin D, particularly in those at risk for vitamin D deficiency, and therefore supplementation should be individualized.

Fractures are important determinants of frailty, a predisability condition that should be mitigated with individualized There are some additional considerations related to medication selection in people with diabetes. Data from a phase 3 trial, Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM), and its 10-year extension have shown that people with diabetes treated with denosumab experienced positive effects on fasting glucose (82) and significant improvements in BMD and lower vertebral fracture risk (67) . However, according to a post hoc subgroup analysis, a higher risk of nonvertebral fractures was observed in people with diabetes treated with denosumab (67) . Romosozumab received FDA approval with a box warning because it may increase risk of myocardial infarction, stroke, or cardiovascular death and should not be prescribed in women who experienced a myocardial infarction or a stroke within the past year (83, 84) .

Secondary Prevention of Fragility Fractures. The risk of subsequent fracture in individuals with hip or vertebral fracture is high, especially in the first 1-2 years after a fracture. Antiosteoporosis treatment reduces the risk of fracture in older individuals with prior hip or vertebral fracture.

As in the general population, people with diabetes who experience fragility fracture should 1) be given the diagnosis of osteoporosis regardless of DXA data and 2) receive the appropriate work-up and therapy to prevent future fractures (85) . Individuals on long-term treatment with antiosteoporosis medications, with multiple fragility fractures, or with multiple comorbidities should be referred to a bone metabolic specialist. In these more complicated cases, a bone specialist may choose to initiate an osteoanabolic agent to optimize bone formation and reduce immediate fracture risk (86) . It is strongly recommended that all individuals with a fragility fracture be started on antiosteoporosis therapy and adequate calcium and vitamin D supplementation (if required) as soon as possible. In the appropriate individual, therapy may even be initiated during an inpatient stay to reduce care delays (85) .

Glucose-Lowering Medications and Bone Health

Care plans for type 2 diabetes treatment should consider individual fracture risk and the potential effect of medications on bone metabolism. Medications other than TZDs are advisable for postmenopausal women or older men with type 2 diabetes due to their safer bone health profiles. While several studies have shown metformin to have a safe profile, special attention should be paid to the wide use of sulfonylureas because of the high risk of hypoglycemic events leading to falls and fractures (87) . Dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been used in clinical practice for more than 15 years, and both clinical trials and postmarketing data suggest a neutral impact on bone health (88, 89) . Tirzepatide may play a positive effect through glucosedependent insulinotropic polypeptide (GIP) receptor agonism, preventing bone loss associated with weight loss (90) , although bone outcomes have not yet been reported in clinical data.

Use of sodium-glucose cotransporter 2 (SGLT2) inhibitors has raised some concerns. The Canagliflozin Cardiovascular Assessment Study (CANVAS) study showed that the proportion of subjects with fracture was higher in the canagliflozin groups than the noncanagliflozin groups (2.7% vs. 1.9%, respectively). Further analyses from the same trial and from the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study found a neutral effect on fracture risk (91) (92) (93) (94) . Although few data are available, use of empagliflozin, ertugliflozin, or dapagliflozin has not been associated with negative effects on bone health (93) (94) (95) . Use of insulin has been shown to be associated with a doubling of the risk of hip fractures (87), likely because of higher risk of hypoglycemia, longer duration of the disease, and comorbidities that may contribute to diminished bone strength.

In conclusion, glucose-lowering medications with a good bone safety profile are preferred. This is especially true in older adults, in people with longer duration of disease, or in people with complications. Aggressive therapeutic approaches should be avoided in those who are frail and in older adults to prevent hypoglycemic events and falls.

Cancer

Diabetes is associated with increased risk of cancers of the liver, pancreas, endometrium, colon and rectum, breast, and bladder (96) . The association may result from shared risk factors between type 2 diabetes and cancer (older age, obesity, and physical inactivity) but may also be due to diabetes-related factors (97) , such as underlying disease physiology or diabetes treatments, although evidence for these links is scarce. People with diabetes should be encouraged to undergo recommended age-and sexappropriate cancer screenings, coordinated with their primary health care professional, and to reduce their modifiable cancer risk factors (obesity, physical inactivity, and smoking). New onset of atypical diabetes (lean body habitus and negative family history) in a middle-aged or older person may precede the diagnosis of pancreatic adenocarcinoma (98) . Additionally, in a nationwide cancer registry in New Zealand, postpancreatitis diabetes mellitus was associated with significantly higher risk (2.4-fold) of pancreatic cancer compared with pancreatitis after type 2 diabetes (99) . However, in the absence of other symptoms (e.g., weight loss and abdominal pain), routine screening for pancreatic cancer is not currently recommended. Metformin and sulfonylureas may have anticancer properties. Data for pioglitazone are mixed, with a previous concern for bladder cancer association. Recommendations cannot be made at this time (100) (101) (102) . Thus far, the use of GLP-1 RAs has not been shown to be associated with the incidence of thyroid cancer, pancreatic cancer, or any other type of cancer in humans (103) .

Cognitive Impairment/Dementia Recommendation 4.14 In the presence of cognitive impairment, diabetes treatment plans should be simplified as much as possible and tailored to minimize the risk of hypoglycemia. B Diabetes is associated with a significantly increased risk and rate of cognitive decline and an increased risk of dementia (104) . A meta-analysis of prospective observational studies found that individuals with diabetes had a 43% higher risk of all types of dementia, a 43% higher risk of Alzheimer dementia, and a 91% higher risk of vascular dementia compared with individuals without diabetes (104) . The reverse is also true: people with Alzheimer dementia are more likely to develop diabetes than people without Alzheimer dementia. In a 15-year prospective study of community-dwelling people > 60 years of age, the presence of diabetes at baseline significantly increased the age-and sex-adjusted incidence of all-cause dementia, Alzheimer dementia, and vascular dementia compared with rates in those with normal glucose tolerance (105) . A new clinical entity of diabetes-related dementia is being recognized as distinct from Alzheimer dementia or vascular dementia. It is characterized by slow progression of dementia, absence of typical neuroimaging findings seen in Alzheimer or vascular dementia, old age, high A1C levels, long duration of diabetes, high frequency of insulin use, frailty, and sarcopenia or dynapenia (106) . See Section 13, "Older Adults," for a more detailed discussion regarding assessment of cognitive impairment.

Glycemic Status and Cognition

In individuals with diabetes, higher A1C level is associated with lower cognitive function (107) . A meta-analysis of randomized trials found that intensive glycemic management, compared with higher A1C goals, was associated with a slightly lower rate of cognitive decline (108) . However, these findings were driven by an older study with an A1C goal of < 7.0% in the intensive treatment arm. Analyses within the ACCORD, Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE), and Veterans Affairs Diabetes Trial (VADT) studies found that intensive glycemic management (A1C goal of < 6.0-6.5%) resulted in no differences in cognitive outcomes compared with standard control (108) (109) (110) . Therefore, intensive glycemic management should not be advised for the improvement of cognitive function in individuals with type 2 diabetes. Additionally, people with type 2 diabetes and dementia are at heightened risk for experiencing hyperglycemic crises (diabetic ketoacidosis and hyperglycemic hyperosmolar state) compared with people without dementia (111) , underscoring the importance of supporting diabetes management for individuals experiencing cognitive decline and diminished capacity for self-care. In addition, these individuals have increased difficulty with complex treatment and monitoring plans and are at risk of frailty, hypoglycemia, and disability (112) .

In type 2 diabetes, severe hypoglycemia is associated with reduced cognitive function, and those with poor cognitive function have more severe or repeated episodes of hypoglycemia. Multiple observational studies of adults with diabetes have found an association between severe hypoglycemic episodes and cognitive decline or incident dementia (113) (114) (115) (116) . Decreased cognitive function also increases the risk for severe hypoglycemia, likely through impaired ability to recognize and respond appropriately to hypoglycemic symptoms (113, 117, 118) . Additionally, long-term followup of Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/ EDIC) showed recurrent severe hypoglycemia was associated with the highest risk of long-term psychomotor and mental function decline (119) . Simplifying or deintensifying glycemic therapy and/or liberalizing A1C goals may prevent hypoglycemia in individuals with cognitive dysfunction. See Section 13, "Older Adults," for more detailed discussion of hypoglycemia in older people with type 1 and type 2 diabetes.

Dental Care Recommendations 4.15 People with diabetes should be referred for a dental exam at least once per year. E 4.16 Coordinate efforts between the medical and dental teams to appropriately adjust glucose-lowering medication and treatment plans prior to and in the post-dental procedure period as needed. B Periodontal disease is more severe, and may be more prevalent, in people with diabetes than in those without and has been associated with higher A1C levels (120) (121) (122) . Longitudinal studies suggest that people with periodontal disease have higher rates of incident diabetes. Current evidence suggests that periodontal disease adversely affects diabetes outcomes, and periodontal treatment using subgingival instrumentation may improve glycemic outcomes (123, 124) . In a randomized controlled trial (RCT), intensive periodontal treatment was associated with better glycemic outcomes (A1C 8.3% vs. 7.8% in control subjects and the intensive-treatment group, respectively) and reduction in inflammatory markers after 12 months of follow-up (125) .

Dental health professionals should be included in the diabetes care team (126) . Early detection of oral health problems by clinicians may be helpful to promote prompt referral to dental care and mitigate the expensive and extensive procedures needed to treat advanced oral disease (127, 128) . Clinical assessment of people with diabetes should include a dental history, and dental professionals should be informed about key aspects of the person's health and diabetes treatment plan, including glycemic goals, medications, and comorbid conditions (127, 128) . It is important for dental professionals to know when people with diabetes have high A1C levels, as this population may have lower oral healing capacity (129, 130) . Hepatic, renal, and pulmonary conditions should also be known by dental professionals to assist in appropriate dosing of antibiotics and other medications. Coordination between dental professionals and the diabetes care team will be especially important for people treated with insulin, sulfonylureas, or meglitinides who are at risk of hypoglycemia during dental procedures, especially if fasting. The risk of hypoglycemia can be mitigated by coordination between the dentist and treating clinician prior to the procedure to make a hypoglycemia prevention plan, which may include medication adjustment, blood glucose monitoring before and during the procedure, and treatment of hypoglycemia if appropriate. Therefore, dental professionals caring for people with diabetes should have access to blood glucose monitors during procedures as well as carbohydrates and glucagon to treat any hypoglycemia that occurs. Disability Recommendation 4.17 Assess for disability at the initial visit and for decline in function at each subsequent visit in people with diabetes. If a disability is impacting functional ability or capacity to manage their diabetes, a referral should be made to an appropriate health care professional specializing in disability (e.g., physical medicine and rehabilitation specialist, physical therapist, occupational therapist, or speechlanguage pathologist). C A disability is defined as a physical or mental impairment that substantially limits one or more major life activities of an individual (131, 132) . Activities of daily living (ADLs) and instrumental activities of daily living (IADLs) comprise basic and complex life care tasks, respectively. The capacity to accomplish such tasks serves as an important measure of function. Diabetes is associated with an increase in the risk of work and physical disability, with estimates of 50-80% increased risk of disability for people with diabetes compared with people without diabetes (133) . Reviews have shown that lower-body functional limitation was the most prevalent disability (47-84%) among people with diabetes (134, 135) . In a systematic review and meta-analysis, the presence of diabetes increased the risk of mobility disability (15 (133) . The mechanisms underlying disability are multifactorial and include obesity, coronary artery disease, stroke, lower extremity complications, and physiological factors such as hyperglycemia, sarcopenia, inflammation, and insulin resistance (136) .

Diabetic peripheral neuropathy (DPN) is a common complication of both type 1 and 2 diabetes and may cause impaired postural balance and gait kinematics (137) , leading to functional disability. DPN can be found in up to half of people with type 1 or type 2 diabetes, resulting in physical disability, and neuropathic pain, resulting in a diminished quality of life (138) . Glycemic management prevents DPN development in type 1 diabetes; in contrast, glycemic management has modest or no benefit in individuals with type 2 diabetes, possibly due to the combined effect of coexisting comorbidities (138) . People with lower-extremity involvement due to DPN have 3 times more risk of restricted mobility, resulting in people with DPN experiencing more physical dysfunctions and impairments than people who have diabetes but not neuropathy (139) . Furthermore, DPN may progress to nontraumatic lower-limb amputation, which significantly impacts quality of life (140) .

In addition to complications of diabetes from microvascular conditions such as CKD, retinopathy, autonomic neuropathy, and peripheral neuropathy, it is important to recognize the disabilities caused by macrovascular complications of diabetes. These macrovascular complications, which include coronary heart disease, stroke, and peripheral arterial disease, can lead to further impairments (134) .

An assessment of disability should be performed as necessary with referrals made to appropriate health care professionals specializing in disability (e.g., physical medicine and rehabilitation physician, physical therapist, occupational therapist, or speech-language pathologist) (133, 141, 142) . Customized rehabilitation interventions for individuals with a disability from diabetes can recover function, allowing for safe physical activity (143) , and improve quality of life (144) . Additionally, frailty is commonly associated with diabetes, with progression to disability, morbidity, and mortality in older adults. People with diabetes as well as frailty or disability may contend with comorbid conditions such as hypoglycemia, sarcopenia, falls, and cognitive dysfunction. A thorough medical evaluation is imperative to identify the best approaches to preventative and therapeutic interventions for frailty and diabetes management (145) .

To assess the impact of diabetes on an individual's daily functioning, clinicians should consider evaluating their ability to perform ADLs and IADLs, ensuring they can manage basic self-care and more complex tasks necessary for specific living situations, services, and supports. A psychosocial assessment should be conducted to screen for behavioral health conditions like depression and anxiety and to understand the individual's social support and coping mechanisms. Functional capacity evaluations, involving tests for physical endurance and strength, are used to gauge the ability of the person with diabetes to work and carry out daily activities. Additionally, standardized disability questionnaires and scales, such as the Diabetes Distress Scale (DDS) and the World Health Organization Disability Assessment Schedule (WHODAS 2.0), are employed to measure the emotional burden of diabetes and overall disability (146, 147) . These suggested structured assessments are particularly relevant if individuals have fallen, had emergency department visits, missed appointments, made significant errors in the treatment plan, or exhibit apathy and depressed mood.

Moreover, when treating people with an acquired disability from diabetes, it is vital to consider social determinants of health, race and ethnicity, and socioeconomic status (148) . Rates of diabetesrelated major amputations are higher in individuals who are from racial and ethnic minoritized groups (149) , live in rural areas, and are from regions with the lowest socioeconomic levels (150) . Addressing the complex challenges faced by individuals with acquired disabilities from diabetes requires a multifaceted approach involving solutions from both within and outside the health care system. By focusing on social determinants of health, health care professionals can develop appropriate interventions, provide advocacy, and establish support systems that cater to the specific needs of this population. See Section 1, "Improving Care and Promoting Health in Populations."

Hepatitis C

Infection with hepatitis C virus (HCV) is associated with a higher prevalence of type 2 diabetes, which is present in up to onethird of individuals with chronic HCV infection. HCV may impair glucose metabolism by several mechanisms, including directly via viral proteins and indirectly by altering proinflammatory cytokine levels (151) . The use of newer direct-acting antiviral drugs produces a sustained virological response (cure) in nearly all cases and has been reported to improve glucose metabolism in individuals with diabetes (152) . A metaanalysis of mostly observational studies found a mean reduction in A1C levels of 0.45% (95% CI -0.60 to -0.30) and reduced requirement for glucose-lowering medication use following successful eradication of HCV infection (153) . ). If symptoms and/or signs of hypogonadism are detected (e.g., low libido, ED, and depression), screen with a morning serum total testosterone level. B Mean levels of testosterone are lower in men with diabetes than in age-matched men without diabetes, but obesity is a major confounder (154, 155) . Testosterone replacement in men with symptomatic hypogonadism may have benefits, including improved sexual function, well-being, muscle mass and strength, and bone density (156) . In men with diabetes who have symptoms or signs of low testosterone (hypogonadism), a morning total testosterone level should be measured using an accurate and reliable assay (157) . In men who have total testosterone levels close to the lower limit, it is reasonable to determine free testosterone concentrations either directly from equilibrium dialysis assays or by calculations that use total testosterone, sex hormone binding globulin, and albumin concentrations (157) . Further tests (such as luteinizing hormone and folliclestimulating hormone levels) may be needed to further evaluate the individual. Testosterone replacement in older men with hypogonadism has been associated with increased coronary artery plaque volume, with no conclusive evidence that testosterone supplementation is associated with increased cardiovascular risk in all men with hypogonadism (157) . Furthermore, erectile dysfunction (ED) is also common in people with diabetes (158) , and it is reasonable to measure and correct testosterone levels close to the lower limit to address the desire component that contributes to erectile difficulties (159) (see ERECTILE DYSFUNCTION, below, for more information on evaluation and further discussion).

Low Testosterone in Men

Erectile Dysfunction Recommendation 4. 19 In men with diabetes or prediabetes, screen for ED, particularly in those with high cardiovascular risk, retinopathy, cardiovascular disease, chronic kidney disease, peripheral or autonomic neuropathy, longer duration of diabetes, depression, and hypogonadism, and in those who are not meeting glycemic goals. B

The most common sexual dysfunction in men is ED, with an estimated prevalence of 52.5% in men with diabetes (160) . The best predictors of ED are age ( > 40 years), CVD, diabetes, hypertension, obesity, dyslipidemia, metabolic syndrome, hypogonadism, smoking, depression, and use of medications such as antidepressants and opioids (161, 162) . Because diabetes, poor nutrition, obesity, lack of exercise, and CVD are often interrelated, it may be challenging to identify the primary risk factor (159) , although the most likely primary underlying risk factor is vascular disease (159).

Men with diabetes are at increased risk for both CVD and ED, and ED is a predictor of cardiovascular events in men with diabetes (163, 164) as well as in men without diabetes. The significant factors associated with ED in men with diabetes are age, peripheral or autonomic neuropathy, presence of microvascular disease including retinopathy, CVD, duration of diabetes, poor glycemic management, hypogonadism, and diuretic therapy (165) . Physical activity may be protective. Men with diabetes and ED report a significant decline in quality-of-life measures and an increase in depressive symptoms (166) , and depression is a wellrecognized risk factor for ED. Given the bidirectional relationship between ED and depression, treatment of either one can result in improvement in the other condition. CKD is also a risk factor for CVD and ED, with prevalence rates of ED > 75% in men on hemodialysis (167) .

Awareness and identification of these characteristics, factors, and behaviors can guide clinicians in early screening, treatment, prevention, and counseling in all men with diabetes and particularly those at higher risk for ED (165) . Given the evidence that ED is strongly associated with diabetes and CVD, men with ED should be evaluated and managed for cardiovascular and endocrine risk factors. Glycemic assessment in men not previously diagnosed with diabetes, lipid profile, and morning total testosterone should be considered mandatory in all men newly presenting with ED (168) .

In a recent meta-analysis, testosterone was superior to placebo in improving erectile function in men with testosterone deficiency; however, the magnitude of the effect was lower in the presence of diabetes and obesity (169).

Meta-analyses show that all phosphodiesterase type 5 inhibitors (PDE5Is) are superior to placebo in treating ED, lower dosages had effects comparable with those of higher dosages, and various PDE5Is show comparable efficacy (159) . PDE5Is are associated with an increased risk of headaches, flushing, and dyspepsia (159) . First-line therapy for ED in men with diabetes is PDE5Is, but men with diabetes may be less responsive than men without diabetes (160) . Strategies to improve response to PDE5Is include daily therapy and optimization of comorbidities. In men with diabetes not responding to PDEIs, other potentially effective treatments may include intracavernosal injections, intraurethral prostaglandin, vacuum erection devices, and penile prosthetic surgery (160) .

Female Sexual Dysfunction

Recommendations 4.20 In women with diabetes or prediabetes, inquire about sexual health by screening for desire (libido), arousal, and orgasm difficulties, particularly in those who experience depression and/or anxiety and those with recurrent urinary tract infections. B 4.21 In postmenopausal women with diabetes or prediabetes, screen for symptoms and/or signs of genitourinary syndrome of menopause, including vaginal dryness and dyspareunia. B Female sexual dysfunction (FSD) is common in women with diabetes. In an epidemiologic cross-sectional study of communityresiding middle-aged and older adults (57-85 years), women with diagnosed diabetes were less likely than men with diagnosed diabetes (adjusted OR 0.28 [95% CI 0.16-0.49]) and women without diabetes (0.63 [0.45-0.87]) to be sexually active (170). Older women with diabetes are as likely as men to have sexual problems but are significantly less likely to have discussed sex with a physician (170).

While studies showing the association between diabetes and FSD are less conclusive than those in men, most have reported a higher prevalence of FSD in women with diabetes compared with women without diabetes (171). A meta-analysis found that sexual dysfunctions are more common in women with type 1 and type 2 diabetes (OR 2.27 and 2.49, respectively) than in women without diabetes (172).

Reviews report a wide range of prevalence rates of sexual dysfunctions in women with diabetes. In women with type 1 diabetes, 16-85% (vs. 0-66% in women without diabetes) report problems with desire, 11-76% (vs. 0-41%) report problems with arousal, and 9-66% (vs. 0-39%) report problems with orgasm; 9-57% (vs. 0-28%) report problems with lubrication, and 7-61% (vs. 5-39%) report problems with pain. In women with type 2 diabetes, 70-82% (vs. 10-66% in women without diabetes) report problems with desire, 54-68% (vs. 3-41%) report problems with arousal, and 33-84% (vs. 2-39%) report problems with orgasm; 33-66% (vs. 4-28%) report problems with lubrication, and 33-46% (vs. 8-39%) report problems with pain (173).

The Diabetes MILES (Management and Impact for Long-term Empowerment and Success) study examined the prevalence of sexual dysfunction in sexually active women with type 1 or type 2 diabetes and the associations between sexual dysfunction and clinical and psychological variables. Overall, 33% of women reported sexual dysfunction (type 1, 36.0%; type 2, 26.2%). The prevalence of specific FSDs according to diabetes type was decreased desire (type 1, 22%; type 2, 15%), decreased arousal (type 1, 9%; type 2, 11%), lubrication problems (type 1, 19%; type 2, 14%), and orgasmic dysfunction (type 1, 16%; type 2, 15%) (173).

Medical comorbidities that are risk factors for FSD include hypertension, obesity, metabolic syndrome, smoking, and hyperlipidemia. Clinical factors for consideration include longer duration of diabetic retinopathy and neuropathy and individuals not meeting glycemic goals. The prevalence of FSD in women with end-stage kidney disease is 74% (174).

In women with diabetes, social and psychological components play a major role in FSD. Depression, anxiety, and emotional adjustments to diabetes have been found to be associated with sexual dysfunctions in women with diabetes. A study from Norway reported that women with type 1 diabetes with scores on the Female Sexual Function Index (FSFI) (a validated instrument) indicating sexual dysfunction were more likely than women without sexual dysfunction to have diabetes distress, depression, and menopausal symptoms. They were also older and more likely to be single and postmenopausal (175). Another study also showed that women with sexual dysfunction were significantly more likely to report impaired well-being, have elevated diabetes distress, have poor adjustment to diabetes, and have more moderate to severe anxiety than women without sexual dysfunctions (173).

In a qualitative study exploring the experiences of sexual health and sexual challenges, women with type 1 diabetes reported that diabetes affected their relationship, including sex life, and had an impact on their partner. Challenges included reduced sexual desire, decline in frequency, less spontaneous desire resulting in lack of initiation, and physical challenges such as pain, vaginal dryness, and impaired sensitivity. Several women explained that vaginal dryness was an obstacle during sexual intercourse, leading to pain or even refraining from sexual activity. Sexual challenges were perceived to become a source of disappointment to the partners and consequential guilt for the women. Women also reported fear of hypoglycemia during sex, and some reported trying to maintain mild hyperglycemia. Technology devices, such as glucose monitors and insulin pumps, could be perceived as both a physical and mental obstacle during sexual activity (176).

Women with type 2 (25%) or type 1 (17%) diabetes would like their health care professional to initiate a discussion on how diabetes is affecting their sex life (177). Women with type 1 diabetes almost unanimously endorsed that sexual health should be addressed, that they would find it a relief that they were not alone, that they should be provided with information when they are young, and that it would be difficult to address the topic themselves (176). Unfortunately, many health care professionals do not actively discuss sexual functioning in consultations, meaning that when the topic is discussed it is mostly the person with diabetes who initiates the conversation (170). This leads to a marked underdiagnosis and undertreatment of sexual dysfunctions in people with diabetes.

While no specific guidelines are available for the treatment of FSD in this population, women with type 1 or type 2 diabetes should be encouraged to engage in lifestyle interventions and, in the absence of contraindications, may benefit from already-approved treatments for FSD (178). The Look AHEAD (Action for Health in Diabetes) study on intervention demonstrated statistical improvements in the FSFI total score and all domains of sexual dysfunction (179) Metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced the term nonalcoholic fatty liver disease (NAFLD) to identify steatotic liver disease. The definition includes the presence of steatotic liver disease and at least one cardiometabolic risk factor associated with insulin resistance (e.g., prediabetes, diabetes, atherogenic dyslipidemia, or hypertension) without other identifiable causes of steatosis (180) . This is in the absence of ongoing or recent consumption of significant amounts of alcohol (defined as ingestion of > 21 standard drinks per week in men and > 14 standard drinks per week in women over a 2-year period preceding evaluation) or other secondary causes of hepatic steatosis (181) . It is estimated that in adults in the U.S., the prevalence of MASLD is > 70% of people with type 2 diabetes (182) (183) (184) . This is consistent with studies from other countries (185, 186) . The new definition of MASLD aims to remove potential stigma from the term "fatty" when referring to steatosis, highlights the role of prediabetes and type 2 diabetes in MASLD, and provides a positive diagnosis by using cardiometabolic risk factors as surrogates for insulin resistance, the main driver for the development of steatosis. The new definition correlates well with the past definition of MASLD for people with prediabetes or type 2 diabetes (who already have, by definition, one cardiometabolic risk factor) (187, 188) . A separate category outside of MASLD, named metabolic dysfunction and alcoholic liver disease, was created for circumstances in which alcohol intake is greater than that allowed for MASLD but less than that attributed to alcoholic liver disease. More research is needed to better characterize the predictive value for metabolic dysfunction-associated steatohepatitis (MASH) of different cardiometabolic risk factors and the natural history of metabolic dysfunction and alcoholic liver disease or steatosis in young adults without cardiometabolic risk factors.

Diabetes is a major risk factor for developing MASH (formerly nonalcoholic steatohepatitis, or NASH) and worse liver outcomes (185, 186) . MASH is defined histologically as having $5% hepatic steatosis with inflammation and hepatocyte injury (hepatocyte ballooning), with or without evidence of liver fibrosis (181) . Steatohepatitis is estimated to affect more than half of people with type 2 diabetes with MASLD (189, 190) . Fibrosis stages are classified histologically as the following: F0, no fibrosis; F1, mild; F2, moderate (significant); F3, severe (advanced); and F4, cirrhosis. In the U.S., between 12% and 20% of people with type 2 diabetes have "at-risk" MASH (i.e., steatohepatitis with clinically significant fibrosis [$F2] and at risk for cirrhosis) (182, 183, 189) . A similar or higher prevalence has been observed worldwide (185, 186, 190) . People with type 2 diabetes and at-risk MASH are at an increased risk of future cirrhosis, hepatocellular carcinoma (HCC) (191, 192) , and liver transplantation (193) . The prevalence of MASLD in people with type 1 diabetes is $20% and is driven by obesity, which is becoming more common in this population (194) , with a large variability across studies using different steatosis measurement methods (195) . The prevalence of liver steatosis in a population with type 1 diabetes by MRI (i.e., the gold standard) with low prevalence of obesity was only 8.8% compared with 68% in people with type 2 diabetes (196) . The prevalence of clinically significant fibrosis ($F2) is estimated to be $5% (197) , which is much lower than the prevalence in type 2 diabetes (182, 183, 189) . Therefore, screening for fibrosis in people with type 1 diabetes should only be considered in the presence of additional risk factors for MASLD, such as obesity, incidental hepatic steatosis on imaging, or elevated plasma aminotransferases.

Clinicians underestimate the prevalence of at-risk MASH and do not consistently implement appropriate screening strategies in people with prediabetes or type 2 diabetes, thus missing a chance to establish an early diagnosis (198) . This pattern of underdiagnosis is compounded by sparse referral to specialists and inadequate prescription of medications with potential efficacy in MASH (199, 200) . The goal of screening for MASLD is to identify people with at-risk MASH to prevent future cirrhosis, HCC, liver transplantation, and all-cause mortality (201) (202) (203) (204) . This risk is higher in people who have central obesity and cardiometabolic risk factors or insulin resistance, are > 50 years of age, and/or have persistently elevated plasma aminotransferases (AST and/or ALT > 30 units/L for > 6 months) (205, 206) . Some genetic variants that alter hepatocyte triglyceride metabolism may also increase the risk of MASH progression and cirrhosis (207, 208) , amplifying the impact of obesity, but the role of genetic testing in clinical practice remains to be established. Individuals with MASLD also are at a greater risk of developing extrahepatic cancer (192) , type 2 diabetes (209) , and CVD (210, 211) . Emerging evidence suggests that MASLD increases the risk of CKD in people with type 2 diabetes, particularly when liver fibrosis is present (212, 213) , although the association of MASLD with diabetic retinopathy is less clear (214) .

The fibrosis-4 index (FIB-4) is the most cost-effective strategy for the initial screening of people with prediabetes and cardiometabolic risk factors or with type 2 diabetes for at-risk MASH in primary care and diabetes clinical settings (186, 200, 205, 206, (215) (216) (217) . The diagnostic algorithm for the screening and liver fibrosis risk stratification of people with prediabetes or type 2 diabetes is shown in Fig. 4 .2. A screening strategy relying on elevated plasma aminotransferases > 40 units/L would miss most individuals with MASH in these settings, as at-risk MASH with clinically significant fibrosis ($F2) is frequently observed with plasma aminotransferases below the commonly used cutoff of 40 units/L (182) (183) (184) 189, 218, 219) . The American College of Gastroenterology considers the upper limit of normal ALT levels to be 29-33 units/L for male individuals and 19-25 units/L for female individuals (220), as higher levels are associated with increased liver-related mortality. The FIB-4 estimates the risk of hepatic cirrhosis and is calculated from the computation of age, plasma aminotransferases (AST and ALT), and platelet count (mdcalc.com/calc/2200/ fibrosis-4-fib-4-index-liver-fibrosis). A value of < 1.3 is considered low risk of having advanced fibrosis (F3-F4) and for developing adverse liver outcomes, while $1.3 is considered as having a higher probability of at-risk MASH clinically significant fibrosis ($F2) and increased risk of adverse liver outcomes. A value of > 2.67 confers a high risk of having advanced fibrosis (F3-F4), and referral to the liver specialist is warranted without additional testing. FIB-4 predicts changes over time in hepatic fibrosis (221, 222) and allows risk stratification of individuals in terms of future liver-related morbidity and mortality (223) . FIB-4 has reasonable specificity but low sensitivity, hence a negative result rules out fibrosis while a positive result requires confirmatory testing (222, 224, 225) . Its low cost, simplicity, and good specificity make it the initial test of choice (Fig. 4 .2). FIB-4 has not been validated in pediatric populations or in adults aged < 35 years. In people with diabetes $65 years of age, higher cutoffs for FIB-4 have been recommended (1.9-2.0 rather than $1.3) (226) .

In people with a FIB-4 $1.3, there is need for additional risk stratification with a liver stiffness measurement (LSM) by transient elastography (Fig. 4 .2). Use of a second nonproprietary diagnostic panel is not recommended (e.g., MASLD fibrosis score and others), as they generally do not perform better than FIB-4 (181, 184, 224) .

Transient elastography (LSM) is the bestvalidated imaging technique for fibrosis risk stratification, and it predicts future cirrhosis and all-cause mortality in MASLD (205, 206, 227) . An LSM value of < 8.0 kPa has a good negative predictive value to exclude advanced fibrosis ($F3-F4) (228) (229) (230) and indicates lower risk for clinically significant fibrosis. Such individuals with prediabetes or type 2 diabetes can be followed in nonspecialty clinics with repeat surveillance testing every $2 years, although the precise time interval remains to be established. If the LSM is $8.0 kPa, the risk for advanced fibrosis ($F3-F4) is higher and such individuals should be referred to the hepatologist (181, 189, 205, 206) within the framework of an interprofessional team (231) (232) (233) . FIB-4 followed by LSM helps stratify people with diabetes by risk level and minimize specialty referrals (227, (234) (235) (236) (237) therefore are at risk for adverse liver outcomes (181, 217) . They should be referred to a gastroenterologist or hepatologist. The optimal cutoff for clinical use of ELF in primary care and endocrinology settings is evolving (239) (240) (241) (242) . An ELF < 9.8 suggests an individual is at low risk of advanced liver fibrosis and may be followed in the nonspecialty clinic with repeat testing in $2 years but may need repeat testing more often if ELF is between 9.2 and 9.7.

Specialists may order additional tests for fibrosis risk stratification in MASH (180, 205, 206, 217) , including magnetic resonance elastography (MRE) (best overall performance, particularly for early fibrosis stages) or multiparametric ironcorrected T1 MRI (cT1) (243) and patented blood-based fibrosis biomarkers. While liver biopsy remains the gold standard for the diagnosis of MASH, its indication is reserved to the discretion of the specialist within an interprofessional team approach due to high costs and potential for morbidity associated with this procedure. (244, 245) , ample evidence implicates excess visceral fat and overall adiposity in people with overweight and obesity in the pathogenesis of the disease (246, 247) . Obesity in the setting of type 2 diabetes worsens insulin resistance and steatohepatitis, promoting the development of cirrhosis (248) . Therefore, clinicians should enact evidence-based interventions (as discussed in Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes") to promote healthy lifestyle change and weight loss for people with overweight or obesity and MASLD. There is consensus that a minimum weight loss goal of 5%, preferably $10%, is needed to improve liver histology (181, 205, 206, 217) , with fibrosis requiring the larger weight reduction to promote change (249, 250) . However, there is significant individual variability in histological outcomes with weight loss. Individualized, structured weight loss and exercise programs offer greater benefit than standard counseling in people with MASLD (251) .

Dietary recommendations to induce an energy deficit are not different from those for people with diabetes with obesity without MASLD and should include a reduction of macronutrient content, limiting saturated fat, starch, and added sugar, with adoption of healthier eating patterns. The Mediterranean eating pattern has the best evidence for improving liver and cardiometabolic health (205, (215) (216) (217) 251) . Both aerobic and resistance training improve MASLD in proportion to treatment engagement and intensity of the program (252) . Obesity pharmacotherapy may assist with weight loss in the context of lifestyle modification if not achieved by lifestyle modification alone (see Section 8, "Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes").

Given the high prevalence of at-risk MASH ($12-20%) (182) (183) (184) 186, 189) , higher risk of disease progression and liver-related mortality (185, 204, 253) , and the lack of pharmacological treatments once cirrhosis is established (254, 255) , optimizing the pharmacological management of hyperglycemia and obesity in people with type 2 diabetes and MASH could serve the dual purpose of addressing these comorbidities while treating the liver disease (Fig. 4 .3). Therefore, early diagnosis and treatment of MASLD offers the best opportunity for cirrhosis prevention. In phase 2 clinical trials, pioglitazone and some GLP-1 RAs have been shown to be potentially effective to treat steatohepatitis (205, (256) (257) (258) (259) and to slow fibrosis progression (260) (261) (262) . They may also decrease CVD (257) , which is the number one cause of death in people with type 2 diabetes and MASLD (210) . Evidence from phase 3 clinical trials still are not fully published (e.g., a phase 3 study on semaglutide, The Effect of Semaglutide in Subjects With Non-cirrhotic Non-alcoholic Steatohepatitis [ESSENSE] trial, is predicted to be published in 2025) (263) , and no glucose-lowering or weight management medication is FDA approved for the treatment of MASH. The recommendation to treat hyperglycemia with GLP-1 RAs and/or pioglitazone in people with type 2 diabetes and MASLD is based on consistent histological benefit for steatohepatitis in several phase 2 RCTs with GLP-1 RAs and with pioglitazone (264-268) compared with no benefit with metformin or other glucose-lowering medications in MASH (181, 205, 206) .

Pioglitazone improves glucose and lipid metabolism and reverses steatohepatitis in people with prediabetes or type 2 diabetes (261, 264, 265) and even in individuals without diabetes (266-268) (Fig. 4 .

3).

Fibrosis also improved in some trials (265, 267) . A meta-analysis (260) concluded that pioglitazone treatment results in resolution of MASH and may improve fibrosis. Furthermore, combination therapy with pioglitazone plus a GLP-1 RA has been reported safe and effective for the treatment of hyperglycemia in adults with type 2 diabetes (269) (270) (271) (272) as well as in reducing hepatic steatosis (269, 271) , suggesting additive benefit in individuals with MASLD. It is important to note that these studies are based on phase 2 clinical trials and await further phase 3 evidence. However, these plans are attractive because they offer potential benefit compared with lack of histological benefit (or clinical trial data) from other oral glucose-lowering therapies in MASLD. In the context of treating hyperglycemia in people with type 2 diabetes with MASLD, where the low cost of pioglitazone and any liver improvement would be an added benefit to glycemic management, these plans would be potentially cost-effective for the treatment of MASLD (273, 274) . Vitamin E may be beneficial for the treatment of MASH in people without diabetes (266) . However, in people with type 2 diabetes, vitamin E monotherapy was found to be ineffective in a small RCT (261) , and it did not seem to enhance pioglitazone's efficacy when used in combination, as reported in an earlier trial in this population (265) . Pioglitazone causes dose-dependent weight gain (15 mg/day, mean weight gain of 1-2%; 45 mg/day, mean weight gain of 3-5%), which can be blunted or reversed if combined with SGLT2 inhibitors or GLP-1 RAs (257, 271, 272, 275) . Pioglitazone increases fracture risk, may promote heart failure if used in individuals with preexisting congestive heart failure, and may increase the risk of bladder cancer, although this remains controversial (181, 205, 206, 257, 258) .

GLP-1 RAs are effective at inducing weight loss and ameliorating elevated Resmetirom is a thyroid hormone receptor-b agonist approved by the FDA for the treatment of adults with MASLD with moderate (F2) or advanced (F3) liver fibrosis on liver histology or a validated imaging-or blood-based test. In a phase 3 RCT, resmetirom for 52 weeks in 966 adults at the highest dose of 100 mg (or placebo) met the primary end point of MASH resolution without worsening of fibrosis in 29.9% of participants compared with 9.7% on placebo (P < 0.001) (283) . Fibrosis improved in up to 25.9% and 14.2%, respectively (P < 0.001). Nausea, vomiting, and diarrhea occurred more often with resmetirom. The gastrointestinal side effects are dose dependent and improve with continued treatment. Resmetirom decreased free thyroxine (T4) levels by $20% and increased sex hormone-binding protein levels two-to threefold. Although a recent review of the data concluded that there is little concern about these changes, long-term postmarketing data must be collected (284, 285) . Guidance by the American Association for the Study of Liver Diseases (AASLD) about optimal individual identification for treatment, safety, and long-term monitoring has recently been published (286) . This is especially relevant because hypothyroidism and hypogonadism are more prevalent in people with MASLD than in the general population (181, 205) , and clinicians should monitor all individuals with MASLD for symptoms of endocrine deficiency and manage according to clinical practice guidelines. Per its label, candidates for resmetirom treatment are those with MASLD and moderate (F2) to advanced (F3) liver fibrosis but not with cirrhosis or other active liver disease (i.e., alcohol-related liver disease, autoimmune hepatitis, or primary biliary cholangitis) or unmanaged hypothyroidism or hyperthyroidism. Given complexities associated with selection of an individual for therapy, drug cost, and treatment monitoring, therapy should be individualized and initiated by a hepatologist or gastroenterologist with expertise in MASH within an interprofessional team.

Insulin is the preferred glucose-lowering agent for the treatment of hyperglycemia in adults with type 2 diabetes with decompensated cirrhosis given the lack of robust evidence about the safety and efficacy of oral agents and noninsulin injectables (i.e., GLP-1 RAs and dual GIP and GLP-1 RAs) (255) , although a recent 48-week study suggested that GLP-1 RAs are safe in individuals with MASH and compensated cirrhosis (287) .

Metabolic surgery leading to sustained weight loss and improvement of type 2 diabetes can improve MASH and cardiometabolic health, altering the natural history of the disease (288) . Meta-analyses report that 70-80% of people have improvement in hepatic steatosis, 50-75% of people have improvement in inflammation and hepatocyte ballooning (necrosis), and 30-40% of people have improvement in fibrosis (289, 290) . It may also reduce the risk of HCC (290) . It is important to note that currently metabolic surgery is not indicated solely for treatment of MASH. Given that many individuals with MASH have metabolic risks (type 2 diabetes and obesity) that are indications for metabolic surgery, the improvement in liver health is expected, but surgical indication should follow current practice guidelines. Metabolic surgery should be used with caution in individuals with compensated cirrhosis (i.e., asymptomatic stage of cirrhosis without associated liver complications), but with experienced surgeons the risk of hepatic decompensation is similar to that for individuals with less advanced liver disease. Because of the paucity of safety and outcome data, metabolic surgery is not recommended in individuals with decompensated cirrhosis (i.e., cirrhosis stage with complications such as variceal hemorrhage, ascites, hepatic encephalopathy, or jaundice) who also have a much higher risk of postoperative development of these liver-related complications (181, 205, 206) .

Adults with type 2 diabetes and MASLD are at an increased risk of CVD and require comprehensive management of cardiovascular risk factors (181, 205, 206) . Within an interprofessional approach, statin therapy should be initiated or continued for cardiovascular risk reduction as clinically indicated. Overall, its use appears to be safe in adults with type 2 diabetes and MASH, including in the presence of compensated cirrhosis (Child-Pugh class A or B cirrhosis) from MASLD. Some studies even suggest that statin use in people with chronic liver disease may reduce episodes of hepatic decompensation and/or overall mortality (291, 292) . Statin therapy is not recommended in decompensated cirrhosis given limited safety and efficacy data (181, 205, 206) .

Obstructive Sleep Apnea

Age-adjusted rates of obstructive sleep apnea, a risk factor for CVD, are significantly higher (4-to 10-fold) with obesity, especially with central obesity (293) (see Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes"). The prevalence of obstructive sleep apnea in the population with type 2 diabetes may be as high as 23%, and the prevalence of any sleep-disordered breathing may be as high as 58% (294, 295) . In participants with obesity enrolled in the Look AHEAD trial, the prevalence exceeded 80% (296) . Obstructive sleep apnea should be evaluated in individuals with suggestive symptoms (e.g., excessive daytime sleepiness, snoring, and witnessed apnea) (297) . Sleep apnea treatment (lifestyle modification, continuous positive airway pressure, oral appliances, and surgery) significantly improves quality of life and blood pressure management. Recently, two phase 3 randomized trials found that among adults with obesity and moderate-to-severe obstructive sleep apnea but without diabetes, treatment with the dual GIP and GLP-1 RA tirzepatide substantially reduced sleep apnea severity (298) . More research is needed to determine the effects of GLP-1 and dual GIP and GLP-1 RAs on sleep apnea in people with diabetes.

Pancreatitis

Diabetes is linked to diseases of the exocrine pancreas, such as pancreatitis, which may disrupt the global architecture or physiology of the pancreas, often resulting in both exocrine and endocrine dysfunction. Up to half of individuals with diabetes may have some degree of impaired exocrine pancreas function (299) . People with diabetes are at an approximately twofold higher risk of developing acute pancreatitis (300) .

Conversely, prediabetes and/or diabetes has been found to develop in approximately one-third of individuals after an episode of acute pancreatitis (301) ; thus, the relationship is likely bidirectional.

Postpancreatitis diabetes may include either new-onset disease or previously unrecognized diabetes (302) . Studies of individuals treated with incretin-based therapies for diabetes have also reported that pancreatitis may occur more frequently with these medications, but results have been mixed and causality has not been established (303) (304) (305) (306) .

Islet autotransplantation should be considered for individuals requiring total pancreatectomy for medically refractory chronic pancreatitis to prevent postsurgical diabetes. Approximately one-third of individuals undergoing total pancreatectomy with islet autotransplantation are insulin free 1 year postoperatively, and observational studies from different centers have demonstrated islet graft function up to a decade after the surgery in some individuals (307) (308) (309) (310) (311) . Both personal factors for the individual with diabetes and disease factors should be carefully considered when deciding the indications and timing of this surgery. Surgeries should be performed in skilled facilities that have demonstrated expertise in islet autotransplantation.

Sensory Impairment

Hearing impairment, both in high-frequency and low-to midfrequency ranges, is more common in people with diabetes than in those without, with stronger associations found in studies of younger people (312) . Proposed pathophysiologic mechanisms include the combined contributions of hyperglycemia and oxidative stress with cochlear microangiopathy and auditory neuropathy (313) . In a National Health and Nutrition Examination Survey (NHANES) analysis, hearing impairment was about twice as prevalent in people with diabetes as in those without, after adjusting for age and other risk factors for hearing impairment (314). Low HDL cholesterol, coronary heart disease, peripheral neuropathy, and general poor health have been reported as risk factors for hearing impairment for people with diabetes, but an association of hearing loss with glycemia has not been consistently observed (315) . In the DCCT/EDIC cohort, increases in the time-weighted mean A1C was associated with increased risk of hearing impairment when tested after long-term ( > 20 years) follow-up, with every 10% increase in A1C leading to 19% high-frequency impairment (316) . Impairment in smell, but not taste, has also been reported in individuals with diabetes (317) . The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Building positive health behaviors and maintaining psychological well-being are foundational for achieving diabetes management goals and maximizing quality of life (1, 2) . Essential to achieving these goals are diabetes self-management education and support (DSMES), medical nutrition therapy (MNT), routine physical activity, adequate quality sleep, support for cessation of tobacco products and vaping, health behavior counseling, and psychosocial care. Following an initial comprehensive health evaluation (see Section 4, "Comprehensive Medical Evaluation and Assessment of Comorbidities"), health care professionals should engage in person-centered collaborative care with people with diabetes (3) (4) (5) (6) . Person-centered collaborative care is guided by shared decision-making in treatment plan selection; facilitating access to medical, behavioral, psychosocial, and technological resources and support; and shared monitoring of agreed-upon diabetes care plans and behavioral goals (7, 8) . Routine care evaluations should include assessments of medical and behavioral health outcomes, particularly during periods of changes in health and well-being.

DIABETES SELF-MANAGEMENT EDUCATION AND SUPPORT

Recommendations 5.1 All people with diabetes should be advised to participate in developmentally and culturally appropriate diabetes self-management education and support (DSMES) to facilitate informed decision-making, self-care behaviors, problemsolving, and active collaboration with the health care team. A 5.2 Provide DSMES at diagnosis, annually and/or when not meeting treatment goals, when complicating factors develop (e.g., medical, functional, and psychosocial), and when transitions in life and care occur. E *A complete list of members of the American Diabetes Association Professional Practice Committee can be found at https://doi.org/10.2337/dc25-SINT.

Duality of interest information for each author is available at https://doi.org/10.2337/dc25-SDIS. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www .diabetesjournals.org/journals/pages/license.

5. FACILITATING POSITIVE HEALTH BEHAVIORS

5.3 Routinely assess clinical outcomes, health status, and well-being as key goals of DSMES. C 5.4 Screen for behavioral health concerns at the same critical times as evaluating the need for DSMES and refer to a qualified behavioral health professional if indicated to increase engagement in DSMES. E 5.5 DSMES should be culturally appropriate and responsive to individual preferences, needs, and values and may be offered in group or individual settings. A Such education and support should be documented and made available to members of the entire diabetes care team. E 5.6 Consider offering DSMES via telehealth and/or digital interventions as needed to meet individual preferences, address barriers to access, and improve satisfaction. B 5.7 DSMES can improve outcomes and reduce costs, so reimbursement by third-party payors is recommended. B 5.8 Identify and address barriers to DSMES that exist at the payor, health system, clinic, health care professional, and individual levels. E 5.9 Screen for and include social determinants of health in guiding design and delivery of DSMES C with the ultimate goal of health equity across all populations.

The overall objectives of DSMES are to support informed decision-making, selfcare behaviors, problem-solving, and active collaboration with the health care team to improve clinical outcomes, health status, and well-being in a costeffective manner (2) . DSMES services facilitate the knowledge, decision-making, and skills mastery necessary for optimal diabetes self-care and incorporate the needs, goals, and life experiences of the person with diabetes (9) . When providing DSMES, health care professionals should consider the individual's burden of treatment, level of self-efficacy for self-care behaviors, and degree of social and family support. Engagement in selfmanagement behaviors and subsequent clinical outcomes, health status, and quality of life, in addition to psychosocial factors affecting the person's ability to self-manage, should be monitored routinely. A randomized controlled trial (RCT) that evaluated a decision-making education and skill-building program (10) showed that addressing these aims improved health outcomes in a population in need of health care resources. Furthermore, following a DSMES curriculum improves quality of care (11) .

Use of judgmental words is associated with increased feelings of shame and guilt; therefore, health care professionals should consider the impact language has on building therapeutic and productive relationships. Health care professionals should use positive, strength-based words and phrases putting people first (4). Please see Section 4, "Comprehensive Medical Evaluation and Assessment of Comorbidities," for more on use of language.

In accordance with the "2022 National Standards for Diabetes Self-Management Education and Support" (here referred to as the National Standards for DSMES) ( 9 ), all people with diabetes should participate in developmentally appropriate and culturally sensitive DSMES, as it helps people with diabetes identify and implement effective self-management strategies and coping skills (2) . DSMES includes collaborative goal setting that improves empowerment, self-management, and quality of life as the person with diabetes encounters new challenges and as advances in treatment become available (12) (13) (14) . Moreover, DSMES should be thought of as an ongoing process-not a one-time occurrence. The National Standards for DSMES (9) In addition to providing DSMES upon diagnosis, there are additional critical time points when the need for DSMES should be evaluated by the health care professional and/or interprofessional team, with referrals made as needed (2):

• Annually and/or when not meeting treatment goals, whichever is more frequent

• When complicating factors (e.g., health conditions, physical or functional limitations, emotional factors, and basic living needs) that influence selfmanagement develop • When transitions in life and care occur DSMES empowers individuals with diabetes by providing them with tools to make informed self-management decisions (4) . DSMES should be person-centeredplacing the person with diabetes and their family and/or support system at the center of the care model as they work in collaboration with health care professionals. Person-centered care is respectful of and responsive to individual and cultural preferences, needs, and values. It ensures the values of the person with diabetes guide all decision-making (15) .

Evidence for the Benefits DSMES is associated with improved diabetes knowledge and self-care behaviors (16, 17) , lower A1C (16) (17) (18) (19) (20) (21) , lower self-reported weight (22) , improved quality of life (23, 24) , reduced all-cause mortality risk (25) , positive coping behaviors (5, 26) , and lower health care costs (27) (28) (29) . DSMES is also associated with an increased use of primary care and preventive services (27, 30) and less frequent use of acute care and inpatient hospital services (22) . People with diabetes who participate in DSMES are more likely to follow best practice treatment recommendations, particularly those with Medicare, and have lower Medicare and insurance claim costs (28, 30) . Better outcomes were reported for DSMES interventions that were > 10 h over the course of 6-12 months (19) , included ongoing support (12, 13, 31) , were culturally (30, (32) (33) (34) and age appropriate (35, 36) , were tailored to individual needs and preferences, addressed psychosocial issues, and incorporated behavioral strategies (4, 26, 37, 38) . Individual and group approaches are effective (22, 39, 40) , with a slight benefit realized by those who engage in both (19) .

Strong evidence now exists for the benefits of telehealth, telemedicine, and telephone-based or internet-based (i.e., virtual) DSMES for diabetes prevention and management in a wide variety of populations and age-groups (9, (41) (42) (43) (44) . When feasible, the best choice for delivery of DSMES is that which will align with individual preferences. A 2023 systematic review and meta-analysis of RCTs reported moderate evidence indicating digital health technologies (e.g., mobile apps, websites, digital coaching, and SMS [i.e., texting]) can be effective modes of intervention delivery for DSMES. In fact, telehealth-based interventions have been found to produce a greater reduction in A1C (À0.30 percentage points; 95% CI À0.42 to À0. 19 ) compared with control (43, 45) . These digital methods provide outcomes that are comparable to or even better than those seen with traditional in-person care (46) . Greater A1C reductions are demonstrated with increased engagement (47) , although data from trials are heterogeneous.

Diabetes care and education specialists (DCES) are effective providers of DSMES. Members of the DSMES team can include a variety of health care professionals such as nurses (registered nurses and nurse practitioners), registered dietitian nutritionists (RDNs), pharmacists, social workers, certified health education specialists, exercise physiologists, care coordinators or navigators, and others who can tailor curricula to individual needs (48) (49) (50) . Team members acting in the DCES capacity should have specialized clinical knowledge of diabetes and behavior change principles. In addition, a DCES needs to be knowledgeable about technology-enabled services and may serve as a technology champion within their practice (51) . Credentialing such as certified diabetes care and education specialists (CDCES) (cbdce.org/) and/or board certification in advanced diabetes management (BC-ADM) (diabeteseducator.org/education/certification/ bc_adm) demonstrates an individual's specialized training in and understanding of diabetes management and support (9), and engagement with qualified professionals has been shown to improve diabetes-related outcomes (52) . There is also continued and growing evidence for the role of community health workers, peer educators, peer support, and lay leaders in providing ongoing diabetes selfmanagement support (53, 54) .

Social determinants of health (SDOH) are an important aspect of diabetes care and should always be weighed in guiding the design and delivery of DSMES. The DSMES team should consider demographic characteristics such as racial identity, ethnic and cultural background, biological sex and gender identity, age, geographic location, technology access, education, literacy, and numeracy (4). For example, a systematic review and meta-analysis of telehealth DSMES interventions with Black and Hispanic adults with diabetes showed a 0.465% decrease in A1C, demonstrating the importance of considering demographic factors in relation to DSMES interventions (44) . Barriers to equitable DSMES access can be mitigated by keeping in mind the SDOH and leveraging creative delivery options (e.g., telehealth and online) that will work best for the population in need of DSMES (9) .

Despite the recognized benefits of DSMES, only about half of individuals eligible for DSMES through their health insurance receive it (55) . Barriers to DSMES exist at multiple levels including the health system, payor, clinic, health care professional, and individual for a myriad of reasons from lack of administrative leadership support to ineffective DSMES referral processes and transportation challenges. Low participation can be due to lack of referrals, logistical issues (e.g., accessibility, timing, and costs), and lack of a perceived benefit (56) . Thus, in addition to educating referring health care professionals about the benefits of DSMES and the critical times to refer, efforts to identify and address potential barriers at all levels need to be made (2) . This was illustrated in a multilevel diabetes care intervention that combined clinical outreach, standardized protocols, and DSMES with SDOH screening and referrals to social needs support; a 15% increase in receipt of DSMES, including among people on Medicaid, was documented (57) . Support from institutional leadership is foundational for DSMES success. Expert stakeholders, including those external to an organization, should also support DSMES by advocating for it and for people with diabetes (9).

Diabetes Technologies

Technology-enabled diabetes selfmanagement solutions (e.g., continuous glucose monitors [CGM], closed-loop pump systems, and connected glucose meters) improve A1C most effectively when there is two-way communication between the person with diabetes and the health care team, individualized feedback, use of person-generated health data, and education (58) . Alternative and innovative models of DSMES delivery (59) , including integration of technology-enabled diabetes and cardiometabolic health services (8), need to be continually explored and evaluated. Technology can facilitate selfmanagement decisions and improve access to DSMES (58) . Additionally, use of diabetes technologies warrants broader adoption because they can reduce therapeutic inertia (60) . One potential model is virtual environments, which allow people with diabetes to self-represent as avatars and interact in a world with embedded informational resources that can be accessed using principles of gamification. An RCT that tested DSMES in a virtual environment demonstrated greater weight loss but similar decreases in A1C, blood pressure, cholesterol, and triglycerides compared with DSMES via a standard website (61) . These versions may not always be reimbursed; however, adoption of reimbursement policies that increase DSMES access and use will positively affect beneficiaries' clinical outcomes, quality of life, health care use, and costs (9, 62, 63) .

Of all the newer diabetes technologies, CGM might be the most widely adopted. When combined with individualized DSMES or behavioral interventions, CGM demonstrated greater improvement of glycemic and psychosocial outcomes than CGM alone (47, 64) . Similarly, DSMES plus intermittently scanned CGM (isCGM) demonstrated increased time in range (70-180 mg/dL [3.9-10.0 mmol/L]), less time above range, and greater reduction in A1C compared with DSMES alone (65) . Incorporating a systematic approach for technology assessment, adoption, and integration into the diabetes care plan could help ensure equity in access and standardized application of technologyenabled solutions (8, 51, (66) (67) (68) .

Reimbursement

Medicare reimburses DSMES (referred to as diabetes self-management training

[DSMT] by Medicare) when the service is in accordance with the National Standards for DSMES (2, 9) and is recognized by the American Diabetes Association (ADA) through the Education Recognition Program (professional.diabetes.org/diabeteseducation) or by the Association of Diabetes Care & Education Specialists (www.adces .org/store/online-education/unlisted-detail/ becoming-an-accredited-dsmes-program).

DSMES is also covered by most other health insurance plans. Ongoing support has been shown to be instrumental for improving outcomes when it is implemented after the completion of formal DSMES. For comprehensive information about Medicare reimbursement, readers may find the following website useful: www. cdc.gov/diabetes-toolkit/php/reimbursement/medicare-reimbursement-guidelines. html. In brief, the Medicare Part B initial DSMT is a "once-in-a-lifetime" benefit. Individual encounters are reimbursable for the first 10 h (1 h of individual training and 9 h of group training). Two hours of follow-up DSMT are allowed each year after the initial DSMT. If a person has special needs that would interfere with effective group participation, these should be identified on the referral order. For Medicaid, DSMES coverage varies by state, but further guidance can be found at www.cdc.gov/diabetes-toolkit/php/ reimbursement/medicare-reimbursementguidelines.html. Additional information addressing implementation of a successful DSMES program can be found in the Centers for Disease Control and Prevention DSMES toolkit at www.cdc.gov/diabetestoolkit/php/index.html.

Programs recognized by the ADA and accredited by the Association of Diabetes Care & Education Specialists are currently included on the list of telehealth professionals approved by Centers for Medicare & Medicaid Services (CMS), via the Consolidated Appropriations Act of 2023 (69) . Continuation of reimbursement for DSMES telehealth services is expected through the end of 2025, after which CMS is likely to reinstate limitations on the number of times certain services in high-acuity settings may be performed via telehealth. During this time, CMS will continue to evaluate whether the removal of these frequency limitations should be made permanent (70) .

DSMES uses an evidence-based curriculum designed to educate people with diabetes about all elements from the National Standards for DSMES, as described above, that can be delivered and billed by a variety of health care professionals on the diabetes care team. While the overarching healthy eating concepts used in DSMES can be taught by all members of the team, MNT, which is more indepth and individualized and derived from the evidence-based Nutrition Care Process, can only be delivered and billed by RDNs. For Medicare Part B, the MNT benefit includes individual encounters reimbursable for 3 h. Each subsequent year is reimbursed for 2 h. However, additional hours are available if a subsequent referral identifies a change in treatment. For further information on Medicare coverage of MNT, readers are encouraged to review www.cdc.gov/diabetes-toolkit/php/ reimbursement/medical-nutrition-therapy. html and www.cms.gov/medicare-coveragedatabase/view/ncacal-decision-memo.aspx? proposed=N & NCAId=53.

MEDICAL NUTRITION THERAPY

When the first ADA Standards of Care guidelines were published in 1989, nutrition was only mentioned in two sentences of the entire 4-page document (71) . Even today, the science of nutrition for diabetes continues to evolve. There has also been a change in how we talk about nutrition. We are moving away from emphasizing macronutrients, which include carbohydrates, proteins, and fats, and micronutrients, which include vitamins and minerals, and instead focusing on foods. More broadly, we are encouraging people to think in terms of eating patterns, also known as dietary patterns or food patterns, or the totality of the foods and beverages a person consumes. Additionally, promoting nutrient-dense food choices, defined as foods high in micronutrients while being relatively low in calories (e.g., vegetables, fruits, and legumes), is useful. This integrative food-based approach aligns with the 2021 American Heart Association dietary guidance to improve cardiovascular health (72) , the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines ( 73 ), the European Association for the Study of Diabetes and ADA type 1 consensus report (74) and type 2 consensus report (75) , and the Dietary Guidelines for Americans, 2020-2025 (76) . Simply put, people eat food, not nutrients, and nutrition recommendations need to be applicable to what people actually eat. Additionally, macronutrients are not interchangeable entities and vary by nutrient type and quality. As an example, carbohydrates include legumes, whole grains, and fruits, which are in the same category as refined grains, but their health effects are quite different (77) .

MNT is effective and beneficial to people with diabetes. When delivered by an RDN, MNT is associated with A1C absolute decreases of 1.0-1.9% for people with type 1 diabetes and 0.3-2.0% for people with type 2 diabetes (78) . Because type 2 diabetes is progressive, behavior modification alone may not be adequate to maintain euglycemia over time. However, after pharmacotherapy is initiated, nutrition therapy continues to be an important component of ongoing diabetes self-management, and RDNs providing diabetes-specific MNT should assess and monitor medication changes in relation to the nutrition care plan (50, 79) . All members of the health care team should also be empowered to reiterate the general and evidence-based nutrition advice to limit processed foods and foods high in added salt, sugars, and fats and, when possible, choose whole foods.

For more detailed information on nutrition therapy, please refer to the ADA consensus report on nutrition therapy (50) . Contained in the report is an important and often repeated tenet, i.e., there is no one-size-fits-all eating pattern for individuals with diabetes, and meal planning should be individualized. Nutrition therapy plays an integral role in overall diabetes management, and each person with diabetes should actively engage in education, self-management, and treatment planning with the health care team and participate in collaborative development of an individualized eating plan (50, 79) .

All health care professionals should refer people with diabetes for individualized MNT provided by an RDN who is experienced and skilled in providing diabetesspecific MNT (80) (81) (82) , at diagnosis and as needed throughout the life span, similar to DSMES. Referrals to RDNs are particularly warranted when a person with diabetes is dealing with additional health conditions such as hypertension, dyslipidemia, heart failure, gastrointestinal disorders, chronic kidney disease, pregnancy-related nutrition concerns, pediatric growth issues, or obesity (83) . See Table 5 .1 for general nutrition recommendations, Table 5 .2 for macronutrient-specific recommendations, and Table 5 .3 for nutrition behaviors that should be encouraged.

Eating Patterns and Meal Planning

For an understanding of the role of nutrition in diabetes, it is important to clarify the terminology. Food patterns, eating plans, and approaches are terms that are often used interchangeably, but they are different and relevant in individualizing nutrition care plans (84) . There is no ideal percentage of calories from carbohydrate, protein, or fat for people with diabetes. Therefore, macronutrient distribution should be based on an individualized assessment of current eating patterns, preferences, and metabolic goals. Members of the health care team should complement and reinforce MNT by providing evidence-based guidance that helps people with diabetes make healthy food choices that meet their individualized needs and improve overall health. Ultimately, ongoing diabetes and nutrition education paired with appropriate support to implement and sustain health behaviors are recommended (82) .

Research confirms that a variety of eating patterns are acceptable for the management of diabetes (50, 78, 86, 87) . Evidence for eating patterns has been informed by RCTs, prospective cohort studies, systematic reviews, and network meta-analyses. Those most frequently recommended based on the evidence include Mediterranean, DASH, low-fat, carbohydrate-restricted, vegetarian, and vegan eating patterns. Until evidence around benefits of different eating patterns is strengthened, health care professionals should focus on the core dimensions common among healthful patterns: inclusion of nonstarchy vegetables, whole fruits, legumes, whole grains, nuts, seeds, and low-fat dairy products and minimizing consumption of red meat, sugar-sweetened beverages, sweets, refined grains, and processed and ultraprocessed foods (88, 89) .

Referral to and ongoing support from an RDN is essential to assess the overall nutrition status of, and to work collaboratively with, the person with diabetes to create a personalized meal plan that coordinates and aligns with the overall lifestyle treatment plan, including physical activity and medication use. Using shared decision-making to collaboratively select a method for how to execute the plan may be part of the nutrition care process.

Eating/Meal Plan Approaches and Methods

Few head-to-head studies have compared different eating approaches. In a systematic review and meta-analysis of carbohydrate counting versus other forms of meal planning advice (e.g., standard education, low glycemic index, and fixed carbohydrate quantities), no significant differences were seen in A1C levels compared with standard education (90) . In another RCT, a simplified carbohydrate counting tool based on individual glycemic response was noninferior to conventional carbohydrate counting in 85 adults with type 1 diabetes (91) . In a randomized crossover trial, carbohydrate counting and qualitative meal size (i.e., low, medium, and high carbohydrate) were compared. Time in range was 74% for carbohydrate counting and 70.5% for the quantitative meal size estimates. Noninferiority was not confirmed for the qualitative method (92) . Newer technologies (e.g., smart phone apps and CGM) and automated insulin delivery may decrease the need for precise carbohydrate counting and allow for personalized nutrition approaches (93, 94) .

One RCT found that two meal-planning approaches (diabetes plate method and carbohydrate counting) were effective in helping achieve improved A1C (95) . The diabetes plate method ( 96 ) is a commonly used visual approach for providing basic meal planning guidance for individuals with type 1 and type 2 diabetes. This simple graphic (featuring a 9-in plate) shows how to portion foods (one-half of the plate for nonstarchy vegetables, one-quarter of the plate for protein, and one-quarter of the plate for carbohydrates). Carbohydrate counting is a more advanced skill that helps plan for and track how much carbohydrate is consumed at meals and snacks. Meal planning approaches should be customized to the individual, including their numeracy (95) and Studies examining the optimal amount of carbohydrate intake for people with diabetes are inconclusive, although monitoring carbohydrate intake is a key strategy in reaching glucose goals in people with type 1 and type 2 diabetes (99,100).

Recommendations 3.7 Metformin for the prevention of type 2 diabetes should be considered in adults at high risk of type 2 diabetes, as typified by the DPP, especially those aged 25-59 years with BMI $35 kg/m 2 , higher fasting plasma glucose (e.g., $110 mg/dL [$6 mmol/L]), and higher A1C (e.g., $6.0% [$42 mmol/mol] ), and in individuals with prior gestational diabetes mellitus. A 3.8 Long-term use of metformin may be associated with vitamin B12 deficiency; consider periodic assessment of vitamin B12 level in metformintreated individuals, especially in those with anemia or peripheral neuropathy. B Because weight loss through behavior changes in nutrition and physical activity may not be sufficient on their own and can be difficult to maintain long term (10) , some people at high risk of type 2 diabetes may benefit from additional support and pharmacotherapeutic options. Various pharmacologic agents used to treat diabetes have been evaluated for diabetes prevention. Metformin, a-glucosidase inhibitors, incretin receptor agonists (e.g., liraglutide and semaglutide), thiazolidinediones, and insulin have been shown to lower the incidence of diabetes in specific populations (63) (64) (65) (66) (67) (68) , whereas diabetes prevention was not seen with nateglinide (69) .

In the DPP, weight loss was an important factor in reducing the risk of progression, with every kilogram of weight loss conferring a 16% reduction in risk of progression over 3.2 years (13) . In individuals with previous history of GDM, the risk of type 2 diabetes increased by 18% for every 1 unit BMI above the preconception baseline (70) . Several medications evaluated for weight loss (e.g., orlistat, phentermine and topiramate, liraglutide, semaglutide, and tirzepatide) have been shown to decrease the incidence of type 2 diabetes in those with prediabetes (68, (71) (72) (73) .

Studies of other pharmacologic agents have shown some efficacy in diabetes prevention with valsartan or testosterone (74, 75) but no efficacy in preventing diabetes with ramipril or anti-inflammatory drugs (75) (76) (77) (78) . Vitamin D therapy has recently been advocated by the U.S. Endocrine Society to prevent progression of high-risk prediabetes to type 2 diabetes in adults (79) . Three randomized controlled trials have been designed and conducted to test whether vitamin D therapy in combination with lifestyle modification reduces the risk of developing diabetes in adults with high-risk prediabetes (i.e., IGT or meeting two or three ADA prediabetes glycemic criteria [fasting glucose, A1C, 2-h glucose after a 75-g OGTT]): the Tromsø study in Norway, with 511 participants; the Vitamin D and Type 2 Diabetes (D2d) study in the U.S., with 2,423 participants; and the Diabetes Prevention with Active Vitamin D (DPVD) study in Japan, with 1,256 participants (80) (81) (82) . Although vitamin D therapy modestly reduced the risk of developing diabetes compared with the placebo to a nearly identical degree in all three trials, none of the results of the individual studies were statistically significant (reportedly due to insufficient power). Subsequently, several meta-analyses related to these (and other smaller) studies have suggested a modest potential benefit in specific populations (83, 84) . However, there are several concerns and uncertainties regarding recommending widespread vitamin D therapy for adults with highrisk prediabetes. 1) The recommended vitamin D dose is unclear. The included trials used varying dosages of vitamin D that were higher than the recommended daily allowance for this population (i.e., 600 IU/day for those aged 18-70 years and 800 IU for those older than 70 years). Due to this variability, it is not possible to recommend a specific vitamin D dosage for diabetes prevention. 2) The benefit-torisk ratio of vitamin D therapy for high-risk prediabetes remains uncertain. Although there was no evidence of safety concerns with vitamin D therapy in study participants with prediabetes, the numbers of adults included in these studies are small compared with the potentially many millions of adults with prediabetes in the U.S. and globally who may have risk of adverse events if treated with unspecified doses of vitamin D without monitoring blood 25-hydroxy vitamin D levels. In light of these and other issues, further research is warranted to better define the population characteristics and determine the dose and clinical pathway of vitamin D therapy for diabetes prevention.

No pharmacologic agent has been approved by the U.S. Food and Drug Administration for prevention of type 2 diabetes. The risk versus benefit of each medication in support of person-centered goals must be weighed in addition to cost and burden of administration. Additionally, pharmacologic interventions must be long-term because of the waning of effect after stopping the medication.

Metformin

Metformin has the most safety data as a pharmacologic therapy for diabetes prevention (85) . Metformin was overall less effective than lifestyle modification in the DPP, though group differences attenuated over time in the DPPOS (11) , and metformin may be cost-saving over a 10-year period (40) . In the DPP, metformin was as effective as lifestyle modification in participants with BMI $35 kg/m 2 and in younger participants aged 25-44 years (5) . In individuals with a history of GDM in the DPP, metformin and intensive lifestyle modification led to an equivalent 50% reduction in diabetes risk (86) . Both interventions remained highly effective during a 10-year follow-up period (87) . By the time of the 15-year follow-up (DPPOS), exploratory analyses demonstrated that participants with a higher baseline fasting glucose ($110 mg/dL [$6 mmol/L] vs. 95-109 mg/dL [5.3-5.9 mmol/L] ), those with a higher A1C (6.0-6.4% [42-46 mmol /mol] vs. < 6.0% [ < 42 mmol/mol]), and individuals with a history of GDM (vs. individuals without a history of GDM) experienced higher risk reductions with metformin, identifying subgroups of participants that may benefit the most from metformin (88) . In the Indian Diabetes Prevention Program (IDPP-1), metformin and lifestyle intervention reduced diabetes risk similarly at 30 months; however, the lifestyle intervention in IDPP-1 was less intensive than that in the DPP (89) . Based on findings from the DPP, metformin should be recommended as an option for high-risk individuals (e.g., younger individuals, those with history of GDM, or those with BMI $35 kg/m 2 ).

Decreased vitamin B12 levels are a known consequence of long-term treatment with metformin (90) . Periodic assessment of vitamin B12 level in those taking metformin chronically should be considered to check for possible deficiency, especially in those receiving a higher dose (e.g. $1,500 mg/day) (91) or longer treatment duration and in those with existing risk factors. Vitamin B12 serum levels should be tested if deficiency is suspected, such as in people with anemia or peripheral neuropathy (90,92) (see Section 9, "Pharmacologic Approaches to Glycemic Treatment," for more details). The effect of metformin on vitamin B12 increases with time (93) , with a higher risk for vitamin B12 deficiency ( < 200 pg/mL [ < 150 pmol/L]) noted at 4-5 years of treatment. A person who has been taking metformin for more than 4 years or is at risk for vitamin B12 deficiency for other reasons (e.g., vegan dietary pattern, previous gastric/small bowel surgery) should be monitored for vitamin B12 deficiency annually (94) .

PREVENTION OF VASCULAR DISEASE AND MORTALITY

Recommendations 3.9 Prediabetes is associated with heightened cardiovascular risk; therefore, screening for and treatment of modifiable risk factors for cardiovascular disease are suggested. B 3.10 Statin therapy may increase the risk of type 2 diabetes in people at high risk of developing type 2 diabetes. In such individuals, glucose status should be monitored regularly and diabetes prevention approaches reinforced. It is not recommended that statins be avoided or discontinued for this adverse effect. B 3.11 In people with a history of stroke and evidence of insulin resistance and prediabetes, pioglitazone may be considered to lower the risk of stroke or myocardial infarction. However, this benefit needs to be balanced with the increased risk of weight gain, edema, and fractures. A Lower doses may mitigate the risk of adverse effects but may be less effective. C

People with prediabetes often have other cardiovascular risk factors, including hypertension and dyslipidemia (95) , and are at increased risk for cardiovascular disease (96, 97) . Evaluation for tobacco use and referral for tobacco cessation should be part of routine care for those at risk for diabetes. Of note, the years immediately following smoking cessation may represent a time of increased risk for diabetes (98, 99) , and individuals should be monitored for diabetes development and receive evidence-based lifestyle behavior change for diabetes prevention as described in this section. See Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes," for more detailed information. The lifestyle interventions for weight loss in study populations at risk for type 2 diabetes have shown a reduction in cardiovascular risk factors and the need for medications used to treat these cardiovascular risk factors (100, 101) . The lifestyle intervention in the Da Qing study was associated with lowering cardiovascular disease and mortality at 23 and 30 years of observational follow-up (7, 9) . Treatment goals and therapies for hypertension and dyslipidemia in the primary and secondary prevention of cardiovascular disease for people with prediabetes should be based on their level of cardiovascular risk. Increased vigilance is warranted to identify and treat these and other cardiovascular disease risk factors (102) . Statin use increases risk of diabetes (103) (104) (105) . In the DPP, statin use was associated with greater diabetes risk irrespective of the treatment group (pooled hazard ratio [HR] [95% CI] for incident diabetes 1.36 [1.17-1.58]) (104) . In trials of primary and secondary prevention of cardiovascular disease, cardiovascular and mortality benefits of statin therapy exceed the risk of diabetes (106, 107) , suggesting a highly favorable benefit-toharm balance with statin therapy. Hence, discontinuation of statins due to concerns of diabetes risk is not recommended in this population.

Cardiovascular outcome trials in people without diabetes also inform risk reduction potential in people without diabetes at increased cardiometabolic risk (see Section 10, "Cardiovascular Disease and Risk Management," for more details). The IRIS (Insulin Resistance Intervention after Stroke) trial of people with a recent ( < 6 months) stroke or transient ischemic attack, without diabetes but with insulin resistance (as defined by a HOMA of insulin resistance index of $3.0), evaluated pioglitazone (goal dose of 45 mg daily) compared with placebo. At 4.8 years, the risk of stroke or myocardial infarction, as well as the risk of diabetes, was lower in the pioglitazone group than in the placebo group; weight gain, edema, and fractures were higher in the pioglitazone treatment group (108) (109) (110) . Lower doses may mitigate the adverse effects but may also be less effective (111) .

PERSON-CENTERED CARE GOALS

3.12

In adults with overweight or obesity at high risk of type 2 diabetes, care goals should include weight loss and maintenance, minimizing the progression of hyperglycemia, and attention to cardiovascular risk. B 3.13 Pharmacotherapy (e.g., for weight management, minimizing the progression of hyperglycemia, and cardiovascular risk reduction) should be considered to support person-centered care goals. B 3.14 More intensive preventive approaches should be considered in individuals who are at particularly high risk of progression to diabetes, including individuals with BMI $35 kg/m 2 , those at higher glucose levels (e.g., fasting plasma glucose 110-125 mg/dL [6.1-6.9 mmol/L], 2-h postchallenge glucose 173-199 mg/dL [9.6-11.0 mmol/L], and A1C $6.0% [$42 mmol/mol] ), and individuals with a history of gestational diabetes mellitus. A Individualized risk-to-benefit ratio should be considered in screening, intervention, and monitoring to lower the risk of type 2 diabetes and associated comorbidities. Multiple factors, including age, BMI, and other comorbidities, may influence the risk of progression to diabetes and lifetime risk of complications (112, 113) . Prediabetes is associated with increased cardiovascular disease and mortality (97) , which emphasizes the importance of attending to cardiovascular risk in this population. However, the new diagnosis of prediabetes in older adults (aged > 70 years) is less relevant for progression to diabetes, because regression to normoglycemia or death was more frequent than progression to diabetes in the Atherosclerosis Risk in Communities (ARIC) study (113) .

In the DPP, which enrolled high-risk individuals with IGT, elevated fasting glucose, and elevated BMI, the crude incidence of diabetes within the placebo group was 11 cases per 100 person-years, with a cumulative 3-year incidence of diabetes of 29% (5) . Characteristics of individuals in the DPP/DPPOS who were at particularly high risk of progression to diabetes (crude incidence of diabetes 14-22 cases per 100 person-years) included BMI $35 kg/m 2 , higher glucose levels (e.g., fasting plasma glucose 110-125 mg/dL [6.0-6.9 mmol/L], 2-h postchallenge glucose 173-199 mg/dL [9.6-11.0 mmol/L], A1C $6.0% [$42 mmol/mol] ), or a history of GDM (5, 86, 87) . In contrast, in the community-based ARIC study, observational follow-up of adults with mean age 75 years with laboratory evidence of prediabetes (based on A1C 5.7-6.4% [39-47 mmol/mol] and/or fasting glucose 100-125 mg/dL [5.6-6.9 mmol/L] ), but not meeting specific BMI criteria, found lower progression to diabetes over 6 years: 9% of those with A1C-defined prediabetes and 8% of those with IFG (113) .

Thus, it is important to individualize the risk-to-benefit ratio of intervention and consider person-centered goals. Risk models have generally found a higher benefit of the intervention in those at highest risk (13) . Diabetes prevention trials and observational studies highlight key principles that may guide person-centered goals. In the DPP, which enrolled a high-risk population meeting criteria for overweight or obesity, weight loss was an important mediator of diabetes prevention or delay, with greater metabolic benefit seen with greater weight loss (13, 114) . In the DPP/ DPPOS, progression to diabetes, duration of diabetes, and mean level of glycemia were important determinants of the development of microvascular complications (11) . Achieving normal glucose regulation, even once, during the DPP was associated with a lower risk of diabetes and lower risk of microvascular complications irrespective of the treatment arm (115) . Observational follow-up of the Da Qing study also showed that regression from IGT to normal glucose tolerance or remaining with IGT rather than progressing to type 2 diabetes at the end of the 6-year intervention trial resulted in significantly lower risk of cardiovascular disease and microvascular disease over 30 years (116) .

Pharmacotherapy for weight management and cardiovascular risk reduction (see Section 10, "Cardiovascular Disease and Risk Management," for more details) can be considered to support individualized person-centered goals, with more intensive preventive approaches considered in individuals at high risk of progression.

PREVENTION OR DELAY OF SYMPTOMATIC TYPE 1 DIABETES

Lifestyle and Type 1 Diabetes Progression

Observational studies suggest that in those with islet autoantibodies, factors that may increase b-cell demand, including less physical activity (117) , higher glycemic index (118) , and total sugar intake (119) , are associated with progression to clinical diabetes. Similar associations have not been seen in the development of autoantibodies. In The Environmental Determinants of Diabetes in the Young (TEDDY) longitudinal study, daily minutes spent in moderate to vigorous physical activity were associated with a reduced risk of progression to type 1 diabetes in children 5-15 years of age with multiple islet autoantibodies (HR 0.92 [95% CI 0.86-0.99] per 10-min increase; P = 0.021) (117) . In the Diabetes Autoimmunity Study in the Young (DAISY), in children with islet autoantibodies, progression to type 1 diabetes was associated with higher glycemic index (HR 2.20 [95% CI 1.17-4.15] ) and total sugar intake (HR 1.75 [95% CI 1.07-2.85]) (118, 119) . In nonobese diabetic mice, an animal model for the development of type 1 diabetes, sustained high-glucose drinking significantly aggravated islet inflammation and accelerated the onset of type 1 diabetes (120) . Lifestyle interventions focusing on such factors in those with stage 1 or stage 2 type 1 diabetes have not yet been reported.

Pharmacologic Interventions to Delay Symptomatic Type 1 Diabetes

Recommendation 3.15 Teplizumab-mzwv infusion to delay the onset of symptomatic type 1 diabetes (stage 3) should be discussed with selected individuals aged $8 years with stage 2 type 1 diabetes. Treatment should be in a setting with appropriately trained personnel. B Teplizumab, a CD3-directed humanized monoclonal antibody engineered to have decreased Fc receptor binding, has been approved to delay the onset of stage 3 type 1 diabetes in people 8 years of age and older with stage 2 type 1 diabetes based in part on the results of a single trial in relatives of people with type 1 diabetes (121) . In this study, 44 individuals were randomized to a 14-day course of teplizumab and 32 to placebo. The median time to stage 3 type 1 diabetes diagnosis was 48.4 months in the teplizumab group and 24.4 months in the placebo group. Type 1 diabetes was diagnosed in 19 (43%) participants who received teplizumab and 23 (72%) participants who received placebo (HR 0.41 [95% CI 0.22-0.78]). In prespecified analyses, the presence of HLA-DR4, absence of HLA-DR3, and absence of anti-zinc transporter 8 antibody predicted response to teplizumab (HR 0.20 [95% CI 09.0.45], 0.18 [0.07-0.45] , and 0.07 [0.02-0.26], respectively). The most common adverse reactions were transient lymphopenia (73%) followed by rash (36%).

Numerous clinical studies are being conducted to test methods for preventing or delaying the onset of stage 3 type 1 diabetes in those with evidence of autoimmunity without symptoms or for delaying loss of insulin secretory capacity after onset of stage 3, some with promising results (see ClinicalTrials.gov and TrialNet.org). People living with diabetes should be engaged in conversation about these aspects of their lives and diabetes management, with routine reassessment as necessary given their changing circumstances across the life span. Various strategies and techniques should be used to support the person's self-management efforts, including providing education on problem-solving and coping skills for all aspects of diabetes management.

Communication by health care professionals with people with diabetes and their families should acknowledge that multiple factors impact glycemic management but also emphasize that collaboratively developed treatment plans and a healthy lifestyle can significantly improve disease outcomes and well-being (5) (6) (7) (8) (9) (10) . Thus, the goal of communication between health care professionals and people with diabetes is to establish a collaborative relationship and to assess and address self-management barriers without blaming people with diabetes for "noncompliance" or "nonadherence" when the outcomes of self-management are not optimal (11) . The familiar terms noncompliance and nonadherence denote a passive, obedient role for a person with diabetes in "following doctor's orders," which is at odds with the active role people with diabetes take in the day-to-day decision-making, planning, monitoring, evaluation, and problem-solving involved in diabetes self-management. Using a nonjudgmental approach that normalizes periodic lapses in management may help minimize the person's resistance to reporting problems with self-management. Empathizing and using active listening techniques, such as open-ended questions, reflective statements, and summarizing what the person said, can help facilitate communication. Perceptions of people with diabetes about their own ability, or self-efficacy, to self-manage diabetes constitute one important psychosocial factor related to improved diabetes self-management and treatment outcomes in diabetes (12) (13) (14) and should be a goal of ongoing assessment, education, and treatment planning.

Language has a strong impact on perceptions and behavior. Empowering language can help to inform and motivate, while shame and judgement can be

GOALS OF CARE

• Prevent complications • Optimize quality of life discouraging. The American Diabetes Association (ADA) and the Association of Diabetes Care & Education Specialists (ADCES) (formerly called the American Association of Diabetes Educators) joint consensus report, "The Use of Language in Diabetes Care and Education," provides the authors' expert opinion regarding the use of language by health care professionals when speaking or writing about diabetes for people with diabetes or for professional audiences (15) . Although further research is needed to address the impact of language on diabetes outcomes, the report includes five key consensus recommendations for language use:

• Use language that is neutral, nonjudgmental, and based on facts, actions, physiology, or biology. • Use language free from stigma.

• Use language that is strength based, respectful, and inclusive and that imparts hope. • Use language that fosters collaboration between people with diabetes and health care professionals. • Use language that is person centered (e.g., "person with diabetes" is preferred over "diabetic"). The comprehensive medical evaluation includes the initial and follow-up evaluations, which comprise assessment of complications, psychosocial assessment, management of comorbid conditions, overall health, functional and cognitive status, and engagement of the person with diabetes throughout the process. While a comprehensive list is provided in Table 4 .1, in clinical practice the health care professional may need to prioritize the components of the medical evaluation given the available resources and time. Engaging other members of the health care team can also support comprehensive diabetes care. The goal of these recommendations is to provide the health care team information so it can optimally support people with diabetes and their care partners. In addition to the medical history, physical examination, and laboratory tests, health care professionals should assess diabetes self-management behaviors, nutrition, social determinants of health, and psychosocial health (see Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes") and give guidance on routine immunizations. The assessment of sleep pattern and duration should also be considered, as this may affect glycemic management. Interval follow-up visits should occur at least every 3-6 months individualized to the person and then at least annually.

COMPREHENSIVE MEDICAL EVALUATION

Lifestyle management and behavioral health care are cornerstones of diabetes management. People with diabetes should be referred for diabetes self-management education and support, medical nutrition therapy, and assessment of behavioral health concerns as appropriate. People with diabetes should receive recommended preventive care services (e.g., immunizations and age-and sex-appropriate cancer screening); smoking cessation counseling; and ophthalmological, dental, podiatric, and other referrals, as needed.

The assessment of risk of acute and chronic diabetes complications and treatment planning are key components of initial and follow-up visits (Table 4 .2). The risk of atherosclerotic cardiovascular disease and heart failure (see Section 10, "Cardiovascular Disease and Risk Management"), chronic kidney disease (CKD) staging (see Section 11, "Chronic Kidney Disease and Risk Management"), presence of retinopathy and neuropathy (see Section 12, "Retinopathy, Neuropathy, and Foot Care"), and risk of treatment-associated hypoglycemia should be used to individualize goals for glycemia (see Section 6, "Glycemic Goals and Hypoglycemia"), blood pressure, and lipids and to select specific glucose-lowering medication(s) (see Section 9, "Pharmacologic Approaches to Glycemic Treatment"), antihypertension medications, and lipidlowering treatment intensity.

Additional referrals should be arranged as necessary (Table 4 .2). Clinicians should ensure that people with diabetes are appropriately screened for complications, comorbidities, and treatment burden. Discussing and implementing an approach to glycemic management with the person is a part, not the sole goal, of the clinical encounter. (18) . Here, we discuss the particular importance of specific vaccines.

IMMUNIZATIONS

COVID-19

People with underlying medical conditions, including diabetes, are more likely to become severely ill with coronavirus disease 2019 (COVID-19). COVID-19 vaccination using an appropriate number of doses of updated vaccines is recommended for everyone aged 6 months and older in the U.S. (18) .

For people with type 2 diabetes, lowcarbohydrate and very-low-carbohydrate eating patterns have been found to reduce A1C and the need for glucose-lowering medications (84, (101) (102) (103) . Systematic reviews and meta-analyses of RCTs found carbohydrate-restricted eating patterns, particularly those considered very low carbohydrate ( < 26% total energy), were effective in reducing A1C in the short term ( < 6 months), with less difference in eating patterns beyond 1 year (84, 104, 105) . However, in a 2022 carefully designed 12-week RCT feeding study among adults with prediabetes and type 2 diabetes, a well-formulated ketogenic diet (20-50 g/day and keeping protein to $1.5 g/kg ideal body weight/day, with the remainder of energy from fat) did not significantly improve A1C and increased LDL cholesterol compared with a low-carbohydrate Mediterranean diet (105) . Therefore, questions still remain about the optimal degree of carbohydrate restriction and long-term effects of those meal patterns on cardiovascular disease (CVD).

The effects of changes in body weight and the wide range of definitions for a low-carbohydrate eating plan are important challenges in interpreting carbohydrate-restricted research studies (106) . Weight reduction is often a goal in many studies on low-carbohydrate eating plans, which complicates evaluating the distinct contribution of the eating pattern (107) (108) (109) . As studies on low-carbohydrate eating plans generally indicate challenges with long-term sustainability (101) , it is important to reassess and individualize meal plan guidance regularly for those interested in this approach.

Table 5.3-Nutrition behaviors to encourage

Vegetables-especially nonstarchy vegetables that are dark green, red, and orange in color; fresh, frozen, or low-sodium canned are all acceptable vegetable options.

Legumes-dried beans, peas, and lentils.

Fruits-especially whole fruit-fresh, frozen, or canned in own juice (or no added sugar) are all acceptable fruit options.

Whole-grain foods-where culturally appropriate, whole-grain versions of commonly consumed foods such as 100% whole-wheat breads or pastas, and brown rice. When not culturally appropriate, focus more on portion control. Foods with at least 3 g of fiber per serving, which generally indicates a food higher in fiber.

Water should be the primary beverage of choice.

For individuals who do not prefer plain water, no-calorie alternatives are the next best choice. Options include adding lemon, lime, or cucumber slices to water; sparkling no-calorie water or flavored no-calorie waters; no-calorie carbonated beverages, etc.

Plant-based proteins can include legumes (e.g., soybeans, pinto beans, black beans, garbanzo beans, dried peas, and lentils), nuts, and seeds.

Meats and poultry should be from fresh, frozen, or low-sodium canned and in lean forms (e.g., chicken breast and ground turkey).

Heart-healthy wild-caught fatty fish such as salmon, tuna, sardines, and mackerel. Fresh, frozen, or low-sodium canned are all acceptable options.

Use herbs (e.g., basil, fennel, mint, parsley, rosemary, and thyme) and spices (e.g., cinnamon, garam masala, ginger, pepper, and turmeric) to season foods instead of salt or salt-containing preparations.

Incorporate onions, garlic, celery, carrots, and other vegetables as a base for preparing various homemade foods.

Cook with vegetable oil (e.g., canola and olive) in place of fats high in saturated fat (e.g., butter, shortening, lard, and coconut oil).

Meal prep by planning out meals for the week, grocery shopping with a list, and cooking on a day off so there are ready-to-eat and readyto-reheat homemade meals waiting in the fridge or freezer.

Include family or roommates in meal preparation; share the responsibilities of grocery shopping and cooking.

Health care professionals should maintain consistent medical oversight of individuals following very-low-carbohydrate eating plans and recognize that insulin and other diabetes medications may need to be adjusted to prevent hypoglycemia, and blood pressure will need to be monitored. In addition, very-low-carbohydrate eating plans are not currently recommended for individuals who are pregnant or lactating, children, people who have kidney disease, or people with or at risk for disordered eating.

Very-low-carbohydrate eating plans should also be used with caution in those taking sodium-glucose cotransporter 2 (SGLT2) inhibitors because of the potential risk of ketoacidosis (110, 111) . Numerous case reports have now been published illustrating that diabetic ketoacidosis (DKA) or euglycemic DKA can occur in people with type 1 and type 2 diabetes using SGLT2 inhibitors in combination with verylow-carbohydrate or ketogenic eating patterns. Additionally, excessive alcohol intake should be avoided when taking SGLT2 inhibitors (110) .

Regardless of the amount of carbohydrate in the meal plan, focus should be placed on high-quality, minimally processed, nutrient-dense carbohydrate sources high in fiber. Dietary fiber modulates gut microbiota composition and increases gut microbial diversity. Although there is still much to be elucidated about the gut microbiome and chronic disease, higherfiber diets are advantageous (112) . Both children and adults with diabetes are encouraged to minimize intake of refined carbohydrates with added sugars, fat, and sodium and instead focus on carbohydrates from vegetables, legumes, fruits, dairy (milk and yogurt) or fortified nondairy alternatives, and whole grains. People with diabetes and those at risk for diabetes are encouraged to consume a minimum of 14 g of fiber/1,000 kcal, with at least half of grain consumption being whole, intact grains, according to the Dietary Guidelines for Americans, 2020-2025 (76) . Regular intake of sufficient dietary fiber is associated with lower all-cause mortality in people with diabetes, and prospective cohort studies have found dietary fiber intake is inversely associated with risk for type 2 diabetes (113, 114) . The consumption of sugar-sweetened beverages and processed food products with large amounts of refined grains and added sugars is strongly discouraged (76) , as these have the capacity to displace healthier, more nutrient-dense food choices and increase inflammation (115) .

The literature concerning glycemic index and glycemic load in individuals with diabetes is complex, often with varying definitions of low-and highglycemic index foods (116) (117) (118) . The glycemic index ranks carbohydrate foods on their postprandial glycemic response, and glycemic load considers both the glycemic index of foods and the amount of carbohydrate eaten. Studies have found mixed results regarding the effect of glycemic index and glycemic load on fasting glucose levels and A1C, with one systematic review finding no significant effect on A1C (117) while others demonstrated A1C reductions of 0.15% (116) to 0.5% (106, 119) . More recently, however, a meta-analysis of large cohorts ($100,000 participants) reported that when people had larger intakes of high glycemic index foods, there was increased incidence of type 2 diabetes (risk ratio 1.27 [95% CI 1.21-1.34]; P < 0.0001), total CVD (1.15 [1.11-1.19] ; P < 0.0001), diabetes-related cancer (1.05 [1.02-1.08]; P = 0.0010), and allcause mortality (1.08 [1.05-1.12]; P < 0.0001) (118) . It is important to note that "low glycemic index" or "low glycemic load" is synonymous with high-fiber eating patterns.

Individuals with type 1 or type 2 diabetes taking insulin at mealtime should be offered comprehensive and ongoing education about nutrition content and the need to couple insulin administration with carbohydrate intake. For people whose meal schedule or carbohydrate consumption is variable, regular education to increase understanding of the relationship between carbohydrate intake and insulin needs is important. In addition, education on using insulin-to-carbohydrate ratios for meal planning can assist individuals with effectively modifying insulin dosing from meal to meal to improve glycemic management (78, 99) . Consumption of fat and protein can affect early and delayed postprandial glycemia (120) , and it appears to have a dose-dependent response (121, 122) . Results from high-fat, high-protein feeding studies highlight the need for additional insulin to cover these meals; however, more research is needed to determine the optimal insulin dose and delivery strategy. Results from these studies also point to individual differences in postprandial glycemic response; therefore, a cautious approach to increasing insulin doses for high-fat and/or high-protein mixed meals is recommended to address delayed hyperglycemia that may occur after eating (50, 123) . For individuals using an insulin pump, a split bolus feature (part of the bolus delivered immediately and the remainder over a programmed duration of time) may provide better insulin coverage for high-fat and/or high-protein mixed meals (124, 125) .

Insulin dosing decisions should be confirmed with a structured approach to blood glucose monitoring or CGM to evaluate individual responses and guide insulin dose adjustments. Checking glucose 3 h after eating may help determine if additional insulin adjustments are required (i.e., increasing or stopping bolus) (124, 125) . Adjusting insulin doses to account for high-fat and/or high-protein meals requires determination of anticipated nutrient intake to calculate the mealtime dose. Food literacy, numeracy, interest, and capability should be evaluated. For individuals on a fixed daily insulin schedule, meal planning should emphasize a relatively fixed carbohydrate consumption pattern with respect to both time and amount while considering insulin action. Attention to hunger and satiety cues will also help with nutrient modifications throughout the day (50) . Most commercially available automated insulin delivery systems still require basic diabetes management skills, including carbohydrate counting and understanding of the effect of protein and fat on postprandial glucose response (126) .

Protein

There is no evidence that adjusting the daily protein intake above or below the recommended amount for the general public (typically 0.8-1.5 g/kg body weight/day or 15-20% of total calories) will improve health, and research is inconclusive regarding the ideal amount of dietary protein to optimize either glycemic management or CVD risk (76, 127) . Therefore, protein intake goals should be individualized based on current eating patterns. Some research has found successful management of type 2 diabetes with meal plans including slightly higher levels of protein (20-30%), which may contribute to increased satiety (128) .

Historically, low-protein eating plans were advised for individuals with diabetes-related chronic kidney disease (CKD) (with albuminuria and/or reduced estimated glomerular filtration rate [eGFR]); however, current evidence does not suggest that people with CKD need to restrict protein to less than the generally recommended protein intake (129) . Reducing the amount of dietary protein below the recommended daily allowance of 0.8 g/ kg is not recommended because it does not alter glycemic measures, cardiovascular risk measures, or the rate at which eGFR declines and may increase risk for malnutrition (129) .

Growing evidence suggests higher plant protein intake and replacement of animal protein with plant protein is associated with lower risk of all-cause and cardiovascular mortality. A meta-analysis of 13 RCTs showed that replacing animal proteins with plant proteins leads to small improvements in A1C and fasting glucose in adults with type 2 diabetes (130) . A 2023 systematic review and meta-analysis of 13 RCTs and 7 cohort studies concluded that there is limitedsuggestive evidence to support replacing animal protein with plant-based protein based on a moderate degree of bias in cohort studies (131) . However, a prospective observational study of more than 11,000 community-dwelling adults over 22 years of follow-up reported that those with higher intakes of plant foods and lower intakes of animal foods had lower diabetes risk (132) . Plant proteins are lower in saturated fat, higher in fiber, and also support planetary health (133) .

Fats

There is no optimal percentage of calories from fat for people with or at risk for diabetes, and macronutrient distribution should be individualized according to the individual's eating patterns, preferences, and metabolic goals (50) . The type of fats consumed is more important than total amount of fat when looking at metabolic goals and CVD risk, and the percentage of total calories from saturated fats should be limited (76, (134) (135) (136) . Multiple RCTs including people with type 2 diabetes have reported that a Mediterranean eating pattern can improve both glycemic management and blood lipids (137) (138) (139) . The Mediterranean eating pattern is based on the traditional eating habits in the countries bordering the Mediterranean Sea. Although eating styles vary by country and culture, they share a number of common features, including consumption of fresh fruits and vegetables, whole grains, beans, and nuts/ seeds; olive oil as the primary fat source; low to moderate amounts of fish, eggs, and poultry; and limited added sugars, sugary beverages, sodium, highly processed foods, refined carbohydrates, saturated fats, and fatty or processed meats.

People with diabetes should be advised to follow the guidelines for the general population for the recommended intakes of saturated fat, cholesterol, and trans fat (76) . In a 12-week double-blinded randomized controlled feeding study among 61 adults with overweight and obesity, without diabetes, higher intakes of saturated fat, compared with polyunsaturated fat, were found to increase liver fat deposition (140) . A 2021 systematic review and meta-analysis including over 22,500 prospective study participants followed for 9.8 years reported that replacing saturated fats with other macronutrients, such as polyunsaturated fats, was associated with reduced CVD occurrence (141) . Trans fats should be avoided. In addition, as foods high in saturated fats are progressively decreased, they should be replaced with foods high in unsaturated fats and not with refined carbohydrate foods (142) .

Evidence does not conclusively support recommending n-3 (eicosapentaenoic acid and docosahexaenoic acid) supplements for all people with diabetes for the prevention or treatment of cardiovascular events (50, 143) . In individuals with type 2 diabetes, two systematic reviews with n-3 and n-6 fatty acids concluded that the dietary supplements did not improve glycemic management (144, 145) . In the ASCEND (A Study of Cardiovascular Events iN Diabetes) trial, when compared with placebo, supplementation with n-3 fatty acids at a dose of 1 g/day did not lead to cardiovascular benefit in people with diabetes without evidence of CVD (146) . However, results from the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) found that supplementation with 4 g/day of pure eicosapentaenoic acid significantly lowered the risk of adverse cardiovascular events. REDUCE-IT included 8,179 participants, of whom over 50% had diabetes, and found a 5% absolute reduction in cardiovascular events for individuals with established atherosclerotic CVD already treated with a statin with residual hypertriglyceridemia (135-499 mg/dL [1.52-5.63 mmol/L]) (147) . See Section 10, "Cardiovascular Disease and Risk Management," for more information.

Sodium

As for the general population, people with diabetes are advised to limit their sodium consumption to < 2,300 mg/day (50, 148) . Sodium intake has been shown to mediate glucose metabolism in a number of studies and affect eGFR, so limiting sodium intake is a valuable strategy for people with diabetes with or without kidney disease (148, 149) . In their post hoc analysis of the DASH-sodium RCT, Morales-Alvarez et al. reported that participants randomized to the low-sodium DASH eating pattern (containing $1,150 mg sodium/day [50 mmol sodium/day]) had change in eGFR of À3.10 mL/min/1.73 m 2 (95% CI À5.46 to À0.73) after 4 weeks compared with 3,450 mg sodium/day (150 mmol sodium/day) (150) .

Limiting sodium intake is most easily achieved through reducing consumption of processed and ultraprocessed foods, which are major contributors of sodium intake. Encouraging people to avoid adding salt to foods and during cooking can also help. Sodium recommendations should consider palatability, availability, affordability, clinical appropriateness, and the difficulty of achieving low-sodium recommendations in a nutritionally adequate eating plan.

Despite lack of evidence of benefit from dietary supplements, consumers continue to take them. Estimates show that up to 59% of people with diabetes in the U.S. use supplements (151) . Without underlying deficiency, there is no benefit from herbal or other (i.e., vitamin or mineral) supplementation for people with diabetes (50, 152) .

Federal law in the U.S. broadly defines dietary supplements as products having one or more dietary ingredients, including vitamins, minerals, herbs or other botanicals, amino acids, enzymes, tissues from organs or glands, or extracts of these (153) . It should also be noted that dietary supplements are not regulated like other over-the-counter medications or prescription drugs in the U.S. (154) . In combination with the strong views on dietary supplements (both positive and negative), this can contribute to consumer confusion (155) . Consumers can also consult the U.S. Food and Drug Administration (FDA) Dietary Supplement Ingredient Directory to locate information about ingredients used in dietary supplements and any action taken by the agency with regard to that ingredient (156) . Routine antioxidant supplementation (such as vitamins E and C) is not recommended due to lack of evidence of efficacy and concern related to long-term safety. Based on the 2022 U.S. Preventative Services Task Force statement, the harms of b-carotene outweigh the benefits for the prevention of CVD or cancer. b-Carotene was associated with increased lung cancer and cardiovascular mortality risk (157) .

Vitamin D in the context of diabetes has generated much research, but universal vitamin D supplementation for people with type 1 or type 2 diabetes without deficiency is not recommended at this time. Although post hoc analyses of the Vitamin D and Type 2 Diabetes Study (D2d) prospective RCT and Diabetes Prevention and Active Vitamin D (DPVD) and some meta-analyses suggest a potential benefit in specific populations (158) (159) (160) , other studies have found no benefit or mixed results (161) (162) (163) . Furthermore, adopting healthy lifestyle habits, including the eating patterns recommended herein, are strongly advised. Additional research is needed to define individual characteristics, clinical indicators, and appropriate dosages if and when vitamin D supplementation might benefit people with type 1 or type 2 diabetes.

There is insufficient evidence to support the routine use of herbal supplements and micronutrients, such as cinnamon (164) , curcumin (e.g., turmeric), aloe vera, or chromium, to improve glycemia in people with type 1 or type 2 diabetes (50) .

Metformin is associated with vitamin B12 deficiency per a report from the Diabetes Prevention Program Outcomes Study (DPPOS), which suggests that periodic testing of vitamin B12 levels should be considered in people taking metformin, particularly in those with anemia or peripheral neuropathy (165) (see Section 9, "Pharmacologic Approaches to Glycemic Treatment").

For special populations, including pregnant or lactating individuals, older adults, vegetarians, and people following very-low-calorie or low-carbohydrate diets, a multivitamin may be necessary (166) .

Alcohol

The long-term effects of alcohol consumption for people with diabetes are unknown. The World Health Organization declared that there is no safe amount of alcohol intake (167, 168) . Risks associated with alcohol consumption include hypoglycemia and/or delayed hypoglycemia (particularly for those using insulin or insulin secretagogue therapies), weight gain, and hyperglycemia (for those consuming excessive amounts) (50, 169) . People with diabetes should be educated about these risks and encouraged to monitor glucose frequently before and after drinking alcohol to minimize such risks. People with diabetes who consume alcohol can follow the same guidelines as those without diabetes consistent with Dietary Guidelines for Americans, 2020-2025 (76), which does not promote alcohol consumption in people who do not currently drink. To reduce risk of alcohol-related harms, adults can choose not to drink or to drink in moderation by limiting intake to #2 drinks a day for men or #1 drink a day for women (one drink is equal to a 12-oz beer, a 5-oz glass of wine, or 1.5 oz of distilled spirits) (76) . Recent meta-analyses have reported the previously recognized J-shaped relationship between alcohol intake and health risks likely varies by sex, obesity status, genetics, and alcohol intake behaviors (170,171). A YMCA-based psychoeducational intervention tailored to those with chronic conditions, including 14-to 18-year-olds with type 1 diabetes, reported improvements in perceived risks of alcohol intake. Importantly, they also reported reduced alcohol consumption (172).

Nonnutritive Sweeteners and Water

The FDA has approved many nonnutritive sweeteners (NNS) (containing few or no calories; commonly referred to as artificial sweeteners) for consumption by the general public, including people with diabetes (50, 173) . However, the safety and role of NNS continue to be sources of concern and confusion for the public.

For some people with diabetes who are accustomed to regularly consuming sugar-sweetened foods or beverages (e.g., regular soda pop, juice drinks, and other items sweetened with cane sugar or high-fructose corn syrup), NNS may be an acceptable substitute for nutritive sweeteners (those containing calories, such as sugar, honey, and agave syrup) when consumed in moderation (174). NNS do not appear to have a significant effect on glycemic management (175,176), and they can reduce overall calorie and carbohydrate intake (174) as long as individuals are not compensating with additional calories from other food sources (50, 177) . A recent meta-analysis and systematic review of RCTs found no evidence that NNS raise liver enzymes (178).

There is mixed evidence from systematic reviews and meta-analyses for NNS use with regard to weight management, with some finding benefit for weight loss (179) (180) (181) while other research suggests an association with weight gain (182, 183) . This may be explained by reverse causality and residual confounding variables (183) . The addition of NNS to eating plans poses no benefit for weight loss or reduced weight gain without energy restriction (184) . In a recent systematic review and metaanalysis using low-calorie and no-calorie sweetened beverages as an intended substitute for sugar-sweetened beverages, a small improvement in body weight and cardiometabolic risk factors was seen without evidence of harm and had a direction of benefit similar to that seen with water (185) . While health care professionals should promote water as the healthiest beverage option, people with overweight or obesity and diabetes may also use a variety of no-calorie or lowcalorie sweetened products so that they do not feel deprived (185) .

Health care professionals should encourage reductions in foods and beverages with added sugars and promote reducing overall sugar intake and calories with or without the use of NNS. Assuring people with diabetes that NNS have undergone extensive safety evaluation by regulatory agencies and are continually monitored can allay unnecessary concern for harm. Health care professionals can regularly assess individual use of NNS based on the acceptable daily intake (amount of a substance considered safe to consume each day over a person's life) and recommend moderation. See the chart from the FDA on safe levels of sweeteners found at fda.gov/food/food-additives-petitions/ aspartame-and-other-sweeteners-food.

Weight Management

Management and reduction of weight is important for people with type 1 diabetes, type 2 diabetes, or prediabetes with overweight or obesity. To support weight loss and improve A1C, CVD risk factors, and well-being in adults with overweight or obesity and prediabetes or diabetes, MNT and DSMES services should include an individualized eating plan resulting in an energy deficit in combination with enhanced physical activity (50) . Lifestyle intervention programs should be intensive and have frequent follow-up to achieve significant reductions in excess body weight and improve clinical indicators. Behavior modification goals should address physical activity, calorie restriction, healthy weight management strategies, and motivation. There is strong and consistent evidence that modest, sustained weight loss can delay the progression from prediabetes to type 2 diabetes (82,186,187) (see Section 3, "Prevention or Delay of Diabetes and Associated Comorbidities") and is beneficial for type 2 diabetes management (see Section 8, "Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes").

In prediabetes, the weight loss goal is at least 3-7% from baseline body weight, and higher for reducing risk of progression to type 2 diabetes. In conjunction with support for healthy lifestyle behaviors, medication-assisted weight loss can be considered for people at risk for type 2 diabetes when needed to achieve and sustain 7-10% weight loss (188,189) (see Section 8, "Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes"). People with prediabetes at a healthy weight should also be considered for behavioral interventions to help establish routine aerobic and resistance exercise (186, 190, 191) as well as healthy eating patterns. Services delivered by health care professionals familiar with diabetes and its management, such as an RDN, have been found to be effective (81) .

For many individuals with overweight or obesity alongside type 2 diabetes, at least 5% weight loss is needed to achieve beneficial outcomes in glycemic management, lipids, and blood pressure (192) .

However, any magnitude of weight loss is recommended. It also should be noted that the clinical benefits of weight loss are progressive, and more intensive weight loss goals (i.e., 15%) may be appropriate to maximize benefit depending on need, feasibility, and safety (193, 194) . Long-term sustainability of weight loss remains a challenge (195) . Medications can augment MNT to support weight loss, weight loss maintenance, and improve cardiovascular outcomes. Newer medications (e.g., glucagon-like peptide 1 receptor agonists [GLP-1 RAs]) may be more viable, positively affect cardiovascular outcomes, and produce weight reduction beyond 10-15% (196) (197) (198) (199) (200) . For more information on the nutritional considerations important for people undergoing metabolic surgery, including prevention of malnutrition, please see MALNUTRITION, below.

In select individuals with type 2 diabetes, an overall healthy eating plan resulting in energy deficit and pharmacotherapy and/or metabolic surgery should be considered to help achieve weight loss and maintenance goals, lower A1C, and reduce CVD risk (188, 201, 202) . A recent systematic review and meta-analysis concluded that when obesity pharmacotherapy is included in intervention efforts (alone or as part of a multipronged intervention), people with obesity can achieve a more significant weight loss of À2.94 kg (P < 0.0001) (203) . However, in some populations such as South Asian adults, traditional interventions have not been as effective in preventing or remission of type 2 diabetes, so those groups will benefit from more culturally tailored interventional approaches (204) .

Overweight and obesity are increasingly prevalent in people with type 1 diabetes and present clinical challenges regarding diabetes treatment and CVD risk factors (205, 206) . Like in adults with type 2 diabetes, there is some evidence that GLP-1 RAs are useful in achieving weight loss among those with type 1 diabetes, although with a higher risk of nausea and ketosis (207) .

Regardless of diabetes type, maintaining weight loss is challenging (208, 209) but has well-recognized long-term benefits. The physiology of weight loss maintenance is complex and involves many hormonal, psychosocial, behavioral, and environmental factors. Following a weight loss of at least 8%, a subsequent "weight loss maintenance" intervention was reported to be only moderately beneficial, as it helped sustain physical health improvements but not glucose metabolism improvements (210) . However, in another RCT with longterm, real-world, clinic-based followup of 10 years, Tomah et al. reported lasting glycemic benefits in their cohort with an average weight loss of 7.7 ± 0.9 kg (À6.9 ± 0.8%) maintained for 10 years (211) .

Starting a conversation about weight management should be based on motivational interviewing techniques (212) beginning with first asking the individual if they want to discuss their weight. Health care professionals should never assume that a person with overweight or obesity wants to discuss their weight at a medical appointment, especially if the appointment is for a seemingly unrelated issue (e.g., back pain, which many people do not realize is often secondary to excess body weight). Using person-centered approaches to weight management conversations involves meeting the individual where they are at in their life and working with what they and their health care professional agree is the most beneficial approach. Guidance from an RDN with expertise in motivational interviewing and diabetes and weight management MNT during any comprehensive structured weight loss program is strongly recommended.

Along with routine medical management visits, people with diabetes and prediabetes should be screened during DSMES and MNT encounters for a history of dieting and past or current disordered eating behaviors. Characterizing an individual's past efforts with weight loss and their body weight history can also be very useful. Nutrition therapy should be individualized to help address maladaptive eating behavior (e.g., purging) or compensatory changes in medical treatment plan (e.g., overtreatment of hypoglycemic episodes and reduction in medication dosing to reduce hunger) (50) (see DISORDERED EATING BEHAVIOR, below). Disordered eating, eating disorders, and/or disrupted eating can increase challenges for weight and diabetes management. For example, caloric restriction may be essential for glycemic management and weight maintenance, but rigid meal plans and strict tracking of food intake and/or body weight may be contraindicated for individuals who are at increased risk of clinically significant maladaptive eating behaviors (213) . If eating disorders are identified during screening with diabetes-specific questionnaires, individuals should be referred to a qualified behavioral health professional (1) .

Nonreligious Fasting

The primary forms of nonreligious fasting are intermittent fasting or timerestricted eating. These are popular strategies for weight and glucose management. One of the key distinctions between nonreligious and religious fasting is water intake. See Fig. 5 .1 for further details on how religious and nonreligious fasting practices compare.

Intermittent fasting is an umbrella term that includes three main forms of restricted eating: alternate-day fasting (energy restriction of 500-600 calories on alternate days), the 5:2 diet (energy restriction of 500-600 calories on consecutive or nonconsecutive days with usual intake the other five), and time-restricted eating (daily calorie restriction based on window of time of 8-15 h). Each produces mild to moderate weight loss (3-8% loss from baseline) over short durations (8-12 weeks) with no significant differences in weight loss when compared with continuous calorie restriction (214, 215) . A 2024 systematic review and meta-analysis of RCTs examined the most common types of fasting in studies lasting 2-52 weeks. The authors concluded that intermittent energy restriction produces small but significant reductions in waist circumference and fat-free mass but were otherwise not superior to continuous energy restriction diets (216) . Generally, time-restricted eating or shortening the eating window can be adapted to any eating pattern and has been shown to be safe for adults with type 1 or type 2 diabetes (217) . People with diabetes who are taking insulin and/or secretagogues should be medically monitored during the fasting period (218) . Because of the simplicity of intermittent fasting and time-restricted eating, these may be useful strategies for people with diabetes who are looking for practical eating management tools.

Use of partial or total meal replacements is an additional strategy for energy restriction. Meal replacements are prepackaged foods (bars, shakes, and soups) that contain fixed amounts of macro nutrients and micronutrients. They can improve nutrient quality and glycemic management and, consequently, reduce portion size and energy intake. In a metaanalysis involving 17 studies incorporating both partial and total meal replacements, greater weight loss and improvements in A1C and fasting blood glucose were demonstrated compared with conventional meal plans (219) . Furthermore, meal replacements have been used in several landmark clinical trials, including Look AHEAD (Action for Health in Diabetes) (220) , DiRECT (Diabetes Remission Clinical Trial) (221) , and PREVIEW (Prevention of Diabetes Through Lifestyle Intervention and Population Studies in Europe and Around the World) (222) . Results of these trials showed that partial or total meal replacements can be a potential short-term strategy for weight loss. Regardless of the specific eating pattern or meal plan selected, long-term follow-up and support from members of the diabetes care team are needed to optimize self-efficacy and maintain behavioral changes (85) .

Chrononutrition is an emerging nutrition and biology subspecialty aimed toward increasing the understanding of how the timing of food ingestion affects metabolic health (223) . Glucose metabolism follows a circadian rhythm through diurnal variation of glucose tolerance and peaks during daylight hours when food is consumed. Some preliminary studies show cardiometabolic benefits when food is consumed earlier (224) . Similarly, circadian disruptions found in shift workers increase risk of type 2 diabetes (225) . This evolving area of research currently lacks conclusive evidence, but future studies are anticipated. Although intermittent fasting and timerestricted eating are specific dietary strategies for energy restriction, religious fasting has been practiced for thousands of years and is part of many faith-based traditions. Duration, frequency, and type of fast vary among different religions (226) . For example, Jewish people abstain from any intake for $25 h during Yom Kippur (227, 228) . For Muslims, Ramadan fasting lasts for a full month, when abstinence from any food or drink is required from dawn to dusk (229) . Individuals with diabetes who fast have an increased risk for hypoglycemia, dehydration, hyperglycemia, and ketoacidosis (230, 231) . Prefasting risk assessment is essential to increase level of safety (230, 231) . Various risk factors need to be considered for every individual wishing to fast. Some of these factors are related to the type of fast, type of diabetes, and/or the individual. Indeed, health care professionals should inquire about any religious fasting for people with diabetes and provide education and support to accommodate their choice. The number of days of fasting is an important factor to consider. In Ramadan fasting, a person fasts from dawn to dusk for a lunar month (29-30 days). It is important for the health care professional to comprehensively assess these risk factors well in advance of fasting date, as some of them are modifiable. Some of these factors are related to the nature of the fasting practice, others are related to diabetes, and others might be due to individual factors. The International Diabetes Federation along with Diabetes and Ramadan International Alliance adopted a risk calculator for the various risk factors (230, 232) . Several clinical studies from different countries have been published that assess the validity of the fasting risk score and the ease of use of it (232) (233) (234) (235) . The accumulation of these risk factors provides a risk score as low, moderate, or high (Table 5 .4) (230) . While the risks of different religious fasting practices may vary, this risk calculator provides some useful guidance for other religious fasting.

INTERMITTENT FASTING

Prefasting education regarding the importance of increasing the frequency of glucose monitoring for people wishing to fast is very important. The timing of glucose monitoring is also especially important, as the last few hours of fasting are frequently associated with approximately 50% of hypoglycemic events (236) . Consequently, avoiding intense physical activity during the last few hours of fasting seems to be a sensible approach.

During religious fasting, some people change their nutrition habits and overindulge after fasting concludes. In many communities, the meal consumed to break the fast is rich in carbohydrates and includes foods and beverages high in added sugars and fat (230) . Indeed, in a recent study in type 2 diabetes, 16.5% of people with diabetes who fasted for Ramadan reported high blood glucose of > 300 mg/dL ( > 16.6 mmol/L) during fasting days (236) . Individualized fluid adjustment and meal advice should be provided with emphasis on higher intake of fiber and replacing added sugars with complex carbohydrates to minimize hypoglycemia and hyperglycemia and emphasis on sustaining adequate daily fluid intake (237) .

Treatment before and after fasting should be culturally sensitive and individualized. Specific recommendations for diabetes management during religious fasting in different faiths are available (230, 231) . In general, for people planning to fast for long hours and for multiple consecutive days, choice of treatment should prioritize drugs with low hypoglycemia risk. Hypoglycemia risk while fasting in people using insulin, sulfonylureas, and other insulin secretagogues is higher than those treated with other types of diabetes medications (230) . The safety of SGLT2 inhibitors was assessed in several studies during Ramadan fasting. These studies did not show significant change in kidney function, dehydration rates, or ketosis (238) . Guidelines do not advise any change in SGLT2 inhibitor dose during fasting; however, they advise against initiating SGLT2 inhibitors close to the start of fasting days to avoid excessive thirst (230) . Table 5 .5 summarizes the effect of fasting on different treatment options and the possible change in doses or timing for people with diabetes.

Technology could be an important tool to enhance safety during fasting. Several studies have investigated the use of monitoring technology during Ramadan fasting (e.g., flash glucose monitoring and realtime CGM [rtCGM]) and confirmed that these tools are able to support high-risk groups wishing to fast, especially if combined with Ramadan-focused education (238) (239) (240) . Meanwhile, the use of insulin pumps has been associated with low rates of hypoglycemia during fasting in people with type 1 diabetes. Diabetes technologies should be considered as a useful adjunct to risk calculation and/or nutrition planning and education during religious fasting for people with diabetes (230) .

Key opportunities for psychosocial screening occur at diabetes diagnosis, during regularly scheduled management visits, during hospitalizations, with new onset of complications, during significant transitions in care such as from pediatric to adult care teams (385), at the time of medical treatment changes, or when problems with achieving A1C goals, quality of life, or self-management are identified. Additionally, significant changes in life circumstances and SDOH are known to affect a person's ability to self-manage their diabetes. Thus, screening for SDOH should also be incorporated into routine care (386). In circumstances where individuals other than the person with diabetes are significantly involved in diabetes management (e.g., caregivers or family members), these issues should be monitored and treated by appropriate professionals (385,387).

Standardized, validated, age-appropriate tools for psychosocial monitoring and screening can also be used (1) . The ADA provides access to tools for screening specific psychosocial topics, such as diabetes distress, fear of hypoglycemia, and other relevant psychological symptoms at professional.diabetes.org/sites/default/ files/media/ada_mental_health_toolkit_ questionnaires.pdf. Additional information about developmentally specific psychosocial screening topics is available in Section 14, "Children and Adolescents," and Section 13, "Older Adults." Health care professionals may also use informal verbal inquires, for example, by asking whether there have been persistent changes in mood during the past 2 weeks or since the individual's last appointment and whether the person can identify a triggering event or change in circumstances. Diabetes care professionals should also ask whether there are new or different barriers to treatment and self-management, such as feeling overwhelmed or stressed by having diabetes (see DIABETES DISTRESS, below), changes in finances, or competing medical demands (e.g., the diagnosis of a comorbid condition).

Psychological Assessment and Treatment

When psychosocial concerns are identified, referral to a qualified behavioral health professional, ideally one specializing in diabetes, should be made for comprehensive evaluation, diagnosis, and treatment (353,369,370). Indications for referral may include positive screening for diabetes distress, depression, anxiety, disordered eating, or cognitive dysfunction (see Table 5 .6 for a complete list).

Incorporating psychosocial assessment and treatment into routine care is preferable to waiting for a specific problem or deterioration in glycemic or psychological status to occur (37, 361) . Health care professionals should identify and refer to behavioral health professionals knowledgeable about diabetes and psychosocial care. The ADA provides a list of behavioral health professionals who have specialized expertise or who have received education about psychosocial and behavioral issues related to diabetes in the ADA Mental Health Professional Directory (professional. diabetes.org/ada-mental-health-providerdirectory). Ideally, behavioral health professionals should be embedded in diabetes care settings. In recognition of limited behavioral health resources and to optimize availability, other health care professionals who have been trained in behavioral health interventions may also provide this specialized psychosocial care (365,367,388). Although some health care professionals may not feel qualified to treat psychological problems (389), strengthening the relationship between a person with diabetes and the health care professional may increase the likelihood of a person accepting a referral for other services. Collaborative care interventions and a team approach have demonstrated efficacy in diabetes self-management, outcomes of depression, and psychosocial functioning (5, 6) . The ADA provides resources for a range of health professionals to support behavioral health in people with diabetes at professional.diabetes.org/meetings/ behavioral-health-toolkit.

Evidence supports interventions for people with diabetes and psychosocial concerns, including issues that affect behavioral health. Successful therapeutic approaches include cognitive behavioral (369,390,391) and mindfulness-based therapies (392). See the sections below for details about interventions for specific psychological concerns. Behavioral interventions may also be indicated in a preventive manner even in the absence of positive psychosocial screeners, such as resiliencepromoting interventions to prevent diabetes distress in adolescence (393,394) and behavioral family interventions to promote collaborative family diabetes management in early adolescence (395, 396) or to support adjustment to a new treatment plan or technology (64) . Psychosocial interventions can be delivered via digital health platforms (397). Group-based or shared diabetes appointments that address both medical and psychosocial issues relevant to living with diabetes are a promising model to consider (366, 398) .

Although psychosocial interventions have demonstrated short-term efficacy, their success in sustained engagement in health behaviors and improved glycemic outcomes associated with behavioral health issues has varied. Thus, health care professionals should systematically monitor these outcomes following implementation of current evidence-based psychosocial treatments to determine ongoing needs.

Diabetes Distress

Recommendation 5.48 Screen for diabetes distress at least annually in people with diabetes, caregivers, and family members, and repeat screening when treatment goals are not met, at transitional times, and/or in the presence of diabetes complications. Health care professionals can Table 5 .6-Situations that warrant referral of a person with diabetes to a qualified behavioral health professional for evaluation and treatment

• A positive screen on a validated screening tool for depressive symptoms, diabetes distress, anxiety, fear of hypoglycemia, suicidality, or cognitive impairment

• The presence of symptoms or suspicions of disordered eating behavior, an eating disorder, or disrupted patterns of eating

• Intentional omission or underdosing of insulin or noninsulin medication to cause weight loss

• A serious mental illness is suspected

• In youth and families with behavioral self-care difficulties, repeated hospitalizations for diabetic ketoacidosis, failure to achieve expected developmental milestones, or significant distress (404, 405 ). Among people with type 1 diabetes, the prevalence of diabetes distress is 22-42%, with a 9-month incidence of 54% (400,406). In the second Diabetes Attitudes, Wishes, and Needs (DAWN2) study, 45% of the participants reported significant diabetes distress, but only 24% reported that their health care teams asked them how diabetes affected their lives (361). Similar rates of diabetes distress have been identified among adolescents with type 1 diabetes (399) and in parents of youth with type 1 diabetes. Diabetes distress negatively affects medication-taking behaviors and is linked to higher A1C, lower selfefficacy, and less optimal eating and exercise behaviors (5, 403, 407) . Diabetes distress is also associated with symptoms of anxiety, depression, and reduced healthrelated quality of life (408). The experience of stigma related to living with diabetes may contribute to increased diabetes distress (409,410). Diabetes distress should be routinely monitored (411) using diabetes-specific validated measures (1), such as those available through the ADA's website (professional.diabetes.org/sites/default/ files/media/ada_mental_health_toolkit_ questionnaires.pdf). As there are validated diabetes distress measures for people with type 1 and type 2 diabetes Several educational and behavioral intervention strategies have demonstrated benefits for diabetes distress and, to a lesser degree, glycemic outcomes. These interventions include educational, psychological, and health behavior change approaches such as DSMES, cognitive behavioral therapy (CBT), mindfulness-based therapies, motivational interviewing, and others (390,391,414,415). Interventions delivered via telephone, smartphone applications, video visits, and/or self-help modalities can be effective in reducing diabetes distress (397,416-418). DSMES has been shown to reduce diabetes distress (5, 419) and may also benefit A1C when combined with peer support (420). It may be helpful to provide counseling regarding expected diabetes-related emotional distress at diagnosis and when the disease state, treatment, or life context changes (413). Two multisite RCTs with adults with type 1 diabetes, elevated diabetes distress, and elevated A1C demonstrated clinically meaningful improvements in diabetes distress and A1C through a combination of group-based intervention approaches including an educational diabetes self-management program and a psychological intervention that included emotion-focused skills (417). In adults with type 2 diabetes in the Veterans Affairs system, an RCT demonstrated that integrating a single session of mindfulness into DSMES, followed by a booster session and 24 weeks of mobile appbased home practice, significantly reduced diabetes distress compared with a DSMES-only control group (421). An RCT of CBT demonstrated positive benefits for diabetes distress, A1C, and depressive symptoms for up to 1 year among adults with type 2 diabetes and elevated symptoms of distress or depression (422). An RCT among people with type 1 and type 2 diabetes found mindful self-compassion There are few outcome data on longterm systematic treatment of diabetes distress integrated into routine care. As the burden of diabetes management can vary over time, diabetes distress may fluctuate and may need varying treatment approaches at different life stages and at different levels of diabetes progression.

Anxiety

Recommendations 5.49 Screen people with diabetes for anxiety symptoms. Health care professionals can discuss diabetes-related worries and should consider referral to a qualified behavioral health professional for further assessment and treatment if anxiety symptoms indicate interference with diabetes self-management behaviors or quality of life. B 5.50 Screen people with diabetes at risk for hypoglycemia or fear of hypoglycemia, especially if they have experienced severe and/or frequent hypoglycemic events. B Anxiety symptoms are common in people with diabetes (425) (see Tables 5.7 and 5.8), and there appear to be higher rates of generalized anxiety disorder, body dysmorphic disorder, obsessive compulsive disorder, specific phobias, and posttraumatic stress disorder in people with diabetes than in those without diabetes. The Behavioral Risk Factor Surveillance System estimated the lifetime prevalence of generalized anxiety disorder to be 19.5% in people with either type 1 or type 2 diabetes (426). A common diabetes-specific concern is fear related to hypoglycemia (427-429), which may explain avoidance of behaviors associated with lowering glucose, such as increasing insulin doses or frequency of monitoring. Factors related to greater fear of hypoglycemia in people with diabetes and family members include history of nocturnal hypoglycemia, presence of other psychological concerns, and sleep concerns (430). See Section 6, "Glycemic Goals and Hypoglycemia," for more information about impaired awareness of hypoglycemia and related fear of hypoglycemia. Other common sources of diabetes-related anxiety include not meeting glycemic goals (425), insulin injections or infusion (431), and onset of complications (1) . People with diabetes who exhibit excessive diabetes self-management behaviors well beyond what is prescribed or needed to achieve glycemic goals may be experiencing symptoms of obsessivecompulsive disorder (432). General anxiety is a predictor of injection-related anxiety and is associated with fear of hypoglycemia (433).

Psychological and behavioral care can be helpful to address symptoms of anxiety in people with diabetes. Among adults with type 2 diabetes and elevated depressive symptoms, an RCT of collaborative care demonstrated benefits on anxiety symptoms for up to 1 year (434). An RCT of CBT for adults with type 2 diabetes showed a reduction in health anxiety, with CBT accounting for 77% of the reduction in health anxiety at 16 weeks of follow-up; this trial also found decreased depressive symptoms and diabetes distress (435). Additionally, an RCT showed switching from isCGM without alerts to rtCGM with alert functionality in adults with type 1 diabetes decreased hypoglycemia-related anxiety at 24 months of follow-up while reducing A1C (436). Similarly, a systematic review and metaanalysis found that people with type 1 diabetes using diabetes technologies, specifically rtCGM, sensor-augmented pumps, and automated insulin delivery, reported decreased fear of hypoglycemia independent of the reduction of hypoglycemia frequency (437). Another RCT of a CBT-based intervention reported reduced fear of hypoglycemia by 8.5% compared with control participants, increased time in range, and improved self-management behaviors in young adults with type 1 diabetes over an 8-week period (438). Thus, specialized behavioral intervention with positive adjunct of diabetes technology from a qualified professional is needed to treat hypoglycemia-related anxiety. Depression Recommendations 5.51 Conduct at least annual screening of depressive symptoms in all people with diabetes and more frequently among those with a history of depression. Use age-appropriate, validated depression screening measures, recognizing that further evaluation will be necessary for individuals who have a positive screen. B 5.52 Rescreen for depression at diagnosis of complications or when there are significant changes in medical status. B 5.53 Refer to qualified behavioral health professionals or other trained health care professionals with experience using evidence-based treatment approaches for depression in conjunction with collaborative care with the diabetes treatment team. A History of depression, current depression, and antidepressant medication use are risk factors for the development of type 2 diabetes, especially if the individual has other risk factors, such as obesity and family history of type 2 diabetes (439,440). Elevated depressive symptoms and depressive disorders are common among people with diabetes (357,429) (Tables 5.7 and 5.8), affecting approximately one in four people with type 1 or type 2 diabetes (360), and among parents of youth with diabetes (441). Routine screening for depressive symptoms is indicated for people with type 1 or type 2 diabetes and gestational diabetes mellitus. Regardless of diabetes type, women have significantly higher rates of depression than men (442). For individuals with type 2 diabetes, the experience of diabetes-related stigma is associated with increased depressive symptoms (410).

Routine monitoring with age-appropriate validated measures (1) can help to identify if referral is warranted (370). Multisite studies have demonstrated feasibility of implementing depressive symptom screening protocols in diabetes clinics and published practical guides for implementation (374,375). Personcentered integrated care approaches have been shown to improve both depression and glycemic outcomes (443). The behavioral health professional providing treatment for depression should be incorporated into or collaborate with the diabetes treatment team (443). Depressive symptoms may also be a manifestation of reduced quality of life secondary to diabetes burden (also see DIABETES DIS- TRESS, above) (411). When depressive symptoms are identified, it is important to query origins and exacerbating factors, both diabetes-specific ones and those due to other life circumstances (408,444).

Trials have shown consistent evidence of improvements in depressive symptoms and variable benefits for A1C when depression is treated simultaneously with diabetes (445), whether through pharmacologic treatment, group therapy, psychotherapy, parenting intervention, mindfulness-based approaches, or collaborative care (6, 390, (446) (447) (448) (449) . Psychological interventions addressing depressive symptoms have shown efficacy when delivered via digital technologies (447,450). A meta-analysis found that internet-and phone-delivered CBT and self-guided interventions improved depressive symptoms (451). For people with diabetes, an RCT comparing internet plus telephonic CBT to usual care found moderate to large improvements in depressive symptoms at 12 months (452). Lifestyle interventions (i.e., changing nutrition and/or physical activity) also demonstrate benefits for depressive symptoms and A1C (295) on their own and when combined with CBT (453-455). Finally, a systematic review and meta-analysis found that use of GLP-1 RAs led to significant improvement in depressive symptoms among adults with type 2 diabetes (456). It is important to note that the medical treatment plan should also be monitored in response to reduction in depressive symptoms.

Disordered Eating Behavior

Recommendations 5.54 Screen for disordered or disrupted eating using validated screening measures. In addition, a review of the medical treatment plan is recommended to identify potential treatment-related effects on hunger/caloric intake. B 5.55 Consider reevaluating the treatment plan of people with diabetes who present with symptoms of disordered eating behavior, an eating disorder, or disrupted patterns of eating, in consultation with a qualified professional. Key qualifications include familiarity with diabetes disease physiology, treatments for diabetes and disordered eating behaviors, and weight-related and psychological risk factors for disordered eating behaviors. B Estimated prevalence of disordered eating behavior and diagnosable eating disorders in people with diabetes varies (457-459) (see Tables 5.7 and 5.8). People with type 1 diabetes have been found to be at greater risk for eating disorders than people without diabetes (460). Prevalence of intentional insulin omission to lose weight is 10% and more common among women than men with type 1 diabetes (460). In people with type 2 diabetes, bingeing (excessive food intake with an accompanying sense of loss of control) is most commonly reported. For people with type 2 diabetes treated with insulin, intentional omission is also frequently reported (461). People with diabetes and diagnosable eating disorders have high rates of comorbid psychiatric disorders (462). People with type 1 diabetes and eating disorders often have high rates of diabetes distress and fear of hypoglycemia (463).

Diabetes care professionals should monitor for disordered eating behaviors using validated measures; diabetes-specific measures are recommended to assess presence of intentional insulin omission and were found in a meta-analysis to be more strongly associated with A1C (464). When evaluating symptoms of disordered or disrupted eating (when the individual exhibits eating behaviors that appear maladaptive but are not volitional, such as bingeing caused by loss of satiety cues), etiology and motivation for the behavior should be evaluated by a qualified disordered eating professional (465). Inconsistent intervention findings point to the need for treatment of eating disorders and disordered eating behavior in the context of the condition and its treatment. Recent intervention efforts have focused on preventing disordered eating behaviors among individuals with type 1 diabetes and on supporting parents of youth with type 1 diabetes who are at risk for disordered eating; however, more RCTs with longer-term follow-up are needed (466-468).

Given the complexities of treating disordered eating behaviors and disrupted eating patterns in people with diabetes, it is recommended that interprofessional care teams include or collaborate with a health professional trained to identify and treat eating behaviors and with expertise in disordered eating and diabetes (469). Key qualifications for such professionals include familiarity with diabetes physiology, weight-related and psychological risk factors for disordered eating behaviors, and treatments for diabetes and disordered eating behaviors. More rigorous methods to identify underlying mechanisms of action that drive change in eating and treatment behaviors, as well as associated mental distress, are needed (470). Health care teams may consider the appropriateness of technology use among people with diabetes and disordered eating behaviors, although more research on the risks and benefits is needed (471). Caution should be taken in labeling individuals with diabetes as having a diagnosable psychiatric disorder, i.e., an eating disorder, when disordered or disrupted eating patterns are found to be associated with the disease and its treatment. In other words, patterns of maladaptive food intake that appear to have a psychological origin may be driven by physiologic disruption in hunger and satiety cues, metabolic perturbations, and/or secondary distress because of the individual's inability to control their hunger and satiety (465).

The use of incretin therapies, specifically GLP-1 RAs and potentially dual GIP and GLP-1 RAs, may have relevance to the treatment of disrupted or disordered eating (see Section 8, "Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes"). These therapies work in the appetite and reward circuitries to modulate food intake, reducing uncontrollable hunger and overeating (472). A systematic review found early evidence for GLP-1 RAs being effective in reducing binge-eating behaviors, but clinical trials are needed (473).

Serious Mental Illness

Recommendations 5.56 Provide an increased level of support for people with diabetes and serious mental illness through enhanced monitoring of and assistance with diabetes self-management behaviors. B 5.57 Monitor changes in body weight, glycemia, and lipids in adolescents and adults with diabetes who are prescribed second-generation antipsychotic medications; adjust the treatment plan accordingly, if needed. C Studies of individuals with serious mental illness, particularly schizophrenia and other thought disorders, show significantly increased rates of type 2 diabetes (474) (see Tables 5.7 and 5.8). People with schizophrenia and other thought disorders who are prescribed antipsychotic medications should be monitored for prediabetes and type 2 diabetes because of the known comorbidity. Changes in body weight, glycemia, and lipids should be monitored every 12-16 weeks, unless clinically indicated to be monitored sooner (475). Disordered thinking and judgment can make it difficult to engage in behaviors that reduce risk factors for type 2 diabetes, such as restrained eating for weight management. Further, people with serious mental illness and diabetes frequently experience moderate psychological distress, suggesting pervasive intrusion of behavioral health issues into daily functioning (476). Serious mental illness is often associated with the inability to evaluate and apply information to make judgments about treatment options. For a person with an established diagnosis of a mental illness affecting judgment, activities of daily living, and the ability to collaborate with care professionals, including a nonmedical caretaker, in treatment decision-making is beneficial. This caretaker can help improve the person's ability to follow the agreed-upon treatment plan through both monitoring and caretaking functions (477).

Coordinated management of prediabetes or diabetes and serious mental illness is recommended to achieve diabetes treatment goals. Attention deficit hyperactivity disorder, which involves deficits in executive functions, has been linked with twice the risk of type 2 diabetes (486). Among youth and young adults with type 1 diabetes, lower executive functioning has been linked with more difficulties with diabetes self-management and higher A1C (487). In contrast, higher self-regulation has been linked with improved emotional and diabetes-specific functioning (488). Thus, monitoring cognitive capacity and skills among individuals with or at risk for diabetes is recommended, particularly regarding their ability to self-monitor and make judgments about their symptoms, physical status, and needed adjustments to their self-management behaviors, all of which are mediated by executive function (484).

As with other disorders affecting mental capacity (e.g., major psychiatric disorders), the key issue is whether the person can collaborate with the care team to achieve optimal metabolic outcomes and prevent complications, both short term and long term (476). When cognitive ability is altered, declining, or absent, a lay care professional should be introduced into the care team to serve in the capacity of a day-to-day monitor as well as a liaison to the care team (1) . Cognitive capacity also contributes to the ability to benefit from DSMES and may indicate the need for alternative teaching approaches as well as remote monitoring. Youth will need second-party monitoring (e.g., parents and adult caregivers) until they are developmentally able to evaluate necessary information for self-management decisions and to inform resultant behavior changes.

Episodes of severe hypoglycemia are independently associated with cognitive decline as well as the more immediate symptoms of mental confusion (489). Early-onset type 1 diabetes is associated with potential long-term deficits in intellectual abilities, especially in the context of repeated episodes of severe hypoglycemia (490), and is correlated with higher A1C and sensor glucose values (491) (See Section 14, "Children and Adolescents," for information on early-onset diabetes and cognitive abilities and the effects of severe hypoglycemia on children's cognitive and academic performance). Thus, for myriad reasons, cognitive capacity should be assessed during routine care to ascertain the person's ability to maintain and adjust self-management behaviors, such as dosing of medications, remediation approaches to glycemic excursions, etc., and to determine whether to enlist a caregiver in monitoring and decision-making regarding management behaviors. If cognitive capacity to conduct self-management behaviors is questioned, an age-appropriate test of cognitive capacity is recommended (1) . Cognitive capacity should be evaluated in the context of the person's age, such as in very young children who are not expected to manage their disease independently and in older adults who may require active monitoring of treatment plan behaviors.

Cognitive decline is more severe in older adults with type 2 diabetes (492). Longitudinal epidemiological studies have documented that chronic hyperglycemia, acute glucose variability, older age, less education, retinopathy, and nephropathy are associated with diabetes-related cognitive dysfunction (493,494). Importantly, the risk of cognitive decline can be reduced through improved A1C (495). Further, glucose-lowering treatments may decrease the risk of cognitive decline. A systematic review and network meta-analysis showed that treatment with SGLT2 inhibitors and GLP-1 RAs had a decreased risk for cognitive impairment, whereas sulfonylureas had the highest increased risk for cognitive impairment (496). Additionally, exercise may be a potential nonpharmacologic treatment pathway for cognitive impairment in older adults with type 2 diabetes (497). The associations between sleep problems and diabetes are complex: sleep disorders are a risk factor for developing type 2 diabetes (498,499) and possibly gestational diabetes mellitus (500). People with diabetes across the life span often experience sleep disruptions and reduced sleep quality (501,502), and sleep problems are also common in parents of youth with diabetes, especially soon after diagnosis (503,504). Disrupted sleep and sleep disorders, including obstructive sleep apnea (OSA) (505), insomnia, and sleep disturbances (506), are common among people with diabetes. In type 1 diabetes, estimates of poor sleep range from 30% to 50% (507), and estimates of moderate to severe OSA are > 50% (505). In type 2 diabetes, 24-86% of people are estimated to have OSA (508), 39% to have insomnia, and 8-45% to have restless leg syndrome (i.e., an uncontrollable urge to move legs) (509). Further, people with type 2 diabetes and restless leg syndrome are more likely to experience microvascular and macrovascular complications (510) as well as depression (511). Additionally, people with diabetes who perform shift work increase their risk for circadian rhythm disorders, which are associated with higher A1C (512), neuropathy (513), and decreased psychological well-being (513). Health care professionals should consider a comprehensive evaluation of the daily lifestyles of people with diabetes to decrease risk factors, including low sleep duration, shift work, and days off, given their associations with hyperglycemia, hypertension, dyslipidemia, and weight gain (514).

The high prevalence of OSA in people with diabetes poses significant clinical implications for diabetes management. Sleep fragmentation and hypoxemia activate the sympathetic nervous system, contributing to hyperglycemia, insulin resistance, increased circulating free fatty acids, impaired microcirculation, oxidative stress, and psychological stress (515). A systematic review and meta-analysis of 11 RCTs with 964 total participants found that continuous positive airway pressure (CPAP) significantly reduced A1C by 0.24% (95% CI À0.43 to À0.06%, P = 0.001) (516). Similarly, a randomized proof-of-concept study with 30 adults with OSA and obesity compared CPAP therapy, GLP-1 RA-mediated weight loss, and both in combination for 24 weeks (517). Findings showed that CPAP alone and in combination reduced apnea-hypopnea severity more than GLP-1 RA-mediated weight loss alone. CPAP therapy also improved vascular inflammation and reduced unstable plaque volume, suggesting potential benefits for early CVD. Two phase 3, double-blind RCTs with 469 adults with OSA and obesity showed that a dual GIP and GLP-1 RA significantly reduced sleep apnea severity and body weight compared with placebo after 52 weeks (518). More RCTs with people with diabetes are needed to determine the effectiveness of GLP-1 RAs and dual GIP and GLP-1 RAs as potential treatments for OSA.

Sleep disturbances are associated with less engagement in diabetes self-management and can interfere with achieving and maintaining glucose levels within the goal range among people with type 1 and type 2 diabetes (502,505). Risk of hypoglycemia poses specific challenges for sleep in people with type 1 diabetes and may require detailed assessment and treatment approaches (519). People with type 1 diabetes and their family members also describe diabetes management needs interfering with sleep and experiencing worries about poor sleep (520). Both helpful and challenging aspects of diabetes technology use have been described in relation to sleep (520), with the greatest perceived benefits being related to automated insulin delivery systems (521-523). For these reasons, detection and treatment of sleep disorders should be considered a part of standardized care for people with type 1 and type 2 diabetes.

As for the general population, there are evidence-based strategies to improve sleep for people with diabetes. CBT shows benefits for sleep in people with diabetes (390), including CBT for insomnia, which demonstrates improvements in sleep outcomes and possible small improvements in A1C (524), fasting glucose (524), and depressive symptoms (525). There is also evidence that sleep extension and pharmacologic treatments for sleep can improve sleep outcomes and possibly insulin resistance (519, 524). Lastly, sleep education, or sleep hygiene, improves sleep quality, reduces A1C, and decreases insulin resistance in adults with type 2 diabetes (526). Thus, diabetes care professionals are encouraged to counsel people with diabetes to use sleep-promoting routines and practices, such as establishing a regular bedtime and rise time, creating a dark, quiet area for sleep with temperature and humidity control, establishing a pre-sleep routine, putting electronic devices (except diabetes management devices) in silent/off mode, exercising during the day, avoiding daytime naps, limiting caffeine and nicotine in the evening, avoiding spicy foods at night, and avoiding alcohol before bedtime (527). For people with diabetes who have significant sleep difficulties, referral to sleep specialists to address the medical and behavioral aspects of sleep is recommended, ideally in collaboration with the diabetes care team (Fig. 5 The A1C test is an indirect measure of average glycemia. Factors that affect hemoglobin or red blood cells may affect A1C. For example, conditions that affect red blood cell turnover (hemolytic anemia and other anemias, glucose-6-phosphate dehydrogenase deficiency, recent blood transfusion, use of drugs that stimulate erythropoiesis, end-stage kidney disease, and pregnancy) can interfere with the accuracy of A1C (5) . Some hemoglobin variants can interfere with some A1C assays; however, most assays in use in the U.S. are accurate in individuals who are heterozygous for the most common variants (6) . A1C cannot be measured in individuals with sickle cell disease (HbSS) or other homozygous hemoglobin variants (e.g., HbEE), since these individuals lack HbA (7) . In individuals with conditions that interfere with the interpretation of A1C, alternative approaches to monitoring glycemic status should be used, including self-monitoring of blood glucose, CGM, and/or the use of glycated serum protein assays (discussed below). A1C does not provide a measure of glycemic variability or hypoglycemia. For individuals prone to glycemic variability, especially people with type 1 diabetes or type 2 diabetes with insulin deficiency and/or treatment with intensive insulin therapy, glycemic status is best evaluated by the combination of results from BGM or CGM and A1C. Discordant results between A1C and BGM or CGM can occur due to high glycemic variability, inaccurate BGM or CGM measurement, or inaccurate A1C due to the factors discussed above.

As discussed in Section 2, "Diagnosis and Classification of Diabetes," there is controversy regarding the clinical significance of differences in A1C by selfreported race and ethnicity (8) (9) (10) (11) . There is an emerging understanding of genetic determinants that may modify the association between A1C and glucose levels (12) . However, race and ethnicity are not good proxies for these genetic differences that are likely present in a small minority of individuals of all racial groups. Therefore, race and ethnicity should not be considerations for how A1C is used clinically for glycemic monitoring. Limitations of laboratory tests and within-person variability in glucose and A1C underscore the importance of using multiple approaches to glycemic monitoring and further evaluation of discordant results in all racial or ethnic groups.

Serum Glycated Protein Assays as Alternatives to A1C

Fructosamine and glycated albumin are alternative measures of glycemia that are approved for clinical use for monitoring glycemic status in people with diabetes. Fructosamine reflects total glycated serum proteins (mostly albumin). Glycated albumin assays reflect the proportion of total albumin that is glycated. Due to the turnover rate of serum protein, fructosamine and glycated albumin reflect glycemia over the past 2-4 weeks, a shorter-term time frame than that of A1C. Fructosamine and glycated albumin are highly correlated in people with diabetes, and the performance of modern assays is typically excellent. Fructosamine and glycated albumin have been linked to long-term complications in epidemiologic cohort studies (13) (14) (15) (16) (17) . However, there have been few clinical trials, and the evidence base supporting the use of these biomarkers to monitor glycemic status is much weaker than that for A1C. In people with diabetes who have conditions where the interpretation of A1C may be problematic or when A1C cannot be measured (e.g., homozygous hemoglobin variants), fructosamine or glycated albumin may be useful alternatives to monitor glycemic status (7) .

Correlation Between A1C and Blood Glucose Monitoring and Continuous Glucose Monitoring Table 6 .1 provides rough equivalents of A1C and mean glucose levels based on data from the international A1C-Derived Average Glucose (ADAG) study. The ADAG study assessed the correlation between A1C and frequent BGM and CGM in 507 adults (83% non-Hispanic White) with type 1, type 2, and no diabetes (18, 19) . The American Diabetes Association (ADA) and the American Association for Clinical Chemistry have determined that the correlation (r = 0.92) in the ADAG trial is strong enough to justify reporting both the A1C result and the estimated average glucose (eAG) result when a clinician orders the A1C test. Clinicians should note that the mean plasma glucose numbers in Table 6 .1 are based on 2,700 readings per A1C measurement in the ADAG trial.

Caveats in interpretation of Table 6 .1 include that these data are from a single study published in 2008. Mean glucose in the ADAG study was calculated from a combination of measurements from an early CGM system and capillary glucose, intermittently, during a 3-month period. This older system required calibration several times a day using a self-monitoring The international consensus on CGM provides guidance on CGM metrics (Table 6 .2) and their clinical interpretation (31) . To make these metrics actionable, standardized reports with visual summaries, such as the ambulatory glucose profile (Fig. 6 .1), are recommended (31) and can help individuals with diabetes and health care professionals interpret the data to guide treatment decisions (26, 29) . BGM and CGM can be useful to guide medical nutrition therapy and physical activity, detect and prevent hypoglycemia, and aid medication management. CGM metrics, including TIR (with time below range and time above range), can provide helpful insights to inform a personalized diabetes management plan. Remote access to glucose data is growing and may help improve diabetes management (32) (33) (34) .

CGM systems have evolved rapidly in both accuracy and affordability. As such, many individuals with diabetes have these data available to assist with self-management and their health care professionals' assessment of glycemic status. Reports generated from CGM will allow the health care professional and person with diabetes to view TIR and a calculated glucose management indicator and assess hypoglycemia, hyperglycemia, and glycemic variability. As discussed in a 2019 consensus report, a report formatted as shown in Fig. 6 .1 can be generated (31) . Published data from two retrospective studies suggest a strong correlation between TIR and A1C, with a goal of 70% TIR aligning with an A1C of 7% (53 mmol/mol) (24, 27) . Note that the goals of therapy next to each metric in Fig. 6 .1 (e.g., low, < 4%; very low, < 1%) serve as values to guide changes in therapy. For older adults using CGM, the recommended percent time spent in target range of 70-180 mg/dL is 50% (or 12 h per day) and the recommended time spent in hypoglycemia of less than 70 mg/dL should not be more than 1%, or 15 min per day, to minimize hypoglycemia risk (35) (36) (37) (38) . In this population, more permissive hyperglycemia is allowed (up to 50% of the time in 24 h).

GLYCEMIC GOALS Recommendations 6.3a An A1C goal of < 7% ( < 53 mmol/ mol) is appropriate for many nonpregnant adults without severe hypoglycemia or frequent hypoglycemia affecting health or quality of life. A 6.3b A goal time in range of > 70% in people using CGM is appropriate for many nonpregnant adults. B 6.3c A goal percent time < 70 mg/dL ( < 3.9 mmol/L) of < 4% (or < 1% for older adults) and a goal percent time < 54 mg/dL ( < 3.0 mmol/L) of < 1% are recommended in people using CGM to prevent hypoglycemia. Deintensify or modify therapy if these goals are not met. B 6.4 Based on health care professional judgment and the preference of the person with diabetes, achievement of lower A1C levels than the goal of 7% (53 mmol/mol) may be acceptable and even beneficial if it can be achieved safely without frequent or severe hypoglycemia or other adverse effects of treatment. B 6.5 Less stringent glycemic goals may be appropriate for individuals with limited life expectancy or where the harms of treatment are greater than the benefits. B 6.6 Deintensify hypoglycemia-causing medications (insulin, sulfonylureas, or meglitinides), or switch to a medication class with lower hypoglycemia risk, for individuals who are at high risk for hypoglycemia, within individualized glycemic goals. B 6.7 Deintensify diabetes medications for individuals for whom the harms and/or burdens of treatment may be greater than the benefits, within individualized glycemic goals. B 6.8 Reassess glycemic goals based on the individualized criteria shown in Fig. 6 .2. E 6.9 Set a glycemic goal during consultations to improve outcomes. A For all populations, it is critical that the glycemic goals be woven into an individualized, person-centered strategy (39) . The glycemic goals for many nonpregnant adults are shown in Health care professionals should engage in shared decision-making with the individual (as well as with family members and caregivers) and should consider adjusting goals for simplifying the treatment plan if this change is needed to improve safety and medication-taking behavior. Setting specific glycemic (and other) goals during consultations has been demonstrated to improve glycemic outcomes for individuals with diabetes (40) .

Glucose Lowering and Microvascular Complications

Hyperglycemia defines diabetes, and achieving glycemic goals is fundamental to diabetes management. The level of chronic hyperglycemia is the best-established concomitant risk factor associated with microvascular complications (i.e., diabetic retinopathy, nephropathy, and neuropathy). This is best understood by the fact that nerve, retinal, and kidney cells do not require insulin for intracellular glucose entry. Consequently, the exposure of these cells to elevated ambient glucose levels even in the presence of insulin deficiency (absolute or relative) will result in intracellular metabolic dysfunction and increased risk of microvascular complications.

The Diabetes Control and Complications Trial (DCCT) (41) , a prospective randomized controlled trial of intensive (mean A1C 7% [53 mmol/mol]) versus standard (mean A1C 9% [75 mmol/mol] ) glycemic management in people with type 1 diabetes, showed definitively that better glycemic status is associated with 50-76% reductions in rates of development and progression of microvascular complications (retinopathy, neuropathy, and diabetic kidney disease). Follow-up of the DCCT cohorts in the Epidemiology of Diabetes Interventions and Complications (EDIC) study (42, 43) demonstrated persistence of these microvascular benefits over two decades despite the fact that the glycemic separation between the treatment groups diminished and disappeared during follow-up.

The Kumamoto study (44) and UK Prospective Diabetes Study (UKPDS) (45, 46) examined the effects of "intensive glycemic control" among people with shortduration type 2 diabetes, although glycemic lowering in these studies was not intensive by current standards (mean A1C was 7.1% vs. 9.4% in Kumamoto and 7.0% vs. 7.9% in UKPDS). These trials found lower rates of microvascular complications in the intervention arms, with long-term follow-up of the UKPDS cohorts showing enduring effects on most microvascular complications (47) . These studies highlight the long-term benefits of early glycemic lowering in type 2 diabetes.

Therefore, improved glycemia has been shown to reduce microvascular complications of type 1 and type 2 diabetes when instituted early in the course of disease (2, 48) . The DCCT (41) and UKPDS (49) studies demonstrated a curvilinear relationship between attained A1C level and microvascular complications. Such results suggest that, on a population level, the greatest number of complications will be averted by taking individuals with diabetes from very high to moderate A1C levels. These analyses also suggest that further lowering of A1C from 7% to 6% (53 mmol/mol to 42 mmol/mol) is associated with further reduction in the risk of microvascular complications, although the absolute risk reductions become much smaller. The implication of these findings is that there is no need to deintensify therapy for an individual with an A1C between 6% and 7% in the setting of low hypoglycemia risk with a long life expectancy. There are newer pharmacologic agents that do not cause hypoglycemia, making it possible to maintain glycemic status without the risk of hypoglycemia (see Section 9, "Pharmacologic Approaches to Glycemic Treatment"). Moreover, CGM use was not as common when these trials were conducted and automated insulin delivery systems were not available; these have been shown to improve glucose levels without increasing hypoglycemia.

Among individuals with type 2 diabetes, three landmark trials (Action to Control

175 mg/dL

Goal: < 154 mg/dL

Glucose Management Indicator (GMI

7.5%

Goal: < 7%

Glucose Variability

45.5%

Defined as percent coefficient of variation Goal: 36% Goal < 5%

Very High 20%

Goal Goal Range

Low 5%

Very Low 5%

Goal: < 1% intervention arm (50) (51) (52) (53) (54) . Importantly, these landmark studies were conducted prior to the approval of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors, and intensive glycemic management was achieved predominantly through greater use of insulin. Findings from these studies, including the concerning increase in mortality in the intensive treatment arm of ACCORD, suggest caution is needed in treating diabetes to near-normal A1C goals in people with long-standing type 2 diabetes using medications with a high risk for hypoglycemia.

Glucose Lowering and Cardiovascular Disease Outcomes

Cardiovascular disease (CVD) is a more common cause of death than microvascular complications in populations with diabetes.

The modern multifaceted management of diabetes, with a focus on the treatment of hypertension and the use of statins, has reduced the prevalence of atherosclerotic CVD to around double compared with that of people without diabetes (55) .

The DCCT in individuals with type 1 diabetes and the UKPDS, ACCORD, ADVANCE, and VADT studies in type 2 diabetes all attempted to address whether intensive glycemic management reduced CVD events (41, 50, 51, 53) . ACCORD, ADVANCE, and VADT were conducted in relatively older participants with a longer duration of diabetes (mean duration 8-11 years) and either CVD or multiple cardiovascular risk factors. Details of these studies are reviewed extensively in the joint ADA position statement "Intensive Glycemic Control and the Prevention of Cardiovascular Events: Implications of the ACCORD, ADVANCE, and VA Diabetes Trials" (56) .

No significant reduction in composite CVD events was demonstrated at the end of the intervention in any of these studies, and ACCORD was stopped prematurely at 3.5 years because of an increase in total mortality, particularly sudden CVD deaths. Serious concerns with the intensive glycemic treatment plan used in or Figure 6 .2-Individualized A1C goals for nonpregnant adults. Select the glycemic goal based on individual health and function as described at the top of the figure. Consider modifying to a more or less stringent goal according to the factors listed in the table. Older adults are classified as healthy (few coexisting chronic illnesses, intact cognitive and functional status), as having complex/intermediate health (multiple coexisting chronic illnesses, two or more instrumental impairments to activities of daily living, or mild to moderate cognitive impairment), or as having very complex/ poor health (long-term care or end-stage chronic illnesses, moderate to severe cognitive impairment, or two or more impairments to activities of daily living). Select glycemic goals that avoid symptomatic hypoglycemia and hyperglycemia in all individuals.

Malnutrition

Malnutrition is defined by the World Health Organization as "deficiencies, excesses, or imbalances in a person's intake of energy and/or nutrients." Malnutrition can occur in people of varying weight status, with the "double burden" of obesity and malnutrition being increasingly recognized among those with chronic conditions. Malnutrition is also more likely to develop in populations experiencing poverty and in older age-groups (241) . Often, malnutrition and sarcopenia, which is a condition of loss in lean body mass combined with declined strength and functionality among older adults, codevelop (242) . A 2022 meta-analysis examined 45 studies including 12,237 adults and reported that 18% of people with type 2 diabetes had sarcopenia with A1C increasing the risk (odds ratio 1.16; 95% CI, 1.09-1.24) (243) .

There is concern that GLP-1 RAs and dual GIP and GLP-1 RAs and metabolic surgery for weight loss, which are more common in some populations with diabetes, can increase the risk for malnutrition and sarcopenia (244, 245) . This is especially concerning among those with heart, kidney, or liver disease and obesity and among racial and ethnic minoritized communities (246, 247) . Health care professionals should encourage resistance training (248) , sufficient protein intake, and screening for sarcopenia and malnutrition in people with diabetes who are experiencing significant or rapid weight loss because they could be at risk for malnutrition. While there is no single best method to screen for both malnutrition and sarcopenia, there are individual instruments available to screen for each respective condition including the Simplified Nutritional Appetite Questionnaire (SNAQ), the Malnutrition Universal Screening Tool (MUST), and others (249) (250) (251) .

Advising a healthy, whole-foods-based eating pattern alongside regular strength training exercise to maintain lean body mass will be of paramount importance for these segments of the diabetes population (244) (see Section 8, "Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes").

Food Insecurity and Access

Food insecurity is a household-level economic and social condition of limited or uncertain access to adequate food (252) . In 2022, almost 13% of Americans were food insecure (252) , and food insecurity affects 16% of adults with diabetes compared with 9% of adults without diabetes (253) . There is a complex bidirectional association between food insecurity and co-occurring diabetes. Food security screening should happen at all levels of the health care system. Any member of the health care team can screen for food insecurity using the Hunger Vital Sign. Households are considered at risk if they answer either or both of the following statements as "often true" or "sometimes true" (compared with "never true") (254):

• "Within the past 12 months, we worried whether our food would run out before we got money to buy more." • "Within the past 12 months, the food we bought just didn't last, and we didn't have money to get more."

If screening is positive for food insecurity, efforts should be made to refer to appropriate programs and resources. See 256 ). An RCT in 1,366 individuals with prediabetes combined a physical activity intervention with text messaging and telephone support, which showed improvement in daily step count at 12 months compared with the control group, but this was not sustained at 48 months (257) . Another RCT, including 324 individuals with prediabetes, showed increased physical activity at 8 weeks with supportive text messages, but by 12 weeks there was no difference between groups (258) . It is important for diabetes care management teams to understand the difficulty that many people have reaching recommended physical activity goals and to identify individualized approaches to improve physical activity and exercise goal achievement, which may need to change over time.

Moderate to high volumes of aerobic activity are associated with substantially lower cardiovascular and overall mortality risks in both type 1 and type 2 diabetes (259) . A prospective observational study of adults with type 1 diabetes suggested that higher amounts of physical activity led to reduced cardiovascular mortality after a mean follow-up time of 11.4 years for people with and without chronic kidney disease (260) . There are also considerable data for the health benefits (e.g., increased cardiovascular fitness, greater muscle strength, and improved insulin sensitivity) of regular exercise for those with type 1 diabetes (261) . Exercise training in type 1 diabetes may also improve several important markers such as triglyceride level, LDL cholesterol, waist circumference, and body mass (262) .

Structured exercise interventions of at least 8 weeks have been shown to lower A1C by 0.66% in people with type 2 diabetes, even without a significant change in BMI (263) . In adults with type 2 diabetes, higher levels of exercise intensity are associated with greater improvements in A1C and in cardiorespiratory fitness (264) ; sustained improvements in cardiorespiratory fitness and weight loss have also been associated with a lower risk of heart failure (265) . Other benefits include slowing the decline in mobility among people with diabetes and overweight (266) .

Physical activity and exercise should be recommended and prescribed to all individuals who are at risk for or have diabetes as part of management of glycemia and overall health, unless otherwise contraindicated. Specific recommendations and precautions will vary by the type of diabetes, age, physical activity, and presence of diabetes-related health complications. Recommendations should be tailored to meet the specific needs of each individual (267) , and different strategies may be used in specific populations to increase engagement in physical activity (268) . Furthermore, physical activity and exercise plans can be modified or adapted to best suit the fitness level of the individual, which may vary due to disability or other complications. Individuals with diabetes may benefit from a team-based approach, including working with an exercise physiologist, physical therapist, or personal trainer, among others, where available and affordable (269) . The ADA position statement "Physical Activity/Exercise and Diabetes" reviews the evidence for the benefits of exercise in people with type 1 and type 2 diabetes and offers specific recommendations (267) .

Exercise and Youth

Youth with diabetes or prediabetes should be encouraged to engage in regular physical activity, including at least 60 min of moderate-to-vigorous aerobic activity every day and muscle-and bone-strengthening activities at least 3 days per week (270) . Structured exercise programs promoting nutrition modification and increasing exercise in adolescents at risk for type 2 diabetes have been shown to reduce risk of type 2 diabetes development (271) . In general, youth with type 1 diabetes benefit from being physically active, and meta-analyses have demonstrated a significant association between physical activity and lower A1C (272) . Thus, an active lifestyle should be recommended to all children and adolescents with type 1 and type 2 diabetes (273) . Youth with type 1 diabetes who engage in more physical activity may have better health outcomes and health-related quality of life (274, 275) . Youth are recommended to limit the amount spent as sedentary time, including recreational screen time, to less than 2 h per day (276, 277) . See Section 14, "Children and Adolescents," for details.

Frequency and Type of Physical Activity

For all people with diabetes, baseline physical activity and time spent in sedentary behavior should be evaluated. People who do not meet activity guidelines should be encouraged to increase physical activity (e.g., walking, yoga, housework, gardening, swimming, and dancing) above baseline (278) . Health care professionals should counsel people with diabetes to engage in aerobic and resistance exercise regularly (267) . Aerobic activity bouts should last at least 10 min, with the goal of $30 min/day or more most days of the week for adults with type 2 diabetes. Daily exercise, or at least not allowing more than 2 days to elapse between exercise sessions, is recommended to decrease insulin resistance, regardless of diabetes type (279, 280) . A study in adults with type 1 diabetes found a dose-response inverse relationship between self-reported bouts of physical activity per week and A1C, BMI, hypertension, dyslipidemia, and diabetes-related complications such as hypoglycemia, DKA, retinopathy, and microalbuminuria (281), and higher physical activity reduces mortality risk in people with type 1 diabetes (260) . Over time, activities should progress in intensity, frequency, and/or duration to at least 150 min/week of moderateintensity exercise. Adults able to run at 6 mph (9.7 km/h) for at least 25 min can benefit sufficiently from shorter durations of vigorous-intensity activity or interval training (75 min/week) (267) . Many adults, including most with type 2 diabetes, may be unable or unwilling to participate in such intense exercise and should engage in moderate exercise for the recommended duration.

Adults with diabetes are encouraged to engage in 2-3 sessions/week of resistance exercise on nonconsecutive days (282) . Although heavier resistance training with free weights or weight machines may improve glycemia and strength (283, 284) , resistance training of any intensity is recommended to improve strength, balance, and the ability to engage in activities of daily living throughout the life span. Health care professionals should support people with diabetes to set stepwise goals toward meeting the recommended exercise goals. As individuals intensify their exercise program, medical monitoring may be indicated to ensure safety and evaluate the effects on glucose management. (See PHYSICAL ACTIVITY AND GLYCEMIC MANAGEMENT, below.)

The use of weight management pharmacotherapy has recently increased. Both weight management pharmacotherapy and metabolic surgery can lead to a decrease in body weight, which often induces fat mass loss as well as loss of lean body mass. This has raised concern about the loss of muscle mass leading over time to the development or worsening of frailty and sarcopenic obesity (285) . One study demonstrated that after discontinuation of weight management pharmacotherapy with GLP-1 RAs in people with obesity but without diabetes, the combination of supervised exercise and GLP-1 RA therapy was more favorable in maintaining body weight and body composition compared with GLP-1 RA therapy alone. Data in people with diabetes and overweight or obesity are emerging. It is recommended that people with diabetes be encouraged to follow the physical activity recommendations, in particular muscle-strengthening activities, to reduce the loss of lean mass (285) .

Evidence supports that all individuals, including those with diabetes, should be encouraged to reduce the amount of time spent being sedentary-waking behaviors with low energy expenditure (e.g., seated work at a computer and watching television)-by breaking up bouts of sedentary activity (at least every 30 min) by briefly standing, walking, or performing other light physical activities (286) (287) (288) . Participating in leisure-time activity and avoiding extended sedentary periods may help prevent type 2 diabetes for those at risk and may also aid in glycemic management for those with diabetes (289, 290) .

A systematic review and meta-analysis found that higher frequency of regular leisure-time physical activity was more effective in reducing A1C (291) . A wide range of activities, including yoga, tai chi, and other types, can significantly affect A1C, flexibility, muscle strength, and balance (255, (292) (293) (294) . Flexibility and balance exercises may be particularly important in older adults with diabetes for maintenance of range of motion, strength, and balance (267) (Fig. 5

.2).

There is strong evidence that exercise interventions in individuals with type 2 diabetes improve depression, A1C, and overall psychosocial well-being (295) .

Physical Activity and Glycemic Management

Clinical trials have provided strong evidence for the A1C-lowering value of resistance training in older adults with type 2 diabetes (267) and for an additive benefit of combined aerobic and resistance exercise on A1C reduction in adults with type 2 diabetes (296) . If not contraindicated, people with type 2 diabetes should be encouraged to do at least two weekly sessions of resistance exercise (free weights, machines, elastic bands, or body weight as resistance), with each session consisting of at least one set (group of consecutive repetitive exercise motions) of five or more different resistance exercises involving the large muscle groups (297) .

For people with type 1 diabetes, there can be a variable glucose response to exercise, possibly leading to hypoglycemia or hyperglycemia. This variability should be taken into consideration when recommending the type, intensity, and duration of exercise for a given individual (261) .

Individuals of childbearing potential with preexisting diabetes, particularly type 2 diabetes, and those at risk for or presenting with gestational diabetes mellitus should be advised to engage in regular moderate-intensity physical activity prior to and during their pregnancies, as tolerated (267) .

High-Intensity Interval Training

High-intensity interval training (HIIT) involves short bursts of aerobic training performed between 65% and 90% VO 2peak (a measure of maximal aerobic capacity) or 75% and 95% heart rate peak for 10 s to 4 min with 12 s to 5 min of active or passive recovery. HIIT is a potentially timeefficient modality that can elicit significant physiologic and metabolic adaptations for individuals with type 1 and type 2 diabetes (298, 299) . Higher intensities of aerobic training are generally considered superior to low-intensity training (300) . HIIT reduces A1C and BMI and improves fitness levels in individuals with type 2 diabetes. Because HIIT can lead to transient increases in post-exercise hyperglycemia, individuals with type 1 diabetes may need to use bolus correction (301) and individuals with type 2 diabetes are encouraged to monitor blood glucose when starting HIIT (297) . In type 1 diabetes, HIIT reduces A1C and insulin requirements and improves cardiometabolic risk profiles (299) . Variability in glucose may occur with an increased risk in delayed hypoglycemia, so careful monitoring of glucose during and after HIIT is advised (299) .

Pre-exercise Evaluation

As discussed more fully in Section 10, "Cardiovascular Disease and Risk Management," the best protocol for assessing asymptomatic people with diabetes for coronary artery disease remains unclear. The ADA consensus report "Screening for Coronary Artery Disease in Patients With Diabetes" (302) concluded that routine testing is not recommended. However, health care professionals should perform a careful history, assess cardiovascular risk factors, and be aware of the atypical presentation of coronary artery disease, such as a recently reported or measured decrease in exercise tolerance. Certainly, those with high risk should be encouraged to start with short periods of low-intensity exercise and slowly increase the duration and intensity as tolerated. Health care professionals should assess for conditions that might contraindicate certain types of exercise or predispose to injury, such as uncontrolled hypertension, untreated proliferative retinopathy, autonomic neuropathy, orthostatic hypotension, peripheral neuropathy, balance impairment, and a history of foot ulcers or Charcot foot. Age and previous physical activity level should be considered when customizing the exercise plan to the individual's needs. Those with complications may need a more thorough evaluation prior to starting an exercise program (261) .

Hypoglycemia

For individuals taking insulin and/or insulin secretagogues, physical activity may cause hypoglycemia if the medication dose or carbohydrate consumption is not adjusted for the exercise session and postbout effect on glucose. Individuals on these therapies may need to ingest

24 HOURS

SWEATING MODERATETOVIGOROUS ACTIVITY

• Encourage ≥150 min/week of moderate-intensity physical activity (i.e., uses large muscle groups, rhythmic in nature) OR 75 min/week vigorous-intensity activity spread over ≥3 days/week, with no more than 2 consecutive days of inactivity. Supplement with two to three resistance, flexibility, and/or balance sessions.

• As little as 30 min/week of moderate-intensity physical activity improves metabolic profiles.

Physical function/ frailty/sarcopenia

• The frailty phenotype in type 2 diabetes is unique, often encompassing obesity alongside physical frailty, at an earlier age. The ability of people with type 2 diabetes to undertake simple functional exercises in middle-age is similar to that in those over a decade older.

SLEEP

Aim for consistent, uninterrupted sleep, even on weekends.

Quantity -Long 8 h) and short 6 h) sleep durations negatively impact A1C.

Quality -Irregular sleep results in poorer glycemic levels, likely influenced by the increased prevalence of insomnia, obstructive sleep apnea, and restless leg syndrome in people with type 2 diabetes.

Chronotype -Evening chronotypes (i.e., night owl: go to bed late and get up late) may be more susceptible to inactivity and poorer glycemic levels than morning chronotypes (i.e., early bird: go to bed early and get up early).

SLEEP QUALITY CHRONOTYPE

STRENGTHENING

Resistance exercise (i.e., any activity that uses the person's own body weight or works against a resistance) also improves insulin sensitivity and glucose levels; activities like tai chi and yoga also encompass elements of flexibility and balance.

SITTING/BREAKING UP PROLONGED SITTING

• Limit sitting. Breaking up prolonged sitting (at least every 30 min) with short regular bouts of slow walking or simple resistance exercises can improve glucose metabolism. carbohydrates if pre-exercise glucose levels are < 90 mg/dL ( < 5.0 mmol/L), depending on whether they are able to lower insulin doses during the workout (such as with an insulin pump or reduced pre-exercise insulin dosage), the time of day exercise is done, and the intensity and duration of the activity (261) . In some people with diabetes, hypoglycemia after exercise may occur and last for several hours due to increased insulin sensitivity. Hypoglycemia is not common in those who are not treated with insulin or insulin secretagogues, and no routine preventive measures for hypoglycemia are usually advised in these cases. Intense activities, such as HIIT, may actually raise glucose levels instead of lowering them, especially if preexercise glucose is elevated (261) . Because of variation in glycemic response to exercise, people with diabetes should be taught to check blood glucose levels and/or monitor CGM values during and after exercise, how to understand the effect of exercise on glucose, and about the potential prolonged effects (depending on intensity and duration) (303) . See Section 6, "Glycemic Goals and Hypoglycemia," for more information on hypoglycemia prevention and management.

Glucose/ insulin

SITTING/BREAKING UP PROLONGED SITTING        STEPPING        SWEATING MODERATETOVIGOROUS ACTIVITY        STRENGTHENING        ADEQUATE SLEEP DURATION        GOOD SLEEP QUALITY        CHRONOTYPE/CONSISTENT TIMING        Importance of

Exercise in the Presence of Microvascular Complications

See Section 11, "Chronic Kidney Disease and Risk Management," and Section 12, "Retinopathy, Neuropathy, and Foot Care," for more information on these long-term complications. A meta-analysis demonstrated that high versus low levels of physical activity were associated with lower CVD incidence and mortality (summary risk ratio 0.84 [95% CI 0.77-0.92], n = 7, and 0.62 [0.55-0.69], n = 11) and fewer microvascular complications (0.76 [0.67-0.86], n = 8). Dose-response metaanalyses showed that physical activity was associated with lower risk of diabetes-related complications even at lower activity levels (304) .

Retinopathy

If proliferative diabetic retinopathy or severe nonproliferative diabetic retinopathy is present, then vigorous-intensity aerobic or resistance exercise may be contraindicated because of the risk of triggering vitreous hemorrhage or retinal detachment (305) . Consultation with an ophthalmologist prior to engaging in an intense exercise plan may be appropriate.

Peripheral Neuropathy

Decreased pain sensation and a higher pain threshold in the extremities can result in an increased risk of skin breakdown, infection, and Charcot joint destruction with some forms of exercise. Therefore, a thorough assessment should be done to ensure that neuropathy does not alter kinesthetic or proprioceptive sensation during physical activity, particularly in those with more severe neuropathy. Moderate-intensity walking may not lead to an increased risk of foot ulcers or reulceration in those with peripheral neuropathy who use proper footwear (306, 307) . In addition, 150 min/week of moderate exercise improved outcomes in people with prediabetic neuropathy (308) .

All individuals with peripheral neuropathy should wear proper footwear and examine their feet daily to detect lesions early. Anyone with a foot injury or open sore should be restricted to non-weight-bearing activities.

Autonomic Neuropathy

Autonomic neuropathy can increase the risk of exercise-induced injury or adverse events through decreased cardiac responsiveness to exercise, postural hypotension, impaired thermoregulation, impaired night vision due to impaired papillary reaction, and greater susceptibility to hypoglycemia (309) . Cardiovascular autonomic neuropathy is also an independent risk factor for cardiovascular death and silent myocardial ischemia (310) . Therefore, individuals with diabetic autonomic neuropathy should undergo cardiac investigation before beginning physical activity more intense than that to which they are accustomed.

Chronic Kidney Disease

Physical activity can acutely increase urinary albumin excretion. However, there is no evidence that vigorous-intensity exercise accelerates the rate of progression of CKD, and there appears to be no need for specific exercise restrictions for people with CKD in general (305) . A causal link between cigarette smoking and diabetes has been established and reported on by the Surgeon General for over a decade (311) . Results from epidemiologic, case-control, and cohort studies provide convincing evidence to support the causal link between cigarette smoking and multiple health risks that can have a profound effect on morbidity and mortality for people with diabetes (311) .

People with diabetes who smoke and are exposed to second-hand smoke have a heightened risk of macrovascular complications (e.g., cardiovascular and peripheral vascular disease), microvascular complications (e.g., kidney disease and visual impairment), worsened glycemic outcomes, and premature death compared with those who do not smoke (312) (313) (314) (315) .

Emerging data suggest that smoking has a role in the development of type 2 diabetes, and quitting has been shown to significantly decrease this risk over time (316) . Routine (every visit with every person), thorough assessment of all types of tobacco use is essential to prevent tobacco product initiation and promote cessation. Evidence demonstrates significant benefits to quitting smoking for all people, resulting in a reduction and even reversal of adverse health effects in addition to an increase in life expectancy by as much as a decade (317) . However, data show that tobacco use prevalence among adults with chronic conditions has remained persistently higher than that in the general population, though with recent declines in smoking in middle-aged and older adults with diabetes (318) . Numerous large RCTs have demonstrated the efficacy and cost-effectiveness of both intensive and brief counseling on smoking cessation, including the use of telephone quit lines and web-based interventions, in reducing tobacco use and maintaining abstinence from smoking (317, 319) . Current recommendations include both counseling and pharmacologic therapy to assist with smoking cessation in nonpregnant adults (320) . A secondary data analysis of the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES), a randomized, double-blind, triple-dummy, placebo-controlled and active-controlled trial, found varenicline to be the most efficacious pharmacotherapy for people with diabetes when compared with placebo (321) . These findings support the American Thoracic Society 2020 guideline recommending varenicline as a firstline pharmacotherapy for tobacco dependence (322) . However, despite the effectiveness of pharmacologic therapy and counseling, more than two-thirds of people trying to quit do not receive treatment following evidence-based guidelines (317) .

Weight gain after smoking cessation has been a concern related to diabetes management and risk for new onset of disease (323) . While post-cessation weight gain is an identified issue, studies have found that an average weight gain of 3-5 kg does not necessarily persist long term nor diminish the substantial cardiovascular benefit realized from smoking cessation (316) . These findings highlight the need for tobacco cessation treatment that addresses eating and physical activity needs. One study in people with newly diagnosed type 2 diabetes who smoke found that smoking cessation was associated with amelioration of microalbuminuria and reduction in blood pressure after 1 year (324) .

In recent years, there has been an increase in the use and availability of multiple noncigarette nicotine products. The evidence regarding the effect of these products on diabetes is not as clear as that for combustible cigarettes. It is known that smokeless tobacco products, such as dip and chew, pose an increased risk for CVD and oral cancer (325,326). Vaping with e-cigarettes and related devices has gained public awareness and popularity because of perceptions that e-cigarette use is less harmful than regular cigarette smoking (327). While combustible tobacco products are clearly the most harmful, electronic products should not be characterized as harmless, as health risks with use that affect the cardiovascular and respiratory systems have been identified (328,329). Findings from the Population Assessment of Tobacco and Health (PATH) Study suggest e-cigarettes may contribute to nicotine dependence, confirming there is no safe tobacco product (330,331). Individuals with diabetes should be advised to avoid vaping and using e-cigarettes, either as an approach to stop smoking combustible cigarettes or as a recreational drug. If people are using e-cigarettes to quit, they should be advised to avoid using both combustible and electronic cigarettes, and if using only e-cigarettes, they should be advised to have a plan to quit these also (319) .

Increased legalization and multiple formulations of cannabis products have resulted in increased prevalence in the use of these products in all age-groups (332,333). Cannabidiol (CBD), which in its pure form has no psychoactive effect, has received attention for its potential therapeutic benefits in diabetes management. However, research shows no noticeable effect on glucose or insulin levels in adults with type 2 diabetes who use CBD (334). Significant increases in tetrahydrocannabinol (THC) concentrations in CBD products and use of additional psychoactive cannabinoid products, such as delta-8 THC, are of specific concern (335). Most of these products are currently unregulated by the FDA, and public health warnings regarding use have been issued (336). The FDA reports adverse effects related to delta-8 THC, some of which may have health implications for people with diabetes (e.g., vomiting) (336). Evidence of specific increased risk of diabetic ketoacidosis associated with cannabis use has been reported in adults with type 1 diabetes (337-339). Diabetic ketoacidosis in individuals with type 1 diabetes using cannabis is associated with cannabis hyperemesis syndrome, which is marked by severe nausea, abdominal pain, and vomiting (337-339). Recommended diagnostic criteria for cannabis hyperemesis syndrome include a blood glucose of $250 mg/dL, an anion gap of > 10, a serum b-hydroxybutyrate level of > 0.6 mmol/L, a pH level of $7.4, and a bicarbonate level of $15 mmol/L (339). Health care professionals should consider cannabis hyperemesis syndrome in people with type 1 diabetes with pH $7.4 and bicarbonate > 15 mmol/L in the presence of ketosis (339).

Diabetes education programs offer potential to systematically reach and engage individuals with diabetes in smoking cessation efforts. A cluster randomized trial found statistically significant increases in quit rates and long-term abstinence rates ( > 6 months) when smoking cessation interventions were offered through diabetes education clinics, regardless of motivation to quit at baseline (340). The increased prevalence in availability and use of tobacco and cannabis products and the effect on the health of people with diabetes highlights the need to ask about use of these products, educate individuals regarding the associated risks, and provide support for cessation.

SUPPORTING POSITIVE HEALTH BEHAVIORS

Recommendation 5.43 Behavioral strategies should be used to support diabetes self-management and engagement in health behaviors (e.g., taking medications, using diabetes technologies, and engaging in physical activity and healthy eating) to promote optimal health-related quality of life and health outcomes. A Given associations with glycemic outcomes and risk for future complications (341,342), diabetes care professionals should support people with diabetes engaging in healthpromoting behaviors (preventive, treatment, and maintenance), including blood glucose monitoring, taking insulin and medications, using diabetes technologies, engaging in physical activity, and making nutritional changes. Evidence-based behavioral strategies and multicomponent interventions, including motivational interviewing (343,344), activation (40) , goal setting and action planning (344-346), problem-solving (7,345), tracking or self-monitoring health behaviors with or without feedback from a health care professional (344-346), and facilitating opportunities for social support (344-346), help people with diabetes and their caregivers or family members develop health behavior routines and overcome barriers to self-management. Behavioral economics strategies (e.g., financial incentives and exposure to information about social norms) show mixed results in the promotion of health behaviors; however, they tend to enhance motivation and demonstrate short-term benefits for behavior change (347). Multicomponent Diabetes" for a list of assessment tools and additional details (1) and the ADA Behavioral Health Toolkit for assessment questionnaires and surveys (professional. diabetes.org/meetings/behavioral-healthtoolkit). Throughout the Standards of Care, the broad term "behavioral health" is used to encompass both 1) health behavior engagement and relevant factors and 2) behavioral health concerns and care related to living with diabetes.

Psychosocial factors, including environmental, social, family, behavioral, and emotional factors, influence living with diabetes and achieving optimal health outcomes. People with diabetes and their families or caregivers face complex, multifaceted challenges integrating diabetes care into daily life (356). Clinically significant behavioral health diagnoses are considerably more prevalent in people with diabetes than in those without (357,358). Psychosocial wellbeing is a critical component of diabetes care and self-management. Psychological and social problems can interfere with a person's (359-361) or family's (361) ability to perform diabetes care tasks and negatively affect health status. In addition to affecting a person's ability to conduct selfmanagement, behavioral health diagnoses are associated with reduced short-term glycemic stability and increased mortality risk (358,362). Therefore, psychological symptoms, both clinical and subclinical, must be addressed.

Diabetes health care professionals should routinely monitor and screen for psychosocial concerns in a timely and efficient manner and refer to appropriate services (363,364). Various health care professionals can contribute to psychosocial care based on training, experience, need, and availability (353,365,366). Ideally, qualified behavioral health professionals with specialized training and experience in diabetes should be integrated with or provide collaborative care as part of diabetes care teams (367,368). Referrals for in-depth assessment and treatment for psychosocial concerns should be made to such behavioral health professionals when indicated (369, 370). A systematic review and meta-analysis showed that psychosocial interventions modestly but significantly improved A1C and behavioral health outcomes (371). It should be noted that the association between the effects on A1C and behavioral health was limited, and no intervention characteristics predicted benefit on both outcomes. Cost analyses also have shown that behavioral health interventions are both effective and cost-effective approaches for the prevention of diabetes (372).

Screening

Health care teams and clinical practices should develop and implement psychosocial screening protocols to ensure routine monitoring of psychosocial well-being and to identify potential concerns among people with diabetes, following published guidance and recommendations (373-376). Topics to screen for may include, but are not limited to, attitudes about diabetes, expectations for treatment and outcomes (especially related to starting a new treatment or technology), general and diabetesrelated mood, stress, and/or quality of life (e.g., diabetes distress, depressive symptoms, anxiety symptoms, and fear of hypoglycemia), available resources (financial, social, family, and emotional), and/or psychiatric history. Given elevated rates of suicidality among people with diabetes (377,378), screening for suicidality may also be appropriate (379-381), similar to U.S. Preventive Services Task Force statements regarding screening for some adolescents and adults in the general population (382, 383) . A list of age-appropriate screening and evaluation measures is provided in the ADA position statement "Psychosocial Care for People with Diabetes" (1), and guidance has been published about selection of screening tools, clinical thresholds, and frequency of screening (374, 384) .

Some authors also suggest approaches to changing therapy plans based on the data reviewed that enable health care professionals to make a simple yet comprehensive review and plan of care even within the time constraints of office visits (96-100).

Real-time Continuous Glucose Monitoring Device Use in Pregnancy

CGM indication is now expanded to include pregnancy for Dexcom G7, FreeStyle Libre 2, and FreeStyle Libre 3, which will enhance care in this population (101, 102) . Prior data from one well-designed RCT showed a reduction in A1C levels in pregnant adults with type 1 diabetes on MDI or insulin pump therapy and using rtCGM in addition to standard care; CGM users experienced more pregnancy-specific TIR (63-140 mg/dL [3.5-7.8 mmol/L]) and less time in hyperglycemia (103) . This study demonstrated the value of rtCGM in pregnancy complicated by type 1 diabetes by showing a mild improvement in A1C levels and a significant improvement in the maternal glucose TIR for pregnancy (63-140 mg/dL [3.5-7.8 mmol/L]), without an increase in hypoglycemia, as well as reductions in large-for-gestational-age births, infant hospital length of stay, and severe neonatal hypoglycemia (103) . An observational cohort study that evaluated the glycemic variables reported using rtCGM and isCGM found that lower mean glucose, lower SD, and higher percentage of TIR were associated with lower risks of large-for-gestational-age births and other adverse neonatal outcomes (104) . Another observational study in pregnancies with and without gestational diabetes mellitus (GDM) wearing blinded CGM found higher mean glucose, more time spent at > 120 mg/dL and > 140 mg/dL, and less time spent at 63-120 mg/dL were associated with large-for-gestational-age births and gestational hypertensive disorders, while lower mean glucose and more time spent at < 63 mg/dL and < 54 mg/dL were associated with small-for-gestational-age birth (105) . Data from one study suggested that the use of rtCGM-reported mean glucose is superior to use of the glucose management indicator and other calculations to estimate A1C levels given the changes to A1C levels that occur in pregnancy (106) . Two studies employing intermittent use of rtCGM showed no difference in neonatal outcomes in individuals with type 1 diabetes (107) or gestational diabetes mellitus (108) . At this time, data are insufficient to recommend the use of CGM in all pregnant people with type 2 diabetes or GDM (109, 110) . The decision of whether to use CGM in pregnant individuals with type 2 diabetes or GDM should be individualized based on treatment plan, circumstances, preferences, and needs.

Although CGM systems for use in pregnancy do not require calibrations and are approved for nonadjunctive use, when using CGM in diabetes and pregnancy, determination of glucose levels by finger stick may be necessary in certain circumstances, such as in the setting of hypoglycemia or hyperglycemia outside the recommended CGM goal ranges (63-140 mg/dL [3.5-7.8 mmol/L]) during pregnancy.

Use of Professional Continuous Glucose Monitoring and Intermittent Use of Continuous Glucose Monitoring

Professional CGM devices, which provide retrospective data, either blinded or unblinded, for analysis can be used to identify patterns of hypoglycemia and hyperglycemia (111, 112) . Professional CGM can be helpful to evaluate an individual's glucose levels when either rtCGM or isCGM is not available to the individual or they prefer a blinded analysis or a shorter experience with unblinded data. It can be particularly useful in individuals using agents that can cause hypoglycemia, as the data can be used to evaluate periods of hypoglycemia and make medication dose adjustments if needed. It can also be useful to evaluate periods of hyperglycemia. Some data have shown the benefit of intermittent use of CGM (rtCGM or isCGM) in individuals with type 2 diabetes on noninsulin and/or basal insulin therapies (60, 73) . In these RCTs, people with type 2 diabetes not on intensive insulin therapy used CGM intermittently compared with those randomized to BGM. Both early (60) and late improvements in A1C levels were found (60, 73) .

Furthermore, in a real-world study, the use of professional CGM in individuals with type 2 diabetes not on insulin at baseline and at 6 months of followup resulted in lower A1C at 6 months as well as a shift toward greater use of glucose-lowering medications with cardiometabolic benefits, such as sodiumglucose transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists (113) . Use of professional or intermittent CGM should always be coupled with analysis and interpretation for people with diabetes along with education, as needed, to adjust medication and change lifestyle behaviors (114) (115) (116) .

Side Effects of Continuous Glucose Monitoring Devices

Contact dermatitis (both irritant and allergic) has been reported with all devices that attach to the skin (20, 117, 118) . In some cases, this has been linked to the presence of isobornyl acrylate, a skin sensitizer that can cause an additional spreading allergic reaction (119) (120) (121) . It is important to ask CGM users periodically about adhesive reactions, as tape formulations may change over time. Patch testing can sometimes identify the cause of contact dermatitis (122) . Identifying and eliminating tape allergens is important to ensure the comfortable use of devices and promote self-care (123) (124) (125) (126) . The PANTHER Program offers resources in English and Spanish at www. pantherprogram.org/skin-solutions. In some instances, using an implanted sensor can help avoid skin reactions in those sensitive to tape (127, 128) .

Substances and Factors Affecting Continuous Glucose Monitoring Accuracy

Sensor interference due to several medications/substances is a known potential source of CGM sensor measurement errors (Table 7 .4). While several of these substances have been reported in the various CGM brands' user manuals, additional interferences have been discovered after the market release of these products. Hydroxyurea, used for myeloproliferative disorders and hematologic conditions, is one of the most recently identified interfering substances that cause a temporary increase in sensor glucose values discrepant from actual glucose values (129) (130) (131) (132) (133) (134) . Similarly, substances such as mannitol and sorbitol, when administered intravenously or as a component of peritoneal dialysis solution, may increase blood mannitol or sorbitol concentrations and cause falsely elevated readings of sensor glucose (135) . Therefore, it is crucial to routinely review the medications and supplements used by the person with diabetes to identify possible interfering substances and advise them accordingly on the need to use additional BGM if sensor values are unreliable due to these substances. below). For people with diabetes who use insulin, insulin syringes and pens both can deliver insulin safely and effectively for the achievement of glycemic goals. Individual preferences, cost, insulin type, dosing therapy, and self-management capabilities should be considered when choosing among delivery systems. Trials with insulin pens generally show equivalence or small improvements in glycemic outcomes compared with using a vial and syringe. Many individuals with diabetes prefer using a pen because of its simplicity and convenience. It is important to note that while many insulin types are available for purchase as either pens or vials, others may be available in only one form or the other, and there may be significant cost differences between pens and vials (see Table 9 .4 for a list of insulin product costs with dosage forms). Insulin pens may allow people with vision impairment or dexterity issues to dose insulin accurately (149) (150) (151) , and insulin injection aids are also available to help with these issues. (For a helpful list of injection aids, see living-with-diabetes/ treatment-care/diabetes-technology-guide).

Inhaled technosphere insulin can be useful for people with diabetes, providing an alternative method of insulin delivery with very fast onset of action. In a recent randomized clinical trial, the use of technosphere inhaled insulin showed lower postprandial hyperglycemia than subcutaneous rapid-acting analog insulin (152) .

The most common syringe sizes are 1 mL, 0.5 mL, and 0.3 mL, allowing doses of up to 100 units, 50 units, and 30 units, respectively, of U-100 insulin. Some 0.3-mL syringes have half-unit markings, whereas other syringes have markings in 1-to 2-unit increments. In a few parts of the world, insulin syringes still have U-80 and U-40 markings for older insulin concentrations and veterinary insulin, and U-500 syringes are available for the use of U-500 insulin. Syringes are generally used once but may be reused by the same individual in resource-limited settings with appropriate storage and cleansing (151) .

Insulin pens offer added convenience by combining the vial and syringe into a single device. Insulin pens, allowing push-button injections, come as disposable pens with prefilled cartridges or reusable insulin pens with replaceable insulin cartridges. Pens vary with respect to dosing increment and minimal dose, ranging from half-unit doses to 2-unit dose increments, with the latter available in U-200 insulin pens. U-500 pens come in 5-unit dose increments. Some reusable pens include a memory function, which can recall dose amounts and timing. Insulin pens, once started, can be kept in use for variable durations, based on the type of insulin, usually for 28 days, ranging from 14 to 56 days. Needle thickness (gauge) and length are other considerations. Needle gauges range from 22 to 34, with a higher gauge indicating a thinner needle. A thicker needle can give a dose of insulin more quickly, while a thinner needle may cause less pain. Needle length ranges from 4 to 12.7 mm, with some evidence suggesting that shorter needles (4-5 mm) lower the risk of intramuscular injection with erratic absorption and possibly the development of lipohypertrophy. When reused, needles may be duller and thus injections may be more painful. Proper insulin injection technique is a requisite for receiving the full dose of insulin with each injection. Concerns with technique and use of the proper technique are outlined in Section 9, "Pharmacologic Approaches to Glycemic Treatment."

Connected insulin pens are insulin pens with the capacity to record and/or transmit insulin dose data. Insulin pen caps are also available and are placed on existing insulin pens and may assist with calculating insulin doses and by providing a memory function. Some connected insulin pens and pen caps can be programmed to calculate insulin doses, can be synced with select CGM systems, and can provide downloadable data reports. These pens and pen caps are useful to people with diabetes for realtime insulin dosing and allow clinicians to retrospectively review the insulin delivery times and, in some cases, doses and glucose data to make informed insulin dose adjustments (153) . A quantitative study showed that people with diabetes preferred connected pens because of their ability to log insulin doses and glucose levels automatically (153) . In a multicenter RCT in people with type 1 diabetes, the use of an insulin pen cap was associated with improved glycemic outcomes at 6 weeks in the insulin cap group, with an increase in TIR and decrease in GMI and TAR (154) . A systematic review of connected insulin pens or pen caps showed improvement of glucose outcomes whether as A1C reduction, TIR increase, or hypoglycemia reduction (155) . A recent realworld study with multinational data collected from 3,954 adults with diabetes using a connected pen and CGM validated the fact that treatment engagement with a connected insulin pen is positively associated with glycemic outcomes. On the other hand, missing as little as two basal doses or four bolus insulin doses over a 14-day period would be associated with a clinically relevant decrease in TIR of $5% (156) .

Bolus calculators have been developed to aid dosing decisions (157) (158) (159) (160) (161) (162) . These systems are subject to FDA approval to ensure safety and efficacy in terms of algorithms used and subsequent dosing recommendations. People interested in using these systems should be encouraged to use those that are FDA approved. Health care professional input and education can be helpful for setting the initial dosing calculations with ongoing follow-up for adjustments as needed.

Insulin Pumps and Automated Insulin Delivery Systems Recommendations 7.26 AID systems should be the preferred insulin delivery method to improve glycemic outcomes and reduce hypoglycemia and disparities in youth and adults with type 1 diabetes A and other types of insulin-deficient diabetes E who are capable of using the device (either by themselves or with a caregiver). Choice of an AID system should be made based on the individual's circumstances, preferences, and needs. A 7.27 Insulin pump therapy, preferably with CGM, should be offered for diabetes management to youth and adults on MDI with type 2 diabetes who can use the device safely (either by themselves or with a caregiver). The choice of device should be made based on the individual's circumstances, preferences, and needs. A 7.28 Individuals with diabetes who have been using CSII should have continued access across third-party payors. E

Insulin Pumps

Insulin pumps have been available in the U.S. for over 40 years. These devices deliver rapid-acting insulin throughout the day to help manage glucose levels. Most insulin pumps use tubing to deliver insulin through a cannula, while a few attach directly to the skin without tubing (pods or patch pumps), and these systems have been approved for use in type 1 and type 2 diabetes. AID systems, which can adjust insulin delivery rates based on sensor glucose values, are preferred over nonautomated pumps and MDI in people with type 1 diabetes and have largely replaced the use of nonintegrated or standard insulin pumps. Recently, one AID system was approved for use by people with type 2 diabetes.

Historically, studies that compared MDI with insulin pump therapy were relatively small and of short duration. However, a systematic review and meta-analysis concluded that pump therapy has modest advantages for lowering A1C levels (À0.30% [95% CI À0.58 to À0.02]) and for reducing severe hypoglycemia rates in children and adults (163) . Real-world data on insulin pump use in individuals with type 1 diabetes show benefits in A1C levels and hypoglycemia reductions as well as total daily insulin dose reduction (164) . There is no consensus to guide choices on which form of insulin administration is best for a given individual, and research to guide this decision-making process is needed (163) . Thus, the choice of MDI or an insulin pump is often based on the characteristics of the person with diabetes and which method is most likely to benefit them. DiabetesWise (diabeteswise.org/), for individuals with diabetes, DiabetesWise Pro (pro.diabeteswise .org/), for health care professionals, and the PANTHER Program (pantherprogram .org/device-comparison-chart) have helpful websites to assist health care professionals and people with diabetes in choosing diabetes devices based on their individual needs and the features of the devices. Newer systems, such as sensor-augmented pumps (SAPs) and AID systems, are discussed below.

Adoption of pump therapy in the U.S. shows geographical variations, which may be related to health care professional preference or center characteristics (165, 166) and socioeconomic status, as pump therapy is more common in individuals of higher socioeconomic status, as reflected by private health insurance, family income, and education (165, 166) . Given the additional barriers to optimal diabetes care observed in disadvantaged groups (167) , addressing the differences in access to insulin pumps and other diabetes technologies may contribute to fewer health disparities.

Pump therapy can be successfully started at the time of diagnosis (168) . Practical aspects of pump therapy initiation include assessment of readiness of the person with diabetes and their family, if applicable (although there is no consensus on which factors to consider in adults [169] or children and adolescents with diabetes), selection of pump type and initial pump settings, individual and family education on potential pump complications (e.g., DKA with infusion set failure), transition from MDI, and introduction of advanced pump settings (e.g., temporary basal rates and extended bolus, square-wave bolus, or dual-wave bolus).

Older individuals with type 1 diabetes benefit from ongoing insulin pump therapy.There are no data to suggest that measurement of C-peptide levels or antibodies predicts success with insulin pump therapy (170,171). Additionally, the frequency of follow-up does not influence outcomes.

Access to insulin pump therapy, including AID systems, should be allowed or continued in older adults as it is in younger people.

Complications of the pump can be caused by issues with infusion sets (dislodgement and occlusion), which put individuals at risk for ketosis and DKA and thus must be recognized and managed early (172). Other pump skin issues include lipohypertrophy or, less frequently, lipoatrophy (173) and pump site infection. Discontinuation of pump therapy is relatively uncommon today; the frequency has decreased over the past few decades, and its causes have changed (174). Current reasons for attrition are problems with cost or wearability, loss of insurance, dislike of the pump, suboptimal glycemic outcomes, or mood disorders (e.g., anxiety or depression) (175).

Insulin Pumps in Youth

The safety of insulin pumps in youth has been established for over 15 years (176). Studying the effectiveness of insulin pump therapy in lowering A1C levels has been challenging because of the potential selection bias of observational studies. Participants on insulin pump therapy may have a higher socioeconomic status that may facilitate better glycemic outcomes (177) than MDI. In addition, the fast pace of development of new insulins and technologies quickly renders comparisons obsolete. However, RCTs that compared insulin pumps and MDI with rapidacting insulin analogs demonstrated a modest improvement in A1C levels in participants on insulin pump therapy (178, 179) . Observational studies, registry data, and meta-analyses have also suggested an improvement in glycemic outcomes in participants on insulin pump therapy (180) (181) (182) . Data suggest that insulin pumps reduce the rates of severe hypoglycemia compared with MDI (182) (183) (184) (185) .

There is also evidence that insulin pump therapy may reduce DKA risk (182, 186) and diabetes complications, particularly retinopathy and peripheral neuropathy in youth, compared with MDI (169). In addition, treatment satisfaction and quality-oflife measures improved on insulin pump therapy compared with MDI (187) . Therefore, insulin pumps can be used safely and effectively in youth with type 1 diabetes to assist with achieving targeted glycemic outcomes while reducing the risk of hypoglycemia and DKA, improving quality of life, and preventing long-term complications. Based on shared decision-making by people with diabetes and health care professionals, insulin pumps may be considered in all children and adolescents with type 1 diabetes. In particular, pump therapy may be the preferred mode of insulin delivery for children under 7 years of age (188) . Because of a paucity of data in adolescents and youth with type 2 diabetes, there is insufficient evidence to make recommendations.

Common barriers to pump therapy adoption in children and adolescents are concerns regarding the physical interference of the device, discomfort with the idea of having a device on the body, therapeutic effectiveness, and financial burden (180, 189) .

Sensor-Augmented Pumps

SAPs (or partial closed-loop systems) consist of three components: an insulin pump, a CGM system, and an algorithm that automates insulin suspension when glucose is low or is predicted to go low within the next 30 min. Predictive lowglucose suspend systems have been shown to reduce time spent with glucose < 70 mg/dL without rebound hyperglycemia during a 6-week randomized crossover trial (190) . Similar results were seen in additional studies in adults and children with reduction of hypoglycemia (191) (192) (193) . SAPs have now been largely replaced by AID systems, which offer superior benefits for glycemic outcomes; nevertheless, some AID systems can still be used in either low-glucose suspend mode or predictive low-glucose suspend mode.

Automated Insulin Delivery Systems

AID systems consist of mainly three components: an insulin pump, a CGM system, and an algorithm that determines insulin delivery. Based on the model and brand of currently FDA approved AID systems, the algorithm can be hosted in the pump body, in an insulin pod, or on a phone app. All AID systems on the market today integrate with one or more CGM systems and adjust insulin delivery either by modulating the preprogrammed basal rates or by replacing the basal rates with microboluses or microdoses of insulin every 5 min.

In people with type 2 diabetes not taking insulin, routine glucose monitoring may be of limited additional clinical benefit. By itself, even when combined with education, this practice has shown limited improvement in outcomes (31) . However, for some individuals, glucose monitoring can provide insight into the impact of nutrition, physical activity, and medication management on glucose levels. Glucose monitoring may also be useful in assessing hypoglycemia, glucose levels during intercurrent illness, or discrepancies between measured A1C and glucose levels when there is concern an A1C result may not be reliable in specific individuals (for more details, see Section 2, "Diagnosis and Classification of Diabetes"). It may be useful when coupled with a treatment adjustment program. In a year-long study of insulin-naive people with diabetes with suboptimal initial glycemic outcomes, a group trained in structured BGM (a paper tool was used at least quarterly to collect and interpret seven-point BGM profiles taken on three consecutive days) reduced their A1C levels by 0.3% more than the control group (32) . A trial of once-daily BGM that included enhanced feedback from people with diabetes through messaging found no clinically or statistically significant change in A1C levels at 1 year (31) . Meta-analyses have suggested that BGM can reduce A1C levels by 0.25-0.3% at 6 months (33) (34) (35) , but the effect was attenuated at 12 months in one analysis (33) . Reductions in A1C levels were greater (À0.3%) in trials where structured BGM data were used to adjust medications, but A1C levels were not changed significantly without such structured diabetes therapy adjustment (35) . A key consideration is that performing BGM alone does not lower blood glucose levels. To be useful, the information must be integrated into clinical and self-management treatment plans.

Glucose Meter Inaccuracy

Although many meters function well under various circumstances, health care professionals and people with diabetes must be aware of factors that impair meter accuracy. A meter reading that seems discordant with the clinical picture needs to be retested or tested in a laboratory. Health care professionals in intensive care unit settings need to be particularly aware of the potential for incorrect meter readings during critical illness, and laboratory-based values should be used if there is any doubt. Some meters give error messages if meter readings are likely to be false (36) .

Oxygen. Currently available glucose monitors use an enzymatic reaction linked to an electrochemical reaction, either glucose oxidase or glucose dehydrogenase (37) . Glucose oxidase monitors are sensitive to the oxygen available and should only be used with capillary blood in people with normal oxygen saturation. Higher oxygen tensions (i.e., arterial blood or oxygen therapy) may result in false low-glucose readings, and low oxygen tensions (i.e., high altitude, hypoxia, or venous blood readings) may lead to falsely elevated glucose readings. Glucose dehydrogenase-based monitors are generally not sensitive to oxygen.

Temperature. Because the reaction is sensitive to temperature, all monitors have an acceptable temperature range (37) . Most will show an error if the temperature is unacceptable, but a few will provide a reading and a message indicating that the value may be incorrect. Humidity and altitude may also alter glucose readings.

Interfering Substances. There are several physiologic and pharmacologic factors that interfere with glucose readings measured with either personal blood glucose meters or professional blood glucose meters used in various inpatient settings (neonatal intensive care unit, hospital wards, and intensive care unit) (37) . They are listed in CGM measures interstitial glucose (which correlates well with plasma glucose, although at times, it can lag if glucose levels are rising or falling rapidly). There are two basic types of CGM devices. The first type includes those that are owned by the user, unblinded, and intended for frequent or continuous use, including real-time CGM (rtCGM), intermittently scanned CGM (isCGM), and over-the-counter CGM devices. The second type is professional CGM devices that are owned by practices and applied in the clinic, which provide data that are blinded or unblinded for a discrete period of time. The types of sensors currently available are either disposable (rtCGM and isCGM) or implantable (rtCGM). Table 7 .3 provides definitions for the types of CGM devices. For people with type 1 diabetes using CGM, frequency of sensor use is an important predictor of A1C lowering for all age-groups (38, 39) . The frequency of scanning with isCGM devices is also correlated with improved outcomes (40) (41) (42) (43) .

Few real-time systems require calibration by the user, which varies in frequency depending on the device. CGM systems are generally nonadjunctive, meaning they do not require BGM confirmation for treatment decisions like insulin dosing or treating hypoglycemia, except in certain clinical situations (see BLOOD GLUCOSE MONITORING, above) (44) (45) (46) .

Most CGM systems are designated as integrated CGM (iCGM), a higher standard set by the FDA for integration with other digitally connected devices. Dexcom G6 rtCGM (no generic form available), Dexcom G7 rtCGM (no generic form available), FreeStyle Libre 2 Plus (no generic form available), FreeStyle Libre 3 Plus (no generic form available), and Eversense E3 (no generic form available) are FDA approved for use with AID systems. Similarly, Dexcom G6 rtCGM, Dexcom G7 rtCGM, FreeStyle Libre 2 isCGM (no generic form available), and Medtronic Simplera rtCGM (no generic form available) are approved for use with connected insulin pens (47) . Currently, Dexcom G6 and Dexcom G7 are integrated with four AID systems (t:slim X2 with Control-IQ, Omnipod 5, iLet, and Mobi). Similarly, at this time in the U.S., the FreeStyle Libre 2 Plus is integrated with one AID system (t:slim X2 with Control-IQ) and the FreeStyle Libre 3 Plus with another AID system (iLet). Finally, the Medtronic Guardian 3 rtCGM (no generic form available) and the Medtronic Guardian 4 rtCGM (no generic form available) are FDA approved for use with the 670/770G and 780G AID systems, respectively.

Benefits of Continuous Glucose Monitoring

Data From Randomized Controlled Trials Multiple randomized controlled trials (RCTs) have been performed using rtCGM devices, and the results have largely been positive in terms of reducing A1C levels and/or episodes of hypoglycemia if participants regularly wore the devices (38) (39) (40) (41) (48) (49) (50) (51) . The initial studies were done primarily in adults and youth with type 1 diabetes on insulin pump therapy and/or MDI (38, 39, 48, 49, 52) . The primary outcome was met and showed benefit in adults of all ages (38, 53, 54) , including seniors (55) (56) (57) . Data in children show that rtCGM use in young children with type 1 diabetes reduced hypoglycemia; in addition, behavioral support of parents of young children with diabetes using rtCGM showed the benefits of reducing hypoglycemia concerns and diabetes distress (38, 49, 58) . Similarly, A1C level reduction was seen in adolescents and young adults with type 1 diabetes using rtCGM (48) . RCT data on rtCGM use in individuals with type 2 diabetes on MDI (59) , mixed therapies (10, 60) , and basal insulin (61, 62) have consistently shown reductions in A1C levels and increases in TIR (70-180 mg/dL [3.9-10 mmol/L]) but not a reduction in rates of hypoglycemia (63) . Although short-term use of rtCGM in youth with type 2 diabetes did not impact short-term glucose changes or A1C improvement, users reported behavioral changes with increased blood glucose measurements, increased insulin administration, and overall improved diabetes management and quality of life (64, 65) . The improvements in type 2 diabetes have largely occurred without changes in insulin doses or other diabetes medications. CGM discontinuation in individuals with type 2 diabetes on basal insulin caused partial reversal of A1C reduction and TIR improvements, suggesting that continued CGM use achieves the greatest benefits (15) . RCT data for rtCGM benefits in people with type 2 diabetes not using insulin are increasing and generally have shown greater benefits of CGM compared with BGM for A1C, TIR, time below range (TBR), and time above range (TAR) as well as greater user-reported satisfaction (66) . These benefits were initially reported in a study where the intermittent use of rtCGM for either one session or two sessions (3 months apart) versus control treatment showed improvement of A1C at 3 months. At 6 months, the two-session rtCGM group achieved significant A1C reduction. For both rtCGM groups, participants who measured BGM at least 1.5 times per day achieved greater A1C improvement compared with the control group (67) .

In addition, rtCGM benefits were reported in a mixed population (including people not using insulin) of adults with type 2 diabetes with reduction in A1C levels, increase in TIR, and reduction of time in hyperglycemia ( > 180 mg/dL [ > 10 mmol/L] and > 250 mg/dL [ > 13.9 mmol/L]) (10) .

RCT data for isCGM are fewer but increasing. One study was performed in adults with type 1 diabetes and met its primary outcome of a reduction in rates of hypoglycemia (68) . In adults with type 2 diabetes using insulin, two studies were done: one study did not meet its primary end point of A1C level reduction (69) but achieved a secondary end point of a reduction in hypoglycemia, and the other study met its primary end point of an improvement in the Diabetes Treatment Satisfaction Questionnaire score as well as a secondary end point of A1C level reduction (70) . In a study of individuals with type 1 or type 2 diabetes taking insulin, the primary outcome of a reduction in severe hypoglycemia was not met and the incidence of severe hypoglycemia was not significantly different between isCGM users and the BGM group (71) . One study in youth with type 1 diabetes did not show a reduction in A1C levels (72) ; however, the device was well received and was associated with an increased frequency of testing and improved diabetes treatment satisfaction (72) . A randomized trial of adults with type 1 diabetes showed that the use of isCGM with optional alerts and alarms resulted in reduction of A1C levels compared with BGM use (9) .

The benefits of isCGM for adults with type 2 diabetes not using insulin were initially reported in a multicenter, openlabel, randomized (1:1), parallel-group study. At 12 weeks, A1C was significantly reduced from baseline in both groups without difference. However, at 24 weeks, the isCGM group showed a greater A1C reduction than the control group. Furthermore, there were no between-group differences in change of antihyperglycemic drugs (73) . In a subsequent post hoc analysis, the isCGM group showed that the effects of isCGM were present 1 week after isCGM initiation for weekly mean glucose, glucose management indicator (GMI), percentage of TIR, percentage of TAR, and mean amplitude glucose excursion and remained stable from baseline to 12 weeks (74) . Additionally, benefits of isCGM were also reported in an RCT where the use of isCGM plus diabetes education versus diabetes education alone showed decreased A1C levels and increased TIR as well as increased time in tight target range (70-140 mg/dL [3.9-7.8 mmol/L]) in the isCGMplus-education group (8) .

Observational and Real-world Studies

CGM systems are widely available in many countries for people with diabetes, and this allows for the collection of large amounts of data across groups of people with diabetes.

Data for isCGM in adults with diabetes include results from observational studies, retrospective studies, and analyses of registry and population data (75, 76) . In individuals with type 1 diabetes wearing isCGM devices, studies have shown improvement in A1C levels (41, 77) , TIR (70-180 mg/dL [3.9-10.0 mmol/L]), and hypoglycemia (41, 43, 75, 78, 79) . Reductions in acute diabetes complications, such as diabetic ketoacidosis (DKA), episodes of severe hypoglycemia or diabetes-related coma, and hospitalizations for hypoglycemia and hyperglycemia, have been observed in adults with type 1 or type 2 diabetes (43, 78, 80) , with persistent effects observed even after 2 years of CGM initiation (81) . Similar reductions of acute diabetes events and all-cause inpatient hospitalizations were seen in a retrospective review of adults with type 2 diabetes treated with basal insulin or with noninsulin therapy 6 months after initiation of isCGM (82) . Prospective observational as well as retrospective studies in adults with type 2 diabetes treated with MDI showed significant reduction of A1C and hypoglycemia (83) after 12 weeks of isCGM use, with increased user satisfaction (83) . Similar results were seen in a retrospective study with adults with type 2 diabetes on basal insulin at 3-6 months (84) . Furthermore, retrospective observational data in adults with type 2 diabetes treated with either basal insulin or noninsulin therapy have shown an improvement in A1C levels (85) . Finally, a retrospective study of continued use of isCGM in adults with nonintensively treated type 2 diabetes showed reduction of A1C and GMI, increase in TIR, and reduction of TAR ( > 180 mg/dL) (86) . Results of self-reported outcomes varied, but, where measured, people with diabetes had an increase in treatment satisfaction with isCGM compared with BGM. In an observational study in youth with type 1 diabetes, a slight increase in A1C levels and weight was seen, but the device was associated with a high user satisfaction rate (76) .

Retrospective data from rtCGM use in adults (87) with type 1 or type 2 diabetes treated with insulin showed that the use of rtCGM significantly lowered A1C levels and reduced rates of emergency department visits or hospitalizations for hypoglycemia but did not significantly lower overall rates of emergency department visits, hospitalizations, or hyperglycemia.

Recent data have emerged from a realworld observational analysis of rtCGM use in adults with type 2 diabetes not treated with insulin. In this study, rtCGM benefits were observed at 6 month and 12 months versus baseline, with reduction of mean glucose levels, reduction of GMI, increase in TIR, increase in time in tight target range (70-140 mg/dL [3.9-7.8 mmol/L]), and reduction in TAR > 180 and > 250 mg/dL (88) .

Real-time Continuous Glucose Monitoring Compared With Intermittently Scanned Continuous Glucose Monitoring

In adults with type 1 diabetes, three RCTs have been conducted comparing isCGM (without predictive alerts/alarms) and rtCGM (with predictive alerts/alarms) (84, 89, 90) . In two of the studies, the primary outcome was a reduction in time spent in hypoglycemia, and rtCGM showed greater benefits compared with isCGM (89, 90) . In the other study, the primary outcome was improved TIR, and rtCGM also showed greater benefits compared with isCGM (84) . A retrospective analysis also showed improvement in TIR with rtCGM compared with isCGM (91) . A more recent 12-month real-world nonrandomized study compared rtCGM with isCGM in adults with type 1 diabetes. At 12 months, A1C levels, time in level 1 hypoglycemia ( < 70 mg/dL [ < 3.9 mmol/L]), and time in level 2 hypoglycemia ( < 54 mg/dL [ < 3.0 mmol/L]) were all lower in the rtCGM group than in the isCGM group; similarly, the TIR was higher in the rtCGM group than in the isCGM group (92) .

Data Analysis

The abundance of data provided by CGM offers opportunities to analyze data for people with diabetes more granularly than previously possible, providing additional information to aid in achieving glycemic goals. A variety of metrics have been proposed (93) and are discussed in Section 6, "Glycemic Goals and Hypoglycemia." CGM is essential for creating an ambulatory glucose profile (AGP) and providing data on TIR, percentage of time spent above and below range, and glycemic variability (94) . Standardized reports for CGM, AID, and connected insulin pens include multiple reports, each providing different degrees of information. These reports, whether single page or with raw data, should be used in clinical practice to identify CGM trends and patterns; in the setting of AID systems, these reports provide important information on insulin delivery and its suspension or modulation as well as information on automated bolus delivery that can assist the clinician in making therapy adjustments (12, 94, 95) . However, data analysis can be burdensome without a systematic approach to its review, and CGM and AID manufacturers should aim to make device data reports as standardized as possible to reduce the burden of data analysis (12) . Several efforts have been made to streamline the interpretation of CGM reports to assist health care professionals in their daily practice. These have various, but overall similar, approaches. The initial steps are focused on assessing the sufficiency and quality of data; subsequent recommendations include reviewing the presence and trends or patterns of hypoglycemia, followed by hyperglycemia patterns and trends. Select glycemic goals that avoid symptomatic hypoglycemia and hyperglycemia in all individuals. Consider individuals' resources and support systems to safely achieve glycemic goals. Incorporate the preferences and goals of people with diabetes through shared decision-making. ACCORD included the rapid escalation of therapies, the early use of large doses of insulin, substantial weight gain, and frequent hypoglycemia. These overall negative results were not unexpected, as blood glucose has subsequently been shown to be a relatively weak CVD risk factor in isolation compared with other CVD risk factors, such as hypertension or hypercholesterolemia. Consequently, even if a wide separation in A1C could be safely obtained, it would take a long time for the CVD benefit to accrue. However, a metaanalysis of individual participant data from UKPDS, ACCORD, ADVANCE, and VADT demonstrated a significant reduction in myocardial infarctions and major CVD events but no difference in stroke, heart failure, or mortality between intensive and less intensive glycemic management (57) .

Longer-term epidemiological follow-up has been performed in these studies, and a clear pattern of CVD benefit has emerged (58) (59) (60) . In the post-DCCT follow-up of the EDIC cohort, participants previously randomized to the intensive arm had a significant 57% reduction in the risk of nonfatal myocardial infarction, stroke, or cardiovascular death compared with those previously randomized to the standard arm (58) . The benefit of intensive glycemic management in this cohort with type 1 diabetes has been shown to persist for several decades (59) and to be associated with a modest reduction in all-cause mortality (61) .

UKPDS post-trial monitoring, with 20 years of total follow-up, has shown reductions in myocardial infarctions and total mortality both in the group of overweight individuals treated with metformin and in the group previously treated intensively with sulfonylureas or insulin (47) . Shorter overall follow-up of the VADT (10 years) has shown a significant reduction in the primary outcome of major CVD events, with myocardial infarctions and heart failure being the commonest outcomes (60) . In contrast, shorter followup of the ADVANCE study in the Action in Diabetes and Vascular Disease Preterax and Diamicron MR Controlled Evaluation Post Trial Observational Study (ADVANCE-ON) demonstrated no significant effect on CVD events (62) . Even in the epidemiological follow-up of ACCORD in the Action to Control Cardiovascular Risk in Diabetes Follow-On Study (ACCORDION), the excess increase in total mortality that was seen during 3.5 years of intensive treatment was reduced by returning to conventional management, and therefore there was no difference in total mortality after a total of 9 years of follow-up (63) . Collectively, the results of these studies confirm that long-term intensive glycemic management reduces CVD events, particularly myocardial infarctions.

As discussed above, these landmark studies in individuals with type 2 diabetes need to be considered with the important caveat that GLP-1 RAs and SGLT2 inhibitors were not yet in clinical use. These agents with established cardiovascular and kidney benefits appear to be safe and beneficial in this group of individuals at high risk for cardiovascular and kidney complications. Randomized clinical trials examining these agents for cardiovascular safety were not designed to test higher versus lower A1C; therefore, beyond post hoc analysis of these trials, we do not have evidence that it is the glucose lowering per se by these agents that confers the CVD and kidney benefits (64) . Additional beneficial pleotropic effects of these agents may include weight loss, hemodynamic effects, blood pressure lowering, and anti-inflammatory changes.

As discussed further below, severe hypoglycemia is a potent marker of high absolute risk of cardiovascular events and mortality (65) . Therefore, health care professionals should be vigilant in preventing hypoglycemia and should not aggressively attempt to achieve near-normal A1C levels in people in whom such goals cannot be safely and reasonably achieved. As discussed in Section 9, "Pharmacologic Approaches to Glycemic Treatment," addition of specific SGLT2 inhibitors or GLP-1 RAs that have demonstrated CVD benefit is recommended in individuals with established CVD, chronic kidney disease, and heart failure. As outlined in more detail in Section 9, "Pharmacologic Approaches to Glycemic Treatment," and Section 10, "Cardiovascular Disease and Risk Management," the cardiovascular benefits of SGLT2 inhibitors or GLP-1 RAs are not contingent upon A1C lowering; therefore, initiation can be considered in people with type 2 diabetes and CVD independent of the current A1C, A1C goal, or metformin therapy. Based on these considerations, the following two strategies are offered (66):

1. If already on dual therapy or multiple glucose-lowering therapies and not on an SGLT2 inhibitor or a GLP-1 RA, consider switching to one of these agents with proven cardiovascular benefit. 2. Introduce SGLT2 inhibitors or GLP-1 RAs in people with CVD at A1C goal (independent of metformin) for cardiovascular benefit, independent of baseline A1C or individualized A1C goal.

Setting and Modifying Glycemic Goals

Glycemic goals and management should be individualized and not one size fits all.

To prevent both microvascular and macrovascular complications of diabetes, there is a major call to overcome therapeutic inertia and treat to individualized goals (56, 67) . Numerous factors must be considered when setting a glycemic goal. The ADA proposes general goals that are appropriate for many people but emphasizes the importance of individualization based on key person characteristics. Glycemic goals must be individualized in the context of shared decision-making to address individual needs and preferences and consider characteristics that influence risks and benefits of therapy; this approach may optimize engagement and selfefficacy.

The factors to consider in individualizing goals are depicted in Fig. 6 .2. This figure is not designed to be applied rigidly in the care of a given individual but to be used as a broad framework to guide clinical decision-making (39) and engage people with type 1 and type 2 diabetes in shared decision-making. More aggressive goals may be recommended if they can be achieved safely and with an acceptable burden of therapy and if life expectancy is sufficient to reap the benefits of stringent goals. Less stringent goals (e.g., A1C up to 8% [64 mmol/mol]) may be recommended if the individual's life expectancy is such that the benefits of an intensive goal may not be realized or if the risks and burdens outweigh the potential benefits. Severe or frequent hypoglycemia is an absolute indication for the modification of treatment plans, including setting higher glycemic goals.

Diabetes is a chronic disease that progresses over decades. Thus, a goal that might be appropriate for an individual early in the course of their diabetes may change over time. Newly diagnosed individuals and/or those without comorbidities that limit life expectancy may benefit from intensive glycemic goals proven to prevent microvascular complications. Both DCCT/EDIC and UKPDS suggested that there is metabolic memory, or a legacy effect, in which a finite period of intensive glucose lowering yielded benefits that extended for decades after that period ended. However, there are few recent data on the effects of long-term glucose lowering using modern treatment strategies. Thus, a finite period of intensive treatment to near-normal A1C may yield enduring benefits even if treatment is subsequently deintensified as characteristics change. Over time, comorbidities may emerge, decreasing life expectancy and thereby decreasing the potential to reap benefits from intensive treatment. Also, with longer disease duration, diabetes may become more difficult to manage, with increasing risks and burdens of therapy. Thus, glycemic goals should be reevaluated over time to balance the risks and benefits.

Accordingly, clinicians should continue to evaluate the balance of risks and benefits of diabetes medications for individuals who have achieved individualized glycemic goals, and they should deintensify (decrease the dose or stop) diabetes medications where their risks exceed their benefits. Hypoglycemia is the major risk to individuals treated with insulin, sulfonylureas, or meglitinides, and it is appropriate to deintensify these medications where there is a high risk for hypoglycemia (see HYPOGLYCEMIA RISK ASSESSMENT, below). Switching a high-hypoglycemia-risk medication to lower-hypoglycemia-risk therapy (see Section 9, "Pharmacologic Approaches to Glycemic Treatment") should be considered if needed to achieve individualized glycemic goals or where individuals have evidence-based indications for alternative medications (e.g., use of SGLT2 inhibitors in the setting of heart failure or diabetic kidney disease and use of GLP-1 RAs in the setting of CVD or obesity). Clinicians should also consider medication burdens other than hypoglycemia, including tolerability, difficulties of administration, impact on education or employment, and financial cost. These factors should be balanced against benefits from glycemic lowering and disease-specific benefits of newer medications that may be independent of glycemic lowering (Section 9, "Pharmacologic Approaches to Glycemic Treatment"). Multiple trials have shown that deintensification of diabetes treatment can be achieved successfully and safely (68) (69) (70) . It is important to partner with people with diabetes during the deintensification process to understand their goals of diabetes treatment and agree upon appropriate glycemic monitoring, glucose levels, and goals of care (71) .

HYPOGLYCEMIA ASSESSMENT, PREVENTION, AND TREATMENT Recommendations 6.10 Review history of hypoglycemia at every clinical encounter for all individuals at risk for hypoglycemia, and evaluate hypoglycemic events as indicated. C 6.11 Screen individuals at risk for hypoglycemia for impaired hypoglycemia awareness at least annually and when clinically appropriate. E Refer to a trained health care professional for evidence-based intervention to improve hypoglycemia awareness. A 6.12 Screen individuals at high risk for hypoglycemia or with severe and/or frequent hypoglycemia for fear of hypoglycemia at least annually and when clinically appropriate. E Refer to a trained health care professional for evidence-based intervention. A 6.13 Clinicians should consider an individual's risk for hypoglycemia (see Table 6 .5) when selecting diabetes medications and glycemic goals. E 6.14 Use of CGM is beneficial and recommended for individuals at high risk for hypoglycemia. A 6.15 Glucose is the preferred treatment for the conscious individual with glucose < 70 mg/dL ( < 3.9 mmol/L), although any form of carbohydrate that contains glucose may be used. Avoid using foods or beverages high in fat and/or protein for initial treatment of hypoglycemia. Fifteen minutes after initial treatment, repeat the treatment if hypoglycemia persists. B 6.16 Glucagon should be prescribed for all individuals taking insulin or at high risk for hypoglycemia. A Family, caregivers, school personnel, and others providing support to these individuals should know its location and be educated on how to administer it. Glucagon preparations that do not have to be reconstituted are preferred. B 6.17 All individuals taking insulin A or at risk for hypoglycemia C should receive structured education for hypoglycemia prevention and treatment, with ongoing education for those who experience hypoglycemic events. 6.18 One or more episodes of level 2 or 3 hypoglycemia should prompt reevaluation of the treatment plan, including deintensifying or switching diabetes medications if appropriate. E 6.19 Regularly assess cognitive function; if impaired or declining cognition is found, the clinician, person with diabetes, and caregiver should increase vigilance for hypoglycemia. B

Hypoglycemia Definitions and Event Rates

Hypoglycemia is often the major limiting factor in the glycemic management of type 1 and type 2 diabetes. Recommendations regarding the classification of hypoglycemia are outlined in Table 6 .4 (72) . Level 1 hypoglycemia is defined as a measurable glucose concentration < 70 mg/dL ( < 3.9 mmol/L) and $54 mg/dL ($3.0 mmol/L). A blood glucose concentration of 70 mg/dL (3.9 mmol/L) has been recognized as a threshold for adrenergic responses to falling glucose in people without diabetes. Symptoms of hypoglycemia include, but are not limited to, shakiness, irritability, confusion, tachycardia, sweating, and hunger (73) . Because many people with diabetes demonstrate impaired counterregulatory responses to hypoglycemia and/or experience impaired hypoglycemia awareness, a measured glucose level < 70 mg/dL ( < 3.9 mmol/L) is considered clinically important, regardless of symptoms. Level 2 hypoglycemia (defined as a blood glucose concentration < 54 mg/dL [ < 3.0 mmol/L]) is the threshold at which neuroglycopenic symptoms begin to occur and requires immediate action to resolve the hypoglycemic event. If an individual has level 2 hypoglycemia without adrenergic or neuroglycopenic symptoms, they likely have impaired hypoglycemia awareness (discussed further in HYPOGLYCEMIA RISK ASSESSMENT, below). This clinical scenario warrants investigation and review of the treatment plan (74, 75) . Lastly, level 3 hypoglycemia is defined as a severe event characterized by altered mental and/or physical functioning that requires assistance from another person for recovery, irrespective of glucose level.

Hypoglycemia has a broad range of negative health consequences (76) . Level 3 hypoglycemia may be recognized or unrecognized and can progress to loss of consciousness, seizure, coma, or death. Level 3 hypoglycemia was associated with mortality in both the standard and the intensive glycemia arms of the ACCORD trial, but the relationships between hypoglycemia, achieved A1C, and treatment intensity were not straightforward (77) . An association of level 3 hypoglycemia with mortality was also found in the ADVANCE trial and in clinical practice (78, 79) . Hypoglycemia can cause acute harm to the person with diabetes or others, especially if it causes falls, motor vehicle accidents, or other injury (80) . Hypoglycemia may also cause substantial anxiety that can reduce the quality of life of individuals with diabetes and their caregivers and may contribute to problems with diabetes self-management and treatment (81) (82) (83) . Recurrent level 2 hypoglycemia and/or level 3 hypoglycemia is an urgent medical issue and requires intervention with medical treatment plan adjustment, behavioral intervention, delivery of diabetes selfmanagement education and support, and use of technology to assist with hypoglycemia prevention and identification (75, (84) (85) (86) (87) .

Studies of rates of hypoglycemia predominantly rely on claims data for hospitalizations and emergency department visits (88) (89) (90) (91) . These studies do not capture the level 1 and level 2 hypoglycemia that represent the vast majority of hypoglycemic events, and they also substantially underestimate level 3 hypoglycemia (88, 92, 93) . Nevertheless, they reveal a substantial burden of hypoglycemiarelated hospital utilization in the community (88) (89) (90) (91) . Level 1 and level 2 hypoglycemia can be ascertained from patient self-report (94) and are strong risk factors for subsequent level 3 hypoglycemia.

Hypoglycemia Risk Assessment

Assessment of an individual's risk for hypoglycemia includes evaluating clinical risk factors as well as relevant social, cultural, and economic factors (Table 6 .5). Recommendations 6.10-6.19 group individuals with diabetes into two hypoglycemia risk categories with clinical significance. Individuals at risk for hypoglycemia are those treated with insulin, sulfonylureas, or meglitinides; clinically significant hypoglycemia is rare among individuals taking other diabetes medication classes (95, 96) . Individuals at high risk for hypoglycemia are the subset of individuals at risk for hypoglycemia who either have a major hypoglycemia risk factor or have multiple other risk factors (determined by the health care professional incorporating clinical judgment) (Table 6 .5). This risk stratification is based on epidemiologic studies of hypoglycemia risk (89, 90, 95, (97) (98) (99) (100) (101) . Validated tools have been developed to estimate hypoglycemia risk using predominantly electronic health record data (102) (103) (104) . However, these tools do not include all of the important hypoglycemia risk factors, and more research is needed to determine how they can best be incorporated into clinical care. Among individuals at risk for hypoglycemia, prior hypoglycemic events, especially level 2 or 3 events, are the strongest risk factors for hypoglycemia recurrence (96, 99, (105) (106) (107) . Hypoglycemia history should be assessed at every clinical encounter and should include hypoglycemic event frequency, severity, precipitants, symptoms (or lack thereof), and approach to treatment. It is essential to correlate home glucose readings, both from glucose meters and CGM systems, with symptoms and treatment, as individuals may experience and treat hypoglycemic symptoms without checking their glucose level (108) , treat normal glucose values as hypoglycemic, or tolerate hypoglycemia without treatment either because of lack of symptoms or to avoid hyperglycemia.

Individuals at risk for hypoglycemia should also be screened for impaired hypoglycemia awareness (also called hypoglycemia unawareness or hypoglycemiaassociated autonomic failure) at least yearly. Impaired hypoglycemia awareness is defined as not experiencing the typical counterregulatory hormone release at low glucose levels or the associated symptoms, which often occurs in individuals with long-standing diabetes or recurrent hypoglycemia (109) . Individuals with impaired hypoglycemia awareness may experience confusion as the first sign of hypoglycemia, which can create fear of hypoglycemia and severely impact quality of life (110) . Impaired hypoglycemia awareness dramatically increases the risk for level 3 hypoglycemia (111) . Validated questionnaires for assessing impaired hypoglycemia awareness include the single-question Pedersen-Bjergaard (112) and Gold (113) tools; the Clarke (114) and HypoA-Q (115) tools are longer questionnaires that evaluate multiple domains of impaired hypoglycemia awareness. Comparisons between these tools largely yield good agreement (116, 117) . To efficiently screen for impaired hypoglycemia awareness in clinical practice, clinicians can ask a single question based on these tools such as "Can you always feel when your blood sugar is low?" and follow up "No" responses with a more detailed evaluation.

Other notable clinical and biological risk factors for hypoglycemia are older age, multimorbidity, cognitive impairment, chronic kidney disease and end-stage kidney disease in particular, CVD, depression, and neuropathy (95, 96) . Female sex has also been found to be an independent risk factor for hypoglycemia in multiple studies, although the mechanisms of this relationship are unclear and require further research (95) . Cognitive impairment has a strong bidirectional association with hypoglycemia, and recurrent severe hypoglycemic episodes were associated with a greater decline in psychomotor and mental efficiency after long-term follow-up of the DCCT/EDIC cohort (118) . Therefore, cognitive function should be routinely assessed among older adults with diabetes.

There are a number of important social, cultural, and economic hypoglycemia risk factors that should be considered. Food insecurity is associated with increased risk of hypoglycemia-related emergency department visits and hospitalizations in lowincome households, and this was shown to be mitigated by increased federal nutrition program benefits (119) . In general, individuals with low annual household incomes (96) , individuals who live in socioeconomically deprived areas (99) , and individuals who are underinsured (100) or experiencing housing instability (120) experience higher rates of emergency department visits and hospitalizations for hypoglycemia. Clinicians should also be aware of cultural practices that may influence glycemic management (which are discussed in detail in Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes"), such as fasting as part of religious observance. Fasting may increase the risk for hypoglycemia among individuals treated with insulin or insulin secretagogues if not properly planned for, so clinicians need to engage these individuals to codevelop a diabetes treatment plan that is safe and respectful of their traditions (121) .

Young children with type 1 diabetes and older adults, including those with type 1 and type 2 diabetes (122, 123) , are noted as being particularly vulnerable to hypoglycemia because of their reduced ability to recognize hypoglycemic symptoms and effectively communicate their needs. Individualized glycemic goals, education, nutrition intervention (e.g., bedtime snack to prevent overnight hypoglycemia when specifically needed to treat low blood glucose), physical activity management, medication adjustment, glucose monitoring, and routine clinical surveillance may improve outcomes (109) . Insulin pumps with automated low-glucose suspend and automated insulin delivery systems have been shown to be effective in reducing hypoglycemia in type 1 diabetes (124) . For people with type 1 diabetes with level 3 hypoglycemia and hypoglycemia unawareness that persists despite medical treatment, pancreas transplant alone or human islet transplantation may be an option, but these approaches remain experimental (125, 126) .

Hypoglycemia Treatment

Health care professionals should counsel individuals with diabetes to treat hypoglycemia with fast-acting carbohydrates at the hypoglycemia alert value of 70 mg/dL (3.9 mmol/L) or less (127) (128) (129) . Individuals should be counseled to recheck their glucose 15 min after ingesting carbohydrates and to repeat carbohydrate ingestion and seek care for ongoing hypoglycemia.These instructions should be reviewed at each clinical visit.

For most individuals, 15 g carbohydrates should be ingested. Individuals using automated insulin delivery systems should ingest 5-10 g carbohydrates unless there is hypoglycemia in conjunction with exercise or there has been significant overestimation of a carbohydrate/meal bolus (130) . The acute glycemic response to food correlates better with the glucose content than with the total carbohydrate content. Pure glucose is the preferred initial treatment, but any form of carbohydrate that contains glucose will raise blood glucose. Added fat may slow and then prolong the acute glycemic response. Dietary protein intake may increase insulin secretion and should not be used to treat hypoglycemia (131) . Ongoing insulin activity or insulin secretagogues may lead to recurrent hypoglycemia unless more food is ingested after recovery.

Glucagon

The use of glucagon is indicated for the treatment of hypoglycemia in people unable or unwilling to consume carbohydrates by mouth. All individuals treated with insulin or who are at high risk of hypoglycemia as discussed above should be prescribed glucagon. For these individuals, clinicians should routinely review their access to glucagon, as appropriate glucagon prescribing is very low in current practice (132) (133) (134) . An individual does not need to be a health care professional to safely administer glucagon. Those in close contact with, or having custodial care of, these individuals (family members, roommates, school personnel, childcare professionals, correctional institution staff, or coworkers) should be instructed on the use of glucagon, including where the glucagon product is kept and when and how to administer it. It is essential that they be explicitly educated to never administer insulin to individuals experiencing hypoglycemia. Glucagon was traditionally dispensed as a powder that requires reconstitution prior to injection. However, intranasal and ready-toinject glucagon preparations are now widely available and are preferred due to their ease of administration resulting in more rapid correction of hypoglycemia (135) (136) (137) . Although the physical and chemical stability of glucagon has improved with newer formulations, care should be taken to replace glucagon products when they reach their expiration date and to store glucagon based on specific product instructions to ensure safe and effective use. For currently available glucagon products and associated costs, see Table 6 .6. Health insurance providers may prefer only select glucagon products, so it is important to check individuals' insurance coverage and prescribe formulary products whenever possible.

Hypoglycemia Prevention

A multicomponent hypoglycemia prevention plan (Table 6 .7) is critical to caring for individuals at risk for hypoglycemia. Hypoglycemia prevention begins by establishing an individual's hypoglycemia history and risk factors, as discussed in HYPOGLYCEMIA RISK ASSESSMENT above. Structured education for hypoglycemia prevention and treatment is critical and has been shown to improve hypoglycemia outcomes (138, 139) . Education should ideally be provided through a diabetes self-management education and support program or by a trained diabetes care and education specialist, although these services are not available in many areas (140, 141) . If structured education is not available, clinicians should educate individuals at risk for hypoglycemia on hypoglycemia definitions, situations that may precipitate hypoglycemia (fasting, delayed meals, physical activity, and illness), blood glucose self-monitoring, avoidance of driving with hypoglycemia, step-by-step instructions on hypoglycemia treatment as discussed above, and glucagon use as appropriate (138) .

CGM can be a valuable tool for detecting and preventing hypoglycemia in many individuals with diabetes, and it is recommended for insulin-treated individuals, especially those using multiple daily insulin injections or continuous subcutaneous insulin infusion. There is clinical trial evidence that CGM reduces rates of hypoglycemia in these populations. CGM can reveal asymptomatic hypoglycemia and help identify patterns and precipitants of hypoglycemic events (142, 143) . Real-time CGM can provide alarms that can warn individuals of falling glucose so that they can intervene (142, 143) . For more information on using BGM and CGM for hypoglycemia prevention, see Section 7, "Diabetes Technology."

An essential component of hypoglycemia prevention is appropriate modification to diabetes treatment in the setting of intercurrent illness (discussed in detail below) or to prevent recurrent hypoglycemic events. Level 2 or 3 hypoglycemic events especially should trigger a reevaluation of the individual's diabetes treatment plan, with consideration of deintensification of therapy within individualized glycemic goals.

Individuals with impaired awareness should be offered training to reestablish awareness of hypoglycemia. Fear of hypoglycemia and hypoglycemia unawareness often co-occur, so interventions aimed at treating one often benefit both (144) . Several evidence-based training programs have been developed for this purpose and have been demonstrated to reduce rates of hypoglycemia and improve quality of life among people with type 1 diabetes and impaired hypoglycemia awareness (75, 145, 146) . However, these programs are not currently available for clinical use. Similar training can be provided through qualified behavioral health professionals, diabetes care and education specialists, or other professionals with experience in this area, although this approach has not been evaluated in clinical trials. In addition, several weeks of avoidance of hypoglycemia, typically accomplished through a temporary relaxation of glycemic goals, can improve counterregulation and hypoglycemia awareness in many people with diabetes (147) . Hence, individuals with impaired hypoglycemia awareness and recurrent hypoglycemic episodes may benefit from short-term relaxation of glycemic goals.

INTERCURRENT ILLNESS

Stressful events (e.g., illness, trauma, and surgery) increase the risk for both hyperglycemia and hypoglycemia among individuals with diabetes. In severe cases, they may precipitate diabetic ketoacidosis or a nonketotic hyperglycemic hyperosmolar state, which are life-threatening [181, 182] or NADAC [183] ; median AWP or NADAC is listed alone when only one product and/or price is described).

conditions that require immediate medical care. Any individuals with diabetes experiencing illness or other stressful events should be assessed for the need for more frequent monitoring of glucose; ketosis-prone individuals also require urine or blood ketone monitoring. Clinicians should reevaluate diabetes treatment during these events and make adjustments as appropriate. Clinicians should be aware of medication interactions that may precipitate hypoglycemia. Notably, sulfonylureas interact with a number of commonly used antimicrobials (fluoroquinolones, clarithromycin, sulfamethoxazole-trimethoprim, metronidazole, and fluconazole) that can dramatically increase their effective dose, leading to hypoglycemia (148) (149) (150) . Clinicians should consider temporarily decreasing or stopping sulfonylureas when these antimicrobials are prescribed. For further information on management of hyperglycemia in the hospital, see Section 16, "Diabetes Care in the Hospital."

HYPERGLYCEMIC CRISES: DIAGNOSIS, MANAGEMENT, AND PREVENTION Recommendations 6.20 Review history of hyperglycemic crises (i.e., diabetic ketoacidosis and hyperglycemic hyperosmolar state) at every clinical encounter for all individuals with diabetes at risk for these events. C 6.21 Provide structured education on the recognition, prevention, and management of hyperglycemic crisis to all individuals with type 1 diabetes, those with type 2 diabetes who have experienced these events, and people at high risk for these events. B Diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS) are serious, acute, and life-threatening hyperglycemic emergencies in individuals with diabetes (151) that incur substantial morbidity, mortality, and costs (152) . Approximately 1% of all hospitalizations in people with diabetes are for hyperglycemic crises. The diagnostic criteria for DKA and HHS are summarized in Table 6 .8; all criteria must be met to establish these diagnoses. Importantly, approximately 10% of people experiencing DKA present with euglycemic DKA (plasma glucose < 200 mg/dL [11.1 mmol/L]); therefore, DKA diagnosis requires either the presence of hyperglycemia or prior history of diabetes (151) . Euglycemic DKA requires insulin deficiency and can be associated with a variety of factors including reduced food intake, pregnancy, alcohol use, liver failure, and/or SGLT2 inhibitor therapy (153) . Additionally, DKA and HHS often present concurrently (154) , though few studies have examined mixed DKA-HHS events.

There has been a concerning rise in the rate of hyperglycemic crises in people with both type 1 diabetes and type 2 diabetes over the past decade (91, (155) (156) (157) (158) (159) (160) (161) . Recent data suggest hyperglycemic crisis rates of up to 44.5-82.6 per 1,000 person-years among people with type 1 diabetes (91, 159) and up to 3.2 per 1,000 person-years among people with type 2 diabetes (91) . While DKA mortality decreased in the first decade of the 21st century (156) , these improvements have Training to reestablish awareness of hypoglycemia ‡ ‡

The listed frequencies are the recommended minimum; actions for hypoglycemia prevention should be taken more often as needed based on clinical judgment. *Indicated with recurrent hypoglycemic events or at initiation of medication with a high risk for hypoglycemia. †Indicated with any level 2 or 3 hypoglycemia, intercurrent illness, or initiating interacting medications. ‡Indicated when impaired hypoglycemia awareness is detected. plateaued in the past decade (155, 159, 162) . Most recently available data for inpatient mortality during hospital admission for DKA ranges from 0.2% in type 1 diabetes (163) to 1.0% in type 2 diabetes (156, 164) . Inpatient mortality among people with type 2 diabetes hospitalized for HHS decreased from 1.44% in 2008 to 0.77% in 2018 (165) . The only study to have examined inpatient mortality for mixed DKA-HHS found it to be higher than mortality for HHS or DKA alone (154) . Mortality rates reported in low-and middleincome countries are much higher than those in developed countries, potentially because of delayed diagnosis and treatment (151) . People discharged after an episode of DKA have a 1-year age-corrected mortality rate that is 13 times higher than the general population (166) .

There are a number of clinical factors associated with an increased risk of hyperglycemic crises (Table 6 .9). In addition, several studies have reported DKA at the presentation of newly diagnosed type 1 diabetes during or after a coronavirus disease 2019 (COVID-19) infection. The precise mechanisms for new-onset diabetes in people with COVID-19 are not known, but several complex interrelated processes may be involved. Some drug classes can affect carbohydrate metabolism and precipitate the development of DKA and HHS, including glucocorticoids, antipsychotic medications, checkpoint inhibitors, and SGLT2 inhibitors. The risk of DKA in people with type 1 diabetes using SGLT2 inhibitors can be 5-17 times higher than that in nonusers. In contrast, observational studies and randomized controlled trials have shown that DKA is uncommon in people with type 2 diabetes treated with SGLT2 inhibitors (0.6-4.9 events per 1,000 patient-years) (167) . A meta-analysis of four randomized controlled trials found the relative risk of DKA in participants with type 2 diabetes treated with SGLT2 inhibitors versus placebo or active comparator arm to be 2.46 (95% CI 1.16-5.21), while a meta-analysis of five observational studies found the relative risk to be 1.74 (95% CI 1.07-2.83) (168) . Risk factors for DKA in individuals with type 2 diabetes treated with SGLT2 inhibitors include very-low-carbohydrate diets and prolonged fasting, dehydration, excessive alcohol intake, and the presence of autoimmunity, in addition to typical precipitating factors (168, 169) . Up to 2% of pregnancies with pregestational diabetes (most often type 1 diabetes) are complicated by DKA. The incidence of DKA in gestational diabetes is low ( < 0.1%) (170). Pregnant individuals may present with euglycemic DKA (glucose < 200 mg/dL [11.1 mmol/L]), and the diagnosis of DKA may be hindered by the presence of mixed acid-based disturbances, particularly in the setting of hyperemesis. Due to significant risk of fetomaternal harm, pregnant individuals at risk for DKA should be counseled on the signs and symptoms suggestive of DKA and seek immediate medical attention if concern for DKA is present.

Hyperglycemic crisis should be considered in all individuals presenting with polyuria, polydipsia, weight loss, vomiting, dehydration, and change in cognitive state (Table 6 .10). Individuals at risk for DKA should be counseled on the early signs and symptoms of DKA, provided with appropriate tools for accurate ketone measurement (urine and/or blood ketone tests), and educated on timely self-management of hyperglycemia and ketonemia ("sick day advice") (171-173) to prevent clinical deterioration and need for acute care. Individuals treated with intensive insulin therapy should not stop or hold their basal insulin even if not eating, and clinicians should provide detailed instructions on insulin dose adjustments in the setting of illness or fasting to prevent DKA occurrence and worsening. Individuals concerned about or experiencing DKA should be encouraged to contact their diabetes care team immediately. Readily available clinical support can help individuals self-manage hyperglycemia during illness and prevent emergency department and hospital care (174). Individuals at risk for DKA should measure urine or blood ketones in the presence of symptoms and potential precipitating factors (e.g., illness, missed insulin doses), particularly if glucose levels exceed 200 mg/dL (11.1 mmol/L). When hemodynamically and cognitively intact, able to tolerate oral hydration, and able to administer subcutaneous insulin, individuals may treat mild DKA with frequent blood glucose and urine or blood ketone monitoring, noncaloric hydration, and subcutaneous insulin administration. However, individuals should seek immediate medical attention if unable to tolerate oral hydration, blood glucose levels do not improve with insulin administration, altered mental status is present, or any signs of worsening illness occur. Because HHS is associated with greater volume depletion and is typically triggered by an acute illness, individuals with suspected HHS should be immediately evaluated and treated in the inpatient setting.

A substantial proportion of individuals hospitalized with DKA experience recurrent episodes (175,176), which underscores the importance of engaging individuals experiencing these events to identify triggers and prevent recurrence. Structured diabetes self-management education and support that includes problem-solving is effective at reducing DKA admissions, as are psychological interventions, peer (11) . In addition, the health care team's knowledge and competency are even more relevant when people with diabetes are started on advanced diabetes technologies, such as AID systems. In such situations, training is vital and should include a discussion about realistic expectations for the ability of the initiated system to achieve glucose goals, the system's features and limitations, and the best way to use the new system to maximize the benefits it can offer (12) .

Use in Schools

Instructions for device use should be outlined in the student's diabetes medical management plan (DMMP). A backup plan should be included in the DMMP for potential device failure (e.g., BGM, CGM, and/or insulin delivery devices). School nurses and designees should complete training to stay up to date on diabetes technologies prescribed for use in the school setting. Updated resources to support diabetes care at school, including training materials and a DMMP template, can be found online at diabetes.org/safe-at-school-state-laws.

Initiation of Device Use

The use of CGM and BGM devices should be considered from the outset of the diagnosis of diabetes that requires insulin management (3, 4) . CGM use allows for close tracking of glucose levels with adjustments of insulin dosing and lifestyle modifications and removes the burden of frequent BGM.

In addition, early CGM initiation after diagnosis of type 1 diabetes in youth has been shown to decrease A1C levels and is associated with high parental satisfaction and reliance on this technology for diabetes management (5, 6) . 7 .1. In Europe, currently marketed meters must meet current ISO standards. In the U.S., currently marketed meters must meet the standard under which they were approved, which may not be the current standard. Moreover, the monitoring of current accuracy postmarketing is left to the manufacturer and not routinely checked by an independent source. People with diabetes assume their glucose meter is accurate because it is FDA cleared, but that may not be the case. There is substantial variation in the accuracy of widely used BGM systems (17, 18) . The Diabetes Technology Society Blood Glucose Monitoring System Surveillance Program provides information on the performance of devices used for BGM (diabetestechnology.org/surveillance/). In one analysis, 6 of the top 18 best-selling glucose meters met the accuracy standard (19) . In a subsequent analysis with updated glucose meters, 14 of 18 glucose meters met the minimum accuracy requirements (20) .There are single-meter studies in which benefits have been found with individual meter systems, but few studies have compared meters head-to-head. Certain meter system characteristics, such as the use of lancing devices that are less painful (21) and the ability to reapply blood to a strip with an insufficient initial sample, or meters with integrated speech that can read aloud glucose levels for visually impaired individuals (22) , may also be beneficial to people with diabetes (23) and may make BGM less burdensome to perform.

Counterfeit Strips

People with diabetes should be advised against purchasing or reselling preowned or secondhand test strips, as these may give incorrect results. Only unopened and unexpired vials of glucose test strips should be used to ensure BGM accuracy.

Optimizing Blood Glucose Monitoring Device Use

Optimal use of BGM devices requires proper review and interpretation of data by both the person with diabetes and the health care professional to ensure that data are used in an effective and timely manner. In people with type 1 diabetes, there is a correlation between greater BGM frequency and lower A1C levels (24) . Among those who check their blood glucose at least once daily, many report taking no action when results are high or low (25) . Some meters now provide advice to the user in real time when monitoring glucose levels (26) , whereas others can be used as a part of integrated health platforms (27) . People with diabetes should be taught how to use BGM data to adjust food intake, physical activity, or pharmacologic therapy to achieve specific goals. The ongoing need for and frequency of BGM should be reevaluated at each routine visit to ensure its effective use (24, 28) .

People With Diabetes on Intensive Insulin Therapies

BGM is especially important for people with diabetes treated with insulin to monitor for and prevent hypoglycemia and hyperglycemia. Most individuals on intensive insulin therapies (multiple daily injections [MDI] or insulin pump therapy) should be encouraged to assess glucose levels using BGM (and/or CGM) prior to meals and snacks, at bedtime, occasionally postprandially, prior (299) . †The range of blood glucose values for which the meter has been proven accurate and will provide readings (other than low, high, or error). ‡Values outside of the "clinically acceptable" A and B regions are considered "outlier" readings and may be dangerous to use for therapeutic decisions (300) .

to, during, and after physical activity, when they suspect hypoglycemia or hyperglycemia, after treating hypoglycemia until they are normoglycemic, and prior to and while performing critical tasks such as driving. For many individuals using BGM, this requires checking up to 6-10 times daily, although individual needs may vary. A database study of almost 27,000 children and adolescents with type 1 diabetes showed that, after adjusting for multiple confounders, increased daily frequency of BGM was significantly associated with lower A1C levels (À0.2% per additional check per day) and with fewer acute complications (29) .

People With Diabetes Using Basal Insulin and/or Oral Agents and Noninsulin Injectables

The evidence is insufficient regarding when to prescribe BGM and how often monitoring is needed for insulin-treated people with diabetes who do not use intensive insulin therapy, such as those with type 2 diabetes taking basal insulin with or without oral agents and/or noninsulin injectables. However, for those taking basal insulin, assessing fasting glucose with BGM to inform dose adjustments to achieve blood glucose goals results in lower A1C levels (30) .

The modulation of insulin delivery is done by increasing, decreasing, or pausing insulin based on the CGM feedback, the predicted direction of the glucose levels, and the speed with which the glucose levels are changing. Different AID systems modulate insulin based on predicted glucose levels at various times, most commonly 30 min or 1 h. Currently available AID systems have either fixed glucose targets or adjustable glucose targets, generally ranging from 100 to 120 mg/dL, with some exceptions where glucose targets can be adjusted up to 150 mg/dL. Glucose targets are generally set up for 24 h but can also be adjusted in some systems with up to eight segments per day. All current AID systems provide automated correction doses, whether embedded in the microdose adjustments every 5 min or by providing additional correction boluses whose doses are dependent on the various types of algorithms with variable frequency and threshold glucose based on the type of control algorithm. Most AID systems can be used in manual mode, although this is generally not recommended, as the benefits of CGM modulation may be partially or totally lost. However, use of AID in manual mode may be necessary in some circumstances, therefore it is important to review and reassess manual-mode settings periodically. Current AID systems still require manual entry of carbohydrates for meal announcements or qualitative meal estimation announcements to calculate prandial doses.

Adjustments for physical activity are available in most AID systems currently on the market. These can be programmed in various time increments. In general, the glucose target is raised to prespecified levels based on AID systems, and these are often accompanied by more conservative insulin delivery to reduce the risk of hypoglycemia in the setting of increased insulin sensitivity other than physical activity, such as prolonged fasting or NPO status for procedures. Of note, some systems may still give autocorrection boluses if the glucose levels rise above a certain threshold even while the exercise/activity mode has been enabled. Details on the available AID systems and their features can be found at pantherprogram.org/device-type.

AID systems have largely replaced other methods of continuous subcutaneous insulin delivery due to the advantages they offer in insulin modulation and sophistication of algorithms to adjust insulin doses and minimize hypoglycemia and hyperglycemia.

Data From Pivotal Trials

All currently FDA-approved AID systems were tested for safety and efficacy in their pivotal trials in children and adults with type 1 diabetes (194) (195) (196) (197) (198) (199) (200) (201) (202) (203) (204) (205) (206) . These studies were conducted either as a single arm of manual mode followed by automated mode of a specific AID system or as an RCT comparing the AID system to an SAP and/or usual care. Regardless of the study design, all AID system pivotal trials that examined individuals 2 years old or older, including older adults, have consistently demonstrated superiority to either standard insulin delivery (or manual mode for the single-arm studies) or SAP and/or usual care (for the randomized trials), with consistent improvement in A1C, increase in TIR, especially overnight, as well as reduction of time spent in hypoglycemia (207) (208) (209) (210) (211) (212) (213) (214) (215) (216) (217) (218) (219) . The greatest improvements were seen with AID when used in individuals with the highest baseline A1C or lowest TIR (220) . These systems may also lower the risk of exercise-related hypoglycemia (219) and have been shown to have psychosocial benefits (221) (222) (223) (224) (225) . A review of the literature on the health and economic value of AID systems in individuals with type 1 diabetes found that AID systems are cost-effective (226) . AID is rapidly becoming the standard of care for people with type 1 diabetes and should be the preferred method of insulin delivery in these individuals. The decision to use AID systems should be made based on the preference of the person with diabetes and the selection of individuals (and/or caregivers) who are capable of safely and effectively using the devices.

Data From Real-world Studies

Data from real-world studies on AID systems have become available and continue to increase rapidly. These studies include large numbers of users, at times even 30-fold higher than the number of people studied in AID pivotal trials (227) . It is important to emphasize that for some AID systems all data are automatically collected to the database (228) , whereas for other systems data are collected based on voluntary sharing to the database by AID users. A recent systematic review of AID real-world studies, with 20 studies representing 171,209 individuals, substantiated the results observed in the pivotal trials and have confirmed the clinical benefits of AID systems in people with type 1 diabetes. Newer systems have shown increased time spent in automation, and the real-world studies have retrospectively analyzed longer duration of system use compared with their respective pivotal trials, with most analyses occurring for more than 6 months and an average duration of 9 months (227) .

Benefits include improvement in A1C levels, TIR, and other glucometrics as well as psychosocial benefits (229) (230) (231) (232) (233) (234) .

Finally, real-world data showed that AID systems provide the same glycemic benefits to Medicare and Medicaid beneficiaries with type 1 and type 2 diabetes, emphasizing that access to this technology should be made available regardless of A1C levels and should be based on the individual's needs (235) .

Automated Insulin Delivery Systems in Pregnancy

The use of AID systems in diabetes and pregnancy presents particular challenges, as the current FDA-approved AID systems (except for one that has been FDA approved but is not yet commercially available) have glucose goals that are not pregnancy specific and do not have algorithms designed to achieve pregnancyspecific glucose goals. Initiating or continuing AID systems during pregnancy needs to be assessed carefully. Selected individuals with type 1 diabetes should be evaluated as potential candidates for AID systems in the setting of expert guidance. Recent data have shown the clinical benefits and safety of AID use, even though only one study used an AID system with a pregnancyspecific glycemic target. This study, a multicenter, controlled trial, enrolled pregnant women with type 1 diabetes before 14 weeks' gestation and randomized them by week 16 to the AID system or standard care (MDI with CGM or standard insulin pump therapy with CGM). The primary outcome of time spent in the pregnancy-specific target range of 63-140 mg/dL was found to be 10.5% higher in the AID group versus standard care (P < 0.001). The secondary outcomes were also met, with less time spent above range ( > 140 mg/dL) in the AID group, greater overnight time in target range, and lower A1C (236) . There were no differences in the number of preterm births, birth weight, neonatal complications, or admission to the neonatal intensive care unit.

Additional data were reported from a pilot RCT of SAP without automation versus assisted hybrid closed-loop therapy in pregnant women with type 1 diabetes that enrolled participants in the first trimester and randomized them at 14-18 weeks' gestation. This system did not have pregnancy-specific glucose targets; however, the results showed that the time in hypoglycemia < 54 mg/dL did not differ between groups. Time at < 63 mg/dL was lower in the hybrid closed-loop group, whereas percentage of the pregnancy-specific TIR was greater in the SAP group in the third trimester, with similar safety and adverse pregnancy outcomes between groups (237) . There were no statistically significant differences in measures of glycemic risk or in measures of glycemic variability between the hybrid closed-loop and the SAP groups at any point during pregnancy or postpartum (238) . In another study with an AID system with a lowest glucose target of 100 mg/dL, participants were randomized to AID or standard of care in the first trimester and for the rest of gestation. The 24-h percentage of pregnancy-specific TIR was not different between groups, but the overnight percentage of pregnancy-specific TIR was higher in the AID group while using assistive techniques. Time spent below range was lower over 24 h and overnight in the AID group as well. Quality-of-life metrics were improved in the AID group in this study (239) .

Therefore, if the decision is made to use AID systems without pregnancy-specific targets in selected pregnant individuals, then using assistive techniques, such as the combination of SAP mode (or manual mode) and hybrid closed-loop mode at different time points in pregnancy or throughout the day or entering fake carbohydrate boluses, should be considered and applied as needed to achieve intended goals (240) . See Section 15, "Diabetes and Pregnancy," for more details.

Insulin Pumps and Automated Insulin Delivery Systems in People With Type 2 and Other Types of Diabetes

Traditional insulin pumps can be considered for the treatment of people with type 2 diabetes who are on MDI as well as those who have other types of diabetes resulting in insulin deficiency, for instance, those who have had a pancreatectomy and/or individuals with cystic fibrosis (241) (242) (243) (244) (245) . Similar to data on insulin pump use in people with type 1 diabetes, reductions in A1C levels have been reported in some studies (243, 246) . More recently, real-world reports have shown reduction of A1C levels and reduction of total daily insulin dose in individuals with type 2 diabetes initiating insulin pump therapy (247) . Use of insulin pumps in insulin-requiring people with any type of diabetes may improve user satisfaction and simplify therapy (171,241).

For people with diabetes judged to be clinically insulin deficient who are treated with an intensive insulin therapy, the presence or absence of measurable C-peptide levels does not correlate with response to therapy (171). A low C-peptide value should not be required for insulin pump coverage in individuals with type 2 diabetes.

The use of insulin pumps and AID systems in type 2 diabetes is still limited, and at this time only one system is FDA approved for use in type 2 diabetes. Nevertheless, data are increasing; a small, single-arm prospective study in adults with type 2 diabetes who were on MDI and started an AID system revealed improvement of TIR by 15% at 6 weeks (248) . Similar findings were reported in a randomized controlled, crossover trial of adults with type 2 diabetes previously treated with conventional insulin pump therapy plus CGM. While on the AID system (5 weeks), the TIR increased by a mean of 15%, with a decrease in TAR ( > 180 mg/dL and > 250 mg/dL) and GMI. Of note, an increase in total daily insulin dose was noted in the subjects while on the AID system (249) , whereas other studies have shown either nonsignificant trends for a lower total daily dose of insulin in the AID group (250) or a reduction of total daily insulin in the AID group previously using MDI (251) . Finally, a recent RCT of older adults with type 2 diabetes who used MDI but were unable to manage insulin therapy on their own revealed an increase of TIR of 27% over 12 weeks of AID system use in addition to tailored home health care services (250) . Real-world studies have also shown benefits of these technologies in adults with type 2 diabetes (235, 251) .

Alternative insulin delivery options in people with type 2 diabetes include disposable patch-like devices, which provide either a continuous subcutaneous insulin infusion of rapid-acting insulin (basal) with bolus insulin in 2-unit increments at the press of a button or bolus insulin only, delivered in 2-unit increments, used in conjunction with basal insulin injections (242, 244, 252, 253) . Use of an insulin pump as a means of insulin delivery is an individual choice for people with diabetes and should be considered an option in those who are capable of safely using the device.

Open-Source Automated Insulin Dosing Recommendation 7.29 Support and provide diabetes management advice to people with diabetes who choose to use an opensource closed-loop system. B Open-source automated insulin dosing (OS-AID) algorithms provide the precise code that governs their operation, so health care professionals and people with diabetes can have a more complete understanding of risks and benefits (254) . Any commercial entity could provide the source code for their interoperable automated glycemic controller, but most choose not to. OS-AID algorithms are largely designed, maintained, and curated by people with diabetes and their loved ones. Thousands of people with diabetes use these algorithms with cleared CGM systems and insulin pump components. The information on how to set up and manage these systems is freely available online.

OS-AID is the preferred term when referring to any open-source system (commercial or otherwise). It is important to note that the term "DIY" is not reflective of any aspect of these community-driven systems. No individual person has written all the code for these algorithms, and a large percentage of users do not build the software themselves (255) . There are two main available algorithms, the Open-APS algorithm and the Loop algorithm, which have been implemented on a variety of platforms.

The OpenAPS heuristic algorithm (implemented on a system on a chip in OpenAPS, Android smartphones as An-droidAPS, and iPhone as iAPS/Trio) is supported by large real-world studies (256) and a multicenter RCT (257) . The OpenAPS algorithm is the only AID system to support unannounced meals. In a singlecenter study of adolescents with type 1 diabetes randomized to AndroidAPS with quantitative carbohydrate announcements, qualitative announcements, and no announcements, TIR was preserved across groups (258) .

Loop, an open-source model predictive control algorithm, is implemented on iPhones as an app. Prospective realworld data from 558 adults and children with type 1 diabetes on this system (255) was used to support the FDA clearance of a variant called Tidepool Loop (259) .

Both the Loop and OpenAPS algorithms offer direct management of algorithm aggressiveness through conventional pump settings. Therefore, it is advisable that health care professionals understand and offer support in tuning settings for these safe and effective technologies (254) . This may include, for example, the adjustment of basal rates, insulin-to-carbohydrate ratios, or insulin sensitivity factors. As with any AID system, a backup insulin treatment plan is advisable.

Digital Health Technology

Recommendation 7.30 Consider combining technology (CGM, insulin pump, and/or diabetes apps) with online or virtual coaching to improve glycemic outcomes in individuals with diabetes or prediabetes. B Increasingly, people are turning to the internet for advice, coaching, connection, and health care. Diabetes, partly because it is both common and numeric, lends itself to the development of apps and online programs. Recommendations for developing and implementing a digital diabetes clinic have been published (260) . The FDA approves and monitors clinically validated, digital, and usually online health technologies intended to treat a medical or psychological condition; these are known as digital therapeutics, or "digiceuticals" (fda. gov/medical-devices/digital-health-centerexcellence/device-software-functionsincluding-mobile-medical-applications) (261) . Other applications, such as those that assist in displaying or storing data, encourage a healthy lifestyle or provide limited clinical data support. Therefore, it is possible to find apps that have been fully reviewed and approved by the FDA and others designed and promoted by people with relatively little skill or knowledge in the clinical treatment of diabetes. There are insufficient data to provide recommendations for specific apps for diabetes management, education, and support in the absence of RCTs and validation of apps unless they are FDA cleared.

An area of particular importance is that of online privacy and security. Established cloud-based data aggregator programs, such as Tidepool, Glooko, and others, have been developed with appropriate data security features and are compliant with the U.S. Health Insurance Portability and Accountability Act of 1996. These programs can help monitor people with diabetes and provide access to their health care teams (262) . Consumers should read the policy regarding data privacy and sharing before entering data into an application and learn how they can manage the way their data will be used (some programs offer the ability to share more or less information, such as being part of a registry or data repository or not).

Many online programs offer lifestyle counseling to achieve weight loss and increased physical activity (263) . Many include a health coach and can create small groups of similar participants on social networks. Some programs aim to treat prediabetes and prevent progression to diabetes, often following the model of the Diabetes Prevention Program (264, 265) . Others assist in improving diabetes outcomes by remotely monitoring clinical data (for instance, wireless monitoring of glucose levels, weight, or blood pressure) and providing feedback and coaching (266) (267) (268) (269) (270) (271) . There are text messaging approaches that tie into a variety of different types of lifestyle and treatment programs, which vary in terms of their effectiveness (272, 273) . There are limited RCT data for many of these interventions, and long-term follow-up is lacking. However, in a real-world observational study in individuals with type 2 diabetes treated with basal insulin, oral medications, or no medications, the use of a digital health solution and rtCGM resulted in reductions of GMI and TAR > 180 and > 250 mg/dL as well as an increase in TIR by 15% and participation in a least one engagement activity per week (274) . Therefore, even with limited data, for an individual with diabetes, opting in to one of these programs can be helpful in providing support and, for many, is an attractive option.

Inpatient Care Recommendations 7.31 In people with diabetes wearing personal CGM, the use of CGM should be continued when clinically appropriate during hospitalization, with confirmatory point-of-care glucose measurements for insulin dosing and hypoglycemia assessment and treatment under an institutional protocol. B 7.32 Continue use of insulin pump or AID in people with diabetes who are hospitalized when clinically appropriate, with confirmatory point-of-care blood glucose measurements for insulin dose decisions and hypoglycemia assessment and treatment. This is contingent upon availability of necessary supplies, resources, and training, ongoing competency assessments, and implementation of institutional diabetes technology protocols. C Individuals who are comfortable using their diabetes devices, such as insulin pumps and CGM, should be allowed to use them in an inpatient setting if they are well enough to take care of the devices and have brought the necessary supplies (273, (275) (276) (277) (278) . People with diabetes who are familiar with treating their own glucose levels can often adjust insulin doses more knowledgeably than inpatient staff who do not personally know the individual or their management style. It is crucial that, when people with diabetes in the inpatient setting need to temporarily disconnect or interrupt their device use for a procedure or imaging studies, etc., the care team is particularly careful to not discard these devices or stop their use without ensuring that an alternate method of insulin delivery has been initiated, if these are insulin delivery devices, and to ensure that close glucose monitoring is continued by finger stick. Therefore, it is particularly important that the use of diabetes devices while in the inpatient setting should occur based on the hospital's policies for diabetes management and use of diabetes technology, and there should be supervision to ensure that the individual is achieving and maintaining glycemic goals during acute illness in a hospitalized setting where factors such as infection, certain medications, immobility, and changes in nutrition can affect insulin sensitivity and the insulin response (279) (280) (281) .

With the advent of the coronavirus disease 2019 pandemic, the FDA exercised enforcement discretion by allowing CGM device use temporarily in the hospital for patient monitoring (282) . This approach has been taken to reduce the use of personal protective equipment and more closely monitor patients so that health care personnel do not have to go into a patient room solely to measure a glucose level (283) (284) (285) (286) . Studies have been published assessing the effectiveness of this approach, which may ultimately lead to the approved use of CGM for monitoring hospitalized individuals (277, (286) (287) (288) (289) (290) (291) (292) (293) (294) (295) . When used in the setting of a clinical trial or when clinical circumstances (such as during a shortage of personal protective equipment) require it, CGM can be used to manage hospitalized individuals in conjunction with BGM. Pointof-care BGM remains the approved method for glucose monitoring in hospitals, especially for dosing insulin and treating hypoglycemia. Similarly, data are emerging on the inpatient use of AID systems and their challenges (277, 296, 297) . For more information, see Section 16, "Diabetes Care in the Hospital."

The Future

The pace of development in diabetes technology is extremely rapid. New approaches and tools are available each year. It is difficult for research to keep up with these advances, because newer versions of the devices and digital solutions are already on the market by the time a study is completed. The most important component in all these systems is the person with diabetes. Technology selection must be appropriate for the individual. Simply having a device or application does not change outcomes unless the human being engages with it to create positive health benefits. This underscores the need for the health care team to assist people with diabetes in device and program selection and to support their use through ongoing education and training. Expectations must be tempered by reality-we do not yet have technology that completely eliminates the self-care tasks necessary for managing diabetes, but the tools described in this section can make it easier to manage. Obesity is a chronic, often relapsing disease with numerous metabolic, physical, and psychosocial complications, including a substantially increased risk for the development and progression of type 2 diabetes (1). There is strong and consistent evidence that obesity management can delay the progression from prediabetes to type 2 diabetes (2-6) and is highly beneficial in treating type 2 diabetes (7-15). In people with type 2 diabetes and overweight or obesity, modest weight loss improves glycemia and reduces the need for glucose-lowering medications (7, 16, 17) , and greater weight loss substantially reduces A1C and fasting glucose and may promote sustained diabetes remission (9, (18) (19) (20) (21) (22) . Metabolic surgery, which results in an average > 20% body weight loss, greatly improving glycemia and often leading to remission of diabetes, improved quality of life, improved cardiovascular outcomes, and reduced mortality (23, 24) . Several therapeutic modalities, including intensive behavioral and lifestyle counseling, weight management pharmacotherapy, and metabolic surgery, may aid in achieving and maintaining meaningful weight loss and reducing obesity-associated health risks. This section aims to provide evidence-based recommendations for obesity management, including behavioral, pharmacologic, and surgical interventions, in people with, or at high risk of, type 2 diabetes. Additional considerations regarding weight management in older individuals and children can be found in Section 13, "Older Adults," and Section 14, "Children and Adolescents." Obesity is defined by the World Health Organization as an abnormal or excessive fat accumulation that presents a risk to health (25) . BMI (calculated as weight in kilograms divided by the square of height in meters [kg/m 2 ]) has been used widely to diagnose and stage obesity (overweight: BMI 25-29.9 kg/m 2 ; obesity class I: BMI 30-34.9 kg/m 2 ; obesity class II: BMI 35-39.9 kg/m 2 ; obesity class III: BMI $40 kg/m 2 ); however, BMI should not be relied on as a sole diagnostic and staging tool (19) . Despite its ease of measurement, BMI is at most an imperfect measure of adipose tissue mass and does not measure adipose tissue distribution or function, and it does not factor in the presence of weight-related health or well-being consequences (26, 27) . BMI is especially prone to misclassification in individuals who are very muscular or frail and in populations with different body composition and cardiometabolic risk (28) . A diagnosis of obesity should be made based on an overall assessment of the individual's adipose tissue mass (BMI can be used as a general guide), distribution (using other anthropometric measurements, like waist circumference, waist-to-hip circumference ratio, or waistto-height ratio), or function and, importantly, the presence of associated health or well-being consequences: metabolic, physical, or psychological (29) .

ASSESSMENT

Obesity is a key pathophysiologic driver of diabetes, other cardiovascular risk factors (e.g., hypertension, hyperlipidemia, metabolic dysfunction-associated steatotic liver disease [MASLD], and inflammatory state), and ultimately cardiovascular and kidney disease (30) . Diabetes can further exacerbate obesity, including through the use of glucose-lowering therapies that lead to weight gain (e.g., insulin, sulfonylurea, and pioglitazone), and obesity can exacerbate hyperglycemia and diabetes, thereby setting up a vicious cycle that contributes to disease progression and occurrence of microvascular and macrovascular complications. As such, treatment goals for both glycemia and weight are recommended in people with diabetes to address both hyperglycemia and its underlying pathophysiologic driver (obesity) and therefore benefit the person holistically.

Weight stigma, fat bias, and anti-fat bias are ways to describe the bias toward people living in larger bodies. Fat bias is prevalent among health care professionals and the general public. Health care professionals are strongly encouraged to increase their awareness of implicit and explicit weight-biased attitudes (31) . Increasing empathy and understanding about the complexity of weight management among health care professionals is a useful avenue to help reduce weight bias (32) .

A person-centered communication style that uses inclusive and nonjudgmental language and active listening to elicit individual preferences and beliefs and assesses potential barriers to care should be used to optimize health outcomes and healthrelated quality of life. Use person-first language (e.g., "person with obesity" rather than "obese person") to avoid defining people by their condition (26, 33, 34) . Measurement of weight and height (to calculate BMI) and other anthropometric measurements should be performed at least annually to aid the diagnosis of obesity. More frequent assessments (at least every 3 months) should be undertaken to monitor response to treatment during active weight management (35) . Clinical considerations, such as the presence of comorbid heart failure or unexplained weight change, may warrant more frequent evaluation (36, 37) . If such measurements are questioned or declined by the individual, the health care professional should be mindful of possible prior stigmatizing experiences and query for concerns, and the value of monitoring should be explained as a part of the medical evaluation process that helps to inform treatment decisions (38, 39) . Accommodations should be made to ensure privacy during weighing and other anthropometric measurements, particularly for those individuals who report or exhibit a high level of disease-related distress or dissatisfaction. Anthropometric measurements should be performed and reported nonjudgmentally; such information should be regarded as sensitive health information.

Health care professionals should advise individuals with overweight or obesity and those with increasing weight trajectories that, in general, greater fat accumulation increases the risk of diabetes, cardiovascular disease, and all-cause mortality and has multiple adverse health and quality of life consequences. Health care professionals should also assess readiness to engage in behavioral changes for weight loss and jointly determine behavioral and weight loss goals and individualized intervention strategies using shared decision-making (40) . Strategies may include nutrition and eating pattern changes, physical activity and exercise, behavioral counseling, pharmacotherapy, medical devices, and metabolic surgery. The initial and subsequent therapeutic choices should be individualized based on the person's medical history, life circumstances, preferences, and motivation (41) . Combination treatment approaches may be appropriate in higherrisk individuals.

Among people with type 2 diabetes and overweight or obesity who have inadequate glycemic, blood pressure, and lipid management and/or other obesity-related metabolic complications, modest and sustained weight loss (3-7% of body weight) improves glycemia, blood pressure, and lipids and may reduce the need for disease-specific medications (7, 16, 17, 42) . In people at risk, 3-7% weight loss reduces progression to diabetes (2, 16, 17, 43, 44) . Greater weight loss produces additional benefits (20, 21) . Mounting data have shown that > 10% body weight loss usually confers greater benefits on glycemia and diabetes remission and improves other metabolic comorbidities, including cardiovascular outcomes, metabolic dysfunctionassociated steatohepatitis (MASH), MASLD, adipose tissue inflammation, and sleep apnea, as well as physical comorbidities and quality of life (6, 20, 21, 30, 43, (45) (46) (47) (48) (49) (50) (51) (52) (53) (54) .

With the increasing availability of more effective treatments, individuals with diabetes and overweight or obesity should be informed of the potential benefits of both modest and more substantial weight loss and guided in the range of available treatment options, as discussed in the sections below. Shared decision-making should be used when counseling on behavioral changes, intervention choices, and weight management goals.

NUTRITION, PHYSICAL ACTIVITY, AND BEHAVIORAL THERAPY

Recommendations 8.7 Nutrition, physical activity, and behavioral therapy are recommended for people with type 2 diabetes and overweight or obesity to achieve both weight and health outcome goals. B 8.8a Interventions including high frequency of counseling ($16 sessions in 6 months) with focus on nutrition changes, physical activity, and behavioral strategies to achieve a 500-750 kcal/day energy deficit should be recommended for weight loss and should be considered when available. A 8.8b If access to such interventions is limited, consider alternative structured programs delivering behavioral counseling (face-to-face or remote). E 8.9 Nutrition recommendations should be individualized to the person's preferences and nutritional needs. Use nutritional plans that create an energy deficit, regardless of macronutrient composition, to achieve weight loss. A 8.10 When developing a plan of care, consider systemic, structural, cultural, and socioeconomic factors that may impact nutrition patterns and food choices, such as food insecurity and hunger, access to healthful food options, and other social determinants of health. C 8.11 For those who achieve weight loss goals, continue to monitor progress, provide ongoing support, and recommend continuing interventions to maintain weight goals long term. E Effective long-term ($1 year) weight maintenance programs provide monthly contact and support, include frequent self-monitoring of body weight (weekly or more frequently) and other selfmonitoring strategies (e.g., food diaries or wearables), and encourage regular physical activity (200-300 min/week). A 8.12 Short-term nutrition intervention using structured, very-low-calorie meals (800-1,000 kcal/day) should be prescribed only to carefully selected individuals by trained practitioners in medical settings with close monitoring. Longterm, comprehensive weight maintenance strategies and counseling should be integrated to maintain weight loss. B 8.13 Nutritional supplements have not been shown to be effective for weight loss and are not recommended. A For a more detailed discussion of lifestyle management approaches and recommendations, see Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes." For a detailed discussion of nutrition-specific interventions, please refer to "Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report" (55) .

Behavioral Interventions

Numerous behavioral interventions have demonstrated positive effects from reducing energy intake, increasing physical activity, or some combination of these key lifestyle behaviors (56) . The Look AHEAD (Action for Health in Diabetes) trial confirmed the feasibility of achieving and maintaining long-term weight loss in people with type 2 diabetes. Approximately half of intensive lifestyle intervention participants lost and maintained $5% of their initial body weight (44) .Tailoring behavioral interventions to cultural context could be an additional useful tool for improving the impact of interventions (57) (58) (59) .

To achieve significant weight loss with lifestyle change programs, creating a 500-750 kcal/day energy deficit is recommended. For most women, this is equal to approximately 1,200-1,500 kcal/day, and for most men, this is equal to approximately 1,500-1,800 kcal/day, with adjustment for the individual's baseline body weight. Clinical benefits of weight loss typically begin upon achieving 3% weight loss (19, 60) , but these benefits are progressive; more intensive weight loss goals ( > 7%, > 10%, > 15%, etc.) can achieve further health improvements if these goals can be feasibly and safely attained. Almost one-third of the Look AHEAD intensive lifestyle group participants lost and maintained $10% of their initial body weight at 8 years (44) and required fewer glucose-, blood pressure-, and lipidlowering medications than those randomly assigned to standard care.

Nutrition interventions can create the necessary energy deficit to promote weight loss in many ways, and no single way is best (19, (61) (62) (63) . Altering macronutrient content and using meal replacement plans prescribed by trained professionals are two commonly used approaches (64) . Reducing processed and ultraprocessed food intake is also an encouraging area of ongoing weight loss research. The Preventing Overweight Using Novel Dietary Strategies (POUNDS) Lost trial reported small but significant improvements when ultraprocessed foods were replaced isocalorically by less processed foods, with improved trunk fat loss (b = 3.9, 95% CI À7.01 to À0.70, P = 0.02) (65) . The specific nutrition and lifestyle choices should be based on the individual's health status, clinical considerations, social determinants of health, overall preferences, and other cultural and personal circumstances that affect eating and activity patterns (66) (see Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes," for more discussion on processed and ultraprocessed foods).

Based on evidence from the Diabetes Prevention Program (DPP) and Look AHEAD, proven intensive behavioral interventions generally include $16 sessions during an initial 6 months and focus on nutritional changes, physical activity, and behavioral strategies to achieve an $500-750 kcal/day energy deficit. Such interventions should be provided by trained individuals and can be conducted face-to-face or remotely and on an individual or group basis (60, 67, 68) . Assessing a person's motivation level, life circumstances, cultural considerations, socioeconomic factors, and ability to implement behavioral changes to achieve weight loss should be considered along with medical status when such interventions are recommended and initiated (40, 69) .

People with type 2 diabetes and overweight or obesity who have lost weight should be offered long-term ($1 year) comprehensive weight loss maintenance programs. Weight loss maintenance programs should be delivered by an interprofessional team with appropriate training and experience in implementing long-term weight maintenance programs. While we acknowledge that most insurers, Medicare, and Medicaid are not currently covering many long-term weight maintenance programs, there is evidence to support their effectiveness and benefits (44,60,70) on both personal and population levels. Weight maintenance programs should include at least monthly contact with trained individuals and focus on ongoing monitoring of body weight (weekly or more frequently) and/or other self-monitoring strategies such as tracking food and beverage intake and steps; continued focus on nutrition and behavioral changes; and participation in high levels of physical activity (200-300 min/week) (71, 72) . Some commercial and proprietary weight loss programs have shown promising weight loss results; however, results vary across programs, most lack evidence of effectiveness, many do not satisfy guideline recommendations, and some promote unscientific and possibly dangerous practices (73, 74) .

Structured, very-low-calorie eating patterns, typically 800-1,000 kcal/day, using high-protein foods and meal replacement products, may increase the pace and/or magnitude of initial weight loss and glycemic improvements compared with standard behavioral interventions (20, 21) . However, such intensive nutritional interventions should be provided only by trained and experienced professionals in medical settings with close ongoing monitoring and integration with behavioral support and counseling, and only for a short term (generally up to 3 months). Furthermore, due to the high risk of complications (electrolyte abnormalities, severe fatigue, cardiac arrhythmias, etc.), such intensive interventions should be prescribed only to carefully selected individuals, such as those requiring weight loss and/or glycemic management before surgery, if benefits exceed potential risks (75) (76) (77) . As weight regain is common, such interventions should include long-term, comprehensive weight maintenance strategies and counseling to maintain weight loss and behavioral changes (78, 79) .

Despite widespread marketing and exorbitant claims, there is no clear evidence that nutrition supplements (e.g., herbs, vitamins and minerals, amino acids, enzymes, and antioxidants) are effective for obesity management or weight loss (80) (81) (82) . Several large systematic reviews show that most trials evaluating nutrition supplements for weight loss are of low quality and at high risk for bias. Highquality published studies show little or no weight loss benefits. In contrast, vitamin and mineral supplementation (e.g., iron, vitamin B12, and vitamin D) may be indicated in cases of documented deficiency (83) , and protein supplements may be indicated as adjuncts to medically supervised weight loss therapies (84) . See METABOLIC SURGERY, below, for more details on nutrition guidance for people who have undergone metabolic surgery.

Health disparities adversely affect people who have systematically experienced greater obstacles to health based on their race or ethnicity, socioeconomic status, gender identity, disability, or other factors. Overwhelming research shows that these disparities can significantly affect health outcomes, including increasing the risk for obesity, diabetes, and diabetes-related complications. Health care professionals should evaluate systemic, structural, and socioeconomic factors that may impact food choices, access to healthful foods, and nutrition patterns; behavioral patterns, such as neighborhood safety and availability of safe outdoor spaces for physical activity; environmental exposures; access to health care; social contexts; and, ultimately, diabetes risk and outcomes. For a detailed discussion of social determinants of health, refer to "Social Determinants of Health: A Scientific Review" (85) . PHARMACOTHERAPY Recommendations 8.14 Whenever possible, minimize medications for comorbid conditions that are associated with weight gain. E 8.15 When choosing glucose-lowering medications for people with type 2 diabetes and overweight or obesity, prioritize medications with beneficial effect on weight. B 8. 16 Weight management pharmacotherapy should be considered for people with diabetes and overweight or obesity along with lifestyle changes. Potential benefits and risks must be considered. A 8.17 In people with diabetes and overweight or obesity, the preferred pharmacotherapy should be a glucagonlike peptide 1 receptor agonist or dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist with greater weight loss efficacy (i.e., semaglutide or tirzepatide), especially considering their added weight-independent benefits (e.g., glycemic and cardiometabolic). A 8.18 Screen people with diabetes and obesity who have lost significant weight for malnutrition, especially those who have undergone metabolic surgery A and those treated with weight management pharmacologic therapy. B 8.19 Weight management pharmacotherapy indicated for chronic therapy should be continued beyond reaching weight loss goals to maintain the health benefits. Sudden discontinuation of weight management pharmacotherapy often results in weight gain and worsening of cardiometabolic risk factors. A 8.20 For those not reaching treatment goals, reevaluate weight management therapies and intensify treatment with additional approaches (e.g., metabolic surgery, additional pharmacologic agents, and structured lifestyle management programs). A

Glucose-Lowering Therapy

Numerous effective glucose-lowering medications are currently available. However, to achieve both glycemic and weight management goals for diabetes treatment, health care professionals should prioritize the use of glucose-lowering medications with a beneficial effect on weight. Agents associated with clinically meaningful weight loss include glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) and a dual glucosedependent insulinotropic polypeptide (GIP) and GLP-1 RA (tirzepatide). Sodium-glucose cotransporter 2 inhibitors, metformin, acarbose, and amylin mimetics are also associated with weight loss, although the magnitude of weight loss is much smaller ( < 5% body weight loss). Dipeptidyl peptidase 4 inhibitors, centrally acting dopamine agonist (bromocriptine), a-glucosidase inhibitors, and bile acid sequestrants (colesevelam) are considered weight neutral. In contrast, insulin secretagogues (sulfonylureas and meglitinides), thiazolidinediones, and insulin are often associated with weight gain (see Section 9, "Pharmacologic Approaches to Glycemic Treatment").

Concomitant Medications

Health care professionals should carefully review the individual's concomitant medications and, whenever possible, minimize or provide alternatives for medications that promote weight gain (86) . Examples of medications associated with weight gain include antipsychotics (e.g., clozapine, olanzapine, and risperidone), some antidepressants (e.g., tricyclic antidepressants, some selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors), glucocorticoids, injectable progestins, some anticonvulsants (e.g., gabapentin and pregabalin), b-blockers (e.g., atenolol, metoprolol, and propranolol), and possibly sedating antihistamines and anticholinergics (87) .

Approved Weight Management Pharmacotherapy

The U.S. Food and Drug Administration (FDA) has approved several medications for weight management as adjuncts to a reduced-calorie eating pattern and increased physical activity in individuals with BMI $30 kg/m 2 or $27 kg/m 2 with one or more obesity-associated comorbid conditions (e.g., type 2 diabetes, hypertension, and/or dyslipidemia). Nearly all FDA-approved weight management medications have been shown to improve glycemia in people with type 2 diabetes and delay progression to type 2 diabetes in at-risk individuals (22) , and some of these agents (e.g., liraglutide, semaglutide, and tirzepatide) have an indication for glucose lowering as well as weight management. Phentermine and other older adrenergic agents are approved for short-term treatment (88) , while all others are approved for long-term treatment (22) (Tables 8.1 and 8.2). (Refer to Section 14, "Children and Adolescents," for medications approved for adolescents with obesity.) In addition, setmelanotide, a melanocortin 4 receptor agonist, is approved for use in cases of rare genetic mutations resulting in severe hyperphagia and extreme obesity, such as leptin receptor deficiency and proopiomelanocortin deficiency.

In people with type 2 diabetes and overweight or obesity, agents with both glucose-lowering and weight loss effects are preferred (refer to Section 9, "Pharmacologic Approaches to Diabetes Treatment") and include agents from the GLP-1 RA class and the dual GIP and GLP-1 RA class (collectively referred to as nutrient-stimulated hormone-based therapeutics, a class that also includes other investigational agents that act on various nutrient-stimulated hormonal pathways, like glucagon and amylin). Should use of these medications not result in achievement of weight management goals, or if they are not tolerated or are contraindicated, other obesity treatment approaches should be considered. In the Effect and Safety of Semaglutide 2.4 mg Once-Weekly in Subjects With Overweight or Obesity and Type 2 Diabetes (STEP 2) trial, semaglutide 2.4 mg resulted in a body weight loss of 6.2% more than placebo and A1C lowering of 1.2% more than placebo after 68 weeks (50). In the Efficacy and Safety of Tirzepatide Once Weekly in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-2), tirzepatide resulted in body weight loss of 9.6% and 11.6% more than placebo and A1C lowering of 1.55% and 1.57% more than placebo after 72 weeks of treatment with the 10 mg and 15 mg doses, respectively, with adverse effects similar to those seen with the GLP-1 RA class (89) . The observed weight loss with weight management pharmacotherapy is lower in people with diabetes than in those of similar baseline weight without diabetes; therefore, it is important to appropriately manage expectations of individuals with diabetes and health care professionals.

Weight management pharmacotherapy has demonstrated multiple additional benefits beyond weight loss and improvement in glucose management. Some such examples include improvements or potential improvements in cardiovascular risk factors (e.g., blood pressure and lipids), inflammation, obstructive sleep apnea, MASLD and MASH, and symptoms related to heart failure with preserved ejection fraction (90-93). Liraglutide 1.8 mg and semaglutide 1 mg (doses approved for type 2 diabetes, which are lower than those approved for the treatment of obesity) demonstrated reduction in cardiovascular events in people with type 2 diabetes who are either at high risk for cardiovascular disease or have cardiovascular disease (51, 94) . Additionally, semaglutide 2.4 mg (dose approved for the treatment of obesity) also demonstrated reduction in cardiovascular events in people with overweight or obesity and preexistent cardiovascular disease but without diabetes (95) .

Health care professionals should be knowledgeable about the dosing, benefits, and risks for each treatment option to balance the potential benefits of successful weight loss against the potential risks for each individual. The high risk and prevalence of cardiovascular disease in people with diabetes must be balanced against the lack of long-term cardiovascular outcomes trial data for agents like combination naltrexone and bupropion and combination phentermine and topiramate. The response to all weight management medications is highly heterogeneous; therefore, their weight loss effectiveness should be reevaluated after initiation and therapy adjustments should be considered, if needed. All these medications are contraindicated in individuals who are pregnant or actively trying to conceive and are not recommended for use in individuals who are nursing. Individuals of childbearing potential should receive counseling regarding the use of reliable methods of contraception while using weight loss medications. Tirzepatide in particular may reduce the efficacy of oral hormonal contraceptives due to delayed gastric emptying, an effect that is largest after the first dose and diminishes over time. Individuals using oral hormonal contraceptives should switch to a nonoral contraceptive method or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation. Of note, while weight loss medications are often used in people with type 1 diabetes, clinical trial data in this population are limited.

Incretin pharmacotherapies and metabolic surgery options for weight loss may increase the risk for malnutrition and sarcopenia (96) . Health care professionals should encourage resistance training (97) and sufficient protein intake. Individuals with diabetes who are experiencing significant ( > 20%) or rapid ( > 4 kg/month) weight loss should be screened for Thus, choice of therapy should be guided by person-centered treatment factors, including comorbidities, considerations of adverse effects and treatment burden, treatment cost and accessibility, and the individual's therapeutic goals and preferences. Medication cost and insurance coverage considerations often influence treatment decisions, and payors should cover evidence-based obesity treatments for people with diabetes and prediabetes to reduce barriers to treatment access. It is also essential that health care teams are knowledgeable about insurance coverage requirements and establish systems to support clinicians in prescribing evidencebased weight management medications and to reduce financial hardship of treatment for individuals, including formulary and medication coverage requirements, eligibility for medication assistance programs, and availability of copayment reduction cards (see Section 1, "Improving Care and Promoting Health in Populations").

Assessing Efficacy and Safety of Weight Management Pharmacotherapy

Upon initiating medications for obesity, assess their effectiveness and safety at least monthly for the first 3 months and at least quarterly thereafter. Modeling from published clinical trials consistently shows that early responders have improved long-term outcomes (101, 102) ; however, it is notable that the response rate with the latest generation of weight management pharmacotherapies is much higher (50, 89) . Unless clinical circumstances (such as poor tolerability) or other considerations (such as financial expense or individual preference) suggest otherwise, those who achieve sufficient early weight loss upon starting a chronic weight management medication (typically defined as > 5% weight loss after 3 months of use) should continue the medication long-term. When early weight loss results are modest (typically < 5% weight loss after 3 months of use), the benefits of ongoing treatment need to be examined in the context of the glycemic response, the availability of other potential treatment options, treatment tolerance, and overall treatment burden. Ongoing monitoring of the achievement and maintenance of weight management goals is recommended. Sudden discontinuation of semaglutide and tirzepatide results in regain of one-half to two-thirds of the weight loss within 1 year (103-105). Shared decision-making should be used to determine the best long-term weight management approach, such as continuing pharmacotherapy on the lowest effective dose, using intermittent therapy, or stopping medication followed by close weight monitoring.

For those not reaching or maintaining weight-related treatment goals, avoid treatment inertia by reevaluating ongoing weight management therapies and intensify treatment with additional approaches (e.g., metabolic surgery, additional pharmacologic agents, and structured lifestyle management programs).

MEDICAL DEVICES FOR WEIGHT LOSS

While gastric banding devices have fallen out of favor due to their limited longterm efficacy and high rate of complications, several minimally invasive medical devices have been approved by the FDA for short-term weight loss, including implanted gastric balloons, a vagus nerve stimulator, and gastric aspiration therapy (106) . High cost, limited insurance coverage, and limited data supporting the efficacy of these devices in the treatment of individuals with diabetes has created uncertainty for their current use and led to the voluntary removal of several of these medical devices from the U.S. market (107) . Surgical procedures for obesity treatmentoften referred to interchangeably as bariatric surgery, weight loss surgery, metabolic surgery, or metabolic/bariatric surgery-can promote significant and durable weight loss and improve glycemic management and long-term outcomes in those with type 2 diabetes. Given the magnitude and rapidity of improvement of hyperglycemia and glucose homeostasis, these procedures have been suggested as treatments for type 2 diabetes even in the absence of severe obesity, hence the current preferred terminology of "metabolic surgery" (108) .

A substantial body of evidence, including data from large cohort studies and randomized controlled (nonblinded) clinical trials, demonstrates that metabolic surgery achieves superior glycemic management and reduction of cardiovascular risk in people with type 2 diabetes and obesity compared with nonsurgical intervention (47) . In addition to improving glycemia, metabolic surgery reduces the incidence of microvascular disease (109), improves quality of life (47, 110, 111) , decreases cancer risk, improves cardiovascular disease risk factors and long-term cardiovascular events (111) (112) (113) (114) (115) (116) (117) (118) (119) , and decreases all-cause mortality (120) . Cohort studies that match surgical and nonsurgical subjects strongly suggest that metabolic surgery reduces all-cause mortality (121, 122) . Studies have also shown that metabolic surgery can improve liver outcomes among individuals with MASH, including biopsy-proven disease (123) (124) (125) .

The overwhelming majority of procedures performed in the U.S. are vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB). Both procedures result in a smaller stomach pouch and often robust changes in enteroendocrine hormones. In VSG, $80% of the stomach is removed, leaving behind a long, thin sleeve-shaped pouch. RYGB creates a much smaller stomach pouch (roughly the size of a walnut), which is then attached to the distal small intestine, thereby bypassing the duodenum and jejunum.

Metabolic surgery has been demonstrated to have beneficial effects on type 2 diabetes irrespective of the presurgical BMI (126) . The American Society for Metabolic and Bariatric Surgery recommends metabolic surgery for people with type 2 diabetes and a BMI $30 kg/m 2 (or $27.5 kg/m 2 for Asian American individuals) in surgically eligible individuals. A real-world data analysis through the National Patient-Centered Outcomes Research Network (PCORnet) in the U.S. compared surgical outcomes between 6,233 individuals with type 2 diabetes who underwent RYGB and 3,477 who underwent VSG. At 1 year after surgery, those who had RYGB lost on average 29.1% of their total body weight, while those who had VSG lost on average 22.8% of their total body weight. At 5 years after surgery, the total body weight loss was 24.1% for those who had RYGB and 16.1% for those who had VSG, with 86.1% of individuals experiencing type 2 diabetes remission after RYGB and 83.5% of individuals experiencing type 2 diabetes remission after VSG. Among the 6,141 individuals who experienced type 2 diabetes remission, the subsequent type 2 diabetes relapse rate was lower for those who had RYGB than for those who had VSG (hazard ratio 0.75 [95% CI 0.67-0.84]). Estimated relapse rates for those who had RYGB and VSG were 33.1% and 41.6%, respectively, at 5 years after surgery. At 5 years, compared with baseline, A1C was reduced, on average, 0.4 percentage points more for individuals who had RYGB than for individuals who had VSG (127) . Most notably, the Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial, which randomized 150 participants with type 2 diabetes, A1C > 7.0%, and BMI 27-43 kg/m 2 to receive either metabolic surgery or medical treatment for type 2 diabetes using glucose-lowering agents, found that 29% of those treated with RYGB and 23% of those treated with VSG achieved A1C of #6.0% after 5 years (47) . Available data suggest an erosion of diabetes remission over time (48) ; 35-50% of individuals who initially achieve remission of diabetes eventually experience recurrence. Still, the median disease-free period among such individuals following RYGB is 8.3 years (128, 129) , and the majority of those who undergo surgery maintain substantial improvement of glycemia from baseline for at least 5-15 years (47, 110, 111, 113) .

Exceedingly few presurgical predictors of diabetes remission have been identified. However, younger age, shorter duration of diabetes (e.g., < 8 years) (101) , and lesser severity of diabetes (better glycemic management, not using insulin) are associated with higher rates of diabetes remission (47, 111, 130, 131) . Greater baseline visceral fat area may also predict diabetes remission, especially among Asian American people with type 2 diabetes (132) .

A review of case series and reports suggests that metabolic surgery also improves the metabolic profiles and cardiovascular risk of people with type 1 diabetes, but larger and longer-term studies with better designs are needed to determine the role of metabolic surgery in such individuals (133) .

Whereas metabolic surgery has greater initial costs than nonsurgical obesity treatments, retrospective analyses and modeling studies suggest that surgery may be cost-effective or even cost-saving for individuals with type 2 diabetes. However, these results largely depend on assumptions about the long-term effectiveness and safety of the procedures, the specific medications being compared, the time horizon for cost-effectiveness assessments, and the population examined (e.g., duration and severity of diabetes) (134, 135) .

The safety of metabolic surgery has improved significantly with continued refinement of minimally invasive (laparoscopic) approaches, enhanced training and credentialing, and involvement of interprofessional teams. Perioperative mortality rates are typically 0.1-0.5%, similar to those for common abdominal procedures such as cholecystectomy and hysterectomy (136, 137) . Major complications occur in 2-6% of those undergoing metabolic surgery, which compares favorably with the rates for other commonly performed elective operations (137) . Postsurgical recovery times and morbidity have also dramatically declined. Minor complications and need for operative reintervention occur in up to 15% (136, (138) (139) (140) (141) (142) (143) . Empirical data suggest that the proficiency of the operating surgeon and surgical team is a key determinant of mortality, complications, reoperations, and readmissions (144) . Accordingly, metabolic surgery should be performed in high-volume centers with interprofessional teams experienced in managing diabetes, obesity, and gastrointestinal surgery. Refer to the American College of Surgeons website for information on accreditation and locations of accredited programs (https://www.facs. org/quality-programs/accreditation-andverification/metabolic-and-bariatric-surgeryaccreditation-and-quality-improvementprogram/).

Beyond the perioperative period, longer-term risks include vitamin and mineral deficiencies, anemia, osteoporosis, dumping syndrome, and severe hypoglycemia (145) . Nutritional and micronutrient deficiencies and related complications occur with variable frequency depending on the type of surgical procedure and require routine monitoring of micronutrient and nutritional status and lifelong vitamin/nutritional supplementation (145) . Dumping syndrome usually occurs shortly (10-30 min) after a meal and may present with diarrhea, nausea, vomiting, palpitations, and fatigue; hypoglycemia is usually not present at the time of symptoms but, in some cases, may develop several hours later. Post-metabolic surgery hypoglycemia can occur with RYGB, VSG, and other gastrointestinal procedures and may severely impact quality of life (146) (147) (148) . Post-metabolic surgery hypoglycemia is driven in part by altered gastric emptying of ingested nutrients, leading to rapid intestinal glucose absorption and excessive postprandial secretion of GLP-1 and other gastrointestinal peptides. As a result, overstimulation of insulin release and a sharp drop in plasma glucose occur, most commonly 1-3 h after a high-carbohydrate meal. Symptoms range from sweating, tremor, tachycardia, and increased hunger to impaired cognition, loss of consciousness, and seizures. In contrast to dumping syndrome, which often occurs soon after surgery and improves over time, post-metabolic surgery hypoglycemia typically presents > 1 year after surgery. Diagnosis is primarily made by a thorough examination of history, detailed records of food intake, physical activity, and symptom patterns, and exclusion of other potential causes of hypoglycemia (e.g., malnutrition, side effects of medications or supplements, dumping syndrome, and insulinoma). Initial management includes education to facilitate reduced intake of rapidly digested carbohydrates while ensuring adequate intake of protein, healthy fats, and vitamin and nutrient supplements. When available, individuals should be offered medical nutrition therapy with a registered dietitian nutritionist experienced in post-metabolic surgery hypoglycemia and the use of continuous glucose monitoring (ideally real-time continuous glucose monitoring, which can detect dropping glucose levels before severe hypoglycemia occurs), especially for those with impaired hypoglycemia awareness. Medication treatment, if needed, is primarily aimed at slowing carbohydrate absorption (e.g., acarbose) or reducing GLP-1 and insulin secretion (e.g., diazoxide, octreotide) (149) .

People who undergo metabolic surgery may be at increased risk for substance use, worsening or new-onset depression and/or anxiety disorders, and suicidal ideation (150) (151) (152) (153) (154) . Candidates for metabolic surgery should be assessed by a behavioral health professional with expertise in obesity management prior to consideration for surgery (155) . Surgery should be postponed in individuals with alcohol or substance use disorders, severe depression, suicidal ideation, or other significant behavioral health conditions until these conditions have been sufficiently addressed. Individuals with preoperative or new-onset psychopathology should be assessed regularly following surgery to optimize behavioral health and postsurgical outcomes.

Finally, no definitive evidence supports the pre-and post-metabolic surgery use of nutrient-stimulated hormone-based therapeutics for chronic obesity. Existing studies suggest that among individuals with a BMI > 50 kg/m 2 , GLP-1 RAs are associated with significant weight loss prior to surgery with no increase in complications or time to surgery (156) . Nutrientstimulated hormone-based therapeutics can be considered as adjuvants after metabolic surgery to augment initial weight loss either shortly after surgery or when weight loss has plateaued (157) . Studies have also shown that GLP-1 RAs can effectively treat weight regain after metabolic surgery and therefore could be considered as an alternative to revisional surgery (158) . Long-term outcomes, however, are lacking in terms of durability of weight loss, effect on weight regain when medications are stopped, and long-term side effects with use and after discontinuation (159)

9. PHARMACOLOGIC APPROACHES TO GLYCEMIC TREATMENT

insulinopenia can contribute to other metabolic disturbances like hypertriglyceridemia and ketoacidosis as well as tissue catabolism that can be life threatening.

Severe metabolic decompensation can be, and was, mostly prevented with once-or twice-daily insulin injections for the six or seven decades after the discovery of insulin. Over the past four decades, evidence has accumulated supporting more intensive insulin replacement, using multiple daily injections of insulin or continuous subcutaneous administration through an insulin pump, as providing the best combination of effectiveness and safety for people with type 1 diabetes. The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy with multiple daily injections or continuous subcutaneous insulin infusion (CSII) reduced A1C and was associated with improved long-term outcomes (1-3). The study was carried out with short-acting (regular) and intermediate-acting (NPH) human insulins. In this landmark trial, lower A1C with intensive management (7%) led to $50% reductions in microvascular complications over 6 years of treatment. However, intensive therapy was associated with a higher rate of severe hypoglycemia than conventional treatment (62 compared with 19 episodes per 100 person-years of therapy) (1) . Followup of participants from the DCCT demonstrated fewer macrovascular and microvascular complications in the group that received intensive treatment. Achieving intensive glycemic goals during the active treatment period of the study had a persistent beneficial impact over the 20 years after the active treatment component of the study ended (1) (2) (3) .

Insulin replacement plans typically consist of basal insulin, mealtime insulin, and correction insulin (Fig. 9 .1) (4). Basal insulin includes NPH insulin, long-acting insulin analogs, and continuous delivery of rapid-acting insulin via an insulin pump. Basal insulin analogs have longer duration of action with flatter, more constant and consistent plasma concentrations and activity profiles than NPH insulin; rapidacting analogs (RAA) have a quicker onset and peak and shorter duration of action than regular human insulin. In people with type 1 diabetes, treatment with analog insulins is associated with less hypoglycemia and weight gain and lower A1C compared with injectable human insulins (5-7). Two injectable ultra-rapid-acting analog (URAA) insulin formulations are available that contain excipients that accelerate absorption and provide more activity in the first portion of their profile compared with the other RAA (8, 9) . Inhaled human insulin has a rapid peak and shortened duration of action compared with RAA (10) (see also subsection ALTERNA-

TIVE INSULIN ROUTES IN PHARMACOLOGIC THERAPY FOR

ADULTS WITH TYPE 2 DIABETES). These newer formulations may cause less hypoglycemia while improving postprandial glucose excursions and administration flexibility (in relation to prandial intake) compared with RAA (10) (11) (12) . In addition, longer-acting basal analogs (U-300 glargine or degludec) may confer a lower hypoglycemia risk compared with U-100 glargine in individuals with type 1 diabetes (13, 14) .

Despite the advantages of insulin analogs in individuals with type 1 diabetes, the expense and/or complexity of treatment required for their use may be prohibitive (Table 9 .1). There are multiple approaches to insulin treatment. The central precept in the management of type 1 diabetes is that some form of insulin be given in a defined treatment plan tailored to the individual to prevent diabetic ketoacidosis (DKA) and minimize clinically relevant hypoglycemia while achieving the individual's glycemic goals. The impact of the introduction of interchangeable biosimilars and unbranded versions of some analog products as well as current and upcoming price reductions on insulin access need to be evaluated. Reassessment of insulin-taking behavior and adjustment of treatment plans to account for specific factors, including cost, that impact choice of treatment is recommended at regular intervals (every 3-6 months).

Most studies comparing multiple daily injections with CSII have been relatively small and of short duration. A systematic review and meta-analysis concluded that CSII via pump therapy has modest advantages for lowering A1C (À0.30% [95% CI À0.58 to À0.02]) and for reducing severe hypoglycemia rates in children and adults (15) . Use of CSII is associated with improvement in quality of life, particularly in areas related to fear of hypoglycemia and diabetes distress, compared with multiple plans plans Figure 9 .1-Choices of insulin plans in people with type 1 diabetes. Continuous glucose monitoring improves outcomes with injected or infused insulin and is superior to blood glucose monitoring. Inhaled insulin may be used in place of injectable prandial insulin in the U.S. The number of plus or dollar signs is an estimate of relative association of the plan with greater flexibility, lower risk of hypoglycemia, and higher costs between the different plans. LAA, long-acting insulin analog; MDI, multiple daily injections; RAA, rapid-acting insulin analog; URAA, ultra-rapid-acting insulin analog. Adapted from Holt et al. (4) .

S182 Pharmacologic Approaches to Glycemic Treatment

Diabetes Care 48, Supplement 1, January 2025 daily injections of insulin (16, 17) . However, there is no consensus to guide the choice of injection or pump therapy in a given individual, and research to guide this decision-making is needed (4). Integration of continuous glucose monitoring (CGM) into the treatment plan soon after diagnosis improves glycemic outcomes, decreases hypoglycemic events, and improves quality of life for individuals with type 1 diabetes (18) (19) (20) (21) (22) (23) . Its use is now considered standard of care for most people with type 1 diabetes (4) (see Section 7, "Diabetes Technology"). Reduction of nocturnal hypoglycemia in individuals with type 1 diabetes using insulin pumps with CGM is improved by automatic suspension of insulin delivery at a preset glucose level, with further improvements when using devices with predictive low-glucose insulin delivery suspension (24, 25) . Automated insulin delivery (AID) systems are safe and effective for people with type 1 diabetes. Randomized controlled trials and real-world studies have demonstrated the ability of commercially available systems to improve achievement of glycemic goals while reducing the risk of hypoglycemia (26) (27) (28) (29) (30) (31) . Data are emerging on the safety and effectiveness of do-ityourself systems (32, 33) . Evidence suggests that an AID hybrid closed-loop system is superior to AID sensor-augmented pump therapy for increased percentage of time in range and reduction of hypoglycemia (34, 35) .

Intensive insulin management using a version of CSII and CGM should be considered in individuals with type 1 diabetes whenever feasible. AID systems are preferred and should be considered for individuals with type 1 diabetes who are capable of using the device safely (either by themselves or with a caregiver) to improve time in range and reduce A1C and hypoglycemia (26, (28) (29) (30) (31) (36) (37) (38) (39) (40) (41) (42) . When choosing among insulin delivery systems, individual preferences, cost, insulin type, dosing plan, and self-management capabilities should be considered. See Section 7, "Diabetes Technology," for a full discussion of insulin delivery devices.

In general, individuals with type 1 diabetes require approximately 30-50% of their daily insulin as basal and the remainder as prandial (43) . This proportion depends on several factors, including but not limited to carbohydrate consumption, age, pregnancy status, and puberty stage (4, (44) (45) (46) (47) (48) . Total daily insulin requirements can be estimated based on weight, with typical doses ranging from 0.4 to 1 unit/ kg/day. Higher amounts may be required during puberty, menses, and medical illness. The American Diabetes Association/ JDRF Type 1 Diabetes Sourcebook notes 0.5 units/kg/day as a typical starting dose in adults with type 1 diabetes who are metabolically stable, with approximately one-half administered as prandial insulin given to manage blood glucose after meals and the remaining portion as basal insulin to manage glycemia in the periods between meal absorption (49) . Starting doses and those soon after diagnosis may be higher, if an individual presents with ketoacidosis, or lower (0.2-0.6 units/kg), particularly in young children and those with continued endogenous insulin production (during the partial remission phase or "honeymoon period," or in people who present with type 1 diabetes in adulthood) (49) (50) (51) . This guideline provides detailed information on intensification of therapy to meet individualized needs. In addition, the American Diabetes Association (ADA) position statement "Type 1 Diabetes Management Through the Life Span" provides a thorough overview of type 1 diabetes treatment (52) .

Typical multidose treatment plans for individuals with type 1 diabetes combine premeal use of prandial insulins with a longer-acting formulation. The long-acting basal dose is titrated to regulate overnight and fasting glucose. Postprandial glucose excursions are best managed by a well-timed injection or inhalation of prandial insulin. Prandial insulin should ideally be administered prior to meal consumption; however, the optimal time to administer varies based on the pharmacokinetics of the formulation (regular, RAA, or inhaled), the premeal blood glucose level, and carbohydrate consumption. Recommendations for prandial insulin dose administration should therefore be individualized. Physiologic insulin secretion varies with glycemia, meal size, meal composition, and tissue demand for glucose. To address this variability in people treated with insulin, strategies have evolved to adjust prandial doses based on predicted needs. Thus, education on how to adjust prandial insulin to account for nutritional intake and the correction dose based on premeal glucose levels, anticipated activity, and sick-day management can be effective and should be offered to most individuals (53-58). Education regarding adjustment of prandial insulin dose for glycemic trends should be provided to individuals who are using CGM alone or an AID system (59) (60) (61) (62) . Further adjustment of prandial insulin doses for nutritional intake of protein and fat, in addition to carbohydrates, is recommended but may be more feasible for individuals using CSII than for those using multiple daily injections (55) . With some AID systems, use of a simplified meal announcement method may be an alternative for prandial insulin dosing (31, 63) . Assessment and education tailored to improve health literacy and numeracy may be necessary for individuals to effectively use various insulin dosing strategies and tools (64,65) (see Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes," and Section 7, "Diabetes Technology").

The 2021 ADA/European Association for the Study of Diabetes (EASD) consensus report on the management of type 1 diabetes in adults summarizes different insulin plans and glucose monitoring strategies in individuals with type 1 diabetes (Fig. 9 .1 and Table 9 .1) (4).

Insulin Administration Technique

Ensuring that individuals and/or caregivers understand correct insulin administration technique is important to optimize glycemic management and insulin use safety. Recommendations have been published elsewhere outlining best practices for insulin administration (66) . Proper insulin administration technique includes the following: injection, insertion of patch or infusion (for CSII or AID systems) into appropriate body areas, or oral inhalation (inhaled human insulin); injection or infusion site rotation; appropriate care of injection or infusion sites to avoid infection or other complications; avoidance of intramuscular (IM) insulin delivery; and filling of the reservoir (for bolus patch, CSII, or AID systems) or inhaler (for inhaled human insulin) depending on the method of administration. Selection of method of administration (vial and syringe, insulin pen, insulin patch, inhaled insulin, connected insulin pens/devices, or insulin pumps) will depend on a variety of individual-specific factors and needs, cost and coverage, and individual preferences. Reassessment of the appropriate administration technique should be completed during routine follow-up.

Exogenously delivered insulin should be injected or infused into subcutaneous tissue, not intramuscularly. Recommended sites for insulin administration include the abdomen, thigh, buttock, and upper arm. Insulin absorption from IM sites differs from that in subcutaneous sites and is also influenced by the activity of the muscle. Inadvertent IM injection can lead to unpredictable insulin absorption and variable effects on glucose and is associated with frequent and unexplained hypoglycemia. Risk for IM insulin delivery is increased in younger, leaner individuals when injecting into the limbs rather than truncal sites (abdomen and buttocks) and when using longer needles. Recent evidence supports the use of short needles (e.g., 4-mm pen needles) as effective and well tolerated compared with longer needles, including a study performed in adults with obesity (67) .

Injection or infusion site rotation is additionally necessary to avoid lipohypertrophy, an accumulation of subcutaneous fat in response to the adipogenic actions of insulin at a site of multiple injections. Lipohypertrophy appears as soft, smooth raised areas several centimeters in breadth and can contribute to erratic insulin absorption, increased glycemic variability, and unexplained hypoglycemic episodes. People treated with insulin and/or caregivers should receive education about proper injection or infusion site rotation and how to recognize and avoid injecting in areas of lipohypertrophy. As noted in Table 4 .1, examination of insulin administration sites for the presence of lipohypertrophy, as well as assessment of administration device use and injection technique, are key components of a comprehensive diabetes medical evaluation and treatment plan. Proper insulin injection, infusion, or inhalation technique may lead to more effective use of this therapy and, as such, holds the potential for improved clinical outcomes.

Noninsulin Treatments for Type 1 Diabetes

Injectable and oral noninsulin glucoselowering medications have been studied for their efficacy as adjuncts to insulin treatment of type 1 diabetes. Pramlintide is based on the naturally occurring b-cell peptide amylin and is approved for use in adults with type 1 diabetes. Clinical trials have demonstrated a modest reduction in A1C (0.3-0.4%) and modest weight loss ($1 kg) with pramlintide (68) . Similar results have been reported for several agents currently approved only for the treatment of type 2 diabetes. The addition of metformin in adults with type 1 diabetes was associated with small reductions in body weight, insulin dose, and lipid levels but did not sustainably improve A1C (69, 70) . The largest clinical trials of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in type 1 diabetes have been conducted with liraglutide 1.8 mg daily, and results showed modest A1C reductions ($0.4%), decreases in weight ($5 kg), and reductions in insulin doses (71, 72) . Liraglutide was also assessed for impact on C-peptide in individuals with type 1 diabetes and residual b-cell function. During treatment there was no impact, and with liraglutide discontinuation there was worsening of Cpeptide loss compared with placebo (73) . Retrospective case series have revealed potential benefits on body weight and glycemic metrics with addition of semaglutide or tirzepatide for individuals with type 1 diabetes and obesity (74, 75) . Prospective studies using semaglutide are ongoing (76, 77) .

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been studied in clinical trials in people with type 1 diabetes, and results showed improvements in A1C, reduced body weight, and improved blood pressure (78) ; however, SGLT2 inhibitor use in type 1 diabetes was associated with an increased rate of DKA (79) . The SGLT1/2 inhibitor sotagliflozin has been studied in clinical trials in people with type 1 diabetes, and results showed improvements in A1C and body weight (80); however, sotagliflozin use was associated with an eightfold increase in DKA compared with placebo (81) . The studies that led to the approved indication for heart failure (HF) excluded individuals with type 1 diabetes or a history of DKA (82, 83) . See SGLT INHIBITION AND RISK OF KETOSIS, later in this section, and PREVENTION AND TREATMENT OF HEART FAILURE in Section 10, "Cardiovascular Disease and Risk Management," for information on risk mitigation with the use of SGLT inhibitors in those with type 1 diabetes. The risks and benefits of adjunctive agents continue to be evaluated, with consensus statements providing guidance on selection of candidates for treatment and precautions (84) .

There are currently no approved therapies for preservation of C-peptide or delaying the progression of symptomatic type 1 diabetes. Higher C-peptide levels have been associated with better A1C, lower risk of retinopathy, lower risk of nephropathy, and lower risk of severe hypoglycemia (85) . Various therapies, including verapamil, menin inhibitors, Janus kinase inhibitors, antithymocyte globulin, several monoclonal antibodies including teplizumab, and cell therapies, are currently under active investigation.

SURGICAL TREATMENT OF TYPE 1 DIABETES

Pancreas and Islet Transplantation

Successful pancreas and islet transplantation can normalize glucose levels and mitigate microvascular complications of type 1 diabetes. However, people receiving these treatments require lifelong immunosuppression to prevent graft rejection and/or recurrence of autoimmune islet destruction. Given the potential adverse effects of immunosuppressive therapy, pancreas transplantation should be reserved for people with type 1 diabetes undergoing simultaneous kidney transplantation, following kidney transplantation, or for those with recurrent ketoacidosis or severe hypoglycemia despite optimized glycemic management (86) . In much of the world, allogenic islet transplantation is regulated as an organ transplant. However, in the U.S., allogenic islet transplantation is regulated as a cell therapy, and the first such allogeneic islet cell therapy, donislecel-jujn, was approved in 2023. Donislecel is indicated for the treatment of adults with type 1 diabetes who are unable to reach their A1C goals because of repeated episodes of severe hypoglycemia despite intensive diabetes management and education (87) . Alternative islet sources are currently under active investigation.

The 2021 ADA/EASD consensus report on the management of type 1 diabetes in adults offers a simplified overview of indications for b-cell replacement therapy in people with type 1 diabetes (Fig. 9 .2) (4).

PHARMACOLOGIC THERAPY FOR ADULTS WITH TYPE 2 DIABETES

Recommendations 9.7 Healthy behaviors, diabetes selfmanagement education and support, avoidance of therapeutic inertia, and social determinants of health should be included in the glucose-lowering management of type 2 diabetes. A 9.8 A person-centered shared decisionmaking approach should guide the choice of glucose-lowering medications for adults with type 2 diabetes. Use medications that provide sufficient effectiveness to achieve and maintain intended treatment goals with consideration of the effects on cardiovascular, kidney, weight, and other relevant comorbidities; hypoglycemia risk; cost and access; risk for adverse reactions and tolerability; and individual preferences (Fig. 9 .3 and Table 9 .2). E 9.9 Combination therapy can be considered in adults with type 2 diabetes at treatment initiation to shorten time to attainment of individualized treatment goals. A 9.10 In adults with type 2 diabetes and established or high risk of atherosclerotic cardiovascular disease, the treatment plan should include medications with demonstrated benefits to reduce cardiovascular events (e.g., glucagon-like peptide 1 receptor agonist [GLP-1 RA] and/or sodium-glucose cotransporter 2 [SGLT2] inhibitor) for glycemic management and comprehensive cardiovascular risk reduction (irrespective of A1C) (Fig. 9 .3 and Table 9 .2). A 9.11 In adults with type 2 diabetes who have heart failure (HF) (with either reduced or preserved ejection fraction), an SGLT2 inhibitor is recommended for both glycemic management and prevention of HF hospitalizations (irrespective of A1C) (Fig. 9 .3). A 9.12 In adults with type 2 diabetes and symptomatic heart failure with preserved ejection fraction (HFpEF) and obesity, a GLP-1 RA with demonstrated benefits for both glycemic management and reduction of HFrelated symptoms (irrespective of A1C) is recommended. A 9.13 In adults with type 2 diabetes who have CKD (with confirmed estimated glomerular filtration rate [eGFR] 20- 60 mL/min/1.73 m 2 and/or albuminuria), an SGLT2 inhibitor or GLP-1 RA with demonstrated benefit in this population should be used for both glycemic management (irrespective of A1C) and for slowing progression of CKD and reduction in cardiovascular events (Fig. 9 .3). The glycemic benefits of SGLT2 inhibitors are reduced at eGFR < 45 mL/min/1.73 m 2 . A 9.14 In adults with type 2 diabetes and advanced CKD (eGFR < 30 mL/min/ 1.73 m 2 ), a GLP-1 RA is preferred for glycemic management due to lower risk of hypoglycemia and for cardiovascular event reduction. B 9.15 In adults with type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD), and overweight or obesity, consider using a GLP-1 RA or a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA with potential benefits in metabolic dysfunction-associated steatohepatitis (MASH) for glycemic management and as an adjunctive to healthy interventions for weight loss.

9.16b

Combination therapy with pioglitazone plus a GLP-1 RA can be considered for the treatment of hyperglycemia in adults with type 2 diabetes with biopsy-proven MASH or those at high risk of liver fibrosis (identified with noninvasive tests) due to potential beneficial effects on MASH. B 9.17 Medication plan and medicationtaking behavior should be reevaluated at regular intervals (e.g., every 3-6 months) and adjusted as needed to incorporate specific factors that impact choice of treatment (Fig. 4 24 In adults with type 2 diabetes and no evidence of insulin deficiency, a GLP-1 RA, including a dual GIP and GLP-1 RA, is preferred to insulin (Fig. 9 .4). A 9.25 If insulin is used, combination therapy with a GLP-1 RA, including a dual GIP and GLP-1 RA, is recommended for greater glycemic effectiveness as well as beneficial effects on weight and hypoglycemia risk for adults with type 2 diabetes. Insulin dosing should be reassessed upon addition or dose escalation of a GLP-1 RA or dual GIP and GLP-1 RA. A 9.26 In adults with type 2 diabetes who are initiating insulin therapy, continue glucose-lowering agents (unless contraindicated or not tolerated) for ongoing glycemic and metabolic benefits (i.e., weight, cardiometabolic, or kidney benefits). A A holistic, multifaceted, person-centered approach that accounts for the complexity of managing type 2 diabetes and its complications across the life span is recommended. Person-specific factors that affect choice of treatment include individualized glycemic goals (see Section 6, "Glycemic Goals and Hypoglycemia"), individualized weight goals (see Section 8, "Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes"), the individual's risk for hypoglycemia, and the individual's history of or risk factors for cardiovascular, kidney, liver, and other comorbidities and complications of diabetes (see Section 4, "Comprehensive Medical Evaluation and Assessment of Comorbidities," Section 10, "Cardiovascular Disease and Risk Management," and Section 11, "Chronic Kidney Disease and Risk Management"). In addition, treatment decisions must consider the tolerability and side effect profiles of medications, complexity of the medication plan and the individual's capacity to implement it given their specific situation and context, and the access, cost, and availability of medications. Lifestyle modifications and health behaviors that improve health (see Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes") should be emphasized along with any pharmacologic therapy. Section 13, "Older Adults," and Section 14, "Children and Adolescents," have recommendations specific for older adults and for children and adolescents with type 2 diabetes, respectively. Section 10, "Cardiovascular Disease and Risk Management," and Section 11, "Chronic Kidney Disease and Risk Management," have recommendations for the use of glucose-lowering drugs in the management of cardiovascular disease and kidney disease, respectively.

Choice of Glucose-Lowering Therapy

Healthy lifestyle behaviors, diabetes selfmanagement education and support (DSMES), avoidance of therapeutic inertia, and social determinants of health should be considered in the glucose-lowering management of type 2 diabetes. Pharmacologic therapy should be guided by person-centered treatment factors, including comorbidities, considerations of adverse effects (including hypoglycemia) and treatment burden, and treatment goals and preferences. Shared decisionmaking can be facilitated during clinical encounters through use of decision aides and has been shown to improve A1C in adults with type 2 diabetes, though in clinical trials the benefits of shared decision-making were limited to face-to-face discussions (not online encounters) and to individuals with elevated A1C ( > 8%) (88) . Pharmacotherapy should be started at the time type 2 diabetes is diagnosed, without delay, unless there are contraindications. Medication plans should have adequate efficacy to achieve and maintain individualized treatment goals with respect to glucose lowering, reduction of cardiovascular and kidney disease risks, weight management, and impacts on other health conditions and treatment burden. In adults with type 2 diabetes and established or high risk of atherosclerotic cardiovascular disease (ASCVD), HF, and/or chronic kidney disease (CKD), the treatment plan should include agents that reduce cardiovascular and kidney disease risk (Fig. 9 .3 and Table 9 .2) (see also Section 10, "Cardiovascular Disease and Risk Management," and Section 11, "Chronic Kidney Disease and Risk Management").

In individuals without ASCVD, HF, or CKD, choice of therapy should be informed by considerations of weight management (see Section 8, "Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes"), mitigation of metabolic dysfunction-associated liver disease (MASLD) or metabolic dysfunctionassociated steatohepatitis (MASH) risk (see Section 4, "Comprehensive Medical Evaluation and Assessment of Comorbidities"), and achievement and maintenance of individualized glycemic goals. In general, higher-efficacy approaches, including combination therapy, have greater likelihood of achieving treatment goals. Weight management is a distinct treatment goal, along with glycemic management, as it has multifaceted benefits, including reduction of A1C, reduction in hepatic steatosis, and improvement in cardiovascular risk factors (89) (90) (91) . For individuals with type 2 diabetes who require initiation or intensification of glucose-lowering therapy to achieve and/or maintain individualized glycemic goals and who do not have additional considerations informing choice of therapy beyond need for glucose lowering, metformin is a commonly used medication that historically has been the first-line treatment for type 2 diabetes (92, 93) . Metformin is effective and safe, is inexpensive and widely available, and reduces risks of microvascular complications, cardiovascular events, and death (92, 94, 95) . Metformin is available in an immediate-release form for twice-daily dosing or as an extended-release form that can be given once daily. Compared with sulfonylureas, metformin as first-line therapy has beneficial effects on A1C, is weight neutral, does not cause hypoglycemia, and reduces cardiovascular mortality (96) . Metformin is also more effective than dipeptidyl peptidase 4 (DPP-4) inhibitors in lowering A1C and weight when used as monotherapy (97) .

The principal side effects of metformin are gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea; these can be mitigated by gradual dose titration and/or using extendedrelease formulation. The drug is cleared by kidney filtration, and metformin may be safely used in people with estimated glomerular filtration rate $30 mL/min/ 1.73 m 2 (98) . Very high circulating levels (e.g., as a result of overdose or acute kidney injury) have been associated with lactic acidosis (99) . However, the occurrence of this complication is very rare (100) and primarily occurs when the estimated glomerular filtration rate (eGFR) is < 30 mL/ min/1.73 m 2 (101). For people with an eGFR of 30-45 mL/min/1.73 m 2 , there is an increased risk for periodic decreases of eGFR to #30 mL/min/1.73 m 2 which heightens the risk of lactic acidosis. Metformin use is also associated with increased risk of vitamin B12 deficiency and worsening of symptoms of neuropathy (102, 103) , suggesting periodic testing of vitamin B12 levels (see Section 3, "Prevention or Delay of Diabetes and Associated Comorbidities").

The comparative glucose-lowering efficacy of different pharmacologic agents has been examined primarily in network meta-analyses, as few prospective clinical trials have compared multiple drug classes head-to-head. In general, the largest reductions in A1C levels are achieved by treatment plans that include insulin, select GLP-1 RAs (particularly semaglutide), and tirzepatide, while DPP-4 inhibitors resulted in the smallest reductions in A1C (104) (105) (106) . In A Diabetes Outcome Progression Trial (ADOPT), rosiglitazone monotherapy was more effective than metformin and glyburide monotherapies in achieving and maintaining fasting plasma glucose below 180 mg/dL (10 mmol/L) among recently diagnosed individuals with type 2 diabetes whose baseline fasting plasma glucose was 126-180 mg/dL (7-10 mmol/L), while glyburide was least effective (107) . More recently, the Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness (GRADE) trial compared use of insulin glargine U-100, liraglutide, sitagliptin, and glimepiride as addon treatments to metformin monotherapy among individuals with type 2 diabetes and baseline A1C 6.8-8.5% (108) . It found that at 5 years, all therapies decreased A1C levels but glargine and liraglutide were modestly more effective in achieving and maintaining A1C below 7%, while sitagliptin was least effective. Severe hypoglycemia was significantly more common in those prescribed glargine or glimepiride. An observational study that emulated many of GRADE's design features and included canagliflozin as a comparator arm, but did not include insulin glargine, found that liraglutide was more effective at achieving and maintaining A1C below 7% than sitagliptin, canagliflozin, or glimepiride, which all had comparable effectiveness (108) .

Thus, when choosing a glucose-lowering medication to achieve individualized glycemic goals, we recommend engaging in shared decision-making and considering factors such as glucose-lowering efficacy, the side effect profile, and medication accessibility and affordability (108) . In all cases, treatment plans need to be continuously reviewed for efficacy, side effects, hypoglycemia, and treatment burden (Table 9 .2).

When A1C is $1.5% above the individualized glycemic goal (see Section 6, "Glycemic Goals and Hypoglycemia," for appropriate goals), many individuals will require dual-combination therapy or a more potent glucose-lowering agent to achieve and maintain their goal A1C level (89) (Fig. 9 .3 and Table 9 .2). Insulin should be considered as part of any combination medication plan when hyperglycemia is severe, especially if catabolic features (weight loss, hypertriglyceridemia, and ketosis) are present. It is common practice to initiate insulin therapy for people who present with blood glucose levels $300 mg/dL ($16.7 mmol/L) or A1C > 10% ( > 86 mmol/mol) or if the individual has symptoms of hyperglycemia (i.e., polyuria or polydipsia) or evidence of catabolism (unexpected weight loss) (Fig. 9 .4). As glucose toxicity resolves, simplifying the medication plan and/or changing to noninsulin agents is possible. Additionally, there is evidence that people with type 2 diabetes and severe hyperglycemia can also be effectively treated with a sulfonylurea, a GLP-1 RA, or dual GIP and GLP-1 RA, though evidence is scarce for individuals with baseline A1C above 10-12% (104, (109) (110) (111) . GLP-1 RAs and tirzepatide have additional benefits over insulin and sulfonylureas, specifically lower risks for hypoglycemia (both) and favorable weight (both), cardiovascular (GLP-1 RAs), kidney (GLP-1 RAs), and liver (both) end points.

Combination Therapy

Because type 2 diabetes is a progressive disease, maintenance of glycemic goals often requires combination therapy. Traditional recommendations have called for the use of stepwise addition of medications to metformin to maintain A1C goals. The advantage of this is to provide a clear assessment of the positive and negative effects of new drugs and reduce potential side effects and expense (112) . However, some data support initial combination therapy for more rapid attainment of glycemic goals (113, 114) and later combination therapy for longer durability of glycemic effect (115) . Initial combination therapy should be considered in people presenting Figure 9 .3-Use of glucose-lowering medications in the management of type 2 diabetes. The left side of the algorithm prioritizes mitigation of diabetes-related complications and end-organ effects, while the right side addresses weight and glucose management goals. ACEi, angiotensinconverting enzyme inhibitor; ACR, albumin-to-creatinine ratio; ARB, angiotensin receptor blocker; ASCVD, atherosclerotic cardiovascular disease; CGM, continuous glucose monitoring; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; CVOT, cardiovascular outcomes trial; DPP-4i, dipeptidyl peptidase 4 inhibitor; DSMES, diabetes self-management education and support; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HHF, hospitalization for heart failure; MACE, major adverse cardiovascular events; MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease; MI, myocardial infarction; SDOH, social determinants of health; SGLT2i, sodium-glucose cotransporter 2 inhibitor; T2D, type 2 diabetes. Adapted from Davies et al. (89) .

• If A1C is above goal and the individual is not already on a GLP-1 RA or dual GIP and GLP-1 RA, consider these

Use principles in Figure 9.3, including reinforcement of behavioral interventions (weight management and physical activity) and provision of DSMES, to meet individualized treatment goals

To avoid therapeutic inertia, reassess and modify treatment regularly (3-6 months) 1. Consider insulin as the first injectable if symptoms of hyperglycemia are present, when A1C or blood glucose levels are very high (i.e., A1C > 10% [ > 86 mmol/mol] or blood glucose ≥300 mg/dL [≥16.7 4. Consider switching from evening NPH to a basal analog if the individual develops hypoglycemia and/or frequently forgets to administer NPH in the evening and would be better managed with a morning dose of a long-acting basal Insulin. Consider dosing NPH in the morning for steroid-induced hyperglycemia.

5. Prandial insulin options include injectable rapid-and ultra-rapid-acting analog insulins, injectable short-acting human insulin, or inhaled human insulin.

6. If adding prandial insulin to NPH, consider initiation of a self-mixed or premixed insulin plan to decrease the number of injections required. with A1C levels 1.5-2.0% above their individualized goal. Finally, incorporation of high-glycemic-efficacy therapies or therapies for cardiovascular and kidney disease risk reduction (e.g., GLP-1 RAs, dual GIP and GLP-1 RA, and SGLT2 inhibitors) may reduce the need for agents that increase the risks of hypoglycemia and weight gain or are less well tolerated. Thus, treatment intensification requires purposeful selection of medications in alignment with multiple individualized person-centered treatment goals simultaneously (Fig. 9 .

If injectable therapy is needed to reduce A1C

Treatment intensification, deintensification, or modification, as appropriate, for people not meeting individualized treatment goals should not be delayed (therapeutic inertia) (116) . Results from comparative effectiveness meta-analyses suggest that each new class of oral noninsulin agents when added to metformin generally lowers A1C by approximately 0.7-1.0% (8-11 mmol/mol). Addition of GLP-1 RAs or the dual GIP and GLP-1 RA to metformin usually results in 1 to $2% lowering of A1C (104, 117, 118) (Fig. 9 .3 and Table 9 .2). We do not recommend using GLP-1 RAs (or the dual GIP and GLP-1 RA) together with a DPP-4 inhibitor as there is no added glucose-lowering benefit beyond that of the GLP-1 RA alone (119) (120) (121) .

When even greater potency of glucose reduction is needed, basal insulin, either human NPH or a long-acting insulin analog, should be initiated. However, if the individual is not already receiving GLP-1 RA or dual GIP and GLP-1 RA therapy, an agent from these classes should be started first, as it may be sufficient for achieving individualized A1C goals but with lower risk of hypoglycemia and with favorable weight, cardiovascular, kidney, and liver profiles. While most GLP-1 RAs are injectable medications, an oral formulation of semaglutide is commercially available (122) . In trials analyzing the addition of an injectable GLP-1 RA, dual GIP and GLP-1 RA, or insulin in people needing further glucose lowering, glycemic efficacies of GLP-1 RAs and the dual GIP and GLP-1 RA were similar to or greater than that of basal insulin (123) (124) (125) (126) (127) (128) (129) (130) . GLP-1 RAs and dual GIP and GLP-1 RA in these trials also had a lower risk of hypoglycemia and beneficial effects on body weight compared with insulin, albeit with greater gastrointestinal side effects. Thus, trial results support high-potency GLP-1 RAs and dual GIP and GLP-1 RA as the preferred options for individuals requiring more intensive glucose management (Fig. 9 .4).

In individuals who are intensified to insulin therapy, combination therapy with a GLP-1 RA or a dual GIP and GLP-1 RA has been shown to have greater efficacy and durability of glycemic treatment effects, as well as weight and hypoglycemia benefits, than treatment intensification with insulin alone (89, 131) . However, cost, accessibility, and tolerability are important considerations for GLP-1 RA and dual GIP and GLP-1 RA use.

In all cases, treatment plans need to be continuously reviewed for efficacy, side effects (including hypoglycemia), and treatment burden (Table 9 .2). In some instances, the individual will require medication reduction or discontinuation. Common reasons for this include ineffectiveness, hypoglycemia, intolerable side effects, new contraindications, expense, or a change in glycemic goals (e.g., in response to development of comorbidities). See below for cost considerations of glucose-lowering therapies (MEDICATION COSTS AND AFFORDABILITY). Section 13, "Older Adults," has a full discussion of treatment considerations in older adults. Treatment deintensification may also be needed in the setting of weight loss and/or optimization of lifestyle behaviors, when fewer pharmacologic agents are needed to maintain A1C goals. In this case, we recommend preferential deescalation of therapies that are most likely to cause side effects, hypoglycemia, and/or treatment burden and do not have cardiovascular, kidney, or metabolic benefits for continued use.

Glucose-Lowering Therapy for People With Cardiovascular Disease or Risk Factors for Cardiovascular Disease

For people with type 2 diabetes and established ASCVD or indicators of high ASCVD risk, HF, or CKD, an SGLT2 inhibitor and/or GLP-1 RA with demonstrated cardiovascular benefit (Table 9 .2) is recommended independent of A1C, with or without metformin use, and in consideration of person-specific factors (Fig. 9 .3). Individuals with these comorbidities already achieving their individualized glycemic goals with other medications may benefit from switching to these preferred medications to reduce risk of ASCVD, HF, and/or CKD in addition to achieving glycemic goals (see Section 10, "Cardiovascular Disease and Risk Management," and Section 11, "Chronic Kidney Disease and Risk Management"). This is particularly important because SGLT2 inhibitors and GLP-1 RAs are associated with lower risk of hypoglycemia and individuals with ASCVD, HF, and CKD have higher hypoglycemia risk than individuals without these conditions (132) .

Individuals at lower risk for ASCVD may still benefit from GLP-1 RA therapy to reduce their risk of future cardiovascular events. The GRADE trial, which was designed to examine the comparative effectiveness of insulin glargine U-100, glimepiride, liraglutide, and sitagliptin in individuals with relatively short duration of diabetes (and, due to study eligibility criteria, low ASCVD risk) with respect to achieving and maintaining A1C below 7%, found that individuals treated with liraglutide had a slightly lower risk of cardiovascular disease than individuals receiving the other three treatments (hazard ratio 0.7 [95% CI 0.6-0.9]), although no significant differences were found for major adverse cardiovascular events, hospitalization for HF, or cardiovascular death (133) . Individuals with type 2 diabetes and moderate levels of CVD risk appear to derive cardiovascular and mortality benefits with preferential use of GLP-1 RA and SGLT2 inhibitors compared with sulfonylurea or DPP-4 inhibitors (134) . Similarly, while greater reductions in HF hospitalization risk are observed with SGLT2 inhibitor therapy in individuals with higher baseline HF risk, some benefit is observed across the full range of HF risk (135) .

Glucose-Lowering Therapy for People With Chronic Kidney Disease

For individuals with type 2 diabetes and CKD, considerations for selection of glucose-lowering medications include their effectiveness and safety when eGFR is reduced as well as the potential to impact CKD progression, CVD risk, and hypoglycemia (136) . Preferred medications for glucose management in individuals with CKD are GLP-1 RAs and SGLT2 inhibitors (can be initiated if eGFR is above 20 mL/ min/1.73 m 2 ). GLP-1 RAs are effective in lowering glucose levels, regardless of kidney function, with a low risk for hypoglycemia, and a recent clinical trial suggests that the GLP-1 RA semaglutide has a beneficial effect on CVD, mortality, and kidney outcomes among people with CKD, leading to the recommendation that semaglutide can be used as another first-line agent for people with CKD (137, 138) . Other GLP-1 RAs (liraglutide and dulaglutide) may also have CKD benefits, but no other dedicated kidney trials have been published. Similarly, no dedicated kidney outcomes studies for the dual GIP and GLP-1 RA (tirzepatide) have been published. Dedicated kidney outcomes trials in people with CKD and type 2 diabetes have shown that the SGLT2 inhibitors empagliflozin, canagliflozin, and dapagliflozin have beneficial effects on slowing progression of CKD and CV outcomes in this population (139) (140) (141) . However, their ability to lower glucose levels declines when the eGFR falls below 45 mL/min/1.73 m 2 (142) (143) (144) . Metformin is also a preferred agent for those with CKD due to its welldocumented efficacy and safety profile for all people with type 2 diabetes. However, there is no documented direct kidney benefit. Importantly, metformin should not be started in those whose eGFR is < 45 mL/min/1.73 m 2 . For those already treated with metformin, the dose of metformin should be reduced once eGFR is < 45 mL/min/1.73 m 2 and should be stopped once eGFR is < 30 mL/ min/1.73 m 2 (98) . A secondary analysis of the GRADE trial found that insulin glargine, liraglutide, sitagliptin, and glimepiride did not prevent the development of CKD when added to metformin monotherapy in individuals without underlying CKD (145) . Importantly, an SGLT2 inhibitor was not included in the GRADE trial.

Individuals with CKD, particularly advanced CKD and kidney failure, are at high risk for hypoglycemia (132) . If treated with insulin and/or sulfonylureas, treatment needs to be closely monitored and adjusted as eGFR declines and individuals need to be educated about and closely monitored for hypoglycemia occurrence (136) . See Section 11, "Chronic Kidney Disease and Risk Management," for more details about prevention and treatment of CKD in individuals with diabetes.

Glucose-Lowering Therapy for People With Metabolic Comorbidities

Many adults with diabetes, either type 2 diabetes or type 1 diabetes, with obesity are at high risk of developing MASLD or MASH as well as MASH cirrhosis. Hence, the presence of MASLD or MASH should be a consideration when choosing glucose-lowering therapies. Accruing randomized clinical trial data suggest that pioglitazone, GLP-1 RA, and a dual GIP and GLP-1 RA have potential benefits in terms of decreasing hepatic steatosis and in the resolution of MASH without worsening of fibrosis in individuals with biopsy-proven MASH or those at higher risk of clinically significant liver fibrosis identified with noninvasive tests (146) (147) (148) (149) (150) (151) (152) (153) . Combination therapy with pioglitazone plus GLP-1 RA should also be considered for treatment of hyperglycemia in adults with type 2 diabetes with biopsyproven MASH or those at higher risk of clinically significant liver fibrosis identified with noninvasive tests, as such therapy is safe and effective and has been shown to reduce hepatic steatosis (154) (155) (156) . It is important to note that these studies are based on phase 2 clinical trials and await further phase 3 confirmation of evidence. However, these plans are preferred as they offer potential benefit compared with lack of histological benefit (or clinical trial data) from other glucose-lowering therapies in MASLD. Further details regarding liver health in diabetes can be found in Section 4, "Comprehensive Medical Evaluation and Assessment of Comorbidities."

Obesity is present in over 90% of people with type 2 diabetes, and in these individuals weight management is a key treatment goal, along with glucose lowering. In the setting of obesity, the choice of glucose-lowering medications should take into consideration their effects on weight. Insulins, sulfonylureas, and thiazolidinediones can promote weight gain and should be used judiciously and at the lowest possible dose. Glucose-lowering medications that promote weight loss should be prioritized. Of the currently available agents, tirzepatide and semaglutide have the highest efficacy in terms of glucose lowering as well as weight loss, followed by dulaglutide, liraglutide, and extendedrelease exenatide (157) (158) (159) (160) (161) . Other glucoselowering medications (metformin, SGLT2 inhibitors, DPP-4 inhibitors, dopamine agonists, bile acid sequestrants, and aglucosidase inhibitors) are weight neutral or have a modest beneficial effect on weight. These medications can be used as add-on therapies in people with type 2 diabetes and obesity who require additional glucose lowering or if the more effective medications are not tolerated, are contraindicated, or are unavailable. Metabolic surgery, especially Roux-en-Y gastric bypass and sleeve gastrectomy, are very effective interventions to achieve both weight and glycemic goals and have additional health benefits beyond improving metabolism (162) . Further details regarding treatment of obesity can be found in Section 8 ("Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes").

Insulin Therapy

Many adults with type 2 diabetes eventually require and benefit from insulin therapy (Fig. 9 .4). See INSULIN ADMINISTRATION TECHNIQUE, above, for guidance on how to administer insulin safely and effectively. The progressive nature of type 2 diabetes should be regularly and objectively explained to individuals with diabetes, and clinicians should avoid using insulin as a threat or describing it as a sign of personal failure. The utility and importance of insulin to achieve and maintain glycemic goals once progression of the disease overcomes the effect of other agents as well as for temporary use for acute situations (such as hospitalization, acute illness, or high-dose glucocorticoid therapy) should be emphasized. Educating and involving people with diabetes in insulin management is beneficial. For example, instruction of individuals with type 2 diabetes initiating insulin on self-titration of insulin doses based on glucose monitoring improves glycemic management (163) . Comprehensive education regarding glucose monitoring, nutrition, physical activity, contingency planning (for illness, fasting, or medication unavailability), and the prevention and appropriate treatment of hypoglycemia are critically important for all individuals using insulin. Assessment and education tailored to improve health literacy and numeracy may be necessary for individuals to effectively use various insulin dosing strategies and tools (64, 65) . See Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes," for guidance on diabetes selfmanagement education.

Although caps on out-of-pocket costs for insulin have been implemented for individuals with Medicare and for individuals on some commercial health plans, and three major insulin manufacturers have capped costs at $35 per month per insulin (199) (200) (201) (202) (see Section 1, "Improving Care and Promoting Health in Populations"), individuals with high-deductible health plans and those without insurance coverage can incur very high out-of-pocket expenses for glucoselowering therapies. Moreover, no such caps exist for diabetes durable medical equipment (i.e., equipment for glucose monitoring and insulin administration) or for noninsulin medications. It is therefore essential to screen all people with diabetes for financial concerns and cost-related barriers to care and to engage members of the health care team, including pharmacists, certified diabetes care and education specialists, social workers, community health workers, community paramedics, and others, to identify cost-saving opportunities for medications, diabetes durable medical equipment, and glucagon (203) .

SPECIAL CIRCUMSTANCES AND POPULATIONS

Recommendations 9.31a Use of compounded products that are not approved by the FDA is not recommended due to uncertainty about their content and resulting concerns about safety, quality, and effectiveness. E 9.31b If a glucose-lowering medication is unavailable (e.g., in shortage), it is recommended to switch to a different FDA-approved medication with similar efficacy, as clinically appropriate. E 9.31c Upon resolution of the unavailability (e.g., shortage), reassess the appropriateness of resuming the original FDA-approved medication. E 9.32a Individuals with diabetes of childbearing potential should be counseled on contraception options A and the impact of some glucose-lowering medications on contraception efficacy. C 9.32b A person-centered shared decision-making approach to preconception planning is essential for all individuals with diabetes and of childbearing potential. A Preconception planning should address attainment of glycemic goals, A the time frame for discontinuing noninsulin glucoselowering medications, E and optimal glycemic management in preparation for pregnancy. A 9.33 Educate individuals with diabetes who are at risk for developing diabetic ketoacidosis and/or follow a ketogenic eating pattern and who are treated with SGLT inhibitors on the risks and signs of ketoacidosis and methods of risk mitigation management, and provide them with appropriate tools for accurate ketone measurement (i.e., serum b-hydroxybutyrate). E

Basal Insulin

Basal insulin alone is the most convenient initial insulin treatment and can be added to noninsulin glucose-lowering medications. For individuals with type 2 diabetes, starting doses can be estimated based on body weight (0.1-0.2 units/kg/day) and the degree of hyperglycemia, with individualized titration over days to weeks as needed to achieve and maintain glycemic goals. The principal action of basal insulin is to restrain hepatic glucose production and limit hyperglycemia overnight and between meals (164, 165) . Attainment of fasting glucose goals can be achieved with human NPH insulin or a long-acting insulin analog. In clinical trials, long-acting basal analogs (U-100 glargine and detemir) have been demonstrated to reduce the risk of level 2 hypoglycemia and nocturnal hypoglycemia compared with NPH insulin (166) . Longer-acting basal analogs (U-300 glargine or degludec) convey a lower nocturnal hypoglycemia risk than U-100 glargine (167, 168) . It is important to understand how to convert individuals from one basal insulin to another, as switching insulins may be required due to the availability of more clinically appropriate insulin alternatives, removal of a product from the market (i.e., insulin detemir), or changes to insurance coverage. Often doses can be converted unit for unit and subsequently adjusted based on glucose monitoring; however, an initial dose reduction of 10-20% can be used for individuals in very tight management or at high risk for hypoglycemia and is typically needed when switching from insulin detemir or U-300 glargine to another insulin (169). Clinicians should also be aware of the potential for overbasalization with insulin therapy (i.e., use of higher than clinically necessary and appropriate dose of basal insulin, typically masking insufficient mealtime insulin). Clinical signals that should prompt evaluation for overbasalization include high bedtime-to-morning or preprandial-to-postprandial glucose differential (e.g., bedtime-to-morning glucose differential $50 mg/dL [$2.8 mmol/L]), hypoglycemia (aware or unaware), and high glucose variability. Evidence of overbasalization should prompt reevaluation of the glucose-lowering treatment plan to better address postprandial hyperglycemia (170).

Combination Injectable Therapy and Prandial Insulin

If basal insulin has been titrated to an acceptable fasting blood glucose level and A1C remains above goal, if there is evidence of significant postprandial hyperglycemia, or if signs of overbasalization are present, advancement to combination injectable therapy is necessary (Fig. 9 .4). This approach can use a GLP-1 RA or dual GIP and GLP-1 RA added to basal insulin or multiple doses of prandial insulin (131, 171) . If an individual is not already being treated with a GLP-1 RA or dual GIP and GLP-1 RA, a GLP-1 RA (either as an individual product or in a fixed-ratio combination with a basal insulin product) or dual GIP and GLP-1 RA should be considered prior to starting prandial insulin to address prandial management and to lower the risks of hypoglycemia and weight gain associated with insulin therapy (131, 172) .

Further intensification of insulin therapy entails adding doses of prandial insulin to basal insulin. Starting with a single prandial dose with the largest meal of the day is simple and effective, and it can be advanced to a plan with multiple prandial doses if necessary (173). We suggest starting with a prandial insulin dose of 4 units or 10% of the amount of basal insulin at the largest meal or the meal with the greatest postprandial excursion. The prandial insulin plan can then be intensified based on individual needs (Fig. 9 .4). Alternatively, for an individual treated with basal insulin in whom additional prandial coverage is desired but administering insulin prior to one or more meals is not feasible, the medication plan can be converted to two doses of a premixed insulin. Each approach has advantages and disadvantages. For example, basal-prandial plans offer greater flexibility for individuals who eat on irregular schedules, have variable meal content, or otherwise benefit from greater individualization and flexibility in insulin administration. On the other hand, two doses of premixed insulin is a simple, convenient means of spreading insulin across the day. Moreover, human insulins, separately, self-mixed, or as premixed NPH/regular (for example, 70/30) formulations, are often less costly alternatives to insulin analogs.

Individuals with type 2 diabetes are generally more insulin resistant than those with type 1 diabetes, require higher daily doses ($1 unit/kg), and have lower rates of hypoglycemia (174). Meta-analyses of trials comparing rapid-acting insulin analogs with human regular insulin in type 2 diabetes have not reported meaningful differences in A1C or hypoglycemia (175, 176) . Titration of prandial insulin can be based on home self-monitored blood glucose or CGM. When significant additions to the prandial insulin dose are made, particularly with the evening meal, consideration should be given to decreasing basal insulin to reduce risk of hypoglycemia. When initiating intensification of insulin therapy, metformin, SGLT2 inhibitors, and GLP-1 RAs (or a dual GIP and GLP-1 RA) should be maintained, unless adverse effects (including significant treatment burden) or contraindications are present. Use of sulfonylureas, meglitinides, and DPP-4 inhibitors should be limited or discontinued, as these medications do not have additional beneficial effects on cardiovascular, kidney, weight, or liver outcomes and (for sulfonylureas and meglitinides) increase risk of hypoglycemia and weight gain. Adjunctive use of pioglitazone may help to improve glycemia and reduce the amount of insulin needed, although potential side effects should be considered.

Once a basal-bolus insulin plan is initiated, dose titration is important, with adjustments made in both prandial and basal insulins based on blood glucose levels and an understanding of the pharmacodynamic profile of each formulation (also known as pattern control or pattern management). In some people with type 2 diabetes with significant clinical complexity, multimorbidity, and/or treatment burden, it may become necessary to simplify or deintensify complex insulin plans to decrease risk of hypoglycemia and improve quality of life (see Section 13, "Older Adults").

Concentrated Insulins

Concentrated preparations may be more convenient (fewer injections to achieve goal dose) and comfortable (less volume to inject the desired dose and/or less injection effort) for individuals and may improve treatment plan engagement in those with insulin resistance who require large doses of insulin. Several concentrated insulin preparations are currently available. U-500 regular insulin is, by definition, five times more concentrated than U-100 regular insulin. U-500 regular insulin has distinct pharmacokinetics with similar onset but a delayed, blunted, and prolonged peak effect and longer duration of action compared with U-100 regular insulin; thus, it has characteristics more like a premixed intermediate-acting (NPH) and regular insulin product and can be used as two or three daily injections (177,178). U-300 glargine and U-200 degludec are three and two times, respectively, as concentrated as their U-100 formulations and allow higher doses of basal insulin administration per volume used. U-300 glargine has a longer duration of action than U-100 glargine but modestly lower efficacy per unit administered (179) (180) (181) . The U-200 formulations of insulin degludec, insulin lispro, and insulin lispro-aabc have pharmacokinetics similar to those of their U-100 counterparts (182) (183) (184) . While U-500 regular insulin is available in both prefilled pens and vials, other concentrated insulins are available only in prefilled pens to minimize the risk of dosing errors. If U-500 regular insulin vials are prescribed, the prescription should be accompanied by a prescription for U-500 syringes to minimize the risk of dosing errors.

Alternative Insulin Routes

Insulin is primarily administered via subcutaneous injection or infusion. Administration devices provide some additional variation in the subcutaneous delivery beyond vial and syringe versus insulin pen. Those devices include continuous insulin pumps (programmable or automated basal and bolus settings and fixed basal and bolus settings) and bolus-only insulin patch pump. In addition, prandial or correction insulin doses may be administered using inhaled human insulin. Inhaled insulin is available as monomers of regular human insulin; studies in individuals with type 1 diabetes suggest that inhaled insulin has pharmacokinetics similar to those of RAA (185) . Studies comparing inhaled insulin with injectable insulin have demonstrated its faster onset and shorter duration compared with the RAA insulin lispro as well as clinically meaningful A1C reductions and weight reductions compared with the RAA insulin aspart over 24 weeks (186) (187) (188) . Use of inhaled insulin may result in a decline in lung function (reduced forced expiratory volume in 1 s [FEV 1 ]). Inhaled insulin is contraindicated in individuals with chronic lung disease, such as asthma and chronic obstructive pulmonary disease, and is not recommended in individuals who smoke or who recently stopped smoking. All individuals require spirometry (FEV 1 ) testing to identify potential lung disease prior to and after starting inhaled insulin therapy.

ADDITIONAL RECOMMENDATIONS FOR ALL INDIVIDUALS WITH DIABETES

Recommendations 9.27 Monitor for signs of overbasalization during insulin therapy, such as significant bedtime-to-morning or postprandial-to-preprandial glucose differential, occurrences of hypoglycemia (aware or unaware), and high glycemic variability. When overbasalization is suspected, a thorough reevaluation should occur promptly to further tailor therapy to the individual's needs. E 9.28 Glucagon should be prescribed for all individuals requiring intensive insulin therapy or at high risk for hypoglycemia. Family, caregivers, school personnel, and others providing support to these individuals should know its location and be educated on how to administer it. Glucagon preparations that do not require reconstitution are preferred. B 9.29 Routinely assess all people with diabetes for financial obstacles that could impede their diabetes management. Clinicians, members of the diabetes care team, and social services professionals should work collaboratively, as appropriate and feasible, to support these individuals by implementing strategies to reduce costs, thereby improving their access to evidence-based care. E 9.30 In adults with diabetes and cost-related barriers, consider use of lower-cost medications for glycemic management (i.e., metformin, sulfonylureas, thiazolidinediones, and human insulin) within the context of their risks for hypoglycemia, weight gain, cardiovascular and kidney events, and other adverse effects. E Several key aspects of insulin management that are relevant to all people with diabetes requiring insulin therapy, including available formulations, insulin plans and delivery systems, administration technique, and overbasalization, were discussed earlier in this section. Additional considerations for glucose-lowering therapy that may be relevant to people with all types of diabetes include glucagon coprescription and affordability of diabetes therapies.

Due to the risk of hypoglycemia with insulin treatment, all individuals treated with insulin or who are at high risk for hypoglycemia should be prescribed glucagon. Individuals with diabetes who are prescribed glucagon and those in close contact with them should be educated on the use and administration of the individual's prescribed glucagon product. The glucagon product available to individuals may differ based on coverage and cost; however, products that do not require reconstitution are preferred for ease of administration (189, 190) . Clinicians should routinely review the individual's access to glucagon, as appropriate glucagon prescribing is low (191) (192) (193) . See Section 6, "Glycemic Goals and Hypoglycemia," for additional information on hypoglycemia and glucagon in individuals with diabetes.

Medication Costs and Affordability

Costs for noninsulin and insulin diabetes medications have increased dramatically over the past two decades, and an increasing proportion of cost is now passed on to people with diabetes and their families (194) . Table 9 .3 provides cost information for currently approved noninsulin therapies, while Table 9 .4 provides these data for insulin. Of note, prices listed are average wholesale prices (AWP) (195) and National Average Drug Acquisition Costs (NADAC) (196) ; these estimates allow for a comparison of drug prices but do not represent the actual costs to people with diabetes because they do not account for various discounts, rebates, and other price adjustments often involved in prescription sales that affect the actual cost incurred by the individual. Medication costs can be a major source of stress for people with diabetes and contribute to worse medication-taking behavior (197) ; cost-reducing strategies may improve medication-taking behavior in some cases (198) .

A 10.11 An ACE inhibitor or ARB, at the maximum tolerated dose indicated for blood pressure treatment, is the recommended first-line treatment for hypertension in people with diabetes and urinary albumin-to-creatinine ratio $300 mg/g creatinine A or 30-299 mg/g creatinine. B If one class is not tolerated, the other should be substituted. B 10.12 Monitor for increased serum creatinine and for increased serum potassium levels when ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists (MRAs) are used, for hypokalemia when diuretics are used at routine visits, and 7-14 days after initiation or after a dose change. B 10.13 ACE inhibitors, angiotensin receptor blockers, MRAs, direct renin inhibitors, and neprilysin inhibitors should be avoided in sexually active individuals of childbearing potential who are not using reliable contraception and are contraindicated in pregnancy. A Initial Number of Antihypertensive Medications. Initial treatment for people with diabetes depends on the severity of hypertension (Fig. 10 .2). Those with blood pressure between 130/80 mmHg and 150/90 mmHg may begin with a single drug. For individuals with blood pressure $150/90 mmHg, initial pharmacologic treatment with two antihypertensive medications is recommended to more effectively achieve blood pressure goals (63) (64) (65) . Single-pill antihypertensive combinations may improve medication taking in some individuals (66).

Classes of Antihypertensive Medications.

Initial treatment for hypertension should include any of the drug classes demonstrated to reduce cardiovascular events in people with diabetes (25): ACE inhibitors (67, 68) , ARBs (67, 68) , thiazide-like diuretics (69) , or dihydropyridine calcium channel blockers (70) . In people with diabetes and established coronary artery disease, ACE inhibitors or ARBs are recommended first-line therapy for hypertension (71) (72) (73) . For individuals with albuminuria (urine albumin-to-creatinine ratio [UACR] $30 mg/g), initial treatment should include an ACE inhibitor or ARB to reduce the risk of progressive kidney disease (21) (Fig. 10 .2). In individuals receiving ACE inhibitor or ARB therapy, continuation of those medications as kidney function declines to estimated glomerular filtration rate (eGFR) < 30 mL/min/ 1.73 m 2 may provide cardiovascular benefit without significantly increasing the risk of end-stage kidney disease (74) . In the absence of albuminuria, risk of progressive kidney disease is low, and ACE inhibitors and ARBs have not been found to afford superior cardioprotection compared with thiazide-like diuretics or dihydropyridine calcium channel blockers (75) . b-Blockers are indicated in the setting of prior MI, active angina, or HFrEF but have not been shown to reduce mortality as blood pressure-lowering agents in the absence of these conditions (33, 76, 77) .

Multiple-Drug Therapy. Multiple-drug therapy is often required to achieve blood pressure goals (Fig. 10 .2), particularly in the setting of CKD in people with diabetes. However, the use of both ACE Figure 10 .2-Recommendations for the treatment of confirmed hypertension in nonpregnant people with diabetes. *An ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) is suggested for the treatment of hypertension in people with coronary artery disease (CAD) or urine albuminto-creatinine ratio 30-299 mg/g creatinine and is strongly recommended for individuals with urine albumin-to-creatinine ratio $300 mg/g creatinine. †Dihydropyridine calcium channel blocker (CCB). ‡Thiazide-like diuretic; long-acting agents shown to reduce cardiovascular events, such as chlorthalidone and indapamide, are preferred. BP, blood pressure. Adapted from de Boer et al. (21) .

diabetesjournals.org/care

Cardiovascular Disease and Risk Management S213 inhibitors and ARBs in combination, or the combination of an ACE inhibitor or ARB and a direct renin inhibitor, is contraindicated given the lack of added ASCVD benefit and increased rate of adverse events-namely, hyperkalemia, syncope, and AKI (78) (79) (80) . Titration of and/or addition of further blood pressure medications should be made in a timely fashion to overcome therapeutic inertia in achieving blood pressure goals.

Bedtime Dosing. Although prior analyses of randomized clinical trials found a benefit to evening versus morning dosing of antihypertensive medications (81,82), these results have not been reproduced in subsequent trials. Therefore, preferential use of antihypertensives at bedtime is not recommended (83) .

Hyperkalemia and Acute Kidney Injury.

Treatment with ACE inhibitors and ARBs or

MRAs can cause AKI and hyperkalemia, while diuretics can cause AKI and either hypokalemia or hyperkalemia (depending on mechanism of action) (84, 85) . Detection and management of these abnormalities is important because AKI and hyperkalemia each increase the risks of cardiovascular events and death (86) . Therefore, serum creatinine and potassium should be monitored after initiation of treatment with an ACE inhibitor or ARB, MRA, or diuretic and monitored during treatment and following uptitration of these medications, particularly among individuals with reduced glomerular filtration who are at increased risk of hyperkalemia and AKI (84, 85, 87) .

Resistant Hypertension Recommendation 10.14 Individuals with hypertension who are not meeting blood pressure goals on three classes of antihypertensive medications (including a diuretic) should be considered for MRA therapy. A Resistant hypertension is defined as blood pressure $140/90 mmHg despite a therapeutic strategy that includes appropriate lifestyle management plus a diuretic and two other antihypertensive drugs with complementary mechanisms of action at adequate doses. Prior to diagnosing resistant hypertension, a number of other conditions should be excluded, including missed doses of antihypertensive medications, white coat hypertension, and primary and secondary hypertension. Difficulty following the care plan may also be a reason for resistant hypertension. International Society of Hypertension guidelines put a strong emphasis on screening for care plan difficulties in management of hypertension and recommend using objective measures such as review of pharmacy records, pill counting, and the chemical analysis of blood or urine rather than subjective methods of detecting inconsistencies in care plan engagement in routine clinical practice. However, this may not be feasible in all practice settings (22) .

People with diabetes and confirmed resistant hypertension should be evaluated for secondary causes of hypertension, including primary hyperaldosteronism, renal artery stenosis, CKD, and obstructive sleep apnea. In general, barriers to medication taking (such as cost and side effects) should be identified and addressed (Fig. 10 .2). MRAs, including spironolactone and eplerenone, are effective for management of resistant hypertension in people with type 2 diabetes when added to existing treatment with an ACE inhibitor or ARB, thiazide-like diuretic, or dihydropyridine calcium channel blocker (88) . In addition, MRAs reduce albuminuria in people with diabetic nephropathy (89) (90) (91) . However, adding an MRA to a treatment plan that includes an ACE inhibitor or ARB may increase the risk for hyperkalemia, emphasizing the importance of regular monitoring for serum creatinine and potassium in these individuals, and long-term outcome studies are needed to better evaluate the role of MRAs in blood pressure management.

LIPID MANAGEMENT Lifestyle Intervention

Recommendations 10.15 Lifestyle modification focusing on weight loss (if indicated); application of a Mediterranean or DASH eating pattern; reduction of saturated fat and trans fat; increase of dietary n-3 fatty acids, viscous fiber, and plant stanol and sterol intake; and increased physical activity should be recommended to improve the lipid profile and reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD) in people with diabetes. A 10.16 Intensify lifestyle therapy and optimize glycemic management for people with diabetes with elevated triglyceride levels ($150 mg/dL [$1.7 mmol/L]) and/or low HDL cholesterol ( < 40 mg/dL [ < 1.0 mmol/L] for men and < 50 mg/dL [ < 1.3 mmol/L] for women). C Lifestyle intervention, including weight loss in people with overweight or obesity (when appropriate) (19, 92) , increased physical activity, and medical nutrition therapy, allows some individuals to reduce ASCVD risk factors. Nutrition intervention should be tailored according to each person's age, pharmacologic treatment, lipid levels, and medical conditions.

Recommendations should focus on application of a Mediterranean (93) or DASH eating pattern, reducing saturated and trans fat intake, and increasing plant stanol and sterol, n-3 fatty acid, and viscous fiber (such as in oats, legumes, and citrus) intake (19, 92) . Glycemic management may also beneficially modify plasma lipid levels, particularly in people with very high triglycerides and poor glycemic management. See Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes," for additional nutrition information.

Ongoing Therapy and Monitoring With Lipid Panel Recommendations 10.17 In adults with prediabetes or diabetes not taking statins or other lipid-lowering therapy, it is reasonable to obtain a lipid profile at the time of diagnosis, at an initial medical evaluation, annually thereafter, or more frequently if indicated. E 10.18 Obtain a lipid profile at initiation of statins or other lipid-lowering therapy, 4-12 weeks after initiation or a change in dose, and annually thereafter, as it facilitates monitoring the response to therapy and informs medication-taking behavior. A In adults with diabetes, it is reasonable to obtain a lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides) at the time of diagnosis, at the initial medical evaluation, and at least every 5 years thereafter in individuals < 40 years of age. In younger people with longer duration of disease (such as those with youth-onset type 1 diabetes), more frequent lipid profiles may be reasonable. A lipid panel should also be obtained immediately before initiating statin therapy. Once an individual is taking a statin, LDL cholesterol levels should be assessed 4-12 weeks after initiation of statin therapy, after any change in dose, and annually (e.g., to monitor for medication taking and efficacy). Monitoring lipid profiles after initiation of statin therapy and during therapy increases the likelihood of dose titration and following the statin treatment plan (94) (95) (96) . If LDL cholesterol levels are not responding despite medication taking, clinical judgment is recommended to determine the need for and timing of lipid panels. In individuals, the highly variable LDL cholesterol-lowering response seen with statins is poorly understood (97) . Clinicians should attempt to find a dose or alternative statin that is tolerable if side effects occur. There is evidence for benefit from even extremely low, less-than-daily statin doses (98) .

STATIN TREATMENT Primary Prevention

Recommendations 10. 19 For people with diabetes aged 40-75 years without ASCVD, use moderate-intensity statin therapy in addition to lifestyle therapy. A 10.20 For people with diabetes aged 20-39 years with additional ASCVD risk factors, it may be reasonable to initiate statin therapy in addition to lifestyle therapy. C 10.21 For people with diabetes aged 40-75 years at higher cardiovascular risk, including those with one or more additional ASCVD risk factors, highintensity statin therapy is recommended to reduce LDL cholesterol by $50% of baseline and to obtain an LDL cholesterol goal of < 70 mg/dL ( < 1.8 mmol/L). A 10.22 For people with diabetes aged 40-75 years at higher cardiovascular risk, especially those with multiple additional ASCVD risk factors and an LDL cholesterol $70 mg/dL ($1.8 mmol/L), it may be reasonable to add ezetimibe or a PCSK9 inhibitor to maximum tolerated statin therapy. B 10. 23 In adults with diabetes aged > 75 years already on statin therapy, it is reasonable to continue statin treatment. B 10. 24 In adults with diabetes aged > 75 years, it may be reasonable to initiate moderate-intensity statin therapy after discussion of potential benefits and risks. C 10. 25 In people with diabetes intolerant to statin therapy, treatment with bempedoic acid is recommended to reduce cardiovascular event rates as an alternative cholesterol-lowering plan. A 10.26 In most circumstances, lipidlowering agents should be stopped prior to conception and avoided in sexually active individuals of childbearing potential who are not using reliable contraception. B In some circumstances (e.g., for individuals with familial hypercholesterolemia or prior ASCVD event), statin therapy may be continued when the benefits outweigh risks. E Secondary Prevention Recommendations 10.27 For people of all ages with diabetes and ASCVD, high-intensity statin therapy should be added to lifestyle therapy. A 10.28 For people with diabetes and ASCVD, treatment with high-intensity statin therapy is recommended to obtain an LDL cholesterol reduction of $50% from baseline and an LDL cholesterol goal of < 55 mg/dL ( < 1.4 mmol/L). Addition of ezetimibe or a PCSK9 inhibitor with proven benefit in this population is recommended if this goal is not achieved on maximum tolerated statin therapy. B 10.29a For individuals who do not tolerate the intended statin intensity, the maximum tolerated statin dose should be used. E 10.29b For people with diabetes and ASCVD intolerant to statin therapy, PCSK9 inhibitor therapy with monoclonal antibody treatment, A bempedoic acid therapy, A or PCSK9 inhibitor therapy with inclisiran siRNA E should be considered as an alternative cholesterol-lowering therapy.

Initiating Statin Therapy

People with type 2 diabetes have an increased prevalence of lipid abnormalities, contributing to their high risk of ASCVD. Multiple clinical trials have demonstrated the beneficial effects of statin therapy on ASCVD outcomes in subjects with and without coronary heart disease (CHD) (99, 100) . Subgroup analyses of people with diabetes in larger trials (101) (102) (103) (104) (105) and trials in people with diabetes (106,107) showed significant primary and secondary prevention of ASCVD events and CHD death in people with diabetes. Meta-analyses including data from > 18,000 people with diabetes from 14 randomized trials of statin therapy (mean follow-up 4.3 years) demonstrated a 9% proportional reduction in all-cause mortality and 13% reduction in vascular mortality for each 1 mmol/L (39 mg/dL) reduction in LDL cholesterol (108) . The cardiovascular benefit in this large meta-analysis did not depend on baseline LDL cholesterol levels and was linearly related to the LDL cholesterol reduction without a low threshold beyond which there was no benefit observed (108) . It is important to note that the effects of statin therapy do not differ based on sex (109) .

Accordingly, statins are the drugs of choice for LDL cholesterol lowering and cardioprotection. Table 10 .1 shows the two statin dosing intensities that are recommended for use in clinical practice. High-intensity statin therapy will achieve an approximately $50% reduction in LDL cholesterol, and moderate-intensity statin plans achieve 30-49% reductions in LDL cholesterol. Low-dose statin therapy is generally not recommended in people with diabetes but is sometimes the only dose of statin that an individual can tolerate. For individuals who do not tolerate the intended intensity of statin, the maximum tolerated statin dose should be used.

As in those without diabetes, absolute reductions in ASCVD outcomes (CHD death and nonfatal MI) are greatest in people with high baseline ASCVD risk (known ASCVD and/or very high LDL cholesterol levels), but the overall benefits of statin therapy in people with diabetes at moderate or even low risk for ASCVD are convincing (110, 111) . The relative benefit of lipidlowering therapy has been uniform across most subgroups tested (100, 108) , including subgroups that varied with respect to age and other risk factors.

Primary Prevention (People Without ASCVD)

For primary prevention, moderate-dose statin therapy is recommended for those aged $40 years (19, 112, 113) , although high-intensity therapy should be considered in the context of additional ASCVD risk factors (Fig. 10 .3). The evidence is strong for people with diabetes aged 40-75 years, an age-group well represented in statin trials showing benefit. Since cardiovascular risk is enhanced in people with diabetes, as noted above, individuals who also have multiple other coronary risk factors have increased risk, equivalent to that of those with ASCVD. Therefore, current guidelines recommend that in people with diabetes who are at higher cardiovascular risk, especially those with one or more ASCVD risk factors, high-intensity statin therapy should be prescribed to reduce LDL cholesterol by $50% from baseline and to obtain an LDL cholesterol of < 70 mg/dL ( < 1.8 mmol/L) (114) (115) (116) . Since, in clinical practice, it is frequently difficult to ascertain the baseline LDL cholesterol level prior to statin therapy initiation, in those individuals, a focus on an LDL cholesterol goal of < 70 mg/dL ( < 1.8 mmol/L) rather than percent reduction in LDL cholesterol is recommended. In those individuals, it may also be reasonable to add ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy to maximum tolerated statin therapy if needed to reduce LDL cholesterol levels by $50% and to achieve the recommended LDL cholesterol goal of < 70 mg/dL ( < 1.8 mmol/L) (117) . While there are no randomized controlled trials specifically assessing cardiovascular outcomes of adding ezetimibe or PCSK9 inhibitors to statin therapy in primary prevention, a portion of the participants without established cardiovascular disease were included in some studies, which also included participants with established cardiovascular disease. A meta-analysis suggests that there is a cardiovascular benefit of adding ezetimibe or PCSK9 inhibitors to treatment for people at high risk (118) . There is less evidence for individuals aged > 75 years; relatively few older people with diabetes have been enrolled in primary prevention trials. However, heterogeneity by age has not been seen in the relative benefit of lipid-lowering therapy in trials that included older participants (100, 107, 108) , and because older age confers higher risk, the absolute benefits are actually greater (100, 119) . Moderate-intensity statin therapy is recommended in people with diabetes who are $75 years of age. However, the riskbenefit profile should be routinely evaluated in this population, with downward titration of dose performed as needed. See Section 13, "Older Adults," for more details on clinical considerations for this population.

In people 40-75 years of age

Consider statin therapy if there are additional ASCVD risk factors.

Use moderate-intensity statin therapy in those without ASCVD risk factors.

Use bempedoic acid for those who are statin intolerant.

Use a high-intensity statin in those with ≥1 ASCVD risk factor, with an LDL cholesterol goal of < 70 mg/dL ( < 1.8 mmol/L).

It may be reasonable to add ezetimibe or PCSK9 inhibitor to maximum tolerated statin therapy if LDL goal is not achieved.

Continue current statin therapy or consider initiating a moderate-intensity statin after weighing benefits and risks.

In people 20-39 years of age

In people > 75 years of age

Lipid Management for Primary Prevention of Atherosclerotic Cardiovascular Disease Events in People With Diabetes in Addition to Healthy Behavior Modification Age < 40 Years and/or Type 1 Diabetes. Very little clinical trial evidence exists for people with type 2 diabetes under the age of 40 years or for people with type 1 diabetes of any age. For pediatric recommendations, see Section 14, "Children and Adolescents." In the Heart Protection Study (lower age limit 40 years), the subgroup of $600 people with type 1 diabetes had a reduction in risk proportionately similar, although not statistically significant, to that in people with type 2 diabetes (102) . Even though the data are not definitive, similar statin treatment approaches should be considered for people with type 1 or type 2 diabetes, particularly in the presence of other cardiovascular risk factors. Individuals < 40 years of age have lower risk of developing a cardiovascular event over a 10-year horizon; however, their lifetime risk of developing cardiovascular disease and experiencing an MI, stroke, or cardiovascular death is high. For people who are < 40 years of age and/or have type 1 diabetes with other ASCVD risk factors, it is recommended that the individual and health care professional discuss the relative benefits and risks and consider the use of moderate-intensity statin therapy. Please refer to "Type 1 Diabetes Mellitus and Cardiovascular Disease: A Scientific Statement From the American Heart Association and American Diabetes Association" (120) for additional discussion.

Secondary Prevention (People With ASCVD)

Intensive therapy is indicated because cardiovascular event rates are increased in people with diabetes and established ASCVD, and it has been shown to be of benefit in multiple large meta-analyses and randomized cardiovascular outcomes trials (99, 100, 108, 119, 121) . High-intensity statin therapy is recommended for all people with diabetes and ASCVD to obtain an LDL cholesterol reduction of $50% from baseline and an LDL cholesterol goal of < 55 mg/dL ( < 1.4 mmol/L) (Fig. 10 .4). The addition of ezetimibe or a PCSK9 inhibitor is recommended if this goal is not achieved on maximum tolerated statin therapy. These recommendations are based on the observation that high-intensity versus moderate-intensity statin therapy reduces cardiovascular event rates in high-risk individuals with established cardiovascular disease in randomized trials (99) . The Cholesterol Treatment Trialists' Collaboration, involving 26 statin trials, of which 5 compared high-intensity versus moderateintensity statins, showed a 21% reduction in major cardiovascular events in people with diabetes for every 39 mg/dL (1 mmol/L) of LDL cholesterol lowering, irrespective of baseline LDL cholesterol or individual characteristics (108) . The evidence to support lower LDL cholesterol goals in people with diabetes and established cardiovascular disease derives from multiple large, randomized trials investigating the benefits of adding nonstatin agents to statin therapy, including combination treatment with statins and ezetimibe (119, 122) or PCSK9 inhibitors (121, (123) (124) (125) . Each trial found a large benefit in reducing ASCVD events that was directly related to the degree of further LDL cholesterol lowering. A large number of participants with diabetes were included in these trials, and prespecified analyses were completed to evaluate cardiovascular outcomes in people with and without diabetes (122, 124, 125) . The decision to add a nonstatin agent should be made following a discussion between a clinician and a person with diabetes about the net benefit, safety, and cost of combination therapy.

Combination Therapy for LDL Cholesterol Lowering

Statins and Ezetimibe

The best evidence for combination therapy of statins and ezetimibe comes from the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT).

The trial showed the addition of ezetimibe to a moderate-intensity statin led to a 6.4% relative benefit and a 2% absolute reduction in major adverse cardiovascular events (atherosclerotic cardiovascular events), with the degree of benefit being directly proportional to the change in LDL cholesterol (119) . A subanalysis of participants with diabetes (27% of the 18,144 participants) showed a significant reduction of major adverse cardiovascular events with the combination treatment over moderate-intensity statin alone (122) .

Statins and PCSK9 Inhibitors

The addition of the PCSK9 inhibitors evolocumab and alirocumab to maximum tolerated doses of statin therapy in participants who were at high risk for ASCVD demonstrated an average reduction in LDL cholesterol ranging from 36% to 59% (126, 127) . No cardiovascular outcome trials have been performed to assess whether PCSK9 inhibitor therapy reduces ASCVD event rates in individuals at low or moderate risk for ASCVD (primary prevention). The evidence on the effect of PSCK9 inhibition on ASCVD outcomes is from studies of treatment with the monoclonal antibodies alirocumab and evolocumab. When added to a maximally tolerated statin, these agents reduced LDL cholesterol by $60% (121) and significantly reduced the risk of major adverse cardiovascular events by 15 (124) .

In addition to the monoclonal antibodies, an siRNA, inclisiran, which also targets PSCK9, has demonstrated the ability to reduce LDL cholesterol by 49-52% in trials evaluating individuals with established cardiovascular disease or ASCVD risk equivalent (129) . Inclisiran allows less frequent administration compared with monoclonal antibodies and was administered on day 1, on day 90, and every 6 months in these trials. In an exploratory analysis, the prespecified cardiovascular end point of nonadjudicated cardiovascular events, including cardiac death, signs or symptoms of cardiac arrest, nonfatal MI, or stroke, occurred less frequently with inclisiran than placebo (7.4% vs. 10.2% in one trial and 7.8% vs. 10.3% in another trial). Cardiovascular outcome trials using inclisiran in people with established cardiovascular disease (130, 131) and for primary prevention in those at high risk for cardiovascular disease (132) are currently ongoing.

Intolerance to Statin Therapy

Statin therapy is a hallmark approach to cardiovascular prevention and treatment; however, a subset of individuals experience partial (inability to tolerate sufficient dosage necessary to achieve therapeutic objectives due to adverse effects) or complete (inability to tolerate any dose) intolerance to statin therapy (133) . Although the definition of statin intolerance differs between organizations and across clinical study methods, these individuals will require an alternative treatment approach. Initial steps in people intolerant to statins may include switching to a different highintensity statin if a high-intensity statin is indicated, switching to moderate-intensity or low-intensity statin, lowering the statin dose, or using nondaily dosing with statins. While considering these alternative treatment plans, the addition of nonstatin treatment plans to maximum tolerated statin therapy should be considered, as these are frequently associated with improved medication-taking behavior and achievement of LDL cholesterol goals (133) .

PCSK9-Directed Therapies

The PCSK9 monoclonal antibodies alirocumab and evolocumab both have been shown to be effective for LDL cholesterol reduction and fewer skeletal musclerelated adverse effects when studied in populations considered statin intolerant. The Study of Alirocumab in Patients With Primary Hypercholesterolemia and Moderate, High, or Very High Cardiovascular Risk, Who Are Intolerant to Statins (ODYSSEY ALTERNATIVE) trial studied the reduction in LDL cholesterol with alirocumab compared with ezetimibe or 20 mg atorvastatin in individuals at moderate to very high cardiovascular risk for 24 weeks. The proportion of the study population with type 2 diabetes was $24%. After the 24 weeks, alirocumab lowered LDL cholesterol levels by 54.8% versus 20.1% with ezetimibe. There were similar rates of any adverse event for all treatments; however, fewer events that led to treatment discontinuation and few skeletal muscle-related adverse events occurred with alirocumab (134) .

The Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects 1, 2, and 3 (GAUSS 1, 2, and 3) trials, as well as the Open-Label Study of Long-term Evaluation Against LDL Cholesterol (OSLER) open-label extension of the GAUSS 1 and 2 trials, evaluated the safety and LDL cholesterol reduction of evolocumab plus ezetimibe compared with ezetimibe alone in individuals with statin intolerance.

Reductions in LDL cholesterol ranged from 55% and 56% for evolocumab biweekly and monthly plus daily oral placebo, respectively, to 19% and 16% for ezetimibe daily plus biweekly or monthly subcutaneous placebo, respectively. Fewer musculoskeletal adverse effects occurred in those treated with evolocumab or ezetimibe than in those treated with ezetimibe plus placebo, although rates of discontinuation due to these effects were similar. Use of low-dose statins was allowed in these studies and was associated with an increase in the incidence of musculoskeletal adverse effects (135, 136) . Similar LDL cholesterol reductions were demonstrated in the GAUSS 3 trial after 24 weeks (54.5% with evolocumab compared with 16.7% with ezetimibe), with slightly higher rates of musculoskeletal adverse events (20.7% with evolocumab and 28.8% with ezetimibe). The higher rates of these adverse events may be due in part to the first phase of this trial, which randomized individuals to a statin rechallenge with either atorvastatin or placebo (137) . , where an LDL cholesterol reduction of $45% was maintained through the end of year 4 (139) . It is important to note that of the ORION-3 participants, only 23% had diabetes and 33% were not taking statin therapy. Although it may be expected that those with statin intolerance experienced a response similar to the response of those on statin therapy, evaluation of response based on background lipid-lowering therapy was not described.

Bempedoic Acid

Bempedoic acid, a novel LDL cholesterollowering agent acting in the same pathway as statin but without activity in skeletal muscle, which limits the muscle-related adverse effects, lowers LDL cholesterol levels by 15% for those on statins and 24% for those not taking statins (140) . Use of this agent with ezetimibe results in an additional 19% reduction in LDL cholesterol (140) . The Evaluation of Major Cardiovascular Events in Patients With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid or Placebo (CLEAR Outcomes) trial found a reduction in four-point major adverse cardiovascular events by 13% compared with placebo for individuals with established ASCVD (70% of population) or at high risk for ASCVD (30% of population) and considered to be intolerant to statin therapy. It is important to note that $19% of individuals were on very-low-dose statin therapy at baseline (141) . Prespecified subanalyses evaluated the impact for individuals with diabetes and showed a 17% reduction in four-point major adverse cardiovascular events when treated with bempedoic acid (142) . For individuals requiring primary prevention, the use of bempedoic acid resulted in a 30% reduction in primary composite outcome compared with placebo (143) .

Lipid-Lowering Care Considerations for Individuals of Childbearing Potential

Individuals of childbearing potential are less likely to be treated with statins or achieve their LDL cholesterol goals based on their cardiovascular risk (144) (145) (146) . This is likely related to concerns and lack of knowledge related to use of lipid-lowering agents during pregnancy. The trials evaluating the efficacy and safety of lipid-lowering medications exclude individuals who are pregnant and require individuals of childbearing potential to use contraception (some requiring two forms). Therefore, for many pregnant individuals, it is recommended that they discontinue lipid-lowering therapies during gestation. However, some individuals are at higher risk for cardiovascular events (e.g., those with familial hypercholesterolemia or preexisting ASCVD), and the risk of discontinuing all lipid-lowering therapy during preconception and pregnancy periods may be associated with an increased risk for cardiovascular events. Consideration of initiating or continuing statin therapy during pregnancy should occur with these high-risk individuals. Although the evidence is limited, statins did not increase teratogenic effects for individuals with familial hypercholesterolemia (147, 148) , and a meta-analysis of pravastatin in pregnant individuals showed a reduction in preeclampsia, premature birth, and neonatal intensive care unit admissions (149) . There is limited information regarding the use of lipid-lowering therapies (other than bile acid sequestrants) during pregnancy. Thus, it is recommended that individuals of childbearing potential use a form of contraception when also using lipid-lowering medications with unknown risks, limited evidence on safety, or known risks during pregnancy regardless of intention to become pregnant, as many pregnancies are unplanned, and preconception counseling should be part of the routine care of individuals with diabetes who have childbearing potential. Counseling should include the known benefits and risks of lipid-lowering medications versus the risks and benefits of not treating the conditions for which they are prescribed, as well as other medications (e.g., noninsulin glucose-lowering therapies and antihypertensive agents), during pregnancy and recommendations for when changes in medications should occur prior to pregnancy (144) (see Section 15, "Management of Diabetes in Pregnancy," for more information on preconception counseling and lipid-lowering treatment during pregnancy).

Treatment of Other Lipoprotein Fractions or Goals

Recommendations 10.30 For individuals with fasting triglyceride levels $500 mg/dL ($5.7 mmol/L), evaluate for secondary causes of hypertriglyceridemia and consider medical therapy to reduce the risk of pancreatitis. C 10. 31 In adults with hypertriglyceridemia (fasting triglycerides > 150 mg/dL [ > 1.7 mmol/L] or nonfasting triglycerides > 175 mg/dL [ > 2.0 mmol/L]), clinicians should address and treat lifestyle factors (obesity and metabolic syndrome), secondary factors (diabetes, chronic liver or kidney disease and/or nephrotic syndrome, and hypothyroidism), and medications that raise triglycerides. C 10. 32 In individuals with ASCVD or other cardiovascular risk factors on a statin with managed LDL cholesterol but elevated triglycerides (150-499 mg/dL [1.7-5.6 mmol/L]), the addition of icosapent ethyl can be considered to reduce cardiovascular risk. B Hypertriglyceridemia should be addressed with nutritional and lifestyle changes, including weight loss and abstinence from alcohol (150) . Severe hypertriglyceridemia (fasting triglycerides $500 mg/dL [$5.7 mmol/L] and especially > 1,000 mg/dL [ > 11.3 mmol/L]) may warrant pharmacologic therapy (fibric acid derivatives and/or fish oil) and reduction in dietary fat to reduce the risk of acute pancreatitis (151) . Moderate-or high-intensity statin therapy should also be used as indicated to reduce risk of cardiovascular events (see STATIN TREATMENT, above) (150, 152) . In people with hypertriglyceridemia (fasting triglycerides > 150 mg/dL [ > 1.7 mmol/L] or nonfasting triglycerides > 175 mg/dL [ > 2.0 mmol/L]), lifestyle interventions, treatment of secondary factors, and avoidance of medications that might raise triglycerides are recommended.

For individuals with established cardiovascular disease or with risk factors for cardiovascular disease with elevated triglycerides (150-499 mg/dL [1.7-5.6 mmol/L]) after maximizing statin therapy, icosapent ethyl may be added to reduce cardiovascular risk. The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) showed that the addition of icosapent ethyl to statin therapy in this population resulted in a 25% relative risk reduction (P < 0.001) for the primary end point composite of cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina compared with placebo. This risk reduction was seen in individuals with or without diabetes at baseline. The composite of cardiovascular death, nonfatal MI, or nonfatal stroke was reduced by 26% (P < 0.001). Additional ischemic end points were significantly lower in the icosapent ethyl group than in the placebo group, including cardiovascular death, which was reduced by 20% (P = 0.03). The proportions of individuals experiencing adverse events and serious adverse events were similar between the active and placebo treatment groups. It should be noted that data are lacking for other n-3 fatty acids, and results of the REDUCE-IT trial should not be extrapolated to other products (153) . As an example, the addition of 4 g per day of a carboxylic acid formulation of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (n-3 carboxylic acid) to statin therapy in individuals with atherogenic dyslipidemia and high cardiovascular risk, 70% of whom had diabetes, did not reduce the risk of major adverse cardiovascular events compared with the inert comparator of corn oil (154) .

Low levels of HDL cholesterol, often associated with elevated triglyceride levels, are the most prevalent pattern of dyslipidemia in people with type 2 diabetes. However, the evidence for the use of drugs that target these lipid fractions is substantially less robust than that for statin therapy (155) . In a large trial in people with diabetes, fenofibrate improved cardiovascular outcomes in subgroups with both elevated triglycerides ( > 200 mg/dL [2.3 mmol/L]) and low HDL cholesterol ( < 40 mg/dL [1.0 mmol/L]) (156) ; however, another fibrate, pemafibrate, failed to reduce overall cardiovascular outcomes in a similar population (157) .

Other Combination Therapy

Recommendations 10.33 Statin plus fibrate combination therapy has not been shown to improve ASCVD outcomes and is generally not recommended. A 10.34 Statin plus niacin combination therapy has not been shown to provide additional cardiovascular benefit above statin therapy alone, may increase the risk of stroke with additional side effects, and is generally not recommended. A

Statin and Fibrate Combination Therapy

Combination therapy (statin and fibrate) is associated with an increased risk for abnormal transaminase levels, myositis, and rhabdomyolysis. The risk of rhabdomyolysis is more common with higher doses of statins and renal insufficiency and appears to be higher when statins are combined with gemfibrozil (compared with fenofibrate) (158) .

In the ACCORD study, in people with type 2 diabetes who were at high risk for ASCVD, the combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal MI, or nonfatal stroke compared with simvastatin alone. Prespecified subgroup analyses suggested heterogeneity in treatment effects with possible benefit for men with both a triglyceride level $204 mg/dL ($2.3 mmol/L) and an HDL cholesterol level #34 mg/dL (#0.9 mmol/L) (159) .

Therapeutic Strategies With Medication Unavailability

Health care professionals and people with diabetes struggle when medication supplies are insufficient to meet the demand. Recent examples of such circumstances include recalls involving a number of metformin products and the marked increase in demand for agents from the GLP-1 RA and dual GIP and GLP-1 RA classes. The latter circumstance led to such a low level of availability that products were determined by the FDA to be in shortage (204) . To assist with supply of medications during the time they are in shortage (as signaled by their inclusion on the FDA Drug Shortages Database), compounding pharmacies and outsourcing compounding facilities are allowed to make copies, or products that are essentially duplicates of the marketed FDA-approved product (205) . A significant number of concerning reports regarding safety and efficacy of compounded incretin products have emerged, however, including using salt forms of the FDA-approved product's active ingredient that are not proven safe or effective for use in humans, incorporation of additional ingredients not clinically tested when mixed with incretin products (e.g. g., vitamin B12 and vitamin B6), products provided in nonstandard concentrations and doses and/or multidose vials and prefilled syringes not accompanied by education or labeling to mitigate administration errors, and the emergence of counterfeit products that pose significant risk to individuals taking these products (206) (207) (208) (209) . Due to safety, quality, and effectiveness concerns, use of non-FDA-approved compounded products is not recommended (210) . Instead, consider switching to a different FDA-approved medication as clinically appropriate (211) . Once the desired FDA-approved product becomes available, individuals should be reassessed to determine the appropriateness of resuming the product based on their current care needs, preferences, and priorities.

Care Considerations for Individuals of Childbearing Potential

The impact of glycemia during pregnancy is well understood; however, evidence for the safe use of noninsulin glucose-lowering medications is limited (see Section 15, "Management of Diabetes in Pregnancy"). Studies on the efficacy and safety of glucose-lowering medications exclude individuals who are pregnant and require individuals of childbearing potential to use one or two forms of contraception. It is recommended that individuals of childbearing potential use a form of contraception when also taking glucose-lowering medications with unknown risks, limited evidence on safety, or known risks during pregnancy, regardless of the individual's intention to become pregnant, as many pregnancies are unplanned. The options for contraception should be discussed with all individuals of childbearing potential with diabetes and should include information regarding the potential impact of glucose-lowering medications on the effectiveness of contraception. Medications that impact gastrointestinal emptying time (e.g., GLP-1 RAs or dual GIP and GLP-1 RA) may affect the absorption of orally administered medications, including oral contraception. The impact on gastric emptying with GLP-1 RAs and the dual GIP and GLP-1 RA is highest at initiation and with dosage increases and then diminishes with continued administration (212) . Tirzepatide, the dual GIP and GLP-1 RA, was shown to impact the levels of oral contraception during the time of its highest impact on gastric emptying; the GLP-1 RAs may impact the levels of oral contraception as well but to a lesser extent than tirzepatide (213, 214) . Thus, individuals starting or increasing doses of tirzepatide who also take oral contraception should use a second form of contraception until the maintenance dose of tirzepatide is achieved and used for at least 4 weeks (215) .

Preconception counseling should be part of the routine care of individuals with diabetes who have childbearing potential. Counseling should include the known benefits and risks of glucose-lowering medications as well as other medications (e.g., lipid-lowering and antihypertensive therapies) during pregnancy and recommendations for when changes in medications should occur prior to pregnancy (see Section 15, "Management of Diabetes in Pregnancy," for more information on preconception counseling and glucose-lowering treatment during pregnancy).

Therapeutic Strategies for Individuals Receiving Cancer Treatment

Hyperglycemia due to chemotherapy may either be transient (improving upon treatment cessation) or represent permanent diabetes. Immune checkpoint inhibitors (ICIs) (agents that block programmed cell death protein 1 [PD-1] and programmed cell death protein ligand 1 [PD-L1] ) suppress physiologic blocks on immune responses, which can result in autoimmune toxicities, including autoimmune diabetes (incidence approximately #1%). ICI-diabetes is an insulin-deficient phenotype that presents as acute severe hyperglycemia or DKA and appears to occur more abruptly than type 1 diabetes (216) (217) (218) .

Alpelisib, a phosphatidylinositol-3-kinase (PI3K) inhibitor, frequently results in hyperglycemia by inhibiting PI3Ka, which systemically blocks the intracellular action of insulin, resulting in a transient state of insulin resistance and hyperglycemia (219) . Hyperglycemia occurs early during therapy (median time of onset of about 2 weeks from initiation of alpelisib) with an incidence of $60% overall and typically resolves upon treatment cessation (220) (221) (222) . Metformin is the first-line oral agent to treat alpelsib-induced hyperglycemia, and prophylactic initiation of metformin has been recommended for people with prediabetes receiving alpelsib (223) . SGLT2 inhibitors and pioglitazone are appropriate second-or third-line agents, depending on side effect and clinical profiles, and may be used in combination with or without metformin. Insulin and sulfonylureas should be considered last-line agents, as insulin can reactivate the PI3K pathway, negating the effects of alpelisib (223, 224) . mTOR kinase inhibitors, including everilomus, cause hyperglycemia by interfering with insulin signaling, leading to impaired insulin secretion and increased insulin resistance. Metformin is the first-line treatment of hyperglycemia secondary to mTOR inhibitor treatment, with insulin and other noninsulin treatments added in a stepwise fashion dependent on glucose level (225) .

Therapeutic Strategies for Individuals With Other Types of Diabetes

Individuals with pancreatogenic diabetes may require early insulin initiation to achieve and maintain glycemic goals. In Individuals with cystic fibrosis-related diabetes should be treated with insulin therapy; insulin pump therapy, including automated insulin delivery systems, should be considered when appropriate (226) .

There are limited data to inform the optimal pharmacologic management of posttransplant diabetes (227) (see Section 2, "Diagnosis and Classification of Diabetes"). While immediately posttransplant many individuals require insulin therapy, noninsulin therapies can be used for long-term management. Studies of metformin, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 RAs, and pioglitazone in individuals who have undergone kidney, heart, or liver transplantation have demonstrated effectiveness and safety but are limited by small sample sizes, short follow-up, and risk of bias due to retrospective or single-arm prospective designs (228) . Metformin should be used with caution; it should not be initiated if eGFR is < 45 mL/min/1.73 m 2 , it should be stopped with eGFR $30 mL/ min/1.73 m 2 , and it should not be used in the setting of clinical instability due to concerns for acute kidney injury and lactic acidosis. Metformin use may be associated with lower risks of cardiac allograph vasculopathy after heart transplantation (229) and all-cause, malignancy-related, and infection-related mortality after kidney transplantation (230) . GLP-1 RA therapy may be preferred for many individuals due to the demonstrated benefit of GLP-1 RAs on cardiovascular, kidney, weight, and liver outcomes. Studies have not found evidence of drug interaction with immunosuppression, including finding no changes in dosing or toxicity (231) (232) (233) . SGLT2 inhibitors may be similarly preferred for individuals with ASCVD, HF, and CKD and appear to be safe and effective in posttransplantation diabetes. However, there is increased risk of genitourinary tract infection, which is a concern in individuals receiving immunosuppression and in those who have undergone kidney transplantation.

Individuals with maturity-onset diabetes of the young due to HNF1A and HNF4A mutations can be treated with low-dose sulfonylurea therapy but may ultimately require insulin therapy (234) (see Section 2, "Diagnosis and Classification of Diabetes") (Table 2.7 ). For those with HNF1A mutations, addition of a DPP-4 inhibitor to the sulfonylurea may help improve glycemic variability and attainment of glycemic goals (235) . Individuals with neonatal diabetes due to KCNJ22 and ABCC8 mutations can be treated with high-dose sulfonylureas, while those with INS, GATA6, EIF2AK3, and FOXP3 mutations require insulin therapy (234) .

SGLT Inhibition and Risk of Ketosis

Individuals with type 1 diabetes (84, 236) and insulin-deficient type 2 diabetes are at increased risk for DKA with SGLT inhibitor therapy. SGLT inhibitor-associated DKA occurs in approximately 4% of people with type 1 diabetes; the risk can be 5-17 times higher than that in people with T1D not treated with SGLT inhibitors (237) . It is important to note that SGLT2 inhibitors are not approved for use in people with type 1 diabetes. In contrast, DKA is uncommon in people with type 2 diabetes treated with SGLT inhibitors, with an estimated incidence of 0.6-4.9 events per 1,000 person-years (238) . Risk factors for DKA in individuals with either type 1 or type 2 diabetes treated with SGLT inhibitors include very-low-carbohydrate diets, prolonged fasting, dehydration, excessive alcohol intake, and other common precipitating factors (84, 236) . Up to a third of people treated with SGLT2 inhibitors who developed DKA present with glucose levels < 200 mg/dL (11.1 mmol/L) (239) , and in one study 71% presented with glucose levels #250 mg/dL (13.9 mmol/L) (240); therefore, it is important to educate atrisk individuals about the signs and symptoms of DKA and DKA mitigation and management and to prescribe accurate tools for ketone measurement. Individuals who have experienced DKA should not be treated with SGLT inhibition. Additional guidance on DKA risk mitigation is available in Section 6, "Glycemic Goals and Hypoglycemia." The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

For prevention and management of diabetes complications in children and adolescents, please refer to Section 14, "Children and Adolescents."

Atherosclerotic cardiovascular disease (ASCVD) broadly refers to a history of acute coronary syndrome, myocardial infarction (MI), stable or unstable angina or coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral artery disease (PAD) including aortic aneurysm and is the leading cause of morbidity and mortality in people with diabetes (1) . Diabetes itself confers independent ASCVD risk, and among people with diabetes, all major cardiovascular risk factors, including hypertension, hyperlipidemia, and obesity, are clustered and common (2) . Numerous studies have shown the efficacy of managing individual cardiovascular risk factors in preventing or slowing ASCVD in people with diabetes. Furthermore, large benefits are seen when multiple cardiovascular risk factors (glycemic, blood pressure, and lipid management) are addressed simultaneously, with evidence for long-lasting benefits (3) (4) (5) . Notably, most of the evidence supporting interventions to reduce cardiovascular risk in diabetes comes from trials of people with type 2 diabetes. No randomized trials have been specifically designed to assess the impact of cardiovascular risk reduction strategies in people with type 1 diabetes. Therefore, the recommendations for cardiovascular risk factor modification for people with type 1 diabetes are extrapolated from data obtained in people with type 2 diabetes and are similar to those for people with type 2 diabetes.

Under the current paradigm of comprehensive risk factor modification, cardiovascular morbidity and mortality have notably decreased in people with both type 1 and type 2 diabetes (1). In addition to the evidence from prospective intervention studies to support comprehensive ASCVD risk factor reduction, a large cohort study confirmed no or only marginally increased mortality, MI, and stroke risk compared with the general population when all major cardiovascular risk factors are managed to goal levels in people with type 2 diabetes (6) . Despite these encouraging opportunities to reduce morbidity and mortality, cardiovascular risk factors are predicted to *A complete list of members of the American Diabetes Association Professional Practice Committee can be found at https://doi.org/10.2337/dc25-SINT. This section has received endorsement from the American College of Cardiology.

10. CARDIOVASCULAR DISEASE AND RISK MANAGEMENT

Diabetes Care Volume 48, Supplement 1, January 2025 increase and only a minority of people with type 2 diabetes achieve recommended risk factor goals and are treated with guideline-recommended therapy (7) (8) (9) . Therefore, continued focus on delivering high-quality comprehensive cardiovascular care and on addressing barriers to risk factor management are required to implement the treatment recommendations (1, 10) outlined in this section.

Diabetes is also an important risk factor for incident heart failure, which is at least twofold more prevalent in people with diabetes compared with those without diabetes and is a major cause of morbidity and mortality (11) . People with diabetes may present with a wide spectrum of heart failure, including heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmEF), or heart failure with reduced ejection fraction (HFrEF) (12) . Comorbid conditions including excess body weight and hypertension often precede the development of HFpEF and have been implicated in the pathophysiology of HFpEF (13) . Coronary artery disease and prior MI are major risk factors and a cause of myocardial injury in ischemic heart disease leading to HFrEF. In addition, people with diabetes are at risk for developing structural heart disease and HFrEF in the absence of obstructive coronary artery disease (14) . The pathophysiology of heart failure in people with diabetes and further details of screening, diagnosis, and treatment of people with heart failure and diabetes are also outlined in a previous consensus statement by the American Diabetes Association (ADA) (15) .

There is an increasing appreciation of the common pathophysiology and interrelationship of cardiometabolic risk factors leading to both adverse cardiovascular and adverse kidney outcomes in people with diabetes, including ASCVD, heart failure, and chronic kidney disease (CKD) (16) . These three comorbidities are frequently caused by metabolic risk, which is frequently driven by obesity and its associated risk factors, and the incidence of all three conditions rises with increasing A1C levels (17) . Collectively, this combination of comorbidities has been termed cardiorenal metabolic disease or cardiovascularkidney-metabolic health (18, 19) . Reasons to concurrently consider cardiovascular and kidney comorbidities in the management of people with diabetes include not only the common metabolic risk but also the major benefit observed across the spectrum of cardiovascular disease, heart failure, and renal outcomes in people with type 2 diabetes treated with sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagon-like peptide 1 receptor agonists (GLP-1 RAs). Therefore, in addition to the management of hyperglycemia, hypertension, and hyperlipidemia, treatment with SGLT2 inhibitors and/or GLP-1 RAs that have demonstrated benefit is considered a fundamental element of risk reduction and the pharmacological strategy to improve cardiovascular and kidney outcomes in people with type 2 diabetes (Fig. 10 .1). In addition to the standards of care for the prevention and treatment of cardiovascular disease outlined below, the reader is referred to Section 9, "Pharmacologic Approaches to

LIFESTYLE MODIFICATION AND DIABETES EDUCATION

Glycemic Management

Blood Pressure Management

Lipid Management

Agents With Cardiovascular and Kidney Benefit

REDUCTION IN DIABETES COMPLICATIONS

.1-Multifactorial approach to reduction in risk of diabetes complications.

Glycemic Treatment," and Section 11, "Chronic Kidney Disease and Risk Management," for a comprehensive review of pharmacological management of hyperglycemia and kidney benefit from SGLT2 inhibitors and GLP-1 RAs.

HYPERTENSION AND BLOOD PRESSURE MANAGEMENT

An elevated blood pressure is defined as a systolic blood pressure 120-129 mmHg and a diastolic blood pressure < 80 mmHg (20) . Hypertension is defined as a systolic blood pressure $130 mmHg or a diastolic blood pressure $80 mmHg (20) . This is in agreement with the definition of hypertension by the American College of Cardiology and American Heart Association (20) . Hypertension is common among people with either type 1 or type 2 diabetes. Hypertension is a major risk factor for ASCVD, heart failure, and microvascular complications. Moreover, numerous studies have shown that antihypertensive therapy reduces ASCVD events, heart failure, and microvascular complications. Please refer to the ADA position statement "Diabetes and Hypertension" for a detailed review of the epidemiology, diagnosis, and treatment of hypertension (21) and hypertension guideline recommendations (22) (23) (24) (25) . (22) . Postural changes in blood pressure and pulse may be evidence of autonomic neuropathy and therefore require adjustment of blood pressure goals. Orthostatic blood pressure measurements should be checked on initial visit and as indicated.

Home blood pressure self-monitoring and 24-h ambulatory blood pressure monitoring may provide evidence of white coat hypertension, masked hypertension, or other discrepancies between office and true blood pressure (27, 28) . In addition to confirming or refuting a diagnosis of hypertension, home blood pressure assessment may be useful to monitor antihypertensive treatment. A systematic review and metaanalysis of prospective studies concluded that blood pressure measurements from either 24-h ambulatory or home blood pressure measurements can predict cardiovascular risk (27) (28) (29) . Moreover, home blood pressure monitoring may improve medication-taking behavior and thus help reduce cardiovascular risk (30) .

Treatment Goals Recommendations 10.3 For people with diabetes and hypertension, blood pressure goals should be individualized through a shared decision-making process that addresses cardiovascular risk, potential adverse effects of antihypertensive medications, and individual preferences. B 10. 4 The on-treatment blood pressure goal is < 130/80 mmHg, if it can be safely attained. A 10.5 In pregnant individuals with diabetes and chronic hypertension, a blood pressure threshold of 140/90 mmHg for initiation or titration of therapy is associated with better pregnancy outcomes than reserving treatment for severe hypertension, with no increase in risk of small-for-gestational-age birth weight. A There are limited data on the optimal lower limit, but therapy should be deintensified for blood pressure < 90/60 mmHg. E A blood pressure goal of 110-135/85 mmHg is suggested in the interest of reducing the risk for accelerated maternal hypertension. A Randomized clinical trials have demonstrated unequivocally that treatment of hypertension reduces cardiovascular events as well as microvascular complications (31) (32) (33) (34) (35) (36) (37) . There has been controversy on the recommendation of a specific blood pressure goal in people with diabetes. The committee recognizes that there has been no randomized controlled trial to specifically demonstrate a decreased incidence of cardiovascular events in people with diabetes by achieving a blood pressure < 130/80 mmHg. The recommendation to support a blood pressure goal of < 130/80 mmHg in people with diabetes is consistent with guidelines from the American College of Cardiology and American Heart Association (21) , the International Society of Hypertension, and Europe European Society of Cardiology/ European Society of Hypertension Blood Pressure/Hypertension Guidelines (24) . The committee's recommendation for the blood pressure goal of < 130/80 mmHg derives primarily from the collective evidence of the following randomized controlled trials. The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that treatment to a goal systolic blood pressure of < 120 mmHg decreases cardiovascular event rates by 25% in high-risk individuals, although people with diabetes were excluded from this trial (38) . The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial included nearly 20% of people with diabetes and noted decreased cardiovascular events with treatment of hypertension to a systolic blood pressure goal of < 130 mmHg (39) . While the ACCORD (Action to Control Cardiovascular Risk in Diabetes) blood pressure trial (ACCORD BP) did not confirm that aiming for a systolic blood pressure < 120 mmHg in people with diabetes results in decreased cardiovascular event rates, the prespecified secondary outcome of stroke was reduced by 41% with intensive treatment (40) . The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial revealed that treatment with perindopril and indapamide to an achieved systolic blood pressure of $135 mmHg significantly decreased cardiovascular event rates compared with a placebo treatment with an achieved blood pressure of 140 mmHg (41) . Therefore, it is recommended that people with diabetes who have hypertension should be treated to blood pressure goals of < 130/80 mmHg. Notably, there is an absence of high-quality data available to guide blood pressure goals in people with type 1 diabetes, but a similar blood pressure goal of < 130/80 mmHg is recommended in people with type 1 diabetes. As discussed below, treatment should be individualized, and treatment goals should not be set to achieve < 120/80 mmHg, as a mean achieved blood pressure < 120/80 mmHg is associated with adverse events. For more information on individualized blood pressure goals in older individuals, please see Section 13, "Older Adults."

Randomized Controlled Trials of Intensive Versus Standard Blood Pressure Management

SPRINT provides the strongest evidence to support lower blood pressure goals in individuals at increased cardiovascular risk, although this trial excluded people with diabetes (38) . The trial enrolled 9,361 individuals with a systolic blood pressure of $130 mmHg and increased cardiovascular risk and treated to a systolic blood pressure goal of < 120 mmHg (intensive treatment) versus a goal of < 140 mmHg (standard treatment). The primary composite outcome of MI, coronary syndromes, stroke, heart failure, or death from cardiovascular causes was reduced by 25% in the intensive treatment group. The achieved systolic blood pressures in the trial were 121 mmHg and 136 mmHg in the intensive versus standard treatment group, respectively. Adverse outcomes, including hypotension, syncope, electrolyte abnormality, and acute kidney injury (AKI), were more common in the intensive treatment arm; risk of adverse outcomes needs to be weighed against the cardiovascular benefit of more intensive blood pressure lowering.

ACCORD BP provides the strongest direct assessment of the benefits and risks of intensive blood pressure management in people with type 2 diabetes (40) . In the study, a total of 4,733 individuals with type 2 diabetes were assigned to intensive therapy (aiming for a systolic blood pressure < 120 mmHg) or standard therapy (aiming for a systolic blood pressure < 140 mmHg). The mean achieved systolic blood pressures were 119 mmHg and 133 mmHg in the intensive and standard groups, respectively. The primary composite outcome of nonfatal MI, nonfatal stroke, or death from cardiovascular causes was not significantly reduced in the intensive treatment group. The prespecified secondary outcome of stroke was significantly reduced by 41% in the intensive treatment group. Adverse events attributed to blood pressure treatment, including hypotension, syncope, bradycardia, hyperkalemia, and elevations in serum creatinine, occurred more frequently in the intensive treatment arm than in the standard therapy arm.

Of note, the ACCORD BP and SPRINT trials aimed for a similar systolic blood pressure < 120 mmHg, but in contrast to SPRINT, the primary composite cardiovascular end point was nonsignificantly reduced in ACCORD BP. The results have been interpreted to be generally consistent between the two trials, but ACCORD BP was viewed as underpowered due to the composite primary end point being less sensitive to blood pressure regulation (38, 40) .

The more recent STEP trial assigned 8,511 individuals aged 60-80 years with hypertension to a systolic blood pressure goal of 110 to < 130 mmHg (intensive treatment) or a goal of 130 to < 150 mmHg (37) . In this trial, the primary composite outcome of stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes occurred in 3.5% of individuals in the intensive treatment group versus 4.6% in the standard treatment group (hazard ratio [HR] 0.74 [95% CI 0.60-0.92] ; P = 0.007). In this trial, 18.9% of individuals in the intensive treatment arm and 19.4% in the standard treatment arm had a diagnosis of type 2 diabetes. Hypotension occurred more frequently in the intensive treatment group (3.4%) compared with the standard treatment group (2.6%) without significant differences in other adverse events, including dizziness, syncope, or fractures. For more information on hypotensive events in older adults, please see Section 13, "Older Adults."

In ADVANCE, 11,140 people with type 2 diabetes were randomized to receive either treatment with a fixed combination of perindopril and indapamide or matching placebo (41) . The primary end point, a composite of cardiovascular death, nonfatal stroke or MI, or new or worsening renal or eye disease, was reduced by 9% in the combination treatment. The achieved systolic blood pressure was $135 mmHg in the treatment group and 140 mmHg in the placebo group.

The Hypertension Optimal Treatment (HOT) trial enrolled 18,790 individuals and aimed for a diastolic blood pressure < 90 mmHg, < 85 mmHg, or < 80 mmHg (42) . The cardiovascular event rates, defined as fatal or nonfatal MI, fatal and nonfatal strokes, and all other cardiovascular events, were not significantly different between diastolic blood pressure goals (#90 mmHg, #85 mmHg, and #80 mmHg), although the lowest incidence of cardiovascular events occurred with an achieved diastolic blood pressure of 82 mmHg. However, in people with diabetes, there was a significant 51% reduction in the treatment group with a goal diastolic blood pressure of < 80 mmHg compared with a goal diastolic blood pressure of < 90 mmHg.

Meta-analyses of Trials

To clarify optimal blood pressure goals in people with diabetes, multiple meta-analyses have been performed. One of the largest meta-analyses included 73,913 people with diabetes. Compared with a less intensive blood pressure management, allocation to a tighter blood pressure management significantly reduced the risk of stroke by 31% but did not reduce the risk of MI (43) . Another metaanalysis of 19 trials that included 44,989 individuals showed that a mean blood pressure of 133/76 mmHg is associated with a 14% risk reduction for major cardiovascular events compared with a mean blood pressure of 140/81 mmHg (37). This benefit was greatest in people with diabetes. An analysis of trials including people with type 2 diabetes and impaired glucose tolerance with achieved systolic blood pressures of < 135 mmHg in the intensive blood pressure treatment group and < 140 mmHg in the standard treatment group revealed a 10% reduction in all-cause mortality and a 17% reduction in stroke (35) . More intensive reduction to < 130 mmHg was associated with a further reduction in stroke but not other cardiovascular events.

Several meta-analyses stratified clinical trials by mean baseline blood pressure or mean blood pressure attained in the intervention (or intensive treatment) arm. Based on these analyses, antihypertensive treatment appears to be most beneficial when mean baseline blood pressure is $140/90 mmHg (20, 31, 32, (34) (35) (36) . Among trials with lower baseline or attained blood pressure, antihypertensive treatment reduced the risk of stroke, retinopathy, and albuminuria, but effects on other ASCVD outcomes and heart failure were not evident. A recent systematic review and meta-analysis of nine trials enrolling 11,005 participants with type 2 diabetes reported that intensive blood pressure lowering resulted in a reduction in risk of stroke (risk ratio 0.64 [95% CI 0.52-0.79]) and macroalbuminuria (0.77 [0.63-0.93) with a posttreatment blood pressure of 125/73 mmHg, suggesting that blood pressure goals could be lowered from the current recommendations of 130/80 mmHg if tolerated (44) .

Individualization of Treatment Goals

People with diabetes and clinicians should engage in a shared decision-making process to determine individual blood pressure goals (20) . This approach acknowledges that the benefits and risks of intensive blood pressure goals are uncertain and may vary across individuals and is consistent with a person-focused approach to care that values individual priorities and health care professional judgment (45) . Secondary analyses of ACCORD BP and SPRINT suggest that clinical factors can help identify individuals more likely to benefit from and less likely to be harmed by intensive blood pressure management (46, 47) .

Absolute benefit from blood pressure reduction correlated with absolute baseline cardiovascular risk in SPRINT and in earlier clinical trials conducted at higher baseline blood pressure levels (47, 48) .

Extrapolation of these studies suggests that people with diabetes may also be more likely to benefit from intensive blood pressure management when they have high absolute cardiovascular risk. This approach is consistent with guidelines from the American College of Cardiology and American Heart Association, which also advocate a blood pressure goal of < 130/80 mmHg for all people, with or without diabetes (21) .

Potential adverse effects of antihypertensive therapy (e.g., hypotension, syncope, falls, AKI, and electrolyte abnormalities) should also be taken into account (38, 40, 49, 50) . Older individuals and those with CKD and frailty have been shown to be at higher risk of adverse effects of intensive blood pressure management (49) . In addition, individuals with orthostatic hypotension, substantial comorbidity, functional limitations, or polypharmacy may be at high risk of adverse effects, and some individuals may prefer higher blood pressure goals to enhance quality of life. However, ACCORD BP demonstrated that intensive blood pressure lowering decreased the risk of cardiovascular events irrespective of baseline diastolic blood pressure in individuals who also received standard glycemic management (51) . Therefore, the presence of low diastolic blood pressure is not necessarily a contraindication to more intensive blood pressure management in the context of otherwise standard care.

Pregnancy and Antihypertensive Medications

There are few randomized controlled trials of antihypertensive therapy in pregnant individuals with diabetes. A 2018 Cochrane systematic review of antihypertensive therapy for mild to moderate chronic hypertension included 63 trials and over 5,909 women and suggested that antihypertensive therapy probably reduces the risk of developing severe hypertension but may not affect the risk of fetal or neonatal death, small-for-gestational-age babies, or preterm birth (52) . The Control of Hypertension in Pregnancy Study (CHIPS) (53) enrolled mostly women with chronic hypertension. In CHIPS, aiming for a diastolic blood pressure of 85 mmHg during pregnancy was associated with reduced likelihood of developing accelerated maternal hypertension and no demonstrable adverse outcome for infants compared with aiming for a higher diastolic blood pressure. The mean systolic blood pressure achieved in the more intensively treated group was 133.1 ± 0.5 mmHg, and the mean diastolic blood pressure achieved in that group was 85.3 ± 0.3 mmHg. A similar approach is supported by the International Society for the Study of Hypertension in Pregnancy, which specifically recommends use of antihypertensive therapy to maintain systolic blood pressure between 110 and 140 mmHg and diastolic blood pressure between 80 and 85 mmHg (54) .

The more recent Chronic Hypertension and Pregnancy (CHAP) trial assigned pregnant individuals with mild chronic hypertension to antihypertensive medications to achieve a blood pressure goal of < 140/90 mmHg (active treatment group) or to control treatment, in which antihypertensive therapy was withheld unless severe hypertension (systolic pressure $160 mmHg or diastolic pressure $105 mmHg) developed (control group) (55) . The primary outcome, a composite of preeclampsia with severe features, medically indicated preterm birth at < 35 weeks of gestation, placental abruption, or fetal or neonatal death, occurred in 30.2% of female participants in the active treatment group versus 37.0% in the control group (P < 0.001). The mean systolic blood pressure between randomization and delivery was 129.5 mmHg in the active treatment group and 132.6 mmHg in the control group. There are subtle difference in recommendations by different guidelines; however, internationally, the majority of hypertension societies endorse a more aggressive approach, recommending therapy when blood pressure is $140/90 mmHg and attaining a therapeutic goal of 130/80 mmHg (56) .

Current evidence supports managing blood pressure to 110-135/85 mmHg to reduce the risk of accelerated maternal hypertension and to minimize impairment of fetal growth. During pregnancy, treatment with ACE inhibitors, angiotensin receptor blockers (ARBs), direct renin inhibitors, mineralocorticoid receptor antagonists (MRAs), and neprilysin inhibitors are contraindicated, as they may cause fetal damage. Special consideration should be taken for individuals of childbearing potential, and people intending to become pregnant should switch from an ACE inhibitor or ARB, renin inhibitor, MRA, or neprilysin inhibitor to an alternative antihypertensive medication approved during pregnancy. Antihypertensive drugs known to be effective and safe in pregnancy include methyldopa, labetalol, and longacting nifedipine, while hydralazine may be considered in the acute management of hypertension in pregnancy or severe preeclampsia (56) . Diuretics are not recommended for blood pressure management in pregnancy but may be used during latestage pregnancy if needed for volume management (56) . The American College of Obstetricians and Gynecologists also recommends that, postpartum, individuals with gestational hypertension, preeclampsia, and superimposed preeclampsia have their blood pressures observed for 72 h in the hospital and 7-10 days postpartum. Long-term follow-up is recommended for these individuals, as they have increased lifetime cardiovascular risk (57) . See Section 15, "Management of Diabetes in Pregnancy," for additional information.

Treatment Strategies

Lifestyle Intervention Recommendation 10.6 For people with blood pressure > 120/80 mmHg, lifestyle intervention consists of weight loss when indicated, a Dietary Approaches to Stop Hypertension (DASH)-style eating pattern including reducing sodium and increasing potassium intake, moderation of alcohol intake, smoking cessation, and increased physical activity. A Lifestyle management is an important component of hypertension treatment because it lowers blood pressure, enhances the effectiveness of some antihypertensive medications, promotes other aspects of metabolic and vascular health, and generally leads to few adverse effects. Lifestyle therapy consists of reducing excess body weight through caloric restriction (see Section 8, "Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes"), at least 150 min of moderate-intensity aerobic activity per week (see Section 3, "Prevention or Delay of Diabetes and Associated Comorbidities"), restricting sodium intake ( < 2,300 mg/day), increasing consumption of fruits and vegetables (8-10 servings per day) and low-fat dairy products (2-3 servings per day), avoiding excessive alcohol consumption (no more than 2 servings per day in men and no more than 1 serving per day in women) (58) , and increasing activity levels (59) (see Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes"). A systematic review of 10 randomized controlled trials reported that compared with control diet, the modified Dietary Approaches to Stop Hypertension (DASH) eating pattern could reduce mean systolic (À3.26 mmHg [95% CI À5.58 to À0.94 mmHg]; P = 0.006) and diastolic (À2.07 mmHg [95% CI À3.68 to À0.46 mmHg] ; P = 0.01) blood pressure (60) .

These lifestyle interventions are reasonable for individuals with diabetes and mildly elevated blood pressure (systolic > 120 mmHg or diastolic > 80 mmHg) and should be initiated along with pharmacologic therapy when hypertension is diagnosed (Fig. 10 .2) (59). A lifestyle therapy plan should be developed in collaboration with the person with diabetes and discussed as part of diabetes management. Use of internet or mobile-based digital platforms to reinforce healthy behaviors may be considered as a component of care, as these interventions have been found to enhance the efficacy of medical therapy for hypertension (61, 62) .

Pharmacologic Interventions Recommendations 10.7 In individuals with confirmed officebased blood pressure $130/80 mmHg, pharmacologic therapy should be initiated and titrated to achieve the recommended blood pressure goal of < 130/80 mmHg. A 10.8 Individuals with confirmed officebased blood pressure $150/90 mmHg should, in addition to lifestyle therapy, have prompt initiation and timely titration of two drugs or a single-pill combination of drugs demonstrated to reduce cardiovascular events in people with diabetes. A 10.9 Treatment for hypertension should include drug classes demonstrated to reduce cardiovascular events in people with diabetes. A ACE inhibitors or angiotensin receptor blockers (ARBs) are recommended first-line therapy for hypertension in people with diabetes and coronary artery disease. A 10.10 Multiple-drug therapy is generally required to achieve blood pressure goals. Avoid combinations of ACE inhibitors and ARBs and combinations of ACE inhibitors or ARBs (including ARBs and neprilysin inhibitors) with direct renin inhibitors. A 10.11 An ACE inhibitor or ARB, at the maximum tolerated dose indicated for blood pressure treatment, is the recommended first-line treatment for hypertension in people with diabetes and urinary albumin-to-creatinine ratio $300 mg/g creatinine A or 30-299 mg/g creatinine.

Statin and Niacin Combination Therapy

Large clinical trials, including the Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) and Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trials, failed to demonstrate a benefit of adding niacin to individuals on appropriate statin therapy. In fact, there was a possible increased risk of ischemic stroke in the AIM-HIGH trial (160) and an increased incidence of new-onset diabetes (absolute excess, 1.3 percentage points; P < 0.001) and disturbances in diabetes management among those with diabetes in the HPS2-THRIVE trial in those on combination therapy (161) . Therefore, combination therapy with a statin and niacin is not recommended, given the lack of efficacy on major ASCVD outcomes and increased side effects.

Diabetes Risk With Statin Use

Several studies have reported a modestly increased risk of incident type 2 diabetes with statin use (162, 163) , which may be limited to those with diabetes risk factors. An analysis of one of the initial studies suggested that although statin use was associated with diabetes risk, the cardiovascular event rate reduction with statins far outweighed the risk of incident diabetes, even for individuals at highest risk for diabetes (164) . The absolute risk increase was small (over 5 years of follow-up, 1.2% of participants on placebo developed diabetes and 1.5% on rosuvastatin developed diabetes) (164) . A meta-analysis of 13 randomized statin trials with 91,140 participants showed an odds ratio of 1.09 for a new diagnosis of diabetes, so that (on average) treatment of 255 individuals with statins for 4 years resulted in one additional case of diabetes while simultaneously preventing 5.4 vascular events among those 255 individuals (163).

Lipid-Lowering Agents and Cognitive Function

Although concerns regarding a potential adverse impact of lipid-lowering agents on cognitive function have been raised, several lines of evidence argue against this association, as detailed in a 2018 European Atherosclerosis Society Consensus Panel statement (165) . First, there are three large, randomized trials of statin versus placebo where specific cognitive tests were performed, and no differences were seen between statin and placebo (166-169). In addition, no change in cognitive function has been reported in studies with the addition of ezetimibe (119) or PCSK9 inhibitors (121, 170) to statin therapy, including among individuals treated to very low LDL cholesterol levels. In addition, systematic reviews of randomized controlled trials and prospective cohort studies evaluating cognition in individuals receiving statins found that published data do not reveal an adverse effect of statins on cognition (171,172). Therefore, a concern that statins or other lipid-lowering agents might cause cognitive dysfunction or dementia is not currently supported by evidence and should not deter their use in individuals with diabetes at high risk for ASCVD (173).

ANTIPLATELET AGENTS Recommendations 10.35 Use aspirin therapy (75-162 mg/day) as a secondary prevention strategy in those with diabetes and a history of ASCVD. A 10.36a For individuals with ASCVD and documented aspirin allergy, clopidogrel (75 mg/day) should be used. B 10.36b The length of treatment with dual antiplatelet therapy using lowdose aspirin and a P2Y12 inhibitor in individuals with diabetes after an acute coronary syndrome, acute ischemic stroke, or transient ischemic attack should be determined by an interprofessional team approach that includes a cardiovascular or neurological specialist, respectively. E 10.37 Combination therapy with aspirin plus low-dose rivaroxaban should be considered for individuals with stable coronary and/or peripheral artery disease (PAD) and low bleeding risk to prevent major adverse limb and cardiovascular events. A 10.38 Aspirin therapy (75-162 mg/day) may be considered as a primary prevention strategy in those with diabetes who are at increased cardiovascular risk after a comprehensive discussion with the individual on the benefits versus the comparable increased risk of bleeding. A

Risk Reduction

Aspirin has been shown to be effective in reducing cardiovascular morbidity and mortality in high-risk individuals with previous MI or stroke (secondary prevention) and is strongly recommended. In primary prevention, however, among individuals with no previous cardiovascular events, its net benefit is more controversial (162, 174) .

Previous randomized controlled trials of aspirin, specifically in people with diabetes, failed to consistently show a significant reduction in overall ASCVD end points, raising questions about the efficacy of aspirin for primary prevention in people with diabetes, although some sex differences were suggested (175-177).

The Antithrombotic Trialists' Collaboration published an individual participantlevel meta-analysis (178) of six large trials of aspirin for primary prevention in the general population. These trials collectively enrolled over 95,000 participants, including almost 4,000 with diabetes. Overall, they found that aspirin reduced the risk of serious vascular events by 12% (relative risk 0.88 [95% CI 0.82-0.94]). The largest reduction was for nonfatal MI, with little effect on CHD death (relative risk 0.95 [95% CI 0.78-1.15]) or total stroke.

Most recently, the ASCEND (A Study of Cardiovascular Events iN Diabetes) trial randomized 15,480 people with diabetes but no evident cardiovascular disease to aspirin 100 mg daily or placebo (179) . The primary efficacy end point was vascular death, MI, stroke, or transient ischemic attack. The primary safety outcome was major bleeding (i.e., intracranial hemorrhage, sight-threatening bleeding in the eye, gastrointestinal bleeding, or other serious bleeding). During a mean follow-up of 7.4 years, there was a significant 12% reduction in the primary efficacy end point (8.5% vs. 9.6%; P = 0.01). In contrast, major bleeding was significantly increased from 3.2% to 4.1% in the aspirin group (rate ratio 1.29; P = 0.003), with most of the excess being gastrointestinal bleeding and other extracranial bleeding. There were no significant differences by sex, weight, or duration of diabetes or other baseline factors, including ASCVD risk score.

Two other large, randomized trials of aspirin for primary prevention, in people without diabetes (ARRIVE [Aspirin to Reduce Risk of Initial Vascular Events]) (180) and in the elderly (ASPREE [Aspirin in Reducing Events in the Elderly]) (181) , in which 11% of participants had diabetes, found no benefit of aspirin on the primary efficacy end point and an increased risk of bleeding. In ARRIVE, with 12,546 individuals over a period of 60 months of follow-up, the primary end point occurred in 4.29% vs. 4.48% of individuals in the aspirin versus placebo groups (HR 0.96 [95% CI 0.81-1.13]; P = 0.60). Gastrointestinal bleeding events (characterized as mild) occurred in 0.97% of individuals in the aspirin group vs. 0.46% in the placebo group (HR 2.11 [95% CI 1.36-3.28] ; P = 0.0007). In ASPREE, which included 19,114 individuals, for cardiovascular disease (fatal CHD, MI, stroke, or hospitalization for heart failure) after a median of 4.7 years of follow-up, the rates per 1,000 person-years were 10.7 vs. 11.3 events in aspirin vs. placebo groups (HR 0.95 [95% CI 0.83-1.08]). The rate of major hemorrhage per 1,000 person-years was 8.6 events versus 6.2 events, respectively (HR 1.38 [95% CI 1.18-1.62]; P < 0.001).

Thus, aspirin appears to have a modest effect on ischemic vascular events, with the absolute decrease in events depending on the underlying ASCVD risk. The main adverse effect is an increased risk of gastrointestinal bleeding. The excess risk may be as high as 5 per 1,000 per year in real-world settings. However, for adults with ASCVD risk > 1% per year, the number of ASCVD events prevented will be similar to the number of episodes of bleeding induced, although these complications do not have equal effects on longterm health (182) .

Recommendations for using aspirin as primary prevention include both men and women aged $50 years with diabetes and at least one additional major risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, or CKD or albuminuria) who are not at increased risk of bleeding (e.g., older age, anemia, or renal disease) (183) (184) (185) (186) . Noninvasive imaging techniques such as coronary calcium scoring may help further tailor aspirin therapy, particularly in those at low risk (187, 188) . For people > 70 years of age (with or without diabetes), the balance appears to have greater risk than benefit (179, 181) . Thus, for primary prevention, the use of aspirin needs to be carefully considered and generally may not be recommended. Aspirin may be considered in the context of high cardiovascular risk with low bleeding risk but generally not in older adults. Aspirin therapy for primary prevention may be considered in the context of shared decision-making, which carefully weighs the cardiovascular benefits with the fairly comparable increase in risk of bleeding.

For people with documented ASCVD, use of aspirin for secondary prevention has far greater benefit than risk; for this indication, aspirin is still recommended (174).

Aspirin Use in People < 50 Years of Age

Aspirin is not recommended for those at low risk of ASCVD (such as men and women aged < 50 years with diabetes with no other major ASCVD risk factors), as the low benefit is likely to be outweighed by the risk of bleeding. Clinical judgment should be used for those at intermediate risk (younger individuals with one or more risk factors or older individuals with no risk factors) until further research is available. Individuals' willingness to undergo longterm aspirin therapy should also be considered in shared decision-making (189) . Aspirin use in individuals aged < 21 years is generally contraindicated due to the associated risk of Reye syndrome.

Aspirin Dosing

Average daily dosages used in most clinical trials involving people with diabetes ranged from 50 to 650 mg but were mostly in the range of 100-325 mg/day. There is little evidence to support any specific dose, but using the lowest possible dose may help to reduce side effects (190) . In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness) trial of individuals with established cardiovascular disease, 38% of whom had diabetes, there were no significant differences in cardiovascular events or major bleeding between individuals assigned to 81 mg and those assigned to 325 mg of aspirin daily (191) . In the U.S., the most common low-dose tablet is 81 mg. Although platelets from people with diabetes have altered function, it is unclear what, if any, effect that finding has on the required dose of aspirin for cardioprotective effects in people with diabetes. Many alternate pathways for platelet activation exist that are independent of thromboxane A 2 and thus are not sensitive to the effects of aspirin (192) . "Aspirin resistance" has been described in people with diabetes when measured by a variety of ex vivo and in vitro methods (platelet aggregometry and measurement of thromboxane B 2 ) (193) , but other studies suggest no impairment in aspirin response among people with diabetes (194) . A trial suggested that more frequent dosing of aspirin may reduce platelet reactivity in individuals with diabetes (195) ; however, these observations alone are insufficient to empirically recommend that higher doses of aspirin be used in this group at this time. Another meta-analysis raised the hypothesis that low-dose aspirin efficacy is reduced in those weighing > 70 kg (196) ; however, the ASCEND trial found benefit of low-dose aspirin in those in this weight range, which would not validate this suggested hypothesis (179) . It appears that 75-162 mg/day is optimal.

Indications for P2Y12 Receptor Antagonist Use

Combination dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is indicated after acute coronary syndromes and coronary revascularization with stenting (197) . In addition, current guidelines recommend short-term dual antiplatelet therapy after high-risk transient ischemic attack and minor stroke (198) . The indications for dual antiplatelet therapy and length of treatment are rapidly evolving and should be determined by an interprofessional team approach that includes a cardiovascular or neurological specialist, as appropriate. Evidence supports use of either ticagrelor or clopidogrel if no percutaneous coronary intervention was performed and clopidogrel, ticagrelor, or prasugrel if a percutaneous coronary intervention was performed (199) . In people with diabetes and prior MI (1-3 years before), adding ticagrelor to aspirin significantly reduces the risk of recurrent ischemic events, including cardiovascular and CHD death (200) . Similarly, the addition of ticagrelor to aspirin reduced the risk of ischemic cardiovascular events compared with aspirin alone in people with diabetes and stable coronary artery disease (201, 202) . However, a higher incidence of major bleeding, including intracranial hemorrhage, was noted with dual antiplatelet therapy. The net clinical benefit (ischemic benefit vs. bleeding risk) was improved with ticagrelor therapy in the large prespecified subgroup of individuals with history of percutaneous coronary intervention, while no net benefit was seen in individuals without prior percutaneous coronary intervention (202) . However, early aspirin discontinuation compared with continued dual antiplatelet therapy after coronary stenting may reduce the risk of bleeding without a corresponding increase in the risks of mortality and ischemic events, as shown in a prespecified analysis of people with diabetes enrolled in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial and a meta-analysis (203, 204) .

Combination Antiplatelet and Anticoagulation Therapy

Combination therapy with aspirin plus low-dose rivaroxaban may be considered for people with stable coronary and/or PAD to prevent major adverse limb and cardiovascular complications. In the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial of 27,395 individuals with established coronary artery disease and/or PAD, aspirin plus rivaroxaban 2.5 mg twice daily was superior to aspirin plus placebo in the reduction of cardiovascular ischemic events, including major adverse limb events. The absolute benefits of combination therapy appeared larger in people with diabetes, who comprised 10,341 of the trial participants (205, 206) . A similar treatment strategy was evaluated in the Vascular Outcomes Study of ASA (acetylsalicylic acid) Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease (VOYAGER PAD) trial (207) , in which 6,564 individuals with PAD who had undergone revascularization were randomly assigned to receive rivaroxaban 2.5 mg twice daily plus aspirin or placebo plus aspirin. Rivaroxaban treatment in this group of individuals was also associated with a significantly lower incidence of ischemic cardiovascular events, including major adverse limb events. However, an increased risk of major bleeding was noted with rivaroxaban added to aspirin treatment in both COMPASS and VOYAGER PAD.

The risks and benefits of dual antiplatelet or antiplatelet plus anticoagulant treatment strategies should be thoroughly discussed with eligible individuals, and shared decision-making should be used to determine an individually appropriate treatment approach. This field of cardiovascular risk reduction is evolving rapidly, as are the definitions of optimal care for individuals with differing types and circumstances of cardiovascular complications. .42 Among people with type 2 diabetes who have established ASCVD or established kidney disease, a sodiumglucose cotransporter 2 (SGLT2) inhibitor or glucagon-like peptide 1 receptor agonist (GLP-1 RA) with demonstrated cardiovascular disease benefit is recommended as part of the comprehensive cardiovascular risk reduction and/or glucose-lowering treatment plans. A 10.42a In people with type 2 diabetes and established ASCVD, multiple ASCVD risk factors, or chronic kidney disease (CKD), an SGLT2 inhibitor with demonstrated cardiovascular benefit is recommended to reduce the risk of major adverse cardiovascular events and/or heart failure hospitalization. A 10.42b In people with type 2 diabetes and established ASCVD or multiple risk factors for ASCVD, a GLP-1 RA with demonstrated car-diovascular benefit is recommended to reduce the risk of major adverse cardiovascular events. A 10.42c In people with type 2 diabetes and established ASCVD or multiple risk factors for ASCVD, combined therapy with an SGLT2 inhibitor with demonstrated cardiovascular benefit and a GLP-1 RA with demonstrated cardiovascular benefit may be considered for additive reduction of the risk of adverse cardiovascular and kidney events. A 10.43a In people with type 2 diabetes and established heart failure with either preserved or reduced ejection fraction, an SGLT2 inhibitor (including SGLT1/2 inhibitor) with proven benefit in this population is recommended to reduce the risk of worsening heart failure and cardiovascular death. A 10.43b In people with type 2 diabetes and established heart failure with either preserved or reduced ejection fraction, an SGLT2 inhibitor with proven benefit in this population is recommended to improve symptoms, physical limitations, and quality of life. A 10.44 For individuals with type 2 diabetes and CKD with albuminuria treated with maximum tolerated doses of ACE inhibitor or ARB, recommend treatment with a nonsteroidal MRA with demonstrated benefit to improve cardiovascular outcomes and reduce the risk of CKD progression. A 10. 45 In individuals with diabetes with established ASCVD or aged $55 years with additional cardiovascular risk factors, ACE inhibitor or ARB therapy is recommended to reduce the risk of cardiovascular events and mortality. A 10.46a In individuals with diabetes and asymptomatic stage B heart failure, an interprofessional approach to optimize guideline-directed medical therapy, which should include a cardiovascular disease specialist, is recommended to reduce the risk for progression to symptomatic (stage C) heart failure. A 10.46b In individuals with diabetes and asymptomatic stage B heart failure, ACE inhibitors or ARBs and b-blockers are recommended to reduce the risk for progression to symptomatic (stage C) heart failure. A 10.46c In individuals with type 2 diabetes and asymptomatic stage B heart failure or with high risk of or established cardiovascular disease, treatment with an SGLT inhibitor with proven heart failure prevention benefit is recommended to reduce the risk of hospitalization for heart failure. A 10.46d In individuals with type 2 diabetes, obesity, and symptomatic heart failure with preserved ejection fraction, therapy with a GLP-1 RA with demonstrated benefit for reduction of heart failure-related symptoms, physical limitations, and exercise function is recommended. A 10.46e In individuals with type 2 diabetes and CKD, recommend treatment with a nonsteroidal MRA with demonstrated benefit to reduce the risk of hospitalization for heart failure. A 10.46f In individuals with diabetes, guideline-directed medical therapy for myocardial infarction and symptomatic stage C heart failure is recommended with ACE inhibitors or ARBs, MRAs, angiotensin receptor or neprilysin inhibitor, b-blockers, and SGLT2 inhibitors, similar to guideline-directed medical therapy for people without diabetes. A 10.47 In people with type 2 diabetes with stable heart failure, metformin may be continued for glucose lowering if estimated glomerular filtration rate remains > 30 mL/min/1.73 m 2 but should be avoided in unstable or hospitalized individuals with heart failure. B 10.48 Individuals with type 1 diabetes and those with type 2 diabetes who are ketosis prone and/or follow a ketogenic eating pattern who are treated with SGLT inhibition should be educated on the risks and signs of ketoacidosis and methods of risk management and provided with appropriate tools for accurate ketone measurement (i.e., serum b-hydroxybutyrate). E

Cardiac Testing

Candidates for advanced or invasive cardiac testing include those with 1) symptoms or signs of cardiac or vascular disease and 2) an abnormal resting electrocardiogram (ECG). Exercise ECG testing without or with echocardiography may be used as the initial test. In adults with diabetes $40 years of age, measurement of coronary artery calcium is also reasonable for cardiovascular risk assessment. Pharmacologic stress echocardiography or nuclear imaging should be considered in individuals with diabetes in whom resting ECG abnormalities preclude exercise stress testing (e.g., left bundle branch block or ST-T abnormalities). In addition, individuals who require stress testing and are unable to exercise should undergo pharmacologic stress echocardiography or nuclear imaging.

Screening Asymptomatic Individuals for Atherosclerotic Cardiovascular Disease

The screening of asymptomatic individuals with high ASCVD risk is not recommended (Fig. 10 .5), in part because these high-risk people should already be receiving intensive medical therapy-an approach that provides benefits similar to those of invasive revascularization (208, 209) . A randomized observational trial demonstrated no clinical benefit of routine screening with adenosine-stress radionuclide myocardial perfusion imaging in asymptomatic people with type 2 diabetes and normal ECGs (210) . Another randomized study showed that routine screening with coronary computed tomography angiography did not reduce the composite rate of all-cause mortality, nonfatal MI, or unstable angina in asymptomatic people with type 1 or type 2 diabetes (211) . Studies have also found that a risk factor-based approach to the initial diagnostic evaluation and subsequent follow-up for coronary artery disease fails to identify which people with type 2 diabetes will have silent ischemia on screening tests (212, 213) .

Any benefit of noninvasive coronary artery disease screening methods, such as computed tomography calcium scoring, to identify subgroups for different treatment strategies remains unproven in asymptomatic people with diabetes, though research is ongoing. Coronary calcium scoring in asymptomatic people with diabetes may help in risk stratification (214, 215) and provide reasoning for treatment intensification and/or guiding informed individual decision-making and willingness for medication initiation and participation. However, their routine use leads to radiation exposure and may result in unnecessary invasive testing, such as coronary angiography and revascularization procedures. The ultimate balance of benefit, cost, and risk of such an approach in asymptomatic individuals remains controversial, particularly in the modern setting of aggressive ASCVD risk factor management.

Screening for Asymptomatic Heart Failure in People With Diabetes

People with diabetes are at an increased risk for developing heart failure, as shown in multiple longitudinal, observational studies (216, 217) . This association is not only observed in people with type 2 diabetes but also evident in people with type 1 diabetes (216, 217) . In a large multinational cohort of 750,000 people with diabetes without established cardiovascular disease, heart failure and CKD were the most frequent first manifestations of cardiovascular or kidney disease (218) . For a detailed review of screening, diagnosis, and treatment recommendations of heart failure in people with diabetes, the reader is further referred to the ADA consensus report "Heart Failure: An Underappreciated Complication of Diabetes. A Consensus Report of the American Diabetes Association" (15) .

People with diabetes are at particularly high risk for progression from asymptomatic stage A and B to symptomatic stage C and D heart failure (219, 220) . Identification, risk stratification, and early treatment of risk factors in people with diabetes and asymptomatic stages of heart failure reduce the risk for progression to symptomatic heart failure (221, 222) . In people with type 2 diabetes, measurement of natriuretic peptides, including B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), identifies people at risk for heart failure development, progression of symptoms, and heart failure-related mortality (223) (224) (225) . A similar association and prognostic values of increased NT-proBNP with increased cardiovascular and all-cause mortality has been reported in people with type 1 diabetes (226) . Results from several randomized controlled trials revealed that more intensive treatment of risk factors in people with increased levels of natriuretic peptides reduces the risk for symptomatic heart failure, heart failure hospitalization, and newly diagnosed left ventricular dysfunction (222, 227, 228) .

Based on collective evidence, consider screening asymptomatic adults with diabetes for the development of cardiac structural or functional abnormalities (stage B heart failure) by measurement of natriuretic peptides, including BNP or NT-proBNP levels. The biomarker threshold for abnormal values is BNP level $50 pg/mL and NT-proBNP level $125 pg/mL. Abnormal levels of natriuretic peptide will need to be evaluated in the context of each person, using clinical judgment, in the absence of any possible competing diagnoses, particularly recognizing conditions that may lead to increased levels of natriuretic peptide, including renal insufficiency, pulmonary disease including pulmonary hypertension and chronic obstructive lung disease, obstructive sleep apnea, ischemic and hemorrhagic stroke, and anemia. Conversely, natriuretic peptide levels may be decreased in the population with obesity, which impairs sensitivity of testing.

In people with diabetes and an abnormal natriuretic peptide level, echocardiography is recommended as the next step to screen for structural heart disease and echocardiographic Doppler indices for evidence of diastolic dysfunction and increased filling pressures (229) . At this stage, an interprofessional approach, which should include a cardiovascular disease specialist, is recommended to implement a guideline-directed medical treatment strategy, which may reduce the risk of progression to symptomatic stages of heart failure (221) . The recommendations for screening and treatment of heart failure in people with diabetes discussed in this section are consistent with the ADA consensus report on heart failure (15) and with current American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines for the management of heart failure (12) .

Screening for Asymptomatic Peripheral Artery Disease in People With Diabetes

The risk for PAD in people with diabetes is higher than that in people without diabetes (230) (231) (232) . In the PAD Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) program, 30% of people aged 50-69 years with a history of cigarette smoking or diabetes, or aged $70 years regardless of risk factors, had PAD (233) . Similarly, in other screening studies, 26% of people with diabetes have been shown to have PAD (234) , and diabetes increased

Who to Screen?

Screen individuals with diabetes and age 65 years, any microvascular disease, foot complications, or end-stage organ damage from diabetes, if a PAD diagnosis would change management. Consider screening anyone with a diabetes duration ≥10 years.

Peripheral Artery Disease

Screen all adults with diabetes, which increases risks for asymptomatic (stage B and symptomatic (stage C HF.

Heart Failure

Routine screening is not recommended for asymptomatic individuals.

Coronary Artery Disease

Screen with ankle-brachial index testing.

Measure BNP or N-terminal pro-BNP.

Echocardiography is recommended for those with abnormal BNP levels.

If signs or symptoms of cardiac or associated vascular disease, or electrocardiogram abnormalities are present, screen using routine methods.

Screening for Undiagnosed Cardiovascular Disease the odds of having PAD by 85% (235) . Notably, classical symptoms of claudication are uncommon, and almost half of people with newly diagnosed PAD were asymptomatic (233) . Conversely, up to twothirds of people with asymptomatic PAD have been shown to have comorbid diabetes (236) . Risk factors associated with an increased risk for PAD in people with diabetes include age, smoking, hypertension, dyslipidemia, worse glycemic management, longer duration of diabetes, neuropathy, and retinopathy as well as a prior history of cardiovascular disease (237, 238) . In addition, the presence of microvascular disease is associated with adverse outcomes in people with PAD, including an increased risk for future limb amputation (239, 240) . While a positive screening test for PAD in an asymptomatic population has been associated with increased cardiovascular event rates (241, 242) , prospective, randomized studies addressing whether screening for PAD in people with improves longterm limb outcomes and cardiovascular event rates are limited. In the randomized controlled Viborg Vascular (VIVA) trial, 50,156 participants, some with and some without diabetes, were randomized to combined vascular screening for abdominal aortic aneurysm, PAD, and hypertension or to no screening. Vascular screening was associated with increased pharmacologic therapy (antiplatelet, lipid-lowering, and antihypertensive therapy), reduced inhospital time for PAD and coronary artery disease, and reduced mortality (243) . Therefore, the committee recommends screening for asymptomatic PAD using ankle-brachial index in people with diabetes in whom a diagnosis of PAD may help further intensify pharmacologic therapies. These people include those with age $65 years, diabetes with duration $10 years, microvascular disease, clinical evidence of foot complications, or any end-organ damage from diabetes.

Lifestyle and Pharmacologic Interventions

Intensive lifestyle intervention focusing on weight loss through decreased caloric intake and increased physical activity, as performed in the Look AHEAD (Action for Health in Diabetes) trial, may be considered for improving glucose management, fitness, and some ASCVD risk factors (244) . Individuals at increased ASCVD risk should receive statin, ACE inhibitor, or ARB therapy if the individual has hypertension, and possibly aspirin, unless there are contraindications to a particular drug class. Clear cardiovascular benefit exists for ACE inhibitor or ARB therapy in people with diabetes. The Heart Outcomes Prevention Evaluation (HOPE) study randomized 9,297 individuals aged $55 years with a history of vascular disease or diabetes plus one other cardiovascular risk factor to either ramipril or placebo. Ramipril significantly reduced cardiovascular and all-cause mortality, MI, and stroke (245) . ACE inhibitors or ARB therapy also have well-established long-term benefit in people with diabetes and CKD or hypertension, and these agents are recommended for hypertension management in people with known ASCVD (particularly coronary artery disease) (72, 73, 246) . People with type 2 diabetes and CKD should be considered for treatment with finerenone to reduce cardiovascular outcomes and the risk of CKD progression (247) (248) (249) (250) . b-Blockers should be used in individuals with active angina or HFrEF and for 3 years after MI in those with preserved left ventricular function (251, 252) .

Glucose-Lowering Therapies and Cardiovascular Outcomes

In 2008, the U.S. Food and Drug Administration (FDA) issued guidance for industry to perform cardiovascular outcomes trials for all new medications for the treatment of type 2 diabetes amid concerns of increased cardiovascular risk (253) . Previously approved diabetes medications were not subject to the guidance. Recently published cardiovascular outcomes trials have provided additional data on cardiovascular and renal outcomes in people with type 2 diabetes with cardiovascular disease or at high risk for cardiovascular disease.

Cardiovascular outcomes trials of dipeptidyl peptidase 4 (DPP-4) inhibitors have all, so far, not shown cardiovascular benefits relative to placebo. In addition, the CAROLINA (Cardiovascular Outcome Study of Linagliptin Versus Glimepiride in Type 2 Diabetes) study demonstrated noninferiority between a DPP-4 inhibitor, linagliptin, and a sulfonylurea, glimepiride, on cardiovascular outcomes despite lower rates of hypoglycemia in the linagliptin treatment group (254) . The BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) showed that treatment with empagliflozin reduced the composite outcome of MI, stroke, and cardiovascular death by 14% (absolute rate 10.5% vs. 12.1% in the placebo group, HR in the empagliflozin group 0.86 [95% CI 0.74-0.99]; P = 0.04 for superiority) and cardiovascular death by 38% (absolute rate 3.7% vs. 5.9%, HR 0.62 [95% CI 0.49-0.77]; P < 0.001) (255) . Similarly, canagliflozin significantly reduced the composite outcome of cardiovascular death, MI, or stroke versus placebo (occurring in 26.9 vs. 31.5 participants per 1,000 person-years; HR 0.86 [95% CI 0.75-0.97]). Of note, there was an increased risk of lower-limb amputation with canagliflozin (6.3 vs. 3.4 participants per 1,000 person-years; HR 1.97 [95% CI 1.41-2.75]) (256) . However, no significant increase in lower-limb amputations, fractures, AKI, or hyperkalemia was noted for canagliflozin relative to placebo in other trials of canagliflozin (257) .

The Dapagliflozin Effect on Cardiovascular Events-Thrombosis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial met the prespecified criteria for noninferiority to placebo with respect to major adverse cardiovascular events but did not show a lower rate of major adverse cardiovascular events compared with placebo (8.8% in the dapagliflozin group and 9.4% in the placebo group; HR 0.93 [95% CI 0.84-1.03]; P = 0.17) (258) . A lower rate of cardiovascular death or hospitalization for heart failure was noted (4.9% vs. 5.8%; HR 0.83 [95% CI 0.73-0.95]; P = 0.005), which reflected a lower rate of hospitalization for heart failure (HR 0.73 [95% CI 0.61-0.88]). No difference was seen in cardiovascular death between groups. Further studies have shown renoprotective effects of dapagliflozin (259) .

The Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial (VERTIS CV) (260) met the prespecified criteria for noninferiority of ertugliflozin to placebo with respect to the primary outcome of major adverse cardiovascular events (11.9% in the pooled ertugliflozin group and 11.9% in the placebo group; HR 0.97 [95% CI 0.85-1.11]; P < 0.001). However, ertugliflozin was not superior to placebo for the key secondary outcomes of death from cardiovascular causes or hospitalization for heart failure; death from cardiovascular causes; or the composite of death from renal causes, renal replacement therapy, or doubling of the serum creatinine level. The HR for a secondary outcome of hospitalization for heart failure (ertugliflozin vs. placebo) was 0.70 [95% CI 0.54-0.90], consistent with findings from other SGLT2 inhibitor cardiovascular outcomes trials.

GLP-1 Receptor Agonist Trials

The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial was a randomized, double-blind trial that assessed the effect of liraglutide, a GLP-1 RA, versus placebo on cardiovascular outcomes in 9,340 people with type 2 diabetes at high risk for cardiovascular disease or with cardiovascular disease (261) . Study participants had a mean age of 64 years and a mean duration of diabetes of nearly 13 years. Over 80% of study participants had established cardiovascular disease. After a median follow-up of 3.8 years, LEADER showed that the primary composite outcome (MI, stroke, or cardiovascular death) occurred in fewer participants in the treatment group (13.0%) than in the placebo group (14.9%) (HR 0.87 [95% CI 0.78-0.97]; P < 0.001 for noninferiority; P = 0.01 for superiority). Deaths from cardiovascular causes were significantly reduced in the liraglutide group (4.7%) compared with the placebo group (6.0%) (HR 0.78 [95% CI 0.66-0.93]; P = 0.007) (261) .

Results of trials with semaglutide, albiglutide, and dulaglutide, once-weekly GLP-1 RAs, were consistent with the LEADER trial (262) (263) (264) . However, lixisenatide and extended-release exenatide were not superior to placebo with respect to the primary end point of cardiovascular outcomes (265) . In summary, there are now numerous large randomized controlled trials reporting statistically significant reductions in cardiovascular events for three of the FDA-approved SGLT2 inhibitors (empagliflozin, canagliflozin, and dapagliflozin, with lesser benefits seen with ertugliflozin) and four FDA-approved GLP-1 RAs (liraglutide, albiglutide [although that agent was removed from the market for business reasons], semaglutide [lower risk of cardiovascular events in a moderate-sized clinical trial but one not powered as a cardiovascular outcomes trial] , and dulaglutide). Meta-analyses of the trials reported to date suggest that GLP-1 RAs and SGLT2 inhibitors reduce risk of atherosclerotic major adverse cardiovascular events to a comparable degree in people with type 2 diabetes and established ASCVD (266, 267) . SGLT2 inhibitors also reduce risk of heart failure hospitalization and progression of kidney disease in people with established ASCVD, multiple risk factors for ASCVD, or albuminuric kidney disease (268, 269) . In people with type 2 diabetes and established ASCVD, multiple ASCVD risk factors, or CKD, an SGLT2 inhibitor with demonstrated cardiovascular benefit is recommended to reduce the risk of major adverse cardiovascular events and/or heart failure hospitalization. In people with type 2 diabetes and established ASCVD or multiple risk factors for ASCVD, a GLP-1 RA with demonstrated cardiovascular benefit is recommended to reduce the risk of major adverse cardiovascular events. For many individuals, use of either an SGLT2 inhibitor or a GLP-1 RA to reduce cardiovascular risk is appropriate. Emerging data suggest that use of both classes of drugs will provide an additive cardiovascular and kidney outcomes benefit; thus, combination therapy with an SGLT2 inhibitor and a GLP-1 RA may be considered to provide the complementary outcomes benefits associated with these classes of medication (270) . Early primary prevention strategies and treatment of associated risk factors reduce incident, symptomatic heart failure and should include lifestyle intervention with nutrition, physical activity, weight management, and smoking cessation (271-274) (Fig. 10 .6). The vast majority of incident heart failure is preceded by hypertension; up to 91% of all new heart failure development in the Framingham cohort occurred in people with a previous diagnosis of hypertension (275) . Therefore, management of hypertension constitutes a key goal in people with diabetes and stage A or B heart failure. For example, in the UK Prospective Diabetes Study (UKPDS) trial, intensive blood pressure management in people with type 2 diabetes reduced the risk for heart failure by 56% (276) . Similarly, in the SPRINT trial, intensive treatment of hypertension decreased the risk for development of incident heart failure by 36% (277) . As discussed in the HYPERTEN- SION AND BLOOD PRESSURE MANAGEMENT section above, use of ACE inhibitors or ARBs is the preferred treatment strategy for management of hypertension in people with diabetes, particularly in the presence of albuminuria or coronary artery disease. The selective nonsteroidal MRA finerenone has been shown in the FIGARO-DKD trial, which included people with type 2 diabetes and CKD, to reduce the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure (248) . A prespecified subgroup analysis from FIGARO-DKD further revealed that in individuals without symptomatic HFrEF, finerenone reduces the risk for new-onset heart failure and improves heart failure outcomes in people with type 2 diabetes and CKD (247) . Furthermore, the incidence of heart failure hospitalization was reduced in finerenonetreated people with type 2 diabetes. Finally, in a pooled analysis from both FIDELIO-DKD and FIGARO-DKD, treatment with finerenone reduced the composite of cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure was reduced (249) . These collective studies indicate that finerenone improves cardiovascular and renal outcomes in people with type 2 diabetes. Therefore, in people Individual is ≥18 years old with T2D and has ≥1 of the following: ASCVD* , HF, CKD †, at high risk for ASCVD. ‡ § Address concurrently.

Optimize guideline-directed medical therapy for prevention (lifestyle, blood pressure, lipids, glucose, antiplatelet).

Recommend starting SGLT2 inhibitor or GLP-1 RA with proven CV benefit depending on patient-specific factors and comorbidities. ˡ

Discuss patient-clinician preferences and priorities.

No additional action taken at this time.

SGLT2 inhibitor selected.

Reassess and consider the addition of the alternative class, if benefits outweigh risks.

GLP-1 RA selected.

* ASCVD is defined as a history of an acute coronary syndrome or myocardial infarction, stable or unstable angina, coronary heart disease with or without revascularization, other arterial revascularization, stroke, or peripheral artery disease assumed to be atherosclerotic in origin. † CKD is a clinical diagnosis marked by reduced eGFR, the presence of albuminuria, or both. ‡ Consider an SGLT2 inhibitor when the individual has established ASCVD, HF, or CKD or is at high risk for ASCVD. Consider a GLP-1 RA when the individual has established ASCVD or is at high risk for ASCVD. § Individuals at high risk for ASCVD include those with end-organ damage such as left ventricular hypertrophy or retinopathy or with multiple CV risk factors (e.g., age, hypertension, smoking, dyslipidemia, and obesity).

ˡ Most individuals enrolled in the relevant trials were on metformin at baseline as glucose-lowering therapy. with type 2 diabetes and CKD with albuminuria treated with maximum tolerated doses of ACE inhibitor or ARB, addition of finerenone should be considered to improve cardiovascular outcomes, including the risk for heart failure hospitalization, and to reduce the risk of CKD progression. Approximately 45% of people admitted for HFpEF have diabetes, and most people with HFpEF have obesity (320, 321) . Conversely, weight loss improves symptoms of HFpEF (322) . Therefore, the Semaglutide Treatment Effect in People with Obesity and HFpEF (STEP-HFpEF) trial evaluated whether the GLP-1 RA semaglutide improves symptoms related to heart failure (323) . In the study, 616 people with type 2 diabetes and a BMI of 30 or greater with HFpEF were assigned receive onceweekly semaglutide at a dose of 2.4 mg or placebo. The primary end point was the change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (range from 0 to 100) and the change in weight. After 1 year of treatment, the mean change in the score was 13.7 points with semaglutide and 6.4 points with placebo, and the mean body weight was reduced by 9.8% in the group assigned to semaglutide compared with 3.4% with placebo. In addition, in the confirmatory secondary end point, semaglutide treatment improved 6-min walk distance. In a hierarchical analysis, semaglutide favored the composite end point of death, heart failure events, change in the Kansas City Cardiomyopathy Questionnaire clinical summary score, and C-reactive protein levels. Therefore, the committee recommends treatment with a GLP-1 RA with demonstrated benefit in individuals with type 2 diabetes, obesity, and symptomatic HFpEF for the reduction of HF-related symptoms, physical limitations, and exercise function in this population.

Clinical Approach

As has been carefully outlined in Fig. 9 .3 in Section 9, "Pharmacologic Approaches to Glycemic Treatment," people with type 2 diabetes with or at high risk for ASCVD, heart failure, or CKD should be treated with a cardioprotective SGLT2 inhibitor and/or GLP-1 RA as part of the comprehensive approach to cardiovascular and kidney risk reduction. Importantly, these agents should be included in the plan of care irrespective of the need for additional glucose lowering and irrespective of metformin use. Such an approach has also been described in the ADA-endorsed American College of Cardiology "2020 Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes" (324) . Figure 10 .7, reproduced from that decision pathway, outlines the approach to risk reduction with SGLT2 inhibitor or GLP-1 RA therapy in conjunction with other traditional, guideline-based preventive medical therapies for blood pressure, lipids, and glycemia and antiplatelet therapy.

Adoption of these agents should be reasonably straightforward in people with type 2 diabetes and established cardiovascular or kidney disease. Incorporation of SGLT2 inhibitor or GLP-1 RA therapy in the care of individuals with diabetes may need to replace some or all of their existing medications to minimize risks of hypoglycemia and adverse side effects and potentially to minimize medication costs. Close collaboration between primary and specialty care professionals can help facilitate these transitions in clinical care and, in turn, improve outcomes for people with type 2 diabetes who are at high risk for ASCVD, heart failure, or CKD. Screening for albuminuria can be most easily performed by urine albumin-tocreatinine ratio (UACR) in a random spot urine collection (1) . Timed or 24-h collections are more burdensome and add little to prediction or accuracy. Measurement of a spot urine sample for albumin alone (whether by immunoassay or by using a sensitive dipstick test specific for albuminuria) without simultaneously measuring urine creatinine is less expensive but susceptible to false-negative and falsepositive determinations as a result of variation in urine concentration due to hydration (7) . Thus, semiquantitative or qualitative (dipstick) screening will need to be confirmed by UACR values in an accredited laboratory (8, 9) . Hence, it is better to simply collect a spot urine sample for albumin-to-creatinine ratio because it will ultimately need to be done. Normal level of urine albumin excretion is defined as < 30 mg/g creatinine, moderately elevated albuminuria is defined as $30-300 mg/g creatinine, and severely elevated albuminuria is defined as $300 mg/g creatinine. However, UACR is a continuous measurement, and differences within the normal and abnormal ranges are associated with kidney and cardiovascular outcomes (6, 10, 11) . Furthermore, because of high biological variability of > 20% between measurements in urinary albumin excretion, two of three specimens of UACR collected within a 3-to 6-month period should be abnormal before considering an individual to have moderately or severely elevated albuminuria (1, 12, 13) . Exercise within 24 h, infection, fever, heart failure, marked hyperglycemia, menstruation, and marked hypertension may elevate UACR independently of kidney damage (14) . Moreover, a recent analysis showed variability in the measurement of UACR when measured weekly over a 1-month period. Thus, repeated measurements and tracking of trending over time are needed to properly follow changes in UACR (12) .

Traditionally, eGFR is calculated from serum creatinine using a validated formula (15) . eGFR is routinely reported by laboratories along with serum creatinine, and eGFR calculators are available online at nkdep.nih.gov. An eGFR persistently < 60 mL/min/1.73 m 2 and/or an urinary albumin value of > 30 mg/g creatinine is considered abnormal, though optimal thresholds for clinical diagnosis are debated in older adults over age 70 years (1, 16) . Historically, a correction factor for muscle mass was included in a modified equation for African American people; however, race is a social and not a biologic construct, making it problematic to apply race to clinical algorithms. Hence, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation was refit without the race variable and should be used for everyone (17, 18) . Additionally, increased use of cystatin C (another marker of eGFR) is suggested in combination with serum creatinine because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone.

DIAGNOSIS OF CHRONIC KIDNEY DISEASE IN PEOPLE WITH DIABETES

CKD in people with diabetes is usually a clinical diagnosis made based on the presence of albuminuria and/or reduced eGFR in the absence of signs or symptoms of other primary causes of kidney damage. The typical presentation of CKD in people with diabetes is considered to include long-standing duration of diabetes, retinopathy, albuminuria without gross hematuria, and gradually progressive loss of eGFR. However, signs of CKD may be present at diagnosis or without retinopathy in type 2 diabetes. Reduced eGFR without albuminuria has been frequently reported in type 1 and type 2 diabetes and is becoming more common over time as the prevalence of diabetes increases in the U.S. (2, 3, 16, (19) (20) (21) . An active urinary sediment (containing red or white blood cells or cellular casts), rapidly increasing albuminuria or total proteinuria, the presence of nephrotic syndrome, rapidly decreasing eGFR, or the absence of retinopathy (in type 1 diabetes) suggests alternative or additional causes of kidney disease. For individuals with these features, referral to a nephrologist for further diagnosis, including the possibility of kidney biopsy, should be considered. It is rare for people with type 1 diabetes to develop kidney disease without retinopathy. In type 2 diabetes, retinopathy is only moderately sensitive and specific for CKD caused by diabetes, as confirmed by kidney biopsy (22) . It cannot be definitively stated that a person with diabetes and CKD has CKD related to diabetes unless the person has a kidney biopsy, as there may be another cause or multiple causes. Hence, without a biopsy, it is recommended to state that the individual has CKD in a person with diabetes. In most people, there is no need for a kidney biopsy, as the other possible diagnoses would not change treatment. Referral to a nephrologist should be done if there are any reasons to consider another cause of CKD in a person with diabetes (Table 11 .1).

STAGING OF CHRONIC KIDNEY DISEASE

Stage G1 and stage G2 CKD are defined by evidence of high albuminuria with eGFR $60 mL/min/1.73 m 2 , and stages G3-G5 CKD are defined by progressively lower ranges of eGFR (23) (Fig. 11 .1). At any eGFR, the degree of albuminuria is associated with risk of cardiovascular disease (CVD), CKD progression, and mortality (6) . Therefore, there is an additional subclassification by level of urine albumin (Fig. 11 .1). Furthermore, Kidney Disease: Improving Global Outcomes (KDIGO) recommends a more comprehensive CKD staging that incorporates albuminuria at all stages of eGFR; this system is more closely associated with risk but is also more complex (1) . Thus, based on the current classification system, both eGFR and albuminuria must be quantified to guide treatment decisions. Quantification of eGFR levels is essential for modifications of medication dosages or restrictions of use (Fig. 11 .1) (23, 24) , and the degree of albuminuria should influence the choice of antihypertensive medications (see Section 10, "Cardiovascular Disease and Risk Management") or glucose-lowering medications (see below). Observed history of eGFR loss (which is also associated with risk of CKD progression and other adverse health outcomes) and cause of kidney damage (including possible causes other than diabetes) may also affect these decisions (25) .

ACUTE KIDNEY INJURY

Acute kidney injury (AKI) is diagnosed by a sustained increase in serum creatinine over a short period of time, which is also reflected as a rapid decrease in eGFR (26, 27) . People with diabetes are at higher risk of AKI than those without diabetes (28) . Other risk factors for AKI include preexisting CKD, the use of medications that cause kidney injury (e.g., nonsteroidal anti-inflammatory drugs), certain intravenous dyes (e.g., iodinated radiocontrast agents) and the use of medications that alter renal blood flow and intrarenal hemodynamics. In particular, many antihypertensive medications (e.g., diuretics, ACE inhibitors, and angiotensin receptor blockers [ARBs]) can reduce intravascular volume, renal blood flow, and/or glomerular filtration. There was concern that sodium-glucose cotransporter 2 (SGLT2) inhibitors may promote AKI through volume depletion, particularly when combined with diuretics or other medications that reduce glomerular filtration; however, this has not been found to be true in randomized controlled trials of advanced kidney disease (29) or high CVD risk with normal kidney function (30) (31) (32) . It is also noteworthy that the nonsteroidal mineralocorticoid receptor antagonists (MRAs) do not increase the risk of AKI when used to slow kidney disease progression (33) . Timely identification and treatment of AKI is important because AKI is associated with increased risks of progressive CKD and other poor health outcomes (34) .

Elevations in serum creatinine (up to 30% from baseline) with renin-angiotensin system (RAS) blockers (such as ACE inhibitors and ARBs) must not be confused with AKI (35) . An analysis of the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD BP) trial demonstrated that participants randomized to intensive blood pressure lowering with up to a 30% increase in serum creatinine did not have any increase in mortality or progressive kidney disease (36, 37) . Moreover, a measure of markers for AKI showed no significant increase of any markers with increased creatinine (37) .

Accordingly, ACE inhibitors and ARBs should not be discontinued for increases in serum creatinine ( < 30%) in the absence of volume depletion.

SURVEILLANCE

Both albuminuria and eGFR should be monitored annually to enable timely diagnosis of CKD, monitor progression of CKD, detect superimposed kidney diseases including AKI, assess risk of CKD complications, dose medications appropriately, and determine whether nephrology referral is needed. Among people with existing kidney disease, albuminuria and eGFR may change due to progression of CKD, development of a separate superimposed cause of kidney disease, AKI, or other effects of medications, as noted above. Serum potassium should also be monitored in individuals treated with diuretics because these medications can cause hypokalemia, which is associated with cardiovascular risk and mortality (38) (39) (40) . Individuals with eGFR < 60 mL/min/1.73 m 2 receiving ACE inhibitors, ARBs, or MRAs should have serum potassium measured periodically. Additionally, people with this lower range of eGFR should have their medication dosing verified, their exposure to nephrotoxins (e.g., nonsteroidal anti-inflammatory drugs and iodinated contrast) should be minimized, and they should be evaluated for potential CKD complications (Table 11

There is a clear need for annual quantitative assessment of UACR. This is especially true after a diagnosis of albuminuria, institution of ACE inhibitors or ARB therapy to maximum tolerated doses, and achievement of blood pressure goals. Early changes in kidney function may be detected by increases in albuminuria before changes in eGFR (41) , and this also significantly affects cardiovascular risk. Continued surveillance can assess both response to therapy and disease progression and may aid in assessing participation in ACE inhibitor or ARB therapy. In addition, in clinical trials of ACE inhibitor or ARB therapy in people with type 2 diabetes, reducing albuminuria to levels < 300 mg/g creatinine or by > 30% from baseline has been associated with improved kidney and cardiovascular outcomes, leading to the recommendation that medications should be titrated to maximize reduction in UACR (8) . See Table 11 .3 for interventions that lower albuminuria.

Data from post hoc analyses demonstrate less benefit on cardiorenal outcomes at half doses of RAS blockade (42) . In type 1 diabetes, remission of albuminuria may occur spontaneously, and cohort studies evaluating associations of change in albuminuria with clinical outcomes have reported inconsistent results (43, 44) .

The prevalence of CKD complications correlates with eGFR (40) . When eGFR is < 60 mL/min/1.73 m 2 , screening for complications of CKD is indicated (Table 11 (129) . eGFR, estimated glomerular filtration rate; UACR, urine albumin-to-creatinine ratio.

Comorbidities," for further information on immunization).

Prevention

The only proven primary prevention interventions for CKD in people with diabetes are blood glucose (A1C goal of 7%) and blood pressure management. There is no evidence that renin-angiotensin-aldosterone system inhibitors or any other interventions prevent the development of CKD in the absence of hypertension or albuminuria. Thus, the American Diabetes Association does not recommend routine use of these medications solely for the purpose of prevention of the development of CKD. In 2023, the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) was published (45) . This large prospective study compared liraglutide, sitagliptin, glimeperide, and insulin glargine with respect to achieving and maintaining A1C goals in people with type 2 diabetes treated with metformin monotherapy; kidney and cardiovascular end points were examined as secondary outcomes. A total of 5,047 participants were enrolled from July 2013 to August 2017 and were followed for an average of 5 years. Almost all participants did not have signs of kidney disease at the time of enrollment. No differences between the examined medications were observed, which suggests that there were no unique reno-protective effects among these medications for prevention. Of note, SGLT2 inhibitors were not included in the study, as these medications were not routinely available at the time the study started.

INTERVENTIONS Nutrition

For people with stages 3-5 non-dialysisdependent CKD, dietary protein intake should be 0.8 g/kg body weight per day (the recommended daily allowance) (1). Compared with higher levels of dietary protein intake, this level slowed GFR decline with evidence of a greater effect over time. Higher levels of dietary protein intake ( > 20% of daily calories from protein or > 1.3 g/kg/day) have been associated with increased albuminuria, more rapid kidney function loss, and CVD mortality and therefore should be avoided. Reducing the amount of dietary protein below the recommended daily allowance of 0.8 g/kg/day is not recommended because it does not alter blood glucose levels, cardiovascular risk measures, or the course of GFR decline (46) . Some organizations recommend a lower protein intake (0.6-0.8 g/ kg/day). In particular, guidelines from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) (47) and the International Society of Renal Nutrition and Metabolism (48) recommend a lower protein intake level for reno-protection and state that this lower level is relatively safe. However, for CKD in diabetes, the expert grade is "opinion" only. The guidelines note that the evidence for lower protein intake in people with CKD has been published for only those without diabetes, which is graded Level 1A. Low-protein eating patterns should only be followed alongside guidance from a health care professional experienced in managing nutrition for people with CKD.

Restriction of dietary sodium (to < 2,300 mg/day) may be useful to manage blood pressure and reduce cardiovascular risk (49, 50) , and individualization of dietary potassium may be necessary to manage serum potassium concentrations (28, (38) (39) (40) . These interventions may be most important for individuals with reduced eGFR, for whom urinary excretion of sodium and potassium may be impaired. For individuals on dialysis, higher levels of dietary protein intake should be considered since protein-energy wasting is a major problem for some individuals on dialysis (51) . Recommendations for dietary sodium and potassium intake should be individualized based on comorbid conditions, medication use, blood pressure, and laboratory data.

Glycemic Goals

Intensive lowering of blood glucose with the goal of achieving near-normoglycemia has been shown in large, randomized studies to delay the onset and progression of albuminuria and reduce eGFR in people with type 1 diabetes (52, 53) and type 2 diabetes (1, (54) (55) (56) (57) (58) (59) . Insulin alone was used to lower blood glucose in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study of type 1 diabetes, while a variety of agents were used in clinical trials of type 2 diabetes, supporting the conclusion that lowering blood glucose itself helps prevent CKD and its progression. The effects of glucose-lowering therapies on CKD have helped define A1C goals. The presence of CKD affects the risks and benefits of intensive lowering of blood glucose and a number of specific glucose-lowering medications. Adverse effects of intensive management of blood glucose levels (hypoglycemia and mortality) were increased among people with kidney disease at baseline (60) . Moreover, there is a lag time of at least 2 years in type 2 diabetes to over 10 years in type 1 diabetes for the effects of intensive glucose control to manifest as improved eGFR outcomes (57, 61, 62) . Therefore, in some people with prevalent CKD and substantial comorbidity, treatment may be less intensive (i.e., A1C goals may be higher) to decrease the risk of hypoglycemia (1, 63) . A1C levels are also less reliable at advanced CKD stages (64, 65) .

Blood Pressure and Use of ACE Inhibitors and Angiotensin Receptor Blockers ACE inhibitors and ARBs remain a mainstay of management for people with CKD with albuminuria and for the treatment of hypertension in people with diabetes (with or without CKD in people with diabetes). Indeed, all the trials that evaluated the benefits of SGLT2 inhibition or nonsteroidal MRA effects were done in individuals who were being treated with an ACE inhibitor or ARB, in some trials up to maximum tolerated doses.

Hypertension is a strong risk factor for the development and progression of CKD (66) . Antihypertensive therapy reduces the risk of albuminuria (67) (68) (69) (70) , and among people with type 1 or 2 diabetes with established CKD (eGFR < 60 mL/min/1.73 m 2 and UACR $300 mg/g creatinine), ACE inhibitor or ARB therapy reduces the risk of progression to ESKD (71) (72) (73) (74) (75) (76) (77) (78) (79) (80) . Moreover, antihypertensive therapy reduces the risk of cardiovascular events (67) .

A blood pressure level < 130/80 mmHg is recommended to reduce CVD mortality and slow CKD progression among all people with diabetes. Lower blood pressure goals (e.g., < 130/80 mmHg) should be considered based on individual anticipated benefits and risks. People with CKD are at increased risk of CKD progression (particularly those with albuminuria) and CVD; therefore, lower blood pressure goals may be suitable in some cases, especially in individuals with severely elevated albuminuria ($300 mg/g creatinine).

ACE inhibitors or ARBs are the preferred first-line agents for blood pressure treatment among people with diabetes, hypertension, eGFR < 60 mL/min/1.73 m 2 , and UACR $300 mg/g creatinine because of their proven benefits for prevention of CKD progression (71, 72, 74) . ACE inhibitors and ARBs are considered to have similar benefits (75, 76) and risks. In the setting of lower levels of albuminuria (30-299 mg/g creatinine), ACE inhibitor or ARB therapy at maximum tolerated doses in trials has reduced progression to more advanced albuminuria ($300 mg/g creatinine), slowed CKD progression, and reduced cardiovascular events but has not reduced progression to ESKD (74, 77) . While ACE inhibitors or ARBs are often prescribed for moderately increased albuminuria (30-299 mg/g creatinine) without hypertension, outcome trials have not been performed in this setting to determine whether they improve kidney outcomes. Moreover, two long-term, double-blind studies demonstrated no renoprotective effect of either ACE inhibitors or ARBs among people with type 1 and type 2 diabetes who were normotensive with or without high albuminuria (formerly microalbuminuria, 30-299 mg/g creatinine) (78, 79) .

It should be noted that ACE inhibitors and ARBs are commonly not dosed at maximum tolerated doses because of concerns that serum creatinine will rise. As previously noted, not maximizing these therapies for this reason would be considered suboptimal care. Note that in all clinical trials demonstrating efficacy of ACE inhibitors and ARBs in slowing kidney disease progression, the maximum tolerated doses were usednot very low doses that do not provide benefit. Moreover, there are now studies demonstrating outcome benefits on both mortality and slowed CKD progression in people with diabetes who have an eGFR < 30 mL/min/1.73 m 2 (80). Additionally, when increases in serum creatinine reach 30% without associated hyperkalemia, RAS blockade should be continued (36, 81) .

Two recent large retrospective analyses provide additional support for the aggressive use of ACE inhibitors and ARBs in individuals with CKD. Ku et al. (82) reviewed 17 trials that included 11,800 individuals with CKD (defined as eGFR < 60 mL/min/1.73 m 2 ); 82% had diabetes. The authors reported that a < 13% decline in eGFR over a 3-month period or a < 21% decline in a 1-month period was associated with better longterm kidney outcomes. Hattori et al. ( 83 ) evaluated 6,065 participants between 2005 and 2021 (approximately 40% had diabetes) with eGFR ranging from 10 to 60 mL/min/1.73 m 2 who had ACE inhibitors or ARBs stopped (usually due to hyperkalemia or AKI) and found that those who restarted the ACE inhibitor or ARB had better long-term kidney outcomes and lower mortality (there was no significant difference in hyperkalemia in those who restarted ACE inhibitors or ARBs). There is also an accompanying editorial that details the strengths and weaknesses of the studies (84) .

In the absence of kidney disease, ACE inhibitors or ARBs are useful to manage blood pressure but have not proven superior to alternative classes of antihypertensive therapy, including thiazide-like diuretics and dihydropyridine calcium channel blockers (85) . In a trial of people with type 2 diabetes and normal urinary albumin excretion, an ARB reduced or suppressed the development of albuminuria but increased the rate of cardiovascular events (86) . In a trial of people with type 1 diabetes exhibiting neither albuminuria nor hypertension, ACE inhibitors or ARBs did not prevent the development of glomerulopathy assessed by kidney biopsy (78) . This was further supported by a similar trial in people with type 2 diabetes (79) .

Two clinical trials studied the combinations of ACE inhibitors and ARBs and found no benefits on CVD or CKD, and the medication combination had higher adverse event rates (hyperkalemia and/or AKI) (87, 88) . Therefore, the combined use of ACE inhibitors and ARBs should be avoided.

Direct Kidney Effects of Glucose-Lowering Medications

Some glucose-lowering medications also have effects on the kidney that are direct, i.e., not mediated through glycemia. For example, SGLT2 inhibitors reduce renal tubular glucose reabsorption, weight, systemic blood pressure, intraglomerular pressure, and albuminuria and slow GFR loss through mechanisms that appear independent of glycemia (31, (89) (90) (91) (92) . Moreover, recent data support the notion that SGLT2 inhibitors reduce oxidative stress in the kidney by > 50% and blunt increases in angiotensinogen as well as reduce NLRP3 inflammasome activity (92) (93) (94) . Glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) have also been shown to improve kidney outcomes (95) (96) (97) (98) (99) (100) . Kidney effects should be considered when selecting agents for glucose lowering (see Section 9, "Pharmacologic Approaches to Glycemic Treatment").

As discussed in the HYPERTEN- SION AND BLOOD PRESSURE MANAGEMENT section above, use of ACE inhibitors or ARBs is the preferred treatment strategy for management of hypertension in people with diabetes, particularly in the presence of albuminuria or coronary artery disease. People with diabetes and stage B heart failure who remain asymptomatic but have evidence of structural heart disease, including history of MI, acute coronary syndrome, or left ventricular ejection fraction (LVEF) #40%, should be treated with ACE inhibitors or ARBs plus b-blockers according to current treatment guidelines (12) . In the landmark Studies of Left Ventricular Dysfunction (SOLVD) study, in which 15% of people had diabetes, treatment with enalapril reduced incident heart failure in people with asymptomatic left ventricular dysfunction by 20% (278) In FIDELIO-DKD, finerenone was compared with placebo for the primary outcome of kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes in people with type 2 diabetes and CKD (285) . A prespecified secondary outcome was death from cardiovascular causes, nonfatal MI, nonfatal stroke, or hospitalization for heart failure, which was reduced by 13% in the finerenone group. The incidence of heart failure hospitalization occurred less in the finerenone-treated group, and only 7.7% of study participants had a prior history of heart failure. In the FIGARO-DKD trial, finerenone reduced the primary outcome of death from cardiovascular causes, nonfatal MI, nonfatal stroke, or hospitalization for heart failure (HR 0.87 [95% CI 0.76-0.98]; P = 0.03) in people with type 2 diabetes and CKD (248) . Only 7.8% of all participants had a prior history of heart failure, and the incidence of hospitalization for heart failure was reduced in the finerenone-allocated treatment arm (HR 0.71 [95% CI 0.56-0.90]). Owing to these observations, treatment with finerenone is recommended in people with type 2 diabetes and CKD to reduce the risk of progression from stage A heart failure to symptomatic incident heart failure.

Treatment of Symptomatic Heart Failure

In general, current guideline-directed medical therapy for a history of MI and symptomatic stage C and D heart failure in people with diabetes is similar to that for people without diabetes. At these advanced stages of heart failure, a collaborative approach with a cardiovascular specialist is recommended. The treatment recommendations are detailed in current 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines for the management of heart failure (12) .

Glucose-Lowering Medications and Heart Failure: Discussion of Heart Failure Outcomes

Data on the effects of glucose-lowering agents on heart failure outcomes have demonstrated that thiazolidinediones have a strong and consistent relationship with increased risk of heart failure (286) (287) (288) . Therefore, thiazolidinedione use should be avoided in people with symptomatic heart failure. Restrictions to use of metformin in people with medically treated heart failure were removed by the FDA in 2006 (289) .

Observational studies of people with type 2 diabetes and heart failure suggest that metformin users have better outcomes than individuals treated with other antihyperglycemic agents (290); however, no randomized trial of metformin therapy has been conducted in people with heart failure. Metformin may be used for the management of hyperglycemia in people with stable heart failure as long as kidney function remains within the recommended range for use (291) .

Studies examining the relationship between DPP-4 inhibitors and heart failure have had mixed results. The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) study showed that individuals treated with the DPP-4 inhibitor saxagliptin were more likely to be hospitalized for heart failure than those given placebo (3.5% vs. 2.8%, respectively) (292). However, three other cardiovascular outcomes trials-Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) (293) , Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) (294) , and the Cardiovascular and Renal Microvascular Outcome Study With Linagliptin (CARMELINA) (295)-did not find a significant increase in risk of heart failure hospitalization with DPP-4 inhibitor use compared with placebo. No increased risk of heart failure hospitalization has been identified in the cardiovascular outcomes trials of the GLP-1 RAs lixisenatide, liraglutide, semaglutide, exenatide once weekly, albiglutide, or dulaglutide compared with placebo (261, 264, 265, 296, 297) .

SGLT2 inhibitors reduce the incidence of heart failure and improve heart failurerelated outcomes, including hospitalization for heart failure and heart failure-related symptoms, in people with diabetes with preserved or reduced ejection fraction (250, (255) (256) (257) (298) (299) (300) (301) (302) (303) (304) (305) (306) . The results of these clinical trials have been extensively outlined in the 2024 American Diabetes Association "Standards of Care in Diabetes" (307) . Briefly, in the EMPA-REG OUTCOME trial, the addition of empagliflozin to standard care led to a significant 35% reduction in hospitalization for heart failure compared with placebo (255) . Similarly, in CANVAS and DECLARE-TIMI 58, there were 33% and 27% reductions, respectively, in hospitalization for heart failure with SGLT2 inhibitor use versus placebo (256, 258) . Additional data from the CREDENCE trial with canagliflozin showed a 39% reduction in hospitalization for heart failure and a 31% reduction in the composite of cardiovascular death or hospitalization for heart failure, in a population with CKD and albuminuria (UACR > 300-5,000 mg/g) (257) .

The DAPA-HF trial specifically evaluated the effects of dapagliflozin on the primary outcome of a composite of worsening heart failure or cardiovascular death in individuals with New York Heart Association (NYHA) class II, III, or IV heart failure and an ejection fraction of 40% or less (299, 307) . Dapagliflozin treatment had a lower risk of the primary outcome (HR 0.74 [95% CI 0.65-0.85]), lower risk of first worsening heart failure event (HR 0.70 [95% CI 0.59-0.83]), and lower risk of cardiovascular death (HR 0.82 [95% CI 0.69-0.98]) compared with placebo. The effect of dapagliflozin on the primary outcome was consistent regardless of the presence or absence of type 2 diabetes (299). Similar results were obtained in clinical trials with empagliflozin (303) . In Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved), the primary outcome of cardiovascular death or hospitalization for heart failure was reduced in adults with NYHA functional class I-IV and chronic HFpEF (LVEF > 40%), extending the previously seen benefit in people with heart failure to those with preserved ejection fraction irrespective of the presence of type 2 diabetes (250). A similar benefit for heart failure outcomes was seen in the Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial for dapagliflozin in people with mildly reduced or preserved ejection fraction (302) . In addition, a large meta-analysis (308) including the EMPEROR-Reduced, EMPEROR-Preserved, DAPA-HF, DELIVER, and the Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF) trials included 21,947 individuals and demonstrated reduced risk for the composite of cardiovascular death or hospitalization for heart failure, cardiovascular death, first hospitalization for heart failure, and all-cause mortality. The findings on the studied end points were consistent in both trials of heart failure with mildly reduced or preserved ejection fraction and in all five trials combined. In addition to the hospitalization and mortality benefit in people with heart failure, SGLT2 inhibitors improve clinical stability and functional status in individuals with heart failure (301, (304) (305) (306) . Collectively, these studies indicate that SGLT2 inhibitors reduce the risk for heart failure hospitalization and cardiovascular death in a wide range of people with heart failure. Therefore, in people with type 2 diabetes and established HFpEF or HFrEF, an SGLT2 inhibitor with proven benefit in this population is recommended to reduce the risk of worsening heart failure and cardiovascular death. In addition, an SGLT2 inhibitor is recommended in this population to improve symptoms, physical limitations, and quality of life.

Sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, was recently approved by the FDA to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure in people with heart failure or type 2 diabetes, CKD, and other cardiovascular risk factors. This drug is distinct from other SGLT inhibitors, as it lowers glucose via delayed glucose absorption in the gut via inhibition of the cotransporter SGLT1 in addition to increasing urinary glucose excretion; however, it is not currently approved by the FDA for glycemic management of type 1 or type 2 diabetes. Sotagliflozin was evaluated in the SCORED trial (284) , which was ended early due to lack of funding, and examined the safety and efficacy of sotagliflozin in people with type 2 diabetes and CKD and risks for cardiovascular disease. Changes to the prespecified primary end points were made prior to unblinding to accommodate a lower-thananticipated number of end point events. The primary end point of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure was reduced with sotagliflozin. In the SOLOIST trial, sotagliflozin initiated during or shortly after hospitalization in people with diabetes also reduced the risk for the primary end point of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure (309) . The trial was originally also intended to evaluate the effects of SGLT inhibition in people with HFpEF, and ultimately no evidence of heterogeneity of treatment effect by ejection fraction was noted. However, the relatively small percentage of such individuals enrolled (only 21% of participants had ejection fraction > 50%) and the early termination of the trial limited the ability to determine the effects of sotagliflozin in HFpEF specifically (309) .

One concern with expanded use of SGLT inhibition is the infrequent but serious risk of diabetic ketoacidosis, including the atypical presentation of euglycemic ketoacidosis. There are multiple proposed pathways through which SGLT inhibition results in ketosis (increased b-hydroxybutyrate and acetoacetate), such as increased production due to reduction in insulin doses, increases in glucagon levels leading to increased lipolysis and ketone production, and decreased renal clearance of ketones (310, 311) . Thus, the use of SGLT inhibitors (whether for glycemic management or another indication) increases the susceptibility to diabetic ketoacidosis, particularly when other risk factors or situations occur (including, but not limited to, insulin pump malfunctions, significant reduction in insulin doses, and nutritional intake plans with prolonged periods of fasting or carbohydrate restriction). Although there were low rates of ketoacidosis in the cardiovascular and heart failure outcomes trials evaluating SGLT inhibition, these studies excluded individuals with type 1 diabetes and/or recent history of diabetic ketoacidosis (309, 312) . To decrease the risk of ketoacidosis when using SGLT inhibition in people with type 1 diabetes, it is recommended that clinicians assess the underlying susceptibility; provide education regarding the risks, symptoms, and prevention strategies; and prescribe home monitoring supplies for b-hydroxybutyrate (311, 313) . Use of these processes may have contributed to the lower rates of ketoacidosis seen in some of the studies of these agents for adjunctive glycemic management in people with type 1 diabetes (314-316) compared with those that did not include preventative strategies (310, 317) . Reassessment of susceptibility, education, and provision of monitoring supplies should reoccur throughout the duration of SGLT inhibitor treatment, particularly as preventative strategies and monitoring can minimize, but not eliminate, the risk of ketoacidosis in those who are susceptible (318, 319) .

Selection of Glucose-Lowering Medications for People With Chronic Kidney Disease

For people with type 2 diabetes and established CKD, special considerations for the selection of glucose-lowering medications include limitations to available medications when eGFR is diminished and a desire to mitigate risks of CKD progression, CVD, and hypoglycemia (101, 102) . Medication dosing may require modification with eGFR < 60 mL/min/ 1.73 m 2 (1). Figure 11 .2 shows the American Diabetes Association and KDIGO consensus recommendation algorithm for medications in people with diabetes and CKD.

The FDA revised its guidance for the use of metformin in CKD in 2016 (103) , recommending use of eGFR instead of serum creatinine to guide treatment and expanding the pool of people with kidney disease for whom metformin treatment should be considered. The revised FDA guidance states that 1) metformin is contraindicated in individuals with an eGFR < 30 mL/min/1.73 m 2 , 2) eGFR should be monitored while taking metformin, 3) the benefits and risks of continuing treatment should be reassessed when eGFR falls to < 45 mL/min/1.73 m 2 (104,105), 4) metformin should not be initiated for individuals with an eGFR < 45 mL/min/1.73 m 2 , and 5) metformin should be temporarily discontinued at the time of or before iodinated contrast imaging procedures in individuals with eGFR 30-60 mL/min/1.73 m 2 .

A number of recent studies have shown cardiovascular protection from SGLT2 inhibitors and GLP-1 RAs as well as kidney protection from SGLT2 inhibitors and from GLP-1 RAs. Selection of which glucose-lowering medications to use should be based on the usual criteria of an individual's risks (cardiovascular and kidney in addition to glucose management) as well as considerations of effects on weight, other adverse effects, individual preferences, and cost.

SGLT2 inhibitors are recommended for people with eGFR $20 mL/min/1.73 m 2 and type 2 diabetes, as they slow CKD progression and reduce heart failure risk independent of glucose management (106) . GLP-1 RAs are suggested for cardiovascular risk reduction if such risk is a predominant problem, as they reduce risks of CVD events and hypoglycemia and slow progression of CKD (100, (107) (108) (109) (110) .

A number of large cardiovascular outcomes trials in people with type 2 diabetes ‡ Figure 11.2-Holistic approach for improving outcomes in people with diabetes and CKD. Icons presented indicate the following benefits: BP cuff, BP lowering; glucose meter, glucose lowering; heart, cardioprotection; kidney, kidney protection; scale, weight management. eGFR is presented in units of mL/min/1.73 m 2 . *ACEi or ARB (at maximal tolerated doses) should be first-line therapy for hypertension when albuminuria is present. Otherwise, dihydropyridine calcium channel blocker or diuretic can also be considered; all three classes are often needed to attain BP targets. †Finerenone is currently the only ns-MRA with proven clinical kidney and cardiovascular benefits. ‡Semaglutide can be used as another first-line agent for people with CKD. ACEi, angiotensin-converting enzyme inhibitor; ACR, albumin-to creatinine ratio; ARB, angiotensin receptor blocker; ASCVD, atherosclerotic cardiovascular disease; BP, blood pressure; CCB, calcium channel blocker; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HTN, hypertension; MRA, mineralocorticoid receptor antagonist; ns-MRA, nonsteroidal mineralocorticoid receptor antagonist; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; RAS, renin-angiotensin system; SGLT2i, sodium-glucose cotransporter 2 inhibitor; T1D, type 1 diabetes; T2D, type 2 diabetes. Adapted from de Boer et al. ( with a mean albuminuria level of > 900 mg/day), had a primary composite end point of ESKD, doubling of serum creatinine, or renal or cardiovascular death (29, 112) . It was stopped early due to positive efficacy and showed a 32% risk reduction for development of ESKD over control (29) . Additionally, the development of the primary end point, which included dialysis for $30 days, kidney transplantation or eGFR < 15 mL/min/1.73 m 2 sustained for $30 days by central laboratory assessment, doubling from the baseline serum creatinine average sustained for $30 days by central laboratory assessment, or renal death or cardiovascular death, was reduced by 30%. This benefit was on background ACE inhibitor or ARB therapy in > 99% of the participants (29) . Moreover, in this advanced CKD group, there were clear benefits on cardiovascular outcomes demonstrating a 31% reduction in cardiovascular death or heart failure hospitalization and a 20% reduction in cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (29, 110, 113) .

A second trial in advanced CKD in people with diabetes was the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) study (114) . This trial examined a cohort similar to that in CREDENCE except 67.5% of the participants had type 2 diabetes and CKD (the other one-third had CKD without type 2 diabetes), and the end points were slightly different. The primary outcome was time to the first occurrence of any of the components of the composite, including $50% sustained decline in eGFR or reaching ESKD or cardiovascular death, or renal death. Secondary outcome measures included time to the first occurrence of any of the components of the composite kidney outcome ($50% sustained decline in eGFR or reaching ESKD or renal death), time to the first occurrence of either of the components of the cardiovascular composite (cardiovascular death or hospitalization for heart failure), and time to death from any cause. The trial had 4,304 participants with a mean eGFR at baseline of 43.1 ± 12.4 mL/min/1.73 m 2 (range 25-75 mL/min/1.73 m 2 ) and a median UACR of 949 mg/g (range 200-5,000 mg/g). There was a significant benefit by dapagliflozin for the primary end point (hazard ratio [HR] 0.61 [95% CI 0.51-0.72] ; P < 0.001) (114) . The HR for the kidney composite of a sustained decline in eGFR of $50%, ESKD, or death from renal causes was 0.56 (95% CI 0.45-0.68; P < 0.001). The HR for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI 0.55-0.92; P = 0.009). Finally, all-cause mortality was decreased in the dapagliflozin group compared with the placebo group (P < 0.004).

The most recently published clinical trial was EMPA-KIDNEY (Study of Heart and Kidney Protection with Empagliflozin) (115) . This study enrolled participants with kidney disease with an eGFR of at least 20 but less than 45 mL/min/1.73 m 2 or who had an eGFR of at least 45 but less than 90 mL/min/1.73 m 2 with a UACR of at least 200 mg/g creatinine. Approximately one-half of the 6,609 participants had diabetes. The empagliflozintreated participants had lower risk of progression of kidney disease and lower risk of death from cardiovascular causes (HR 0.72 [95% CI 0.64-0.82]; P < 0.001).

With respect to cardiovascular outcomes, SGLT2 inhibitors have demonstrated reduced risk of heart failure hospitalizations and some also demonstrated cardiovascular risk reduction. GLP-1 RAs have clearly demonstrated cardiovascular benefits. (See Section 10, "Cardiovascular Disease and Risk Management," for further detailed discussion.)

Of note, while the glucose-lowering effects of SGLT2 inhibitors are blunted with eGFR < 45 mL/min/1.73 m 2 , the renal and cardiovascular benefits were still seen at eGFR levels as low as 20 mL/min/1.73 m 2 even with no significant change in glucose (29, 31, 52, 63, 98, 111, (114) (115) (116) . Most participants with CKD in these trials also had diagnosed atherosclerotic cardiovascular disease (ASCVD) at baseline, although 28% of CANVAS participants with CKD did not have diagnosed ASCVD (32) .

Based on evidence from the CREDENCE, DAPA-CKD, and EMPA-KIDNEY trials, as well as secondary analyses of cardiovascular outcomes trials with SGLT2 inhibitors, cardiovascular and renal events are reduced with SGLT2 inhibitor use in individuals with an eGFR of 20 mL/min/1.73 m 2 , independent of glucose-lowering effects (110, 113) .

The recently published FLOW study demonstrated that the GLP-1 RA semaglutide had reno-protective effects in people with CKD (100) . The study enrolled 3,533 participants with significant kidney disease defined by level of eGFR and/or by level of albuminuria (of note, all participants had an albuminuria level of at least 100 mg/g). The primary outcome was defined as the first major kidney disease event (onset of > 50% in eGFR, onset of persistent eGFR of < 15 mL/min/1.73 m 2 , initiation of dialysis or transplant, renal death, and cardiovascular death). The study was stopped early due to reaching a prespecified outcome. There was a 24% lower HR for those taking semaglutide compared with the placebo group. Of note, cardiovascular deaths comprised about 38% of the events. When the cardiovascular deaths are removed from the analysis, the HR for kidney specific events was 21% lower in those taking semaglutide. Thus, the study supports a beneficial effect of semaglutide in slowing decline in kidney function as well as being cardioprotective in people with CKD and type 2 diabetes. Of note, the participants who took semaglutide had lower A1C, lower blood pressure, and more weight loss-all of which are beneficial for slowing decline in kidney function and reducing cardiovascular adverse events. Whether this beneficial combination of effects was the primary cause for the renoprotective outcomes or whether there is a unique reno-protective effect of semaglutide remains to be determined.

Adverse event profiles of these agents also must be considered. Please refer to Table 9 .2 for medication-specific factors, including adverse event information, for these agents. Additional clinical trials focusing on CKD and cardiovascular outcomes in people with CKD are ongoing and will be reported in the next few years.

For people with type 2 diabetes and CKD, the selection of specific agents may depend on comorbidity and CKD stage. SGLT2 inhibitors are recommended for individuals at high risk of CKD progression (i.e., with albuminuria or a history of documented eGFR loss) (Fig. 9 .3). For people with type 2 diabetes and CKD, use of an SGLT2 inhibitor in individuals with eGFR $20 mL/min/1.73 m 2 is recommended to reduce CKD progression and cardiovascular events. The reason for the limit of eGFR is as follows. The major clinical trials for SGLT2 inhibitors that showed benefit for CKD in people with diabetes are CREDENCE, DAPA-CKD, and EMPA-KIDNEY. CREDENCE enrollment criteria included eGFR > 30 mL/min/1.73 m 2 and UACR > 300 mg/g (29, 110) . DAPA-CKD enrolled individuals with eGFR > 25 mL/min/1.73 m 2 and UACR > 200 mg/g. Subgroup analyses from DAPA-CKD (117) and analyses from the EMPEROR heart failure trials suggest that SGLT2 inhibitors are safe and effective at eGFR levels of > 20 mL/min/1.73 m 2 . The Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved) enrolled 5,998 participants (118) , and the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure and a Reduced Ejection Fraction (EMPEROR-Reduced) enrolled 3,730 participants (119) ; enrollment criteria included eGFR > 60 mL/min/1.73 m 2 , but efficacy was seen at eGFR > 20 mL/min/ 1.73 m 2 in people with heart failure. Most recently, the EMPA-KIDNEY trial showed efficacy in participants with eGFR as low as 20 mL/min/1.73 m 2 (115) . Hence, the new recommendation is to use SGLT2 inhibitors in individuals with eGFR as low as 20 mL/min/1.73 m 2 . In addition, the DE-CLARE-TIMI 58 trial suggested effectiveness in participants with normal urinary albumin levels (120) . In sum, for people with type 2 diabetes and CKD, use of an SGLT2 inhibitor is recommended to reduce CKD progression and cardiovascular events in people with an eGFR $20 mL/min/ 1.73 m 2 .

Of note, GLP-1 RAs may also be used at low eGFR for cardiovascular protection but may require dose adjustment (121) .

Renal and Cardiovascular Outcomes of Mineralocorticoid Receptor

Antagonists in Chronic Kidney Disease MRAs historically have not been well studied in people with diabetes and CKD because of the risk of hyperkalemia (122, 123) . However, data that do exist suggest sustained benefit on albuminuria reduction. There are two different classes of MRAs, steroidal and nonsteroidal, with one group not extrapolatable to the other (124) . Late in 2020, the results of the first of two trials, the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) trial, which examined the kidney effects of finerenone, demonstrated a significant reduction in CKD progression and cardiovascular events in people with diabetes and advanced CKD (33, 125) . This trial had a primary end point of time to first occurrence of the composite end point of onset of kidney failure, a sustained decrease of eGFR > 40% from baseline over at least 4 weeks, or renal death. A prespecified secondary outcome was time to first occurrence of the composite end point of cardiovascular death or nonfatal cardiovascular events (myocardial infarction, stroke, or hospitalization for heart failure). Other secondary outcomes included all-cause mortality, time to allcause hospitalizations, and change in UACR from baseline to month 4, and time to first occurrence of the following composite end point: onset of kidney failure, a sustained decrease in eGFR of $57% from baseline over at least 4 weeks, or renal death.

The double-blind, placebo-controlled trial randomized 5,734 people with CKD and type 2 diabetes to receive finerenone, a nonsteroidal MRA, or placebo. Eligible participants had a UACR of 30 to < 300 mg/g, an eGFR of 25 to < 60 mL/min/ 1.73 m 2 , and diabetic retinopathy, or a UACR of 300-5,000 mg/g and an eGFR of 25 to < 75 mL/min/1.73 m 2 . The potassium level had to be #4.8 mmol/L. The mean age of participants was 65.6 years, and 30% were female. The mean eGFR was 44.3 mL/min/1.73 m 2 , and the mean albuminuria was 852 mg/g (interquartile range 446-1,634 mg/g). The primary end point was reduced with finerenone compared with placebo (HR 0.82 [95% CI 0.73-0.93]; P = 0.001), as was the key secondary composite of cardiovascular outcomes (HR 0.86 [95% CI 0.75-0.99]; P = 0.03). Hyperkalemia resulted in 2.3% discontinuation in the study group compared with 0.9% in the placebo group. However, the study was completed, and there were no deaths related to hyperkalemia. Of note, 4.5% of the total group were being treated with SGLT2 inhibitors.

The Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial assessed the safety and efficacy of finerenone in reducing cardiovascular events among people with type 2 diabetes and CKD with elevated UACR (30 to < 300 mg/g creatinine) and eGFR 25-90 mL/min/1.73 m 2 (126) . The potassium level had to be #4.8 mmol/L The study randomized eligible subjects to either finerenone (n = 3,686) or placebo (n = 3,666). Participants with an eGFR of 25-60 mL/min/1.73 m 2 at the screening visit received an initial dose at baseline of 10 mg once daily, and if eGFR at screening was $60 mL/min/ 1.73 m 2 , the initial dose was 20 mg once daily. An increase in the dose from 10 to 20 mg once daily was encouraged after 1 month, provided the serum potassium level was #4.8 mmol/L and eGFR was stable. The mean age of participants was 64.1 years (31% were female), and the median follow-up duration was 3.4 years. The median A1C was 7.7%, the mean systolic blood pressure was 136 mmHg, and the mean GFR was 67.8 mL/min/1.73 m 2 . People with heart failure with a reduced ejection fraction and uncontrolled hypertension were excluded. The primary composite outcome was cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure. The finerenone group showed a 13% reduction in the primary end point compared with the placebo group (12.4% vs. 14.2%; HR 0.87 [95% CI 0.76-0.98]; P = 0.03). This benefit was primarily driven by a reduction in heart failure hospitalizations: 3.2% vs. 4.4% in the placebo group (HR 0.71 [95% CI 0.56-0.90]).

Of the secondary outcomes, the most noteworthy was a 36% reduction in ESKD: 0.9% vs. 1.3% in the placebo group (HR 0.64 [95% CI 0.41-0.995]). There was a higher incidence of hyperkalemia in the finerenone group, 10.8% vs. 5.3%, although only 1.2% of the 3,686 individuals on finerenone stopped the study due to hyperkalemia.

The FIDELITY prespecified pooled efficacy and safety analysis incorporated individuals from both the FIGARO-DKD and FIDELIO-DKD trials (N = 13,171) to allow for evaluation across the spectrum of severity of CKD, since the populations were different (with a slight overlap) and the study designs were similar (127) . The analysis showed a 14% reduction in composite cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure for finerenone vs. placebo (12.7% vs. 14.4%; HR 0.86 [95% CI 0.78-0.95]; P = 0.0018).

It also demonstrated a 23% reduction in the composite kidney outcome, consisting of sustained $57% decrease in eGFR from baseline over $4 weeks, or renal death, for finerenone vs. placebo (5.5% vs. 7.1%; HR 0.77 [95% CI 0.670.88]; P = 0.0002).

The pooled FIDELITY trial analysis confirms and strengthens the positive cardiovascular and kidney outcomes with finerenone across the spectrum of CKD, irrespective of baseline ASCVD history (with the exclusion of those with heart failure with reduced ejection fraction).

Of note, there has not been a direct comparison of MRAs and SGLT2 inhibitors. At this time, they can be used interchangeably or together for the goal of slowing progression of CKD and providing cardiovascular protection. There have also been no studies directly comparing MRAs, SGLT2 inhibitors, and GLP-1 RAs. Health care professionals should use their best judgement as to which medication to prescribe initially and in combination. As noted, all of these studies included participants taking either an ACE inhibitor or an ARB, often at maximally tolerated doses.

REFERRAL TO A NEPHROLOGIST

Health care professionals should consider referral to a nephrologist if the individual with diabetes has continuously rising UACR levels and/or continuously declining eGFR, if there is uncertainty about the etiology of kidney disease, for difficult management issues (anemia, secondary hyperparathyroidism, significant increases in albuminuria despite good blood pressure management, metabolic bone disease, resistant hypertension, or electrolyte disturbances), or when there is advanced kidney disease (eGFR < 30 mL/min/1.73 m 2 ) requiring discussion of renal replacement therapy for ESKD (1) . The threshold for referral may vary depending on the frequency with which a health care professional encounters people with diabetes and kidney disease. Consultation with a nephrologist when stage 4 CKD develops (eGFR < 30 mL/min/1.73 m 2 ) has been found to reduce cost, improve quality of care, and delay dialysis (128) .

However, other specialists and health care professionals should also educate people with diabetes about the progressive nature of CKD, the kidney preservation benefits of proactive treatment of blood pressure and blood glucose, and the potential need for renal replacement therapy. In addition to diabetes duration, factors that increase the risk of, or are associated with, retinopathy include chronic hyperglycemia (2, 3) , nephropathy (4), hypertension (5), and dyslipidemia (6) (7) (8) . Intensive diabetes management with the goal of achieving near-normoglycemia has been shown in large prospective randomized studies to prevent and/or delay the onset and progression of diabetic retinopathy, reduce the need for future ocular surgical procedures, and potentially improve self-reported visual function (2, 6, (9) (10) (11) . A meta-analysis of data from cardiovascular outcomes studies showed no association between glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment and retinopathy per se, except through the association between retinopathy and average A1C reduction at the 3-month and 1-year follow-up. Long-term impact of improved glycemic management on retinopathy was not studied in these trials. However, GLP-1 RAs including liraglutide, semaglutide, and dulaglutide have been shown to be *A complete list of members of the American Diabetes Association Professional Practice Committee can be found at https://doi.org/10.2337/dc25-SINT.

Duality of interest information for each author is available at https://doi.org/10.2337/dc25-SDIS. Suggested citation: American Diabetes Association Professional Practice Committee. 12. Retinopathy, neuropathy, and foot care: Standards of Care in Diabetes-2025. Diabetes Care 2025;48(Suppl. 1): S252-S265 © 2024 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www .diabetesjournals.org/journals/pages/license. 12. RETINOPATHY, NEUROPATHY, AND FOOT CARE associated with a risk of mildly worsening diabetic retinopathy in randomized trials (12, 13) . Further data from clinical studies with longer follow-up purposefully designed for diabetic retinopathy risk assessment, particularly including individuals with established diabetic retinopathy, are needed. Retinopathy status should be assessed when glucose-lowering therapies are intensified, such as those using GLP-1 RAs, since rapid reductions in A1C can be associated with initial worsening of retinopathy (14) . 5 If there is no evidence of retinopathy from one or more annual eye exams and glycemic indicators are within the goal range, then screening every 1-2 years may be considered. If any level of diabetic retinopathy is present, subsequent dilated retinal examinations should be repeated at least annually by an ophthalmologist or optometrist. If retinopathy is progressing or sightthreatening, then examinations by an ophthalmologist will be required more frequently. B 12.6 Programs that use retinal photography with remote reading or the use of U.S. Food and Drug Administrationapproved artificial intelligence algorithms to improve access to diabetic retinopathy screening are appropriate screening strategies for diabetic retinopathy. Such programs need to provide pathways for timely referral for a comprehensive eye examination when indicated. B 12.7 Counsel individuals of childbearing potential with preexisting type 1 or type 2 diabetes who are planning pregnancy or who are pregnant on the risk of development and/or progression of diabetic retinopathy. B 12.8 Individuals with preexisting type 1 or type 2 diabetes should receive an eye exam before pregnancy as well as in the first trimester and may need to be monitored every trimester and for 1 year postpartum as indicated by the degree of retinopathy. B Identifying individuals with diabetesrelated eye disease is important because people with vision-threatening retinopathy may be asymptomatic. Additionally, current therapies can not only prevent vision loss but also help improve vision for many individuals. Prompt diagnosis allows triage of people with diabetes and timely intervention that may prevent vision loss in individuals who are asymptomatic despite advanced diabetes-related eye disease.

Diabetic retinopathy screening should be performed using validated approaches and methodologies. Youth with type 1 or type 2 diabetes are also at risk for complications and need to be screened for diabetic retinopathy (15-17) (see Section 14, "Children and Adolescents"). If diabetic retinopathy is evident on screening, prompt referral to an ophthalmologist is recommended. Subsequent examinations for individuals with type 1 or type 2 diabetes are generally repeated annually for individuals without or with mild retinopathy. Exams every 1-2 years may be cost-effective after one or more normal eye exams. In a population with well-managed type 2 diabetes, there was little risk of development of significant retinopathy within a 3-year interval after a normal examination (18) , and less frequent intervals have been found in simulated modeling to be potentially effective in screening for diabetic retinopathy in individuals without diabetic retinopathy (19) . However, it is important to adjust screening intervals based on the presence of specific risk factors for retinopathy onset and worsening retinopathy. More frequent examinations by the ophthalmologist will be required if retinopathy is progressing or risk factors such as not meeting glycemic goals, advanced retinopathy, or diabetic macular edema are present.

Retinal photography with remote reading by experts has great potential to provide screening services in areas where qualified eye care professionals are not readily available (20) (21) (22) . High-quality fundus photographs can detect most clinically significant diabetic retinopathy. Interpretation of the images should be performed by a trained eye care professional or reading center technician or by artificial intelligence (AI) programs that are U.S. Food and Drug Administration (FDA) approved for this purpose. Retinal photography may also enhance efficiency and reduce costs when the expertise of ophthalmologists can be used for more complex examinations and for treatment (20, 23, 24) . In-person exams are still necessary when the retinal photos are of unacceptable quality and for follow-up if abnormalities are detected. Retinal photos are not a substitute for dilated comprehensive eye exams, which should be performed at least initially and at yearly intervals thereafter or more frequently as recommended by an eye care professional. AI systems that detect more than mild diabetic retinopathy and diabetic macular edema that have been authorized for use by the FDA represent an alternative to traditional screening approaches (25) . Three AI platforms have been approved by the FDA for diabetic retinopathy screening and examination: AEYE diagnostic screening technology, or AEYE-DS (AEYE Health); EyeArt AI screening system (Eyenuk); and Lumi-neticsCore, formerly IDx-DR (Digital Diagnostics). These services are covered by most insurance plans. Prospective multicenter clinical trials on diagnostic accuracy have been published for each platform (26) . However, the benefits and optimal utilization of this type of screening have yet to be fully determined. Results of all screening eye examinations should be documented and transmitted to the referring health care professional.

Type 1 Diabetes

Because retinopathy is estimated to take at least 5 years to develop after the onset of hyperglycemia, people with type 1 diabetes should have an initial dilated and comprehensive eye examination within 5 years after the diagnosis of diabetes (19) .

Type 2 Diabetes

People with type 2 diabetes who may have had undiagnosed diabetes for years and have a significant risk of prevalent diabetic retinopathy at the time of diagnosis should have an initial dilated and comprehensive eye examination at the time of diagnosis.

Pregnancy

Individuals who develop gestational diabetes mellitus do not require eye examinations during pregnancy, since they do not appear to be at increased risk of developing diabetic retinopathy during pregnancy (27) . However, individuals of childbearing potential with preexisting type 1 or type 2 diabetes who are planning pregnancy or who have become pregnant should be counseled on the baseline prevalence and risk of development and/or progression of diabetic retinopathy. In a systematic review and meta-analysis of 18 observational studies of pregnant individuals with preexisting type 1 or type 2 diabetes, the prevalence of any diabetic retinopathy and proliferative diabetic retinopathy (PDR) in early pregnancy was 52.3% and 6.1%, respectively. The pooled progression rate per 100 pregnancies for new diabetic retinopathy development was 15.0 (95% CI 9.9-20.8), worsened nonproliferative diabetic retinopathy was 31.0 (95% CI 23.2-39.2), pooled sight-threatening progression rate from nonproliferative diabetic retinopathy to PDR was 6.3 (95% CI 3.3-10.0), and worsened PDR was 37.0 (95% CI 21.2-54.0), demonstrating that close follow-up should be maintained during pregnancy to prevent vision loss (28) . In addition, rapid implementation of intensive glycemic management in the setting of retinopathy is associated with early worsening of retinopathy, and these individuals may also benefit from more frequent follow-up initially (29) .

A systematic review and meta-analysis and a controlled prospective study demonstrate that pregnancy in individuals with type 1 diabetes may aggravate retinopathy and threaten vision, especially when glycemic management is suboptimal or retinopathy severity is advanced at the time of conception (28, 29) . Laser photocoagulation surgery can minimize the risk of vision loss during pregnancy for individuals with high-risk PDR or center-involved diabetic macular edema (29) . The use of anti-vascular endothelial growth factor (anti-VEGF) injections in pregnant individuals may be justified only if the potential benefit outweighs the potential risk to the fetus and only if clearly indicated. Current anti-VEGF medications have been assigned to pregnancy category C by the FDA (animal studies have revealed evidence of embryo-fetal toxicity, but there are no controlled data in human pregnancy), and caution should be used in pregnant individuals with diabetes because of theoretical risks to the vasculature of the developing fetus. Treatment Recommendations 12.9 Promptly refer individuals with any level of diabetic macular edema, moderate or worse nonproliferative diabetic retinopathy (a precursor of proliferative diabetic retinopathy [PDR]), or any PDR to an ophthalmologist who is knowledgeable and experienced in the management of diabetic retinopathy. A 12.10 Panretinal laser photocoagulation therapy is indicated to reduce the risk of vision loss in individuals with high-risk PDR and, in some cases, severe nonproliferative diabetic retinopathy. A 12.11 Intravitreous injections of antivascular endothelial growth factor (anti-VEGF) are a reasonable alternative to traditional panretinal laser photocoagulation for some individuals with PDR and also reduce the risk of vision loss in these individuals. A 12.12 Intravitreous injections of anti-VEGF are indicated as first-line treatment for most eyes with diabetic macular edema that involves the foveal center and impairs vision acuity. A 12.13 Macular focal/grid photocoagulation and intravitreal injections of corticosteroid are reasonable treatments in eyes with persistent diabetic macular edema despite previous anti-VEGF therapy or eyes that are not candidates for this first-line approach. A 12.14 The presence of retinopathy is not a contraindication to aspirin therapy for cardioprotection, as aspirin does not increase the risk of retinal hemorrhage. A Two of the main motivations for screening for diabetic retinopathy are to prevent loss of vision and to intervene with treatment when vision loss can be prevented or reversed.

Photocoagulation Surgery

Two large trials, the Diabetic Retinopathy Study (DRS) in individuals with PDR and the Early Treatment Diabetic Retinopathy Study (ETDRS) in individuals with macular edema, provide the strongest support for the therapeutic benefits of laser photocoagulation surgery. The DRS (30) showed that panretinal photocoagulation surgery reduced the risk of severe vision loss from PDR from 15.9% in untreated eyes to 6.4% in treated eyes with the greatest benefit ratio in those with more advanced baseline disease (disc neovascularization or vitreous hemorrhage). Later, the ETDRS verified the benefits of panretinal photocoagulation for high-risk PDR and in older-onset individuals with severe nonproliferative diabetic retinopathy or less-than-high-risk PDR (31) . Panretinal laser photocoagulation is still commonly used to manage proliferative diabetic retinopathy. A macular focal/grid laser photocoagulation technique was shown in the ETDRS to be effective in treating eyes with clinically significant macular edema from diabetes (31) , but this is now largely considered a second-line treatment for diabetic macular edema.

Anti-VEGF Treatment

Data from the DRCR Retina Network (formerly the Diabetic Retinopathy Clinical Research Network) and others demonstrate that intravitreal injections of anti-VEGF agents are effective at regressing proliferative disease and lead to noninferior or superior visual acuity outcomes compared with panretinal laser over 2 years of follow-up (32, 33) . In addition, it was observed that individuals treated with ranibizumab tended to have less peripheral visual field loss, fewer vitrectomy surgeries for secondary complications from their proliferative disease, and a lower risk of developing diabetic macular edema (32) . However, a potential drawback in using anti-VEGF therapy to manage proliferative disease is that individuals were required to have a greater number of visits and received a greater number of treatments than is typically required for management by panretinal laser, which may not be optimal for some individuals. Additionally, unlike panretinal laser, anti-VEGF therapy requires participation in scheduled follow-up. Individuals with nonintentional lapses in treatment are at risk for worse visual acuity and anatomic outcomes (34) . The FDA has approved aflibercept and ranibizumab for the treatment of eyes with diabetic retinopathy. Other emerging therapies for retinopathy that may use sustained intravitreal delivery of pharmacologic agents are currently under investigation. Anti-VEGF treatment of eyes with nonproliferative diabetic retinopathy has been demonstrated to reduce subsequent development of retinal neovascularization and diabetic macular edema but has not been shown to improve visual outcomes over 2 years of therapy and therefore has not been widely adopted for this indication (35) .

While the ETDRS (31) established the benefit of focal laser photocoagulation surgery in eyes with clinically significant macular edema (defined as retinal edema located at or threatening the macular center), current data from well-designed clinical trials demonstrate that intravitreal anti-VEGF agents provide more effective treatment for center-involved diabetic macular edema than monotherapy with laser (36, 37) . With ranibizumab and aflibercept, most individuals require administration of intravitreal therapy with anti-VEGF agents every 4-8 weeks during the first 12 months of treatment, with fewer injections needed in subsequent years to maintain remission from center-involved diabetic macular edema. Five anti-VEGF agents currently are used to treat eyes with center-involved diabetic macular edema, namely, bevacizumab, ranibizumab, aflibercept (2 mg and 8 mg), brolucizumab, and faricimab (1) , and a comparative effectiveness study demonstrated that aflibercept provides vision outcomes superior to those of bevacizumab when eyes have moderate visual impairment (vision of 20/50 or worse) from diabetic macular edema (38) . For eyes that have good vision (20/25 or better) despite diabetic macular edema, close monitoring with initiation of anti-VEGF therapy if vision worsens provides 2-year vision outcomes similar to those of immediate initiation of anti-VEGF therapy (39) .

Eyes that have persistent diabetic macular edema despite anti-VEGF treatment may benefit from macular laser photocoagulation or intravitreal therapy with corticosteroids (40) . Both of these therapies are also reasonable first-line approaches for individuals who are not candidates for anti-VEGF treatment due to systemic considerations such as pregnancy.

Adjunctive Therapy

Lowering blood pressure has been shown to decrease retinopathy progression, although strict goals (systolic blood pressure < 120 mmHg) do not impart additional benefit (6) . In individuals with dyslipidemia, retinopathy progression may be slowed by the addition of fenofibrate, particularly with early diabetic retinopathy at baseline (41) (42) (43) . Several studies have shown an association with GLP-1 RA and lower intraocular pressure (44) as well as a reduced risk of glaucoma (45) (46) (47) .

Visual Rehabilitation Recommendations 12.15 People who experience vision loss from diabetes should be counseled on the availability and scope of vision rehabilitation care and provided, or referred for, a comprehensive evaluation of their visual impairment by a practitioner experienced in vision rehabilitation. E 12.16 People with vision loss from diabetes should receive educational materials and resources for eye care support in addition to self-management education (e.g., glycemic management and hypoglycemia awareness). E In the U.S., 12% of adults with diabetes have some level of vision impairment (48) . They may have difficulty reaching their diabetes treatment goals and performing many other activities of daily living, which can lead to depression, anxiety, social isolation, and difficulties at home, in the workplace, or at school (49) .

People with diabetes are at increased risk of chronic vision loss, subsequent functional decline, and resulting disability. Vision impairment has physical, psychological, behavioral, and social consequences that affect people with diabetes, their families, friends, and caregivers. Health care professionals and stakeholders may not be aware of the overall impact of vision loss on an individual's health and well-being. People with diabetic vision loss should be evaluated to determine their potential to benefit from comprehensive vision restoration. Vision rehabilitation can help people with vision loss achieve maximum function, independence, and quality of life. NEUROPATHY Screening Recommendations 12.17 All people with diabetes should be assessed for diabetic peripheral neuropathy starting at diagnosis of type 2 diabetes and 5 years after the diagnosis of type 1 diabetes and at least annually thereafter. B 12.18 Assessment for distal symmetric polyneuropathy should include a careful history and assessment of either temperature or pinprick sensation (small-fiber function) and vibration sensation using a 128-Hz tuning fork (for large-fiber function). All people with diabetes should have annual 10-g monofilament testing to identify feet at risk for ulceration and amputation. B 12.19 Symptoms and signs of autonomic neuropathy should be assessed in people with diabetes starting at diagnosis of type 2 diabetes and 5 years after the diagnosis of type 1 diabetes, and at least annually thereafter, and with evidence of other microvascular complications, particularly kidney disease and diabetic peripheral neuropathy. Screening can include asking about orthostatic dizziness, syncope, early satiety, erectile dysfunction, changes in sweating patterns, or dry cracked skin in the extremities. Signs of autonomic neuropathy include orthostatic hypotension, a resting tachycardia, or evidence of peripheral dryness or cracking of skin. E Diabetic neuropathies are a heterogeneous group of disorders with diverse clinical manifestations. The early recognition and appropriate management of neuropathy in people with diabetes is important. Points to be aware of include the following:

1. Diabetic neuropathy is a diagnosis of exclusion. Non-diabetic neuropathies may be present in people with diabetes and may be treatable. 2. Up to 50% of diabetic peripheral neuropathy may be asymptomatic. If not recognized and if preventive foot care is not implemented, people with diabetes are at risk for injuries as well as diabetic foot ulcers (DFUs) and amputations. 3. Recognition and treatment of autonomic neuropathy may improve symptoms, reduce sequelae, and improve quality of life.

Specific treatment to reverse the underlying nerve damage is currently not available. Glycemic management can effectively prevent diabetic peripheral neuropathy (DPN) and cardiovascular autonomic neuropathy (CAN) in type 1 diabetes (50, 51) and may modestly slow their progression in type 2 diabetes ( 52 ), but it does not reverse neuronal loss. Treatments of other modifiable risk factors (including obesity, lipids, and blood pressure) can aid in prevention of DPN progression in type 2 diabetes and may reduce disease progression in type 1 diabetes (53) (54) (55) (56) . Therapeutic strategies (pharmacologic and nonpharmacologic) for the relief of painful DPN and symptoms of autonomic neuropathy can potentially reduce pain (57) and improve quality of life.

Diabetic Peripheral Neuropathy

Individuals with a type 1 diabetes duration $5 years and all individuals with type 2 diabetes should be assessed annually for DPN using medical history and simple clinical tests (57) . Symptoms vary according to the class of sensory fibers involved. The most common early symptoms are induced by the involvement of small fibers and include pain and dysesthesia (unpleasant sensations of burning and tingling). The involvement of large fibers may cause balance issues, numbness, and loss of protective sensation (LOPS). LOPS indicates the presence of distal sensory polyneuropathy and is a risk factor for diabetic foot ulceration. The following clinical tests may be used to assess small-and large-fiber function and protective sensation:

1. Small-fiber function: pinprick and temperature sensation. 2. Large-fiber function: lower-extremity reflexes, vibration perception, and 10-g monofilament. 3. Protective sensation: 10-g monofilament.

These tests not only screen for the presence of dysfunction but also predict future risk of complications. Electrophysiological testing or referral to a neurologist is rarely needed, except in situations where the clinical features are atypical (acute or subacute presentation, non-length dependent, asymmetric, and/or motor involvement) or the diagnosis is unclear.

Diabetes management in older adults requires regular assessment of medical, psychological, functional, and social domains. When assessing older adults with diabetes, it is important to accurately categorize the type of diabetes as well as other factors, including diabetes duration, the presence of complications, and treatmentrelated concerns, such as fear of hypoglycemia. Screening for diabetes complications in older adults should be individualized and periodically revisited, as the results of screening tests may impact treatment goals and therapeutic approaches (3) (4) (5) . Older adults with diabetes have higher rates of functional disability, accelerated muscle loss, mobility impairment, frailty, and coexisting illnesses, such as hypertension, chronic kidney disease, coronary heart disease, stroke, and premature death than those without diabetes. At the same time, older adults with diabetes also require greater caregiver support and are at greater risk than other older adults for *A complete list of members of the American Diabetes Association Professional Practice Committee can be found at https://doi.org/10.2337/dc25-SINT.

Duality of interest information for each author is available at https://doi.org/10.2337/dc25-SDIS.

several common geriatric syndromes such as cognitive impairment, depression, urinary incontinence, injurious falls, persistent pain, and frailty as well as polypharmacy (1) . These conditions may impact older adults' diabetes self-management abilities and quality of life if left unaddressed (2, 6, 7) . See Section 4, "Comprehensive Medical Evaluation and Assessment of Comorbidities," for the full range of issues to consider when caring for older adults with diabetes. The Institute for Healthcare Improvement has developed an evidence-based "4Ms" framework for age-friendly health care that is being adopted by many health systems caring for older adults. The key elements of this approach to the care of older adults are Mentation, Medications, Mobility, and What Matters Most (person centered), with the understanding that any one of the components may affect another domain (8) . approach has been conceptualized to address person-specific issues that may be interrelated and affect diabetes management in older individuals in Fig. 13 .1.

The comprehensive assessment described above provides a framework to determine goals and therapeutic approaches (9) (10) (11) , including whether referral for diabetes self-management education is appropriate (when complicating factors arise or when transitions in care occur) or whether the current plan is too complex for the individual's self-management ability or for the care partners providing care (12) . Particular attention should be paid to complications that can develop over short periods of time and/or would significantly impair functional status, such as visual and lower-extremity complications. Please refer to the American Diabetes Association (ADA) consensus report "Diabetes in Older Adults" for details (3) . Older adults with diabetes are at higher risk of cognitive decline and institutionalization (13, 14) . Presentation of cognitive impairment ranges from subtle executive dysfunction to memory loss to overt dementia. People with diabetes have higher incidences of all-cause dementia, Alzheimer disease, and vascular dementia than people without diabetes (15) . Both hyperglycemia and hypoglycemia are associated with a decline in cognitive function (16) (17) (18) , and longer duration of diabetes is associated with worsening cognitive function. A newly recognized clinical entity, diabetesrelated dementia, is emerging as distinct from Alzheimer disease and vascular dementia. Diabetes-related dementia is characterized by a slower progression of dementia, absence of typical neuroimaging findings, advanced age, elevated A1C levels, long duration of diabetes, high frequency of insulin use, frailty, sarcopenia, and dynapenia (loss of muscle strength not caused by neurologic or muscular diseases) (18) . Ongoing studies are evaluating whether lifestyle interventions may help to maintain cognitive function in older adults (19) . However, studies on diabetes prevention or intensive glycemic and blood pressure management have not demonstrated a reduction in cognitive decline (20, 21) . A recent systematic review and meta-analysis showed that glucoselowering drugs, such as thiazolidinediones, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors, have shown small benefits on slowing progression of cognitive decline (22) . Cardiovascular risk factors are also associated with an increased risk of cognitive decline and Recently, the U.S. Food and Drug Administration (FDA) approved two new anti-amyloid monoclonal antibodies for the treatment of early Alzheimer disease (23, 24) . While these drugs lower the amyloid burden in the brain and appear to slow cognitive decline, the slowing is modest and of unclear significance and duration. In addition, a substantial minority of individuals developed imaging abnormalities consistent with brain edema or hemorrhage. Whether these drugs will provide net benefit for older adults with diabetes remains to be determined.

Identifying cognitive impairment early has important implications for diabetes care. The presence of cognitive impairment can make it challenging for health care professionals to help people with diabetes reach individualized glycemic, blood pressure, and lipid goals. Cognitive dysfunction may make it difficult for individuals to perform complex self-care tasks (25) , such as monitoring glucose and administering and adjusting insulin doses. Also, it can hinder their ability to appropriately maintain the timing and nutritional content of their meals. These factors increase risk for hypoglycemia, which, in turn, can worsen cognitive function and have multiple other adverse effects in older individuals with diabetes. When clinicians are providing care for people with cognitive dysfunction, it is critical to simplify care plans and to ascertain and engage the appropriate support structure to assist individuals in all aspects of care.

Older adults with diabetes should be carefully screened and monitored for cognitive impairment (2) . Several simple assessment tools are available to screen for cognitive impairment (25, 26) , such as the Mini-Mental State Examination (27) , Mini-Cog (28) , and the Montreal Cognitive Assessment (29) , which may help to identify individuals requiring neuropsychological evaluation, particularly when dementia is suspected (i.e., in those experiencing memory loss, a decrease in executive function, and declines in their basic and instrumental activities of daily living). Annual screening is indicated for adults 65 years of age or older for early detection of mild cognitive impairment or dementia (4, 30) . Screening for cognitive impairment should also be considered when an individual presents with a significant decline in clinical status due to increased problems with self-care activities and medication management, such as errors in calculating insulin dose, difficulty counting carbohydrates, skipped meals, skipped insulin doses, and difficulty recognizing, preventing, or treating hypoglycemia. People who screen positive for cognitive impairment should receive diagnostic assessment as appropriate, including referral to a behavioral health professional for formal cognitive and neuropsychological evaluation if indicated and feasible (31) . HYPOGLYCEMIA Recommendations 13.4 Ascertain and address episodes of hypoglycemia at routine visits because older adults with diabetes have a greater risk of hypoglycemia, especially when treated with hypoglycemic agents (e.g., sulfonylureas, meglitinides, and insulin). B 13.5 Recommend continuous glucose monitoring (CGM) for older adults with type 1 diabetes to improve glycemic outcomes, reduce hypoglycemia, and reduce treatment burden. A 13.6 Offer CGM for older adults with type 2 diabetes on insulin therapy to improve glycemic outcomes and reduce hypoglycemia. B 13.7 Consider the use of automated insulin delivery systems, A mechanical insulin delivery systems, E and other advanced insulin delivery devices such as connected pens E to reduce risk of hypoglycemia for older adults, based on individual ability and support system. Older adults may be at higher risk of hypoglycemia for many reasons, including irregular meal intake, insulin deficiency necessitating insulin therapy, and worsening kidney function (32) . As described above, older adults have higher rates of unidentified cognitive impairment and dementia, leading to difficulties in performing complex self-care activities (e.g., glucose monitoring and insulin dose adjustment). Cognitive decline has been associated with increased risk of hypoglycemia, and conversely, severe hypoglycemia has been linked to increased risk of dementia (33) (34) (35) . Therefore, as discussed in Recommendation 13.3, it is important to routinely screen older adults for cognitive impairment and dementia and discuss findings with the individuals and their care partners.

People with diabetes and their care partners should be routinely queried about their history of hypoglycemic events, impaired hypoglycemia awareness, and fear of hypoglycemia as discussed in Section 6, "Glycemic Goals and Hypoglycemia." Older adults can also be stratified for future risk for hypoglycemia with validated risk calculators (e.g., Kaiser Hypoglycemia Model for adults with type 2 diabetes) (36) and with consideration of hypoglycemia risk factors (Table 6.5 ). An important step to mitigate hypoglycemia risk is to determine whether the person with diabetes is skipping meals or inadvertently repeating doses of their medications. Glycemic goals and pharmacologic treatments may need to be adjusted to minimize the occurrence of hypoglycemic events (2). This recommendation is supported by results from multiple randomized controlled trials, such as the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and the Veterans Affairs Diabetes Trial (VADT), which showed that intensive treatment protocols aimed to achieve an A1C < 6.0% with complex drug plans significantly increased the risk for hypoglycemia requiring assistance compared with standard treatment (37, 38) . However, these intensive treatment plans included extensive use of insulin and minimal use of GLP-1 RAs, and they preceded the availability of SGLT2 inhibitors.

Use of Continuous Glucose Monitoring and Advanced Insulin Delivery Devices

For older adults with type 1 diabetes, continuous glucose monitoring (CGM) is a useful approach to predicting and reducing the risk of hypoglycemia (39) . In the Wireless Innovation in Seniors with Diabetes Mellitus (WISDM) trial, adults over 60 years of age with type 1 diabetes were randomized to CGM or standard blood glucose monitoring. Over 6 months, use of CGM resulted in a small but statistically significant reduction in time spent with hypoglycemia (glucose level < 70 mg/dL) compared with standard blood glucose monitoring (adjusted treatment difference À1.9% [À27 min/day]; 95% CI À2.8% to À1.1% [À40 to À16 min/day] ; P < 0.001) (40, 41) . Among secondary outcomes, time spent in range between 70 and 180 mg/dL increased by 8% (95% CI 6.0-11.5) and glycemic variability (%CV) decreased. In the 6-month trial extension, these benefits were sustained for up to a year (42) . These and other short-term trials are supported by observational data from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study indicating that among older adults (mean age 58 years) with long-standing type 1 diabetes, routine CGM and insulin pump use was associated with fewer hypoglycemic events and hyperglycemic excursions and lower A1C levels (43) . While the current evidence base for older adults is primarily in type 1 diabetes, the evidence demonstrating the clinical benefits of CGM for people with type 2 diabetes using insulin is growing (44) (see Section 7, "Diabetes Technology"). The DIAMOND (Multiple Daily Injections and Continuous Glucose Monitoring in Diabetes) study demonstrated that in adults $60 years of age with either type 1 or type 2 diabetes using multiple daily injections of insulin, CGM use was associated with improved A1C and reduced glycemic variability (45) . An analysis of the results of the MOBILE study, which focused on adults aged $65 years and compared CGM with blood glucose meter monitoring, showed that the mean A1C change at 8 months was greater in older adults than in younger adults (À0.65% vs. -0.35%) with type 2 diabetes treated with basal insulin and oral glucose-lowering agents. Similarly, the increase in time in range (TIR) at 8 months was greater in the older adult group than in the younger adult group (19% vs. 12%, P = 0.01) and the decrease in time above range was greater in the older adult group as well, which shows that CGM benefits extend to older adults with type 2 diabetes who are nonintensively treated (46) . Older adults with physical or cognitive limitations who require monitoring of blood glucose by a surrogate or reside in group homes or assisted living facilities are other populations for which CGM may play a useful role.

The availability of accurate CGM devices that can communicate with insulin pumps through Bluetooth has enabled the development of advanced insulin delivery algorithms for pumps. These algorithms fall into two categories: predictive low-glucose suspend algorithms that automatically shut off insulin delivery if a hypoglycemic event is imminent and hybrid closed-loop algorithms that automatically adjust insulin infusion rates based on feedback from a CGM to keep glucose levels in a goal range. Advanced insulin delivery devices have been shown to improve glycemic outcomes in both children and adults with type 1 diabetes. Most trials of these devices have included people with type 1 diabetes but relatively few older adults; however, data from two small randomized controlled trials in older adults are available. The Older Adult Closed Loop (ORACL) trial in 30 older adults (mean age 67 years) with type 1 diabetes found that an automated insulin delivery (AID) strategy was associated with significant improvements in TIR compared with sensoraugmented pump therapy (47) . Moreover, they found small but significant decreases in hypoglycemia with the AID strategy. Boughton et al. (48) reported results of an open-label, crossover design clinical trial in 37 older adults ($60 years) in which 16 weeks of treatment with a hybrid closed-loop advanced insulin delivery system was compared with sensor-augmented pump therapy. They found that hybrid closed-loop insulin delivery improved the proportion of time glucose was in range largely due to decreases in hyperglycemia. In contrast to the ORACL study, no significant differences in hypoglycemia were observed. Both studies enrolled older individuals whose blood glucose was relatively well managed (mean A1C $7.4%), and both used a crossover design comparing hybrid closed-loop insulin delivery to sensoraugmented pump therapy. A recent randomized controlled trial of older adults with type 2 diabetes using multiple daily injections who were unable to manage insulin therapy on their own revealed an increase of TIR of 27% over 12 weeks of AID use in addition to tailored home health care services (49) .

These trials provide the first evidence that older individuals with long-standing type 1 and type 2 diabetes can successfully use advanced insulin delivery technologies to improve glycemic outcomes, as has been seen in younger populations. A recent real world evidence analysis of a Medicare population (n = 4,243, 89% with type 1 diabetes, mean age 67.4 years) also indicated that initiating hybrid closedloop insulin delivery was associated with improvements in mean glucose and a 10% increase in TIR (50) . Use of such technologies should be periodically reassessed, as the burden may outweigh the benefits in those with declining cognitive or functional status. mol] and/or TIR 70-180 mg/dL [3.9-10.0 mmol] of $50% and time below range < 70 mg/dL [3.9 mmol/L] of < 1%) for those with significant cognitive and/or functional limitations, frailty, severe comorbidities, and a less favorable risk-tobenefit ratio of diabetes medications. C 13.8c Older adults with very complex or poor health receive minimal benefit from stringent glycemic goals. Clinicians should focus on avoiding hypoglycemia and symptomatic hyperglycemia rather than achieving stringent glycemic goals. C 13.9 Screening for diabetes complications should be individualized in older adults with diabetes. Particular attention should be paid to complications that would lead to impairment of functional status or quality of life. C 13.10 Treatment of hypertension to individualized goal levels is indicated in most older adults with diabetes. B 13.11 Treatment of other cardiovascular risk factors should be individualized in older adults with diabetes, considering the time frame of benefit. Lipid-lowering therapy and antiplatelet agents may benefit those with life expectancies at least equal to the time frame of primary prevention or secondary intervention trials. E

The care of older adults with diabetes is complicated by their clinical, cognitive, and functional heterogeneity and their varied prior experience with disease management. Some older individuals may have developed diabetes years earlier and have significant complications, others are newly diagnosed and may have had years of undiagnosed diabetes with resultant complications, and still, other older adults may have truly recent-onset disease with few or no complications (51) . Some older adults with diabetes have other underlying chronic conditions, substantial diabetes-related comorbidity, limited cognitive or physical functioning, or frailty (52, 53) . Other older individuals with diabetes have little comorbidity and are active.

Life expectancy is affected by the age of the individual, disease burden, and degree of disability. Multiple prognostic tools for life expectancy for older adults are available (54, 55) . Notably, the Life Expectancy Estimator for Older Adults with Diabetes (LEAD) tool was developed and validated among older adults with diabetes, and a high risk score was strongly associated with having a life expectancy of < 5 years (56) . These data may be a useful starting point to inform decisions about selecting less stringent glycemic goals (56, 57) . Older adults also vary in their preferences for the intensity and mode of glucose management (58) . Health care professionals caring for older adults with diabetes must take this heterogeneity into consideration when setting and prioritizing treatment goals (10,11) (Table 13 .1). In addition, older adults with diabetes should be assessed for disease treatment and self-management knowledge, health literacy, and mathematical literacy (numeracy) at the onset and throughout treatment. See Fig. 6 .2 for individual/ disease-related factors to consider when determining individualized glycemic goals.

A1C results may be inaccurate in those who have received blood transfusions and who have medical conditions that impact red blood cell turnover (see Section 2, "Diagnosis and Classification of Diabetes," for additional details on the limitations of A1C) (59) . Conditions affecting red blood cell turnover that are common in older adults include end-stage kidney disease, recent significant blood loss, and erythropoietin therapy. In these instances, blood glucose monitoring and/or CGM should be used for glycemic goal setting (Table 13 .1). Serum glycated protein assays such as fructosamine may also be useful for glycemic monitoring in conjunction with other measures (see Section 6, "Glycemic Goals and Hypoglycemia") (60) (61) (62) .

Older Adults With Good Functional Status and Without Complications

There are few long-term studies in older adults demonstrating the benefits of intensive glycemic, blood pressure, and lipid management. Older adults who can be expected to live long enough to realize the benefits of long-term intensive diabetes management, who have good cognitive and physical function, and who choose to do so via shared decision-making may be treated using therapeutic interventions and goals similar to those for younger adults with diabetes (Table 13.

1).

As for all people with diabetes, diabetes self-management education and ongoing diabetes self-management support are vital components of diabetes care for older adults and their caregivers. Selfmanagement knowledge and skills should be reassessed following a significant clinical change or hospitalization, when treatment plan changes are made, or when an individual's functional abilities diminish. In addition, declining or impaired ability to perform diabetes self-care behaviors may be an indication that an older person with diabetes needs a referral for cognitive and physical functional assessment, using agenormalized evaluation tools, as well as help establishing a support structure for diabetes care (3, 31) .

Older Adults With Complications and Reduced Functionality

Older adults with diabetes categorized as having complex or intermediate health (Table 13 .1) are heterogeneous with respect to their function and life expectancy (63) (64) (65) . Based on concepts of competing mortality and time to benefit, some people in this category with shorter life expectancy will have less benefit from glucose lowering and should have less stringent glycemic goals (66) . This is especially true for individuals with advanced diabetes complications, life-limiting comorbid illnesses, frailty, or substantial cognitive or functional impairments. These individuals are also more likely to experience serious adverse effects of therapeutics, such as hypoglycemia (67) . However, those with poorly managed diabetes may be subject to acute complications of diabetes, including dehydration, poor wound healing, and hyperglycemic crises. Glycemic goals should, at a minimum, avoid these consequences. Factors to consider for individualizing glycemic goals are outlined in Fig. 6 .2 and Fig. 13 .1 (4Ms framework). Clinicians should also consider the balance of risks and benefits of an individual's diabetes medications, including disease-specific benefits (such as reducing symptomatic heart failure or stabilizing chronic kidney disease) and burdens such as hypoglycemia risk, tolerability, difficulties of administration, inadequate support system, and financial cost. In addition, attention to oral health, vision and hearing loss, foot care, fall prevention, and early detection of depression will improve quality of life.

While Table 13 .1 provides overall guidance for identifying complex and very complex individuals, there is not yet global consensus on geriatric people classification. Ongoing empiric research on the classification of older adults with diabetes based on comorbid illness has repeatedly found three major classes of individuals: a healthy, a geriatric, and a cardiovascular class (10, 63, 68) . The geriatric class has the highest prevalence of obesity, hypertension, arthritis, and incontinence, and the cardiovascular class has the highest prevalence of myocardial infarctions, heart failure, and stroke. Compared with the healthy class, the cardiovascular class has the highest risk of frailty and subsequent mortality. Additional research is needed to develop a reproducible classification scheme to distinguish the natural history of disease as well as differential response to glucose management and specific glucose-lowering agents (69) .

Vulnerable Older Adults at the End of Life

For people with diabetes receiving palliative care and end-of-life care, the focus should be to avoid hypoglycemia and symptomatic hyperglycemia while reducing the burdens of glycemic management. Thus, as organ failure develops, the treatment plan will have to be deintensified and one or more agents will need to be discontinued. At the end of life, most agents for type 2 diabetes may be removed (70) . There is, however, no consensus for the management of type 1 diabetes in this scenario (71) . Consultation with a geriatric specialist might be warranted to assist with complex medical and functional issues as well as advance care planning. See the section END-OF-LIFE CARE below for additional information.

Beyond Glycemic Management

Although minimizing hyperglycemia may be important in older individuals with diabetes, greater reductions in morbidity and mortality are likely to result from a clinical focus on comprehensive cardiovascular risk factor modification. There is strong evidence from clinical trials of the value of treating hypertension in older adults (72, 73) , with treatment of hypertension to individualized target levels indicated in most. There is less evidence for lipid-lowering therapy and aspirin therapy, although the benefits of these interventions for primary and secondary prevention are likely to apply to older adults whose life expectancies equal or exceed the time frames of the clinical trials (74).

In the case of statins, the follow-up time of clinical trials ranged from 2 to 6 years. While the time frame of trials can be used to inform treatment decisions, a more specific concept is the time to benefit for a therapy. For statins, a meta-analysis of the previously mentioned trials showed that the time to benefit is 2.5 years (75) . (97) . Accordingly, the costs of care and insurance coverage rules should be considered when developing treatment plans to reduce the risk of cost-related barriers to use (98, 99) . See Table 9 .3 and Table 9 .4 for median monthly cost in the U.S. of noninsulin glucose-lowering agents and insulin, respectively. It is important to match complexity of the treatment plan to the self-management ability of older adults with diabetes and their available social and medical support. Many older adults with diabetes struggle to maintain the frequent blood glucose monitoring and insulin injection plans they previously followed, perhaps for many decades, as they develop medical conditions that may impair their ability to follow their treatment plan safely. Individualized glycemic goals should be established (Fig. 6 .2 and Table 13 .1) and periodically adjusted based on coexisting chronic illnesses, cognitive function, functional status, life expectancy, and risk of complications (2) . Intensive glycemic management with medication plans including insulin and sulfonylureas in older adults with complex medical conditions has been identified as overtreatment and found to be very common in clinical practice (100-104) and may increase the risk of mortality (37) . Ultimately, the determination of whether a person is considered overtreated requires an elicitation of the person's perceptions of the current medication burden and preferences for treatments. For those seeking to simplify their diabetes medication plan, deintensification of plans in individuals taking noninsulin glucose-lowering medications can be achieved by either lowering the dose or discontinuing some medications, as long as individualized glycemic goals are maintained (105) . When older adults are found to have an insulin plan with complexity beyond their selfmanagement abilities, lowering the dose of insulin may not be adequate (106) . Simplification of the insulin plan to match an individual's self-management abilities and their available social and medical support in these situations has been shown to reduce hypoglycemia and disease-related distress without worsening glycemic outcomes (107) (108) (109) (110) . Figure 13 .2 depicts an algorithm that can be used to simplify the insulin administration plan (109) . There are now multiple studies evaluating deintensification protocols in diabetes as well as hypertension, demonstrating that deintensification is safe and possibly beneficial for older adults (105). Extended-release formulation may be used as an alternative to immediate-release formulation in older adults experiencing difficulties in maintaining medication plans or gastrointestinal effects.

Pioglitazone

Pioglitazone, if used at all, should be used very cautiously in older adults on insulin therapy as well as in those with or at risk for heart failure, fluid retention, weight gain, osteoporosis, falls or fractures, and/or macular edema (113, 114) . Lower doses of pioglitazone in combination therapy may mitigate these side effects.

Insulin Secretagogues

Sulfonylureas and other insulin secretagogues such as the meglitinides (repaglinide and nateglinide) are associated with hypoglycemia, bone loss (115) , and fracture risk (116) and should be used with caution.

If used, sulfonylureas with a shorter duration of action, such as glipizide, are preferred, and frequency of hypoglycemia monitored at each visit. Glyburide is a longer-acting sulfonylurea and should be avoided in older adults (117) . Many antimicrobials (most commonly fluroquinolones and sulfamethoxazole-trimethoprim) interact with sulfonylureas to increase the effective sulfonylurea dose, which may precipitate hypoglycemia (118) (119) (120) . Sulfonylureas should be reduced or temporarily discontinued in these circumstances.

Incretin-Based Therapies

Oral dipeptidyl peptidase 4 (DPP-4) inhibitors have few side effects and minimal risk of hypoglycemia, but their cost may be a barrier to some older adults. DPP-4 inhibitors are relatively weak agents and do not reduce or increase major adverse cardiovascular outcomes generally, and there is no interaction by age-group (121) . A challenge of interpreting the age-stratified analyses of this drug class and other cardiovascular outcomes trials is that while most of these analyses were prespecified, they were not powered to detect differences. In general, these medications may be useful in older adults with mild hyperglycemia or with high risk of hypoglycemia, or when metformin is contraindicated. Among DPP-4 inhibitors, linagliptin may be used as alternative to metformin in older adults with low GFR.

GLP-1 RAs have demonstrated cardiovascular benefits among people with diabetes and established atherosclerotic cardiovascular disease (ASCVD) and those at higher ASCVD risk, and newer trials are expanding our understanding of their benefits in other populations (122) . See Section 9, "Pharmacologic Approaches to Glycemic Treatment," and Section 10, "Cardiovascular Disease and Risk Management," for a more extensive discussion regarding the specific indications for this class of agents. In a systematic review and meta-analysis of GLP-1 RA trials, these agents have been found to reduce major adverse cardiovascular events, cardiovascular deaths, stroke, and myocardial infarction to the same degree for people over and under 65 years of age (123) . While the evidence for this class of agents for older adults continues to grow, there are a number of practical issues that should be considered specifically for older people. These drugs are injectable agents (with the exception of oral semaglutide) (124) , which require visual, motor, and cognitive skills for appropriate administration, although most of them have a weekly dosing schedule. GLP-1 RAs may also be associated with nausea, vomiting, diarrhea, or constipation and should be titrated slowly. Given the gastrointestinal side effects of this class, GLP-1 RAs are not preferred in older adults experiencing unexplained weight loss or undernutrition or in those who have recurrent gastrointestinal problems. GLP-1 RAs should be avoided especially in people with problematic constipation, significant gastroparesis, recurrent ileus, or bowel obstruction. Individuals should be monitored regularly for excessive weight loss.

Tirzepatide is a novel dual-acting glucose-dependent insulinotropic polypeptide and GLP-1 RA administered as a onceweekly subcutaneous injection. In phase 3 trials, tirzepatide decreased A1C and weight-generally to a greater extent than other glucose-lowering drugs including semaglutide and insulin-with no significant differences in the safety or efficacy in older compared with younger individuals (125) . As the adverse effect profile of tirzepatide is similar to that for GLP-1 RAs, the same precautions for older adults apply (125) .

Sodium-Glucose Cotransporter 2 Inhibitors

SGLT2 inhibitors are administered orally, which may be convenient for older adults with diabetes. In those with established ASCVD, these agents have shown cardiovascular benefits (122) . This class of agents has also been found to be beneficial for • If eGFR is ≥45 mL/min/1.73 m2, start metformin 500 mg daily and increase dose every 2 weeks, as tolerated • If eGFR is < 45 mL/min/1.73 m2, individual is already taking metformin, or metformin is not olerated, proceed to second-line agent Using Individual comorbidities (e.g., CKD, ASCVD, low body weight, and risk of dehydration) and drug characteristics to guide decision-making, as depicted in Fig. 9 .3 and Table 9 .2, select additional agent(s) as needed:

Simplification of Complex Insulin Therapy

• Every 2 weeks, adjust insulin dose and/or add glucose-lowering medications based on finger-stick glucose testing performed before lunch and before dinner • Do not use rapid-and short-acting insulin at bedtime • While adjusting prandial insulin, a simplified sliding scale may be used, for example:

• For premeal glucose > 250 mg/dL ( > 13.9 mmol/L), give 2 units of short-or rapid-acting insulin • For premeal glucose > 350 mg/dL ( > 19.4 mmol/L), give 4 units of short-or rapid-acting insulin • Stop sliding scale when not needed daily Figure 13 .2-Algorithm to simplify insulin administration plans in older individuals. ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate. *Basal insulins: glargine U-100 and U-300, detemir, degludec, and human NPH. †Prandial insulins: short-acting (regular human insulin) or rapid-acting (lispro, aspart, and glulisine). ‡Premixed insulins: 70/30, 75/25, and 50/50 products. §Examples of noninsulin agents include metformin, sodium-glucose cotransporter 2 inhibitors, dipeptidyl peptidase 4 inhibitors, and glucagon-like peptide 1 receptor agonists. jjSee Table 13

The use of insulin therapy requires that individuals or their caregivers have good visual and motor skills and cognitive ability to manage the appropriate insulin dose using insulin pens or syringes. Insulin therapy relies on the ability of the older person with diabetes to administer insulin on their own or with the assistance of a care partner, to monitor glucose levels, and, eventually, to recognize and treat hypoglycamia. Insulin doses should be titrated to meet individualized glycemic goals and to avoid hypoglycemia.

Once-daily basal insulin injection therapy is associated with minimal side effects and may be a reasonable option in many older adults (134) . When choosing a basal insulin, long-acting insulin analogs have been found to be associated with a lower risk of hypoglycemia compared with NPH insulin in the Medicare population. Multiple daily injections of insulin may be too complex for an older person with advanced diabetes complications, life-limiting coexisting chronic illnesses, or limited functional status or social support. Moreover, if affordable, use of insulin pens should be prefered to syringes, mostly in older adults with functional impairment. Figure 13 .2 provides a potential approach to simplification of insulin plans.

Other Factors to Consider

The needs of older adults with diabetes and their care partners should be evaluated to construct a tailored care plan. Inadequate social support and reduced access to long-term services and support may reduce these individuals' quality of life and increase the risk of functional dependency (7) . The living situation must be considered as it may affect diabetes management and support needs. Social and instrumental support networks (e.g., adult children and care partners) that provide instrumental or emotional support for older adults with diabetes should be included in diabetes management discussions and shared decision-making.

The need for ongoing support of older adults becomes even greater when transitions to acute care and long-term care (LTC) become necessary. Unfortunately, these transitions can lead to discontinuity in goals of care, errors in dosing, and changes in nutrition and activity (135) . Older adults in assisted living facilities may not have support to administer their own medications, whereas those living in a nursing home for short-term rehabilitation or LTC may rely on first-line care partners including nursing and care professionals with variable clinical expertise. Those receiving palliative care (with or without hospice) may require an approach that emphasizes comfort and symptom management while deemphasizing strict metabolic and blood pressure management.

SPECIAL CONSIDERATIONS FOR OLDER ADULTS WITH TYPE 1 DIABETES

Due in part to the success of modern diabetes management, people with type 1 diabetes are living longer, and the population of these people over 65 years of age is growing (136) (137) (138) . Many of the recommendations in this section regarding a comprehensive geriatric assessment and personalization of goals and treatments are directly applicable to older adults with type 1 diabetes; however, this population has unique challenges and requires distinct treatment considerations (139) . Insulin is an essential life-preserving therapy for people with type 1 diabetes, unlike for those with type 2 diabetes. To avoid diabetic ketoacidosis, older adults with type 1 diabetes need some form of basal insulin even when they are unable to ingest meals. Insulin may be delivered through an insulin pump or injections. CGM is approved for use by Medicare and can play a critical role in improving A1C, reducing glycemic variability, and reducing risk of hypoglycemia (45) (see Section 7, "Diabetes Technology," and Section 9, "Pharmacologic Approaches to Glycemic Treatment"). In older people with type 1 diabetes, administration of insulin may become more difficult as complications, cognitive impairment, and functional impairment arise. This increases the importance of care partners in the lives of these individuals. Many older people with type 1 diabetes require placement in PALTC settings (i.e., nursing homes and skilled nursing facilities), and unfortunately staff in these settings are less familiar with CGM devices, insulin pumps, or advanced insulin delivery devices. Nevertheless, a feasibility study in LTC facilities showed that CGM can be useful in older adults with diabetes, although it requires substantial staff training (140) . Furthermore, an observational study of older adults with diabetes living in LTC facilities using CGM revealed a high prevalence of hypoglycemia both in people using insulin and in those using sulfonylureas, thus showing that this population of older adults in LTC facilities are at increased risk for hypoglycemia (141) . Therefore, using CGM can provide useful and more prompt information on hypoglycemia in this vulnerable population. Of note, a recent randomized controlled trial in LTC facilities showed that real-time CGM use for up to 60 days was safe and effective in guiding insulin doses compared with BGM by point of care. There were no differences in TIR, time below range, or mean glucose levels (142) . Some staff may be less knowledgeable about the differences between type 1 and type 2 diabetes. Diabetic ketoacidosis may be mistaken for sepsis, end-organ failure, or other electrolyte abnormalities. In these instances, the individual or their family may be more familiar with their diabetes management plan than the staff or health care professionals. Education of relevant support staff and health care professionals in rehabilitation and PALTC settings regarding insulin dosing and use of pumps and CGM is recommended as part of general diabetes education (see Recommendations 13.18 and 13.19).

TREATMENT IN POST-ACUTE AND LONG-TERM CARE SETTINGS

Recommendations 13.18 Recommend diabetes education/ training (including that for CGM devices, insulin pumps, and advanced insulin delivery systems) for the staff of long-term care and rehabilitation facilities to improve the management of older adults with diabetes. E 13.19 People with diabetes residing in long-term care facilities need careful assessment of mobility, mentation, medications, and management preferences to establish individualized glycemic goals and to make appropriate choices of glucose-lowering agents and devices (including CGM devices, insulin pumps, and advanced insulin delivery systems) based on their clinical and functional status. E See Fig. 13 .1 for the 4Ms framework to address person-specific issues that affect diabetes management in older individuals.

Management of diabetes in the LTC setting is unique. Individualization of health care is important for all people with diabetes; however, practical guidance is needed for health care professionals as well as the LTC staff and care partners (143, 144) . Training should include diabetes detection and institutional quality assessment. PALTC facilities should develop their own policies and procedures for prevention, recognition, and management of hypoglycemia. With the increased longevity of populations, the care of people with diabetes and its complications in PALTC is an area that warrants greater study.

Resources

Staff of PALTC facilities should receive appropriate diabetes education to improve the management of older adults with diabetes. Treatments for each person with diabetes should be individualized. Special management considerations include the need to avoid both hypoglycemia and the complications of hyperglycemia (2, 145) . For more information, see the ADA position statement "Management of Diabetes in Long-term Care and Skilled Nursing Facilities" (135, 143, 144) .

Nutritional Considerations

An older adult residing in a PALTC facility may have irregular and unpredictable meal consumption, undernutrition, anorexia, and impaired swallowing. Furthermore, therapeutic nutrition plans or modified food consistencies may inadvertently lead to decreased food intake and contribute to unintentional weight loss and undernutrition. Meals tailored to a person's culture, preferences, and personal goals may increase quality of life, satisfaction with meals, and nutrition status (146) . It may be helpful to give insulin immediately after meals to ensure that the dose is appropriate for the amount of carbohydrate the individual consumed in the meal.

Older adults with diabetes in PALTC are especially vulnerable to hypoglycemia. They have a disproportionately high number of clinical complications and comorbidities that can increase hypoglycemia risk: impaired cognitive and renal function, slowed hormonal regulation and counterregulation, suboptimal hydration, variable appetite and nutritional intake, requirement for feeding assistance, polypharmacy, and slowed intestinal absorption (147) . Oral agents may achieve glycemic outcomes similar to basal insulin in PALTC populations (100, 148) . CGM may be a useful approach to monitoring for hypoglycemia among individuals treated with insulin in LTC, but the data are limited.

In all people with diabetes and DPN, causes of neuropathy other than diabetes should be considered, including toxins (e.g., alcohol), neurotoxic medications (e.g., chemotherapy), vitamin B12 deficiency, hypothyroidism, kidney disease, malignancies (e.g., multiple myeloma, bronchogenic carcinoma), infections (e.g., HIV), chronic inflammatory demyelinating neuropathy, inherited neuropathies, and vasculitis (58) . See the American Diabetes Association position statement "Diabetic Neuropathy" for more details (57) .

Diabetic Autonomic Neuropathy

Individuals who have had type 1 diabetes for $5 years and all individuals with type 2 diabetes should be assessed annually for autonomic neuropathy (57) . The symptoms and signs of autonomic neuropathy should be elicited carefully during the history and physical examination. Major clinical manifestations of diabetic autonomic neuropathy include resting tachycardia, orthostatic hypotension, gastroparesis, constipation, diarrhea, fecal incontinence, erectile dysfunction, neurogenic bladder, and sudomotor dysfunction with either increased or decreased sweating. Screening for symptoms of autonomic neuropathy includes asking about symptoms of orthostatic intolerance (dizziness, lightheadedness, or weakness with standing), syncope, exercise intolerance, constipation, diarrhea, urinary retention, urinary incontinence, or changes in sweat function. Further testing can be considered if symptoms are present and will depend on the end organ involved but might include cardiovascular autonomic testing, sweat testing, urodynamic studies, gastric emptying, or endoscopy or colonoscopy. Impaired counterregulatory responses to hypoglycemia in type 1 and type 2 diabetes can lead to impaired hypoglycemia awareness but are not directly linked to autonomic neuropathy.

Cardiovascular Autonomic Neuropathy

CAN is associated with mortality independent of other cardiovascular risk factors (59, 60) . In its early stages, CAN may be completely asymptomatic and detected only by decreased heart rate variability with deep breathing. Advanced disease may be associated with resting tachycardia ( > 100 bpm) and orthostatic hypotension (a fall in systolic or diastolic blood pressure by > 20 mmHg or > 10 mmHg, respectively, upon standing without an appropriate increase in heart rate). CAN treatment is generally focused on alleviating symptoms.

Gastrointestinal Neuropathies

Gastrointestinal neuropathies may involve any portion of the gastrointestinal tract, with manifestations including esophageal dysmotility, gastroparesis, constipation, diarrhea, and fecal incontinence. Gastroparesis should be suspected in individuals with erratic glycemic management or with upper gastrointestinal symptoms without another identified cause. Exclusion of reversible/iatrogenic causes such as medications or organic causes of gastric outlet obstruction or peptic ulcer disease (with esophagogastroduodenoscopy or a barium study of the stomach) is needed before considering a diagnosis of or specialized testing for gastroparesis. The diagnostic gold standard for gastroparesis is the measurement of gastric emptying with scintigraphy of digestible solids at 15-min intervals for 4 h after food intake. The use of 13 C octanoic acid breath test is an approved alternative.

Genitourinary Disturbances

Diabetic autonomic neuropathy may also cause genitourinary disturbances, including sexual dysfunction and bladder dysfunction. In men, diabetic autonomic neuropathy may cause erectile dysfunction and/or retrograde ejaculation (57) . Female sexual dysfunction occurs more frequently in those with diabetes and presents as decreased sexual desire, increased pain during intercourse, decreased sexual arousal, and inadequate lubrication (61) . Lower urinary tract symptoms manifest as urinary incontinence and bladder dysfunction (nocturia, frequent urination, urination urgency, and weak urinary stream). Evaluation of bladder function should be performed for individuals with diabetes who have recurrent urinary tract infections, pyelonephritis, incontinence, or a palpable bladder. Treatment Recommendations 12.20 Optimize glucose management to prevent or delay the development of neuropathy in people with type 1 diabetes A and to slow the progression of neuropathy in people with type 2 diabetes. C Optimize weight, blood pressure, and serum lipid management to reduce the risk or slow the progression of diabetic neuropathy. B 12.21 Assess and treat pain related to diabetic peripheral neuropathy B and symptoms of autonomic neuropathy to improve quality of life. E 12.22 Gabapentinoids, serotoninnorepinephrine reuptake inhibitors, tricyclic antidepressants, and sodium channel blockers are recommended as initial pharmacologic treatments for neuropathic pain in diabetes. A Opioids, including tramadol and tapentadol, should not be used for neuropathic pain treatment in diabetes given the potential for adverse events. B

Near-normal glycemic management, implemented early in the course of diabetes, has been shown to effectively delay or prevent the development of DPN and CAN in people with type 1 diabetes (62) (63) (64) (65) . Although the evidence for the benefit of near-normal glycemic management is not as strong for type 2 diabetes, some studies have demonstrated a modest slowing of progression without reversal of neuronal loss (52, 66) . Specific glucose-lowering strategies may have different effects. In a post hoc analysis, participants, particularly men, in the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) trial treated with insulin sensitizers had a lower incidence of distal symmetric polyneuropathy over 4 years than those treated with insulin or sulfonylurea (67) . Additionally, recent evidence from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed benefit of intensive glucose and blood pressure management on the prevention of CAN in type 2 diabetes (68) .

Obesity is consistently associated with neuropathy in cross-sectional and longitudinal studies (69) . While obesity has been established as a risk factor for neuropathy, including in those with diabetes, treatments of obesity are less well studied. The Look AHEAD (Action for Health in Diabetes) randomized trial found that a lifestyle intervention primarily focused on dietary weight loss led to improvements in neuropathy symptoms but not neuropathy examination scores (53) . Observational studies of metabolic surgery have also revealed improvements in neuropathy outcomes, but randomized trials are lacking (55, 56) . Weight loss medications have not been well studied to date with two negative trials (topiramate and exenatide). Trials investigating the impacts of exenatide and topiramate on DPN and CAN measurements led to no substantial weight loss (70, 71) . Exercise often leads to a small reduction in weight and may also have positive effects on diabetic neuropathy through other mechanisms. Two systematic reviews have shown that exercise interventions improve diabetic neuropathy outcomes, including symptoms, examination findings, balance, and functional assessments, but the strength of the evidence is low (72, 73) .

Dyslipidemia is a key factor in the development of neuropathy in people with type 2 diabetes and may contribute to neuropathy risk in people with type 1 diabetes (74, 75) . Although the evidence for a relationship between lipids and neuropathy development has become increasingly clear in type 2 diabetes, the optimal therapeutic intervention has not been identified. Positive effects of physical activity, weight loss, and metabolic surgery have been reported in individuals with DPN, but use of conventional lipid-lowering pharmacotherapy (such as statins or fenofibrates) does not appear to be effective in treating or preventing DPN development (76) .

There are multiple reasons for blood pressure management in people with diabetes, and neuropathy progression (especially in type 2 diabetes) has now been added to this list. Although data from many studies have supported the role of hypertension in the risk of neuropathy development, a meta-analysis of data from 14 countries in the International Prevalence and Treatment of Diabetes and Depression (INTERPRET-DD) study revealed hypertension as an independent risk factor for DPN development with an odds ratio of 1.58 (95% CI 1.18-2.12) (77). In the ACCORD trial, intensive blood pressure intervention also decreased CAN risk by 25% (68) .

Neuropathic Pain

Neuropathic pain can be severe and can impact quality of life, affect sleep, limit mobility, and contribute to depression and anxiety (78) . No compelling evidence exists in support of glycemic or lifestyle management as therapies for neuropathic pain in diabetes or prediabetes, which leaves only pharmaceutical interventions (79) . A recent guideline by the American Academy of Neurology recommends that the initial treatment of pain should also focus on the concurrent treatment of both sleep and mood disorders because of increased frequency of these problems in individuals with DPN (80) .

Several pharmacologic therapies exist for treatment of pain in diabetes. The American Academy of Neurology (AAN) update suggested that gabapentinoids, serotonin-norepinephrine reuptake inhibitors (SNRIs), sodium channel blockers, and tricyclic antidepressants (TCAs) all could be considered in the treatment of pain in DPN (80) . These AAN recommendations offer a supplement to a recent American Diabetes Association pain monograph (81) . A head-to-head trial suggested therapeutic equivalency for TCAs, SNRIs, and gabapentinoids in the treatment of pain in DPN (82) . The trial also supported the role of combination therapy over monotherapy for the treatment of pain in DPN.

Gabapentinoids. Gabapentinoids include several calcium channel a2-d subunit ligands. Several high-quality and mediumquality studies support the role of pregabalin in treatment of pain in DPN. One high-quality study and many small studies support the role of gabapentin in the treatment of pain in DPN. Medium-quality studies suggest that mirogabalin has a small effect on pain in DPN (80) . Adverse effects may be more severe in older individuals (83) and may be attenuated by lower starting doses and more gradual titration.

SNRIs. SNRIs include duloxetine, venlafaxine, and desvenlafaxine, all selective SNRIs. Two high-quality studies and five medium-quality studies support the role of duloxetine in the treatment of pain in DPN. A high-quality study supports the role of venlafaxine in the treatment of pain in DPN. Only one medium-quality study supports a possible role for desvenlafaxine for treatment of pain in DPN (80) . Adverse events may be more severe in older people but may be attenuated with lower doses and slower titration of duloxetine.

Tricyclic Antidepressants. TCAs have been studied for treatment of pain. Most of the relevant data were acquired from trials of amitriptyline and include two highquality studies and two medium-quality diabetesjournals.org/care Retinopathy, Neuropathy, and Foot Care S257

studies supporting the effectiveness of amitryiptylinein in the treatment of painful DPN (80, 82) . Anticholinergic side effects may be dose limiting and restrict use in individuals $65 years of age.

Sodium Channel Blockers. Sodium channel blockers include lamotrigine, lacosamide, carbamazepine, oxcarbazepine, and valproic acid. Five medium-quality studies support the role of sodium channel blockers in treating pain in DPN (80) .

Capsaicin. Capsaicin has received FDA approval for treatment of pain in DPN using an 8% patch, with one high-quality study reported. One medium-quality study of 0.075% capsaicin cream has been reported. In individuals with contraindications to oral pharmacotherapy or who prefer topical treatments, the use of topical capsaicin can be considered.

Lidocaine 5% Plaster/Patch. Lidocaine patches have limited data supporting their use in DPN and are not effective in more widespread distribution of pain (although they may be of use in individuals with nocturnal neuropathic foot pain). Lidocaine patches cannot be used for more than 12 h in a 24-h period (84) .

Opioids. Several randomized controlled trials (RCTs) have demonstrated that opioids (dextromethorphan, oxycodone, morphine sulfate) can reduce pain in individuals with DPN (84) . However, evidence for the long-term efficacy of opioids in neuropathic pain is lacking. In fact, the Centers for Disease Control and Prevention (CDC) performed a systematic review that found no studies of opioids for chronic pain have evaluated long-term outcomes, including pain, function, and quality of life (85) . Moreover, CDC and AAN reviews have documented the long-term harms from opioids, including abuse, addiction, fractures, heart attacks, motor vehicle accidents, overdose, and mortality (85, 86) . The current evidence balancing risks and benefits has led the AAN to recommend against opioids for the treatment of painful DPN (80) .

Tapentadol and Tramadol. Tapentadol and tramadol exert their analgesic effects through both m-opioid receptor agonism (opioid) and norepinephrine and serotonin reuptake inhibition. Given that opioids and SNRIs are both effective for painful DPN, it is not surprising that these SNRI and opioid agents are effective in the treatment of pain in DPN too (80) . However, the effect size is similar to that of other effective therapies, such as SNRIs, and these medications have the same risks as other opioids listed above. In fact, tramadol has been shown to be associated with all-cause mortality with an effect size similar to that of codeine (87) . Similar to other opioids, risks likely outweigh benefits, and the AAN guidelines also recommend against their use for painful DPN (80) .

Orthostatic Hypotension

Treating orthostatic hypotension is challenging. The therapeutic goal is to minimize postural symptoms rather than to restore normotension. Most individuals require both nonpharmacologic measures (e.g., ensuring adequate salt intake, avoiding medications that aggravate hypotension, or using compressive garments over the legs and abdomen) and pharmacologic measures. Physical activity and exercise should be encouraged to avoid deconditioning, which is known to exacerbate orthostatic intolerance, and volume repletion with fluids and salt is critical. Additionally, supine blood pressure tends to be much higher in these individuals, often requiring treatment of blood pressure at bedtime with shorter-acting drugs that also affect baroreceptor activity such as guanfacine or clonidine, shorteracting calcium blockers (e.g., isradipine), or shorter-acting b-blockers such as atenolol or metoprolol tartrate. Alternatives can include enalapril if an individual is unable to tolerate preferred agents (88) (89) (90) . Midodrine and droxidopa are approved by the FDA for the treatment of orthostatic hypotension.

Gastroparesis

Treatment of diabetic gastroparesis may be very challenging. A small-particle diet may provide some symptom relief (91) (92) (93) . In addition, foods with small particle size may improve key symptoms (94) . Withdrawing drugs with adverse effects on gastrointestinal motility, including opioids, anticholinergics, TCAs, GLP-1 RAs, and pramlintide, may also improve intestinal motility (91, 95) . However, the risk of removal of GLP-1 RAs should be balanced against their potential benefits.

In cases of severe gastroparesis, pharmacologic interventions are needed. Only metoclopramide, a prokinetic agent, is approved by the FDA for the treatment of gastroparesis (96) . However, the level of evidence regarding the benefits of metoclopramide for the management of gastroparesis is weak, and given the risk for serious adverse effects (extrapyramidal signs such as acute dystonic reactions, drug-induced parkinsonism, akathisia, and tardive dyskinesia), its use in the treatment of gastroparesis beyond 12 weeks is no longer recommended by the FDA. It should be reserved for severe cases that are unresponsive to other therapies (95) .

Other treatment options include domperidone (available outside the U.S.) and erythromycin, which is only effective for short-term use due to tachyphylaxis (96) . Gastric electrical stimulation using a surgically implantable device has received approval from the FDA, although there are very limited data on DPN and the results do not support gastric stimulation as an effective therapy in diabetic gastroparesis (97) .

Erectile Dysfunction

In Identifying the at-risk foot begins with a detailed history documenting diabetes management, smoking history, exercise tolerance, history of claudication or rest pain, and prior ulcerations or amputations. A thorough examination of the feet should be performed annually in all people with diabetes and more frequently in at-risk individuals (98) . The examination should include assessment of skin integrity, assessment for LOPS using the 10-g monofilament along with at least one other neurological assessment tool, pulse examination of the dorsalis pedis and posterior tibial arteries, and assessment for foot deformities such as bunions, hammertoes, and prominent metatarsals, which increase plantar foot pressures and increase risk for ulcerations. At-risk individuals should be assessed at each visit and should be referred to foot care specialists for ongoing preventive care and surveillance. The physical examination can stratify people with diabetes into different categories and determine the frequency of these visits (99) (Table 12 .1).

Evaluation for Loss of Protective Sensation

The presence of peripheral sensory neuropathy is the single most common component cause for foot ulceration. In a multicenter trial, peripheral neuropathy was found to be a component cause in 78% of people with diabetes with ulcerations and that the triad of peripheral sensory neuropathy, minor trauma, and foot deformity was present in > 63% of participants (100) . All people with diabetes should undergo a comprehensive foot examination at least annually or more frequently for those in higher-risk categories (98, 99) .

LOPS is vital to risk assessment. One of the most useful tests to determine LOPS is the 10-g monofilament test.

Studies have shown that clinical examination and the 10-g monofilament test are the two most sensitive tests in identifying the foot at risk for ulceration (101) . The monofilament test should be performed with at least one other neurologic assessment tool (e.g., pinprick, temperature perception, ankle reflexes, or vibratory perception with a 128-Hz tuning fork or similar device). Absent monofilament sensation and one other abnormal test confirms the presence of LOPS. Further neurological testing, such as nerve conduction, electromyography, nerve biopsy, or intraepidermal nerve fiber density biopsies, are rarely indicated for the diagnosis of peripheral sensory neuropathy (57) .

Evaluation for Peripheral Arterial Disease

Initial screening for PAD should include a history of leg fatigue, claudication, and rest pain relieved with dependency. Physical examination for PAD should include assessment of lower-extremity pulses, capillary refill time, rubor on dependency, pallor on elevation, and venous filling time (98, 102) . Any individual exhibiting signs and symptoms of PAD should be referred for noninvasive arterial studies in the form of Doppler ultrasound with pulse volume recordings. While anklebrachial indices will be calculated, they should be interpreted carefully, as they are known to be inaccurate in people with diabetes due to noncompressible vessels. Toe systolic blood pressure tends to be more accurate. Toe systolic blood pressure < 30 mmHg is suggestive of PAD and an inability to heal foot ulcerations (103) . Individuals with abnormal pulse volume recording tracings and toe pressures < 30 mmHg with foot ulcers should be referred for immediate vascular evaluation. Due to the high prevalence of PAD in people with diabetes, the Society for Vascular Surgery and the American Podiatric Medical Association guidelines recommend that all people with diabetes > 50 years of age should undergo screening via noninvasive arterial studies (102, 104) . If normal, these should be repeated every 5 years (102) .

Education for People With Diabetes

All people with diabetes (and their caregivers), particularly those with the aforementioned high-risk conditions, should receive general foot care education, including appropriate management strategies (105) (106) (107) . This education should be provided to all newly diagnosed people with diabetes as part of an annual comprehensive examination and to individuals with high-risk conditions at every visit. Recent studies have shown that while education improves knowledge of diabetic foot problems and self-care of the foot, it does not improve behaviors associated with active participation in their overall diabetes care and the achievement of personal health goals (108) . Evidence also suggests that while education for people with diabetes and their families is important, the knowledge is quickly forgotten and needs to be reinforced regularly (109) . Individuals considered at risk should understand the implications of foot deformities, LOPS, and PAD; the proper care of the foot, including nail and skin care; and the importance of daily foot inspections. Individuals with LOPS should be educated on appropriate ways to examine their feet (palpation or visual inspection with an unbreakable mirror) for daily surveillance of early foot problems. People with diabetes should also be educated on the importance of referrals to foot care specialists. A recent study showed that people with diabetes and foot disease lacked awareness of their risk status and why they were being referred to an interprofessional team of foot care specialists. Further, they exhibited a variable degree of interest in learning further about foot complications (110) .

Individuals' understanding of these issues and their physical ability to conduct proper foot surveillance and care should be assessed. Those with visual difficulties, physical constraints preventing movement, or cognitive problems that impair their ability to assess the condition of the foot and to institute appropriate responses will need other people, such as family members, to assist with their care.

The selection of appropriate footwear and footwear behaviors at home should also be discussed (e.g., no walking barefoot, avoiding open-toed shoes). Therapeutic footwear with custom-made orthotic devices have been shown to reduce peak plantar pressures (107) . Most studies use reduction in peak plantar pressures as an outcome as opposed to ulcer prevention. Certain design features of the orthoses, such as rocker soles and metatarsal accommodations, can reduce peak plantar pressures more significantly than insoles alone. A systematic review, however, showed there was no significant reduction in ulcer incidence after 18 months compared with standard insoles and extra-depth shoes. Further, it was also noted that evidence to prevent first ulcerations was nonexistent (111) .

Treatment

Treatment recommendations for people with diabetes will be determined by their risk category. No-risk or low-risk individuals often can be managed with education and self-care. People in the moderate-to high-risk category should be referred to foot care specialists for further evaluation and regular surveillance as outlined in Table 12 .1. This category includes individuals with LOPS, PAD, and/or structural foot deformities, such as Charcot foot, bunions, or hammertoes. Individuals with any open ulceration or unexplained swelling, erythema, or increased skin temperature should be referred urgently to a foot care specialist or interprofessional team.

Initial treatment recommendations should include daily foot inspection, use of moisturizers for dry, scaly skin, and avoidance of self-care of ingrown nails and calluses. Well-fitted athletic or walking shoes with customized pressurerelieving orthoses should be part of initial recommendations for people with increased plantar pressures (as demonstrated by plantar calluses). Individuals with deformities such as bunions or hammertoes may require specialized footwear such as extra-depth shoes. Those with even more significant deformities, as in Charcot joint disease, may require custom-made footwear. For recalcitrant deformities or for recurrent ulcerations not amenable to conservative footwear therapy alone, appropriate surgical reconstruction by an experienced diabetic foot surgeon should be considered (112, 113) . Special consideration should be given to individuals with neuropathy who present with a warm, swollen, red foot with or without a history of trauma and without an open ulceration. These individuals require a thorough workup for possible Charcot neuroarthropathy (114, 115) . Foot and ankle X-rays should be performed in all individuals presenting with the above clinical findings. Early diagnosis and treatment of this condition is of paramount importance in preventing deformities and instability that can lead to ulceration and amputation. These individuals require total non-weight-bearing and urgent referral to a foot care specialist for further management. Surgical reconstruction of these complex limb-threatening deformities has assumed an important role in recent years, with many surgeries yielding high levels of success and limb salvage (113, 116, 117) . Nonetheless, such procedures need to be approached by experienced surgeons with an appreciation not only for the complexities of the deformity but also for the complexities of the individuals themselves.

There have been a number of developments in the treatment of ulcerations over the years (118) . These include negative-pressure therapy, growth factors, bioengineered tissue, acellular matrix tissue, stem cell therapy, hyperbaric oxygen therapy, and, most recently, topical oxygen therapy (119) (120) (121) . While there is literature to support many modalities currently used to treat diabetic foot wounds, robust RCTs are often lacking. However, it is agreed that the initial treatment and evaluation of ulcerations include the following five basic principles of ulcer treatment:

• Offloading of plantar ulcerations • Debridement of necrotic, nonviable tissue • Revascularization of ischemic wounds when necessary • Management of infection: soft tissue or bone • Use of physiologic, topical dressings However, despite following the above principles, some ulcerations will become chronic and fail to heal. Careful evaluation is necessary to determine if there are associated deformities predisposing to high plantar pressures that need to be addressed with surgical offloading procedures to expedite healing (112, 122, 123) . Additionally, underlying osteomyelitis must be ruled out as a cause for the nonhealing ulcer and treated as necessary. Once these complicating factors have been addressed, adjunctive advanced wound therapy can play an important role. When to use advanced wound therapy has been the subject of much discussion, as the therapy is often quite expensive. It has been determined that if a wound fails to show a reduction of 50% or more after 4 weeks of appropriate wound management (i.e., the five basic principles above), consideration should be given to the use of advanced wound therapy (124) . Treatment of these chronic wounds is best managed in an interprofessional setting.

Evidence to support advanced wound therapy is challenging to produce and to assess. Randomization of trial participants is difficult, as there are many variables that can affect wound healing. In addition, many RCTs exclude certain cohorts of people, e.g., individuals with chronic renal disease or those on dialysis. Finally, blinding of participants and clinicians is not always possible. Metaanalyses and systematic reviews of observational studies are used to determine the clinical effectiveness of these modalities. Such studies can augment formal RCTs by including a greater variety of participants in various clinical settings who are typically excluded from the more rigidly structured clinical trials.

Advanced wound therapy can be classified into nine broad categories (118) (Table 12 .2). Topical growth factors, acellular matrix tissues, and bioengineered cellular therapies are commonly used in offices and wound care centers to expedite healing of chronic, more superficial ulcerations. Numerous clinical reports and retrospective studies have demonstrated the clinical effectiveness of each of these modalities. Over the years, there has been increased evidence to support the use of these modalities. Nonetheless, use of those products or agents with robust RCTs or systematic reviews should generally be preferred over those without level 1 evidence (Table 12 .2).

Negative-pressure wound therapy was first introduced in the early to mid-1990s. It has become especially useful in wound preparation for skin grafts and flaps and assists in the closure of deep, large wounds (125, 126) . A variety of types exist in the marketplace and range from electrically powered to mechanically powered in different sizes depending upon the specific wound requirements.

Electrical stimulation, pulsed radiofrequency energy, and extracorporeal shockwave therapy are biophysical modalities that are believed to upregulate growth factors or cytokines to stimulate wound healing, while low-frequency noncontact ultrasound is used to debride wounds. However, most of the studies advocating the use of these modalities have been retrospective observational studies or poor-quality RCTs.

Hyperbaric oxygen therapy is the delivery of oxygen through a chamber, either individual or multiperson, with the intention of increasing tissue oxygenation to increase tissue perfusion and neovascularization, combat resistant bacteria, and stimulate wound healing. While there had been great interest in this modality being able to expedite healing of chronic diabetic foot ulcers (DFUs), there is one RCT with positive results that reported increased healing rates at 9 and 12 months compared with control participants (127) . More recent studies with significant design deficiencies and participant dropouts have failed to provide corroborating evidence that hyperbaric oxygen therapy should be widely used for managing nonhealing DFUs (128, 129) . While there may be some benefit in prevention of amputation in selected chronic neuroischemic ulcers, recent studies have shown no benefit in healing DFUs in the absence of ischemia and/or infection (120, 130) .

Topical oxygen therapy has been studied rather vigorously in recent years, with several high-quality RCTs and at least five systematic reviews and meta-analyses all supporting its efficacy in healing chronic DFUs at 12 weeks (119, 121, (131) (132) (133) (134) (135) . Three types of topical oxygen devices are available, including continuous-delivery, low-constant-pressure, and cyclical-pressure modalities. Importantly, topical oxygen therapy devices provide for home-based therapy and replace the need for daily visits to specialized centers. Very high participation with very few reported adverse events combined with improved healing rates makes this therapy another attractive option for advanced wound care.

If DFUs fail to heal despite appropriate standard or surgical wound care, adjunctive advanced therapies should be instituted and are best managed in an interprofessional manner. Once healed, all individuals should be enrolled in a formal comprehensive prevention program focused on reducing the incidence of recurrent ulcerations and subsequent amputations (98, 136, 137) . The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. Recommendations 13.1 Assess the medical, psychological, functional (self-management abilities), and social domains in older adults with diabetes to provide a framework to determine goals and therapeutic approaches for diabetes management. B 13.2 Screen at least annually for geriatric syndromes (e.g., cognitive impairment, depression, urinary incontinence, falls, persistent pain, and frailty), hypoglycemia, and polypharmacy in older adults with diabetes, as they may affect diabetes management and diminish quality of life. B Diabetes is a highly prevalent health condition in the aging population. Over 29% of people over the age of 65 years have diabetes (1, 2) . The number of older adults living with these conditions is expected to increase rapidly in the coming decades. Diabetes in older adults is a highly heterogeneous condition. While type 2 diabetes predominates in the older population as in the younger population, improvements in insulin delivery, technology, and care over the last few decades have led to increasing numbers of people with childhood and adult-onset type 1 diabetes surviving and thriving into their later decades.

Another consideration for the PALTC setting is that unlike in the hospital setting, health care professionals are not required to evaluate individuals daily. According to federal guidelines, at a minimum, assessments should be done at least every 30 days for the first 90 days after admission and then at least once every 60 days and as clinically indicated. Although in practice individuals may actually be seen more frequently, the concern is that these individuals may have poorly managed glucose levels or wide excursions without the practitioner being notified. Health care professionals may adjust treatment plans by telephone, fax, or in person directly at the PALTC facilities, provided they are given timely notification of blood glucose management issues from a standardized alert system.

The following alert strategy could be considered:

1. Call a health care professional immediately in cases of low blood glucose levels ( < 70 mg/dL [ < 3.9 mmol/L]). However, treatment of hypoglycemia should not be delayed. (145, 149) .

In the setting of palliative care, health care professionals should initiate conversations with people with diabetes and their care partners regarding the goals and intensity of diabetes care; strict glucose and blood pressure management may not be consistent with achieving comfort and quality of life. Avoidance of severe hypertension and hyperglycemia aligns with the goals of palliative care. In a multicenter trial, withdrawal of statins among people with diabetes in palliative care was found to improve quality of life (150) (151) (152) . The evidence for the safety and efficacy of deintensification protocols in older adults is growing for both glucose and blood pressure management (104, 153) and is clearly relevant for palliative care. An individual has the right to refuse testing and treatment, whereas health care professionals may consider withdrawing treatment and limiting diagnostic testing, including a reduction in the frequency of blood glucose monitoring (154, 155) . CGM could be considered when frequent blood glucose testing is burdensome but monitoring for hypoglycemia and hyperglycemia is needed. Glycemic goals should aim to prevent hypoglycemia and hyperglycemia. Treatment interventions need to be mindful of quality of life. Careful monitoring of oral intake is warranted. The decision process may need to involve the individual, family, and care partners, leading to a care plan that is both convenient and effective for the goals of care (156) . The pharmacologic therapy may include oral agents as first line, followed by a simplified insulin plan. If needed, basal insulin can be implemented, accompanied by oral agents and without rapidacting insulin. Agents that can cause gastrointestinal symptoms such as nausea or excess weight loss may not be good choices in this setting. As symptoms progress, some agents may be slowly tapered and discontinued.

Different categories have been proposed for diabetes management in those with advanced disease (70).

1. A stable individual: Continue with the person's previous medication plan, with a focus on 1) the prevention of hypoglycemia and 2) the management of hyperglycemia using blood glucose monitoring, keeping levels below the renal threshold of glucose, and hyperglycemia-mediated dehydration.

There is no role for A1C monitoring. 2. An individual with organ failure: Preventing hypoglycemia is of greatest significance. Dehydration must be prevented and treated. In people with type 1 diabetes, insulin administration may be reduced as the oral intake of food decreases but should not be stopped. For those with type 2 diabetes, agents that may cause hypoglycemia should be reduced in dose.

The main goal is to avoid hypoglycemia, allowing for glucose values in the upper level of the desired goal range. 3. A dying individual: For people with type 2 diabetes, the discontinuation of all medications may be a reasonable approach, as these individuals are unlikely to have any oral intake. In people with type 1 diabetes, there is no consensus, but a small amount of basal insulin may maintain glucose levels and prevent acute hyperglycemic complications and symptom burden.

Finally, diabetes health care professionals are well positioned to support people with diabetes in advance care planning. Health care professionals can assist people with diabetes in clarifying and documenting their values, preferences, and goals for care in an advance care plan (157) . Advance care plans are guides and decision aids to help health care professionals and care partners make difficult treatment decisions when the person with diabetes is no longer able to make decisions for themselves. Research shows that people with diabetes want to discuss end-of-life care plans with their health care professional (158) . Two validated tools exist to support health care professionals in this process: the Supportive and Palliative Care Indicators Tool (159) and the Gold Standards Framework Proactive Identification Guidance (160) .

In conclusion, the management of diabetes in older adults at the end of life necessitates a person-centered approach that prioritizes comfort, symptom management, quality of life, and the preservation of dignity. The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes .org/SOC.

The management of diabetes in children and adolescents (individuals < 18 years of age) cannot simply be derived from care routinely provided to adults with diabetes. The epidemiology, pathophysiology, developmental considerations, and response to therapy in pediatric diabetes are often different from those of adult diabetes. There are also differences in recommended care for children and adolescents with type 1 diabetes, type 2 diabetes, and other forms of diabetes. This section is divided into two major parts: the first part addresses care for children and adolescents with type 1 diabetes, and the second part addresses care for children and adolescents with type 2 diabetes. Monogenic diabetes (neonatal diabetes and maturity-onset diabetes of the young) and cystic fibrosis-related diabetes, which are often present in youth, are discussed in Section 2, "Diagnosis and Classification of Diabetes." Table 14 .1A and Table 14 .1B provide an overview of the recommendations for screening and treatment of complications and related conditions in pediatric type 1 diabetes and type 2 diabetes, respectively. In addition to comprehensive diabetes care, youth with diabetes should receive age-appropriate and developmentally appropriate pediatric care, including immunizations as recommended by the Centers for Disease Control and Prevention (CDC) (1). To ensure continuity of care as a person with diabetes becomes an adult, guidance is provided at the end of this section on the transition from pediatric to adult diabetes care.

Due to the nature of pediatric clinical research, the recommendations for children and adolescents with diabetes are less likely to be based on clinical trial evidence. However, expert opinion and a review of available and relevant experimental data are summarized in the American Diabetes Association (ADA) position statements "Type 1 Diabetes in Children and Adolescents" (2) and "Evaluation and Management of Youth-Onset Type 2 Diabetes" (3). Finally, other sections in the Standards of Care may have recommendations that apply to youth with diabetes and are referenced in the narrative of this section.

TYPE 1 DIABETES

Type 1 diabetes is the most common form of diabetes in youth (4), although there are more adults living with and diagnosed with type 1 diabetes (5). The health care professional must consider the unique aspects of care and management of children and adolescents with type 1 diabetes, such as changes in insulin sensitivity related to physical growth and sexual maturation, ability to provide self-care, supervision in the childcare and school environment, neurological vulnerability to hypoglycemia and hyperglycemia in young children, and possible adverse neurocognitive effects of diabetic ketoacidosis (DKA) (6, 7) . Attention to family dynamics, developmental stages, and physiologic differences related to sexual maturity is essential in developing and implementing an optimal diabetes treatment plan (8) . Additionally, more people (adults and youth) with type 1 diabetes are experiencing obesity than in the past, which adds to the complexity of living with and managing type 1 diabetes ( 9 ). An interprofessional team trained in pediatric diabetes management and sensitive to the challenges of children and adolescents with type 1 diabetes and their families should provide diabetesspecific care for this population. It is essential that diabetes self-management education and support (DSMES), medical nutrition therapy (MNT), and psychosocial and behavioral support be provided at diagnosis and routinely (e.g., at each follow-up visit) thereafter in a developmentally appropriate format that builds on prior knowledge by a team of health care professionals experienced with the biological, educational, nutritional, behavioral, and emotional needs of the growing child and family. The diabetes team, considering the youth's developmental and psychosocial needs, should ask about and discuss diabetes management responsibilities with youth and parents or caregivers on an ongoing basis.

Diabetes Self-Management Education and Support Recommendation 14.1 Youth with type 1 diabetes and their parents or caregivers (for individuals aged < 18 years) should receive culturally sensitive and developmentally appropriate individualized diabetes self-management education and support (DSMES) according to national standards at diagnosis and routinely thereafter. B Self-management in pediatric diabetes involves both the youth and their parents or adult caregivers. No matter how sound the medical plan is, it will only be effective if the family and/or affected individuals can implement it. Family involvement is a vital component of optimal diabetes management throughout childhood and adolescence. As parents or caregivers are critical to diabetes self-management in youth, diabetes care requires an approach that places the youth and their parents or caregivers at the center of the care model. The pediatric diabetes care team must be capable of evaluating the educational, behavioral, emotional, and psychosocial factors that impact treatment plan implementation and must work with the youth and family to overcome barriers or redefine goals as appropriate. As the youth grows, develops, and acquires the need and desire for greater independent self-care skills, DSMES requires periodic and routine (e.g., at each follow-up visit) reassessment. The pediatric diabetes team should work with the youth and their parents or caregivers to ensure there is not a premature transfer of self-management tasks to the youth during this time. In addition, it is important to assess the educational needs and skills of, and provide training to, daycare workers, school nurses, and school personnel who are responsible for the care and supervision of the child with diabetes (2, 10, 11) .

Nutrition Therapy Recommendations 14.2 Individualized medical nutrition therapy (MNT) is recommended for youth with type 1 diabetes as an essential component of the overall treatment plan. A 14.3 Monitoring carbohydrate intake, whether by carbohydrate counting or experience-based estimation, is a key component to optimizing glycemic management. B 14.4 Advise youth with type 1 diabetes and their caregivers to strive for an eating pattern emphasizing key nutrition principles (including nonstarchy vegetables, whole fruits, legumes, fish and other lean protein, whole grains, nuts and seeds, and low-fat dairy products, and minimize consumption of red meat, sugar-sweetened beverages, sweets, refined grains, and processed foods). B 14.5 Meal composition impacts postprandial glucose excursions. Education on the impact of high-fat and high-protein meals and the adjustment of insulin dosing is necessary. A 14.6 Strongly advise comprehensive nutrition education at diagnosis, and at least annually as needed, by an experienced registered dietitian nutritionist to assess the eating pattern in relation to weight status, age-appropriate growth, and cardiovascular disease risk factors. E Nutrition management should be individualized: family habits, food preferences, religious or cultural needs, finances, schedules, physical activity, and the youth's and family's abilities in numeracy, literacy, and self-management should be considered. Visits with a registered dietitian nutritionist, preferably experienced in working with pediatric populations with diabetes, should include assessment for changes in food preferences over time, access to food, growth and development, weight status, cardiovascular risk, and potential for disordered eating. Following recommended eating patterns is associated with better glycemic outcomes in youth with type 1 diabetes (12) .

Although carbohydrate content is the primary variable for calculation of mealtime insulin doses, meals with higher fat and protein content can cause early hypoglycemia and delayed postprandial glucose excursions. Some adjustments in insulin dosing, including an increase in the calculated dose and a split dose, will improve postprandial glucose management (13) (14) (15) (16) (17) .

Physical Activity and Exercise

Recommendations 14.7 Physical activity is recommended for all youth with type 1 diabetes with the goal of 60 min of moderate-to vigorous-intensity aerobic activity daily, with vigorous muscle-strengthening and bone-strengthening activities at least 3 days per week. C 14.8 Advise frequent glucose monitoring before, during, and after exercise, via blood glucose meter and/or continuous glucose monitoring (CGM), to prevent, detect, and treat hypoglycemia and hyperglycemia associated with exercise. C 14.9 Youth and their parents or caregivers should receive education on goals and management of glycemia before, during, and after physical activity, individualized according to the type and intensity of the planned physical activity. C 14.10 Youth and their parents or caregivers should be educated on strategies to prevent hypoglycemia during, after, and overnight following physical activity and exercise. Treatment for hypoglycemia should be accessible before, during, and after engaging in activity. C Physical activity and structured exercise positively impact metabolic and psychological health in children with type 1 diabetes (18) . While it can have positive effects on insulin sensitivity, physical fitness, strength building, cardiorespiratory fitness, weight management, social interaction, mood, self-esteem building, and the creation of healthful habits for adulthood, it also has the potential to cause both hypoglycemia and hyperglycemia.

See below for strategies to mitigate hypoglycemia risk and minimize hyperglycemia associated with exercise. For an in-depth discussion, see previously published reviews and guidelines (19) (20) (21) (22) (23) .

Overall, it is recommended that all youth participate in 60 min of moderateintensity (e.g., brisk walking and dancing) to vigorous-intensity (e.g., running and jumping rope) aerobic activity daily, including resistance and flexibility training (24) . Although uncommon in the pediatric population, youth should be medically evaluated for comorbid conditions or diabetes complications that may restrict participation in an exercise program. As hyperglycemia can occur before, during, and after physical activity, it is important to ensure the elevated glucose level is not related to insulin deficiency, as that can lead to worsening hyperglycemia with exercise and ketosis risk. Intense activity should be postponed with marked hyperglycemia (glucose $350 mg/dL [$19.4 mmol/L]), moderate to large urine ketones, and/or b-hydroxybutyrate (B-OHB) > 1.5 mmol/L. Caution may be needed when B-OHB levels are $0.6 mmol/L (12, 19) .

Prevention and treatment of hypoglycemia associated with physical activity includes decreasing prandial insulin for the meal or snack before exercise and/or increasing food intake. Youth on insulin pumps without automated insulin delivery (AID) can lower basal rates by 10-50% or more or suspend for 1-2 h during exercise (25) . Decreasing basal rates or long-acting insulin doses by 20% after exercise may reduce delayed exerciseinduced hypoglycemia (26) . Accessible rapid-acting carbohydrates and frequent blood glucose monitoring before, during, and after exercise, with or without continuous glucose monitoring (CGM), maximize safety with exercise. Using AID systems may improve time in range (TIR) (70-180 mg/dL) during exercise, and youth can use brand-specific settings that are more conservative or increase the glycemic goal to prevent hypoglycemia (27) .

Blood glucose goals prior to physical activity and exercise are 126-180 mg/dL (7.0-10.0 mmol/L) but should be individualized based on the type, intensity, and duration of activity (19, 21) . The accuracy of CGM systems varies depending on the type of exercise (28) (29) (30) . Consider additional carbohydrate intake during and/or after exercise, depending on duration and intensity of physical activity, to prevent hypoglycemia. For low-to moderateintensity aerobic activities (30-60 min), and if the youth is fasting, 10-15 g of carbohydrate may prevent hypoglycemia (21) . After insulin boluses (relative hyperinsulinemia), consider 0.5-1.0 g of carbohydrates/kg per hour of exercise (30-60 g), similar to carbohydrate requirements for optimizing performance in athletes without type 1 diabetes (31, 32) .

For children and adolescents with type 1 diabetes and obesity, physical activity and exercise are key components of diabetes care. Obesity is equally common in youth with or without type 1 diabetes. Having obesity is associated with a higher frequency of cardiovascular risk factors, and it disproportionately affects youth from racial and ethnic minoritized groups (e.g., Black and Latino youth) (9, (33) (34) (35) (36) . Therefore, diabetes health care professionals should monitor weight status and encourage a healthy eating pattern, physical activity, and healthy weight as key components of pediatric type 1 diabetes care.

School and Child Care

As a large portion of a youth's day is spent in school and/or daycare, training of school or daycare personnel to provide care in accordance with the child's individualized diabetes medical management plan is essential for optimal diabetes management and safe access to all school-or daycare-sponsored opportunities (11, 37, 38) . In addition, federal and state laws require schools, daycare facilities, and other entities to provide needed diabetes care to enable the child to safely access the school or daycare environment. Refer to the ADA position statements "Diabetes Care in the School Setting" (11) and "Care of Young Children With Diabetes in the Childcare and Community Setting" (38) and the ADA's Safe at School website (diabetes.org/ resources/know-your-rights/safe-at-schoolstate-laws) for additional details.

Psychosocial Care Recommendations 14.11 At diagnosis and during routine follow-up care, screen youth with type 1 diabetes for psychosocial concerns (e.g., diabetes distress, depressive symptoms, and disordered eating), family factors, and behavioral health concerns that could impact diabetes management with age-appropriate standardized and validated tools. Refer to a qualified behavioral health professional, preferably experienced in childhood diabetes, when indicated. B 14.12 Behavioral health professionals should be considered integral members of the pediatric diabetes interprofessional team. E 14.13 Encourage developmentally appropriate family involvement in diabetes management tasks for children and adolescents, recognizing that premature or unsupportive transfer of diabetes care responsibility to the youth can contribute to diabetes distress, lower engagement in diabetes selfmanagement behaviors, and deterioration in glycemia. A 14.14 Health care professionals should screen for food security, housing stability, health literacy, financial barriers, and social or community support and apply that information to treatment decisions. E 14.15 Health care professionals should consider asking youth and their parents or caregivers about social adjustment (peer relationships) and school performance to determine whether further intervention is needed. B 14.16 Offer adolescents time by themselves with their health care professional(s) at a developmentally appropriate age. E 14.17 Starting at puberty, preconception counseling should be incorporated into routine diabetes care for all individuals of childbearing potential. A Rapid and dynamic cognitive, developmental, and emotional changes occur during childhood, adolescence, and emerging adulthood. Diabetes management during childhood and adolescence places substantial burdens on the youth and family, necessitating ongoing assessment of psychosocial status, social determinants of health, and diabetes distress in the youth and the parents or caregivers during routine diabetes visits (39) (40) (41) . It is important to consider the impact of diabetes on quality of life as well as the development of behavioral health problems related to diabetes distress, symptoms of depression, symptoms of anxiety, fear of hypoglycemia (and hyperglycemia), disordered eating behaviors, and eating disorders (39, 42) .

Consider screening youth for diabetes distress, generally starting at 7 or 8 years of age (42) , using validated tools for youth and their parents or caregivers (43) . The U.S. Preventive Services Task Force recommends screening for depression in youth aged 12-18 years (44) . Additional times to consider screening for depression include when youth are not meeting treatment goals or when there are significant changes in medical status or life circumstances. The U.S. Preventive Services Task Force also recommends screening for anxiety in youth aged 8-18 years (45) . Parents or caregivers and youth at risk for hypoglycemia or fear of hypoglycemia, especially if they have experienced severe and/or frequent hypoglycemic events, should be screened for fear of hypoglycemia; youth as young as 6 years old can provide reliable self-reports for fear of hypoglycemia (46) . Lastly, health care professionals should consider screening for disordered eating behaviors when signs and symptoms (e.g., unexplained weight loss, hyperglycemia, and DKA) and/or behavioral and emotional indicators (e.g., secrecy around eating and excessive concern about weight) are present using available screening tools (47) . Youth with type 1 diabetes have an increased risk of disordered eating behavior as well as clinical eating disorders, with serious short-term and long-term negative effects on diabetes outcomes and health in general. It is important to recognize the unique and dangerous disordered eating behavior of insulin omission for weight management in type 1 diabetes (48) .

Given the complexity of psychosocial concerns in the management of type 1 diabetes in youth, collaboration between the diabetes health care team and a behavioral health professional, ideally with expertise in diabetes, is recommended. Early detection of diabetes distress, depression, anxiety, fear of hypoglycemia, and disordered eating can facilitate effective treatment options and help minimize adverse effects on diabetes management and disease outcomes (39, 42) . When psychological symptoms are identified, referral to a behavioral health professional, ideally with experience in pediatric diabetes, may be warranted. Such professionals can provide individualized, evidence-based behavioral health care services, including cognitive-behavioral, mindfulness-based, and other interventions (49) , to improve psychosocial functioning in youth with type 1 diabetes (50) (51) (52) .

The complexities of diabetes management require ongoing parental involvement in care throughout childhood and adolescence. Developmentally appropriate, supportive family teamwork between the growing youth and parent(s) can help maintain engagement in self-management behaviors and reduce deterioration in glycemia (53, 54) . It is appropriate to inquire about diabetes-specific family relationships, including family teamwork and conflict, during visits; health care professionals can both help families negotiate a plan and refer to an appropriate behavioral health professional for more in-depth support (55) . Such professionals can conduct further assessment and deliver evidencebased behavioral interventions to support developmentally appropriate, collaborative family involvement in diabetes selfmanagement (50, 52) . Monitoring of social adjustment (peer relationships) and school performance can facilitate both well-being and academic achievement (56, 57) . Diabetes management and glycemic levels may be related to academic progress and students' functioning in the school setting, which highlights the need for appropriate accommodations and access to diabetesrelated support in school (58) .

Shared decision-making with youth regarding the adoption of management plan components and self-management behaviors can improve diabetes self-efficacy, participation in diabetes care, and glycemic outcomes (9, 59) . For example, welldesigned decision aids can engage youth in comprehensive, unbiased conversations with their diabetes care team about treatment options (60) . Other examples include creating self-care contracts (61) and technology-integrated care that uses blood glucose records shared with the care team to facilitate shared decisionmaking (62) . Importantly, health care professionals working with youth who are not yet able to provide legal consent must balance clinical oversight with promoting developmentally appropriate independence. Recommendations include providing education tailored to the developmental stage, encouraging gradual responsibility with selfcare, guiding parental involvement as responsibilities change, teaching selfadvocacy to prepare for transitions in care, and incorporating psychosocial support at all stages (57, 63) . Although cognitive abilities vary, the ethical position often adopted is the "mature minor rule," whereby children after age 12 or 13 years who appear to be mature have the right to consent or withhold consent to general medical treatment, except in cases in which refusal would significantly endanger health (64) .

Beginning at the onset of puberty or at diagnosis of diabetes, all individuals with childbearing potential should receive education about the effective use of contraception to prevent unplanned pregnancy, as risks of fetal malformations are associated with elevated A1C. Preconception counseling using developmentally appropriate educational and behavioral strategies enables individuals of childbearing potential to make wellinformed decisions (65) . Preconception counseling resources tailored for adolescents are available at no cost through the ADA (66) . Refer to the ADA position statement "Psychosocial Care for People With Diabetes" for further details (42) .

The presence of a behavioral health professional on pediatric interprofessional teams highlights the importance of attending to the psychosocial issues of diabetes. These psychosocial factors are significantly related to self-management difficulties, elevated A1C, reduced quality of life, and higher rates of acute and chronic diabetes complications. Lower goals may also be appropriate during the honeymoon phase. B 14.27 CGM metrics derived from CGM use over the most recent 14 days (or longer for youth with more glycemic variability), including time in range (70-180 mg/dL [3.9-10.0 mmol/L]), time below range ( < 70 mg/dL [ < 3.9 mmol/L] and < 54 mg/dL [ < 3.0 mmol/L]), and time above range ( > 180 mg/dL [ > 10.0 mmol/L] and > 250 mg/dL [ > 13.9 mmol/L]), are recommended to be used in conjunction with A1C whenever possible. E Current standards for diabetes management reflect the need to minimize hyperglycemia as safely as possible. The Diabetes Control and Complications Trial (DCCT), which did not enroll children < 13 years of age, demonstrated that near normalization of blood glucose levels was more difficult to achieve in adolescents than in adults. Nevertheless, the increased use of basal-bolus plans, insulin pumps, frequent blood glucose monitoring, CGM, AID systems, goal setting, and improved education has been associated with more children and adolescents reaching the blood glucose goals recommended by the ADA (67, 68) , particularly in families in which the parents or caregivers as well as the child with diabetes participate jointly to perform the required diabetes-related tasks.

Lower A1C in adolescence and young adulthood is associated with a lower risk and rate of microvascular and macrovascular complications (69-71) and demonstrates the effects of metabolic memory (72) (73) (74) (75) .

In addition, type 1 diabetes can be associated with adverse effects on cognition during childhood and adolescence (6, 76) , and neurocognitive imaging differences related to hyperglycemia in children provide another motivation for achieving glycemic goals (6) . Several factors, including young age, severe hypoglycemia at < 6 years of age, DKA, and chronic hyperglycemia (76, 77) , contribute to adverse effects on brain development and function. However, meticulous use of therapeutic modalities such as rapid-and long-acting insulin analogs, technological advances (e.g., CGM, sensor-augmented pump therapy, and AID systems), and intensive self-management education now make it more feasible to achieve glycemic goals while reducing the incidence of severe hypoglycemia . Please refer to Section 7, "Diabetes Technology," for more information on technology to support people with diabetes.

Recent data with newer devices and insulins indicate that the risk of hypoglycemia with lower A1C is less than it was before (100-108). In addition, achieving lower A1C levels is likely facilitated by setting lower A1C goals (109) . Lower goals may be possible during the honeymoon phase of type 1 diabetes. Special consideration should be given to the risk of hypoglycemia in young children (aged < 6 years) who are often unable to recognize, articulate, and/or manage hypoglycemia. However, registry data indicate that lower A1C goals can be achieved in children, including those aged < 6 years, without increased risk of severe hypoglycemia (101) . Recent data have demonstrated that the use of real-time CGM lowered A1C and increased TIR in adolescents and young adults and was associated with a lower risk of hypoglycemia (110) . Please refer to Section 6, "Glycemic Goals and Hypoglycemia," for more information on glycemic assessment.

A strong relationship exists between the frequency of blood glucose monitoring and glycemic management (97-99, 111,112) . Glucose levels for all children and adolescents with type 1 diabetes should be monitored multiple times daily by blood glucose monitoring and/or CGM. Recent data on children and adults suggest that use of CGM soon after type 1 diabetes diagnosis is associated with improved A1C (84, 85, 113) . In the U.S., real-time CGM is approved for nonadjunctive use in children aged 2 years and older, and intermittently scanned CGM is approved for nonadjunctive use in children aged 4 years and older. Parents, caregivers, and youth should be offered initial and ongoing education and support for CGM use. Behavioral support may further improve ongoing CGM use (114) . Metrics derived from CGM include percent TIR, time below target range, and time above target range (115) . While studies indicate a relationship between TIR and A1C (116, 117) , it is still uncertain what the ideal goal TIR should be for children, and further studies are needed. Please refer to Section 7, "Diabetes Technology," for more information on the use of blood glucose meters, CGM, and insulin pumps. More information on insulin injection technique can be found in Section 9, "Pharmacologic Approaches to Glycemic Treatment."

Key Concepts in Setting Glycemic Goals

• Glycemic goals should be individualized, and lower goals may be reasonable based on a benefit-risk assessment. diabetes, screening for thyroid dysfunction and celiac disease should be considered (118) (119) (120) (121) (122) . Periodic screening in asymptomatic individuals has been recommended, but the optimal frequency of screening is unclear.

Although much less common than thyroid dysfunction and celiac disease, other autoimmune conditions, such as Addison disease (primary adrenal insufficiency), autoimmune hepatitis, autoimmune gastritis, dermatomyositis, and myasthenia gravis, occur more commonly in the population with type 1 diabetes than in the general pediatric population and should be assessed and monitored as clinically indicated. In addition, relatives of youth with type 1 diabetes should be offered testing for islet autoantibodies through research studies (e.g., TrialNet) and national programs for early diagnosis of preclinical type 1 diabetes (stages 1 and 2). (119, 123, 124) . At the time of diagnosis, 25% of children with type 1 diabetes have thyroid autoantibodies (125) , the presence of which is predictive of thyroid dysfunction-most commonly hypothyroidism, although hyperthyroidism occurs in 0.5% of people with type 1 diabetes (126, 127) . For thyroid autoantibodies, a study from Sweden indicated that antithyroid peroxidase antibodies were more predictive than antithyroglobulin antibodies in multivariate analysis (128) . Thyroid function tests may be misleading (euthyroid sick syndrome) if performed at the time of diagnosis owing to the effect of previous hyperglycemia, ketosis or ketoacidosis, weight loss, etc. Therefore, if performed at diagnosis and slightly abnormal, thyroid function tests should be repeated soon after a period of metabolic stability and achievement of glycemic goals. Subclinical hypothyroidism may be associated with an increased risk of symptomatic hypoglycemia and dyslipidemia (129, 130) and a reduced linear growth rate. Hyperthyroidism alters glucose metabolism and usually causes deterioration of glycemia. 32 Repeat screening for celiac disease within 2 years of diabetes diagnosis and then again after 5 years and consider more frequent screening in youth who have symptoms or a firstdegree relative with celiac disease. B 14.33 Individuals with confirmed celiac disease should be placed on a gluten-free diet for treatment and to avoid complications. Youth and their caregivers should also have a consultation with a registered dietitian nutritionist experienced in managing both diabetes and celiac disease. B Celiac disease is an immune-mediated disorder that occurs with increased frequency in people with type 1 diabetes (1.6-16.4% of individuals compared with 0.3-1% in the general population) (118, 121, 122, (131) (132) (133) (134) . Screening people with type 1 diabetes for celiac disease is further justified by its association with osteoporosis, iron deficiency, growth failure, and potential increased risk of retinopathy and albuminuria (135) (136) (137) .

Screening for celiac disease includes measuring serum levels of IgA and tissue transglutaminase (tTG) IgA antibodies, or, with IgA deficiency, screening can include measuring tTG IgG antibodies or deamidated gliadin peptide IgG antibodies. Because most cases of celiac disease are diagnosed within the first 5 years after the diagnosis of type 1 diabetes, screening should be considered at the time of diagnosis and repeated at 2 and then 5 years (132) or if clinical symptoms indicate, such as poor growth or increased hypoglycemia (135) .

Although celiac disease can be diagnosed more than 10 years after diabetes diagnosis, there are insufficient data after 5 years to determine the optimal screening frequency. Measurement of tTG antibody should be considered at other times in individuals with symptoms suggestive of celiac disease (132) . Monitoring for symptoms should include an assessment of linear growth and weight gain (135) . A small-bowel biopsy in antibodypositive children is recommended to confirm the diagnosis (138) . European guidelines on screening for celiac disease in children (not specific to children with type 1 diabetes) suggest that biopsy may not be necessary in symptomatic children with high antibody titers (i.e., > 10 times the upper limit of normal) provided that further testing is performed (verification of endomysial antibody positivity on a separate blood sample). Whether this approach may be appropriate for asymptomatic children in high-risk groups remains an open question, though evidence is emerging (139) . It is also advisable to check for celiac disease-associated HLA types in individuals who are diagnosed without a small intestinal biopsy. In symptomatic children with type 1 diabetes and confirmed celiac disease, gluten-free diets reduce symptoms and rates of hypoglycemia (140) . The challenging eating plan restrictions associated with having both type 1 diabetes and celiac disease place a significant burden on individuals. Therefore, a biopsy to confirm the diagnosis of celiac disease is recommended, especially in asymptomatic children, before establishing a diagnosis of celiac disease and endorsing significant eating plan changes.

Management of Cardiovascular Risk Factors

Hypertension Screening Recommendation 14.34 Blood pressure should be measured at every routine visit. In youth with high blood pressure (blood pressure $90th percentile for age, sex, and height or, in adolescents aged $13 years, blood pressure $120/80 mmHg) on three separate measurements, ambulatory blood pressure monitoring should be strongly considered. B Blood pressure measurements should be performed using the appropriate size cuff with the youth seated and relaxed. Elevated blood pressure should be confirmed on at least three separate days, and ambulatory blood pressure monitoring should be considered. Evaluation should proceed as clinically indicated (141, 142) . Treatment is generally initiated with an ACE inhibitor, but an angiotensin receptor blocker can be used if the ACE inhibitor is not tolerated (e.g., due to cough) (143) . (144) (145) (146) , and the prevalence of cardiovascular disease (CVD) risk factors increase with age (146) and among racial and ethnic minoritized groups (33) , with girls having a higher risk burden than boys (145) .

Pathophysiology. The atherosclerotic process begins in childhood, and although atherosclerotic cardiovascular disease events are not expected to occur during childhood, observations using a variety of methodologies show that youth with type 1 diabetes may have subclinical CVD within the first decade of diagnosis (147) (148) (149) . Studies of carotid intima media thickness have yielded inconsistent results (142, 143) .

Screening. Diabetes predisposes the individual to the development of accelerated arteriosclerosis. Lipid evaluation for these individuals contributes to risk assessment and identifies an important proportion of those with dyslipidemia. Therefore, initial screening should be done soon after diagnosis. If the initial screen is normal, subsequent screening may be done at 9-11 years of age, which is a stable time for lipid assessment in children (150) . Children with a primary lipid disorder (e.g., familial hyperlipidemia) should be referred to a lipid specialist. Non-HDL cholesterol level has been identified as a significant predictor of the presence of atherosclerosis-as powerful as any other lipoprotein cholesterol measure in children and adolescents. For both children and adults, non-HDL cholesterol level seems to be more predictive of persistent dyslipidemia and, therefore, atherosclerosis and future events than total cholesterol, LDL cholesterol, or HDL cholesterol level alone. A major advantage (151) of non-HDL cholesterol is that it can be accurately calculated in a nonfasting state and therefore is practical to obtain in clinical practice as a screening test (152) . Youth with type 1 diabetes have a high prevalence of lipid abnormalities (144, 151) . Even if normal, screening should be repeated within 3 years, as A1C and other cardiovascular risk factors can change dramatically during adolescence (153) .

Treatment. Pediatric lipid guidelines provide some guidance relevant to children with type 1 diabetes and secondary dyslipidemia (142, 154, 155) ; however, there are few studies on modifying lipid levels in children with type 1 diabetes. A 6-month trial of nutritional counseling produced a significant improvement in lipid levels (156) ; likewise, a lifestyle intervention trial with 6 months of exercise in adolescents demonstrated improvement in lipid levels (157) . Data from the SEARCH for Diabetes in Youth (SEARCH) study show that improved glucose over a 2-year period is associated with a more favorable lipid profile; however, improved glycemia alone will not normalize lipids in youth with type 1 diabetes and dyslipidemia (158) .

Although intervention data are sparse, the American Heart Association categorizes children with type 1 diabetes in the highest tier for cardiovascular risk and recommends both lifestyle and pharmacologic treatment for those with elevated LDL cholesterol levels (159, 160) . Initial therapy should include a nutrition plan that restricts saturated fat to 7% of total calories and dietary cholesterol to 200 mg/ day (150) . Data from randomized clinical trials in children as young as 7 months of age indicate that this nutrition plan is safe and does not interfere with normal growth and development.

Long-term safety and cardiovascular outcome efficacy of statin therapy have been established for children with familial hypercholesterolemia (161) . At the time of this writing, rosuvastatin is indicated for children as young as 6 years old (162) . Statins should be avoided in individuals of childbearing age who are not using reliable contraception (see Section 15, "Management of Diabetes in Pregnancy," for more information). The multicenter, randomized, placebocontrolled Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) provides safety data on pharmacologic treatment with an ACE inhibitor and statin in adolescents with type 1 diabetes (142) .

Microvascular Complications

Nephropathy Screening Recommendation 14.43 Annual screening for albuminuria with a random (morning sample preferred to avoid effects of exercise) spot urine sample for albuminto-creatinine ratio should be considered at puberty or at age > 10 years, whichever is earlier, once the youth has had diabetes for 5 years. B Nephropathy Treatment Recommendation 14.44 An ACE inhibitor or an angiotensin receptor blocker, titrated to normalization of albumin excretion, may be considered when elevated urinary albumin-to-creatinine ratio ( > 30 mg/g) is documented (two of three urine samples obtained over a 6-month interval following efforts to improve glycemia and normalize blood pressure). E Due to the potential teratogenic effects, individuals of childbearing age should receive reproductive counseling, and ACE inhibitors and angiotensin receptor blockers should be avoided in individuals of childbearing age who are not using reliable contraception. B Data from 7,549 participants < 20 years of age in the T1D Exchange clinic registry emphasize the importance of meeting glycemic and blood pressure goals, particularly as diabetes duration increases, to reduce the risk of diabetic kidney disease. The data also underscore the importance of routine screening to ensure early diagnosis and timely treatment of albuminuria (163) . An estimation of glomerular filtration rate (GFR), calculated with GFR-estimating equations using serum creatinine, height, age, and sex (164) , should be considered at baseline and repeated as indicated based on clinical status, age, diabetes duration, and therapies. Improved methods are needed to screen for early GFR loss, since estimated GFR is inaccurate at GFR > 60 mL/min/1.73 m 2 (164, 165) . The AdDIT study in adolescents with type 1 diabetes demonstrated the safety of ACE inhibitor treatment, but the treatment did not change the albumin-to-creatinine ratio over the course of the study (142) . Retinopathy Recommendations 14.45 An initial dilated and comprehensive eye examination is recommended once youth have had type 1 diabetes for 3-5 years, provided they are aged $11 years or puberty has started, whichever is earlier. B 14.46 After the initial examination, repeat dilated and comprehensive eye examination every 2 years. Less frequent examinations, every 4 years, may be acceptable on the advice of an eye care professional and based on risk factor assessment, including a history of A1C < 8% ( < 64 mmol/mol). B 14.47 Programs that use retinal photography (with remote reading or use of a validated assessment tool) to improve access to diabetic retinopathy screening can be appropriate screening strategies for diabetic retinopathy. Such programs need to provide pathways for timely referral for a comprehensive eye examination when indicated. B Retinopathy (like albuminuria) most commonly occurs after the onset of puberty and after 5-10 years of diabetes duration (166) . It is currently recognized that there is a low risk of development of visionthreatening retinal lesions prior to 12 years of age (167, 168) . A 2019 publication based on the follow-up of the DCCT adolescent cohort supports a lower frequency of eye examinations than previously recommended, particularly in adolescents with A1C closer to the goal range (169,170). Autonomous artificial intelligence screening for diabetic retinopathy has been shown to increase access to this routine health maintenance (171). Referrals should be made to eye care professionals with expertise in diabetic retinopathy and experience in counseling pediatric individuals and families on the importance of prevention, early detection, and intervention. Neuropathy Recommendation 14.48 Consider an annual comprehensive foot exam at the start of puberty or at age $10 years, whichever is earlier, once the youth has had type 1 diabetes for 5 years. The examination should include inspection, assessment of foot pulses, pinprick, and 10-g monofilament sensation tests, testing of vibration sensation using a 128-Hz tuning fork, and ankle reflex tests. B Diabetic neuropathy rarely occurs in prepubertal children or after only 1-2 years of diabetes (166) , although data suggest a prevalence of distal peripheral neuropathy of 7% in 1,734 youth with type 1 diabetes and association with the presence of CVD risk factors (172,173). A comprehensive foot exam, including inspection, palpation of dorsalis pedis and posterior tibial pulses, and determination of proprioception, vibration, and monofilament sensation, should be performed annually along with an assessment of symptoms of neuropathic pain (173). Foot inspection can be performed at each visit to educate youth regarding the importance of foot care (see Section 12, "Retinopathy, Neuropathy, and Foot Care").

TYPE 2 DIABETES

For information on risk-based screening for type 2 diabetes and prediabetes in youth, please refer to Section 2, "Diagnosis and Classification of Diabetes." For additional support for these recommendations, see the ADA position statement "Evaluation and Management of Youth-Onset Type 2 Diabetes" (3).

The prevalence of type 2 diabetes in youth has continued to increase over the past 20 years (4). The CDC published projections for type 2 diabetes prevalence using the SEARCH database. Assuming a 2.3% annual increase, the prevalence in those under 20 years of age will quadruple in 40 years (174,175).

Evidence suggests that type 2 diabetes in youth is different not only from type 1 diabetes but also from type 2 diabetes in adults and has unique features, such as a more rapidly progressive decline in b-cell function and accelerated development of diabetes complications (3, 176) . Long-term follow-up data from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study reported most individuals with type 2 diabetes diagnosed as youth had microvascular complications by young adulthood (177). Type 2 diabetes disproportionately impacts youth from historically marginalized communities and can occur in complex psychosocial and cultural environments, which may make it difficult to implement and sustain healthy lifestyle changes and self-management behaviors (9, (178) (179) (180) (181) . Additional risk factors associated with type 2 diabetes in youth include obesity and excess adiposity (182) , family history of diabetes possibly mediated by shared genetics, lifestyle, and environmental factors (183) , female sex, maternal gestational diabetes mellitus (184) , and adverse social determinants of health (176).

As with type 1 diabetes, youth with type 2 diabetes spend much of the day in school. Therefore, close communication with and the cooperation of school personnel are essential for optimal diabetes management and safety and maximal academic opportunities.

Screening and Diagnosis

Recommendations 14.49 Risk-based screening for prediabetes and/or type 2 diabetes should be considered after the onset of puberty or $10 years of age, whichever occurs earlier, in youth with overweight (BMI $85th percentile) or obesity (BMI $95th percentile) and who have one or more additional risk factors for diabetes (see In recent years, incidence and prevalence of type 2 diabetes in adolescents have increased dramatically, especially in historically marginalized communities (185) . A few studies suggest oral glucose tolerance tests or fasting plasma glucose values as more suitable diagnostic tests than A1C in the pediatric population, especially among certain ethnicities (186) , while fasting glucose alone may overdiagnose diabetes in children (187, 188) . In addition, many of these studies do not recognize that diabetes diagnostic criteria are based on longterm health outcomes, and validations are not currently available in the pediatric population (189) . An analysis of National Health and Nutrition Examination Survey (NHANES) data suggests using A1C for screening of high-risk youth (190) . The ADA acknowledges the limited data supporting A1C for diagnosing type 2 diabetes in children and adolescents. Although A1C is not recommended for diagnosis of diabetes in children with cystic fibrosis or symptoms suggestive of acute onset of type 1 diabetes, and only A1C assays without interference are appropriate for children with hemoglobinopathies, the ADA continues to recommend A1C for diagnosis of type 2 diabetes in this population (186) .

Diagnostic Challenges

Given the current obesity epidemic, distinguishing between type 1 and type 2 diabetes in children can be difficult. Overweight and obesity are common in children with type 1 diabetes (34), and diabetes-associated autoantibodies and ketosis may be present in pediatric individuals with clinical features of type 2 diabetes (including obesity and acanthosis nigricans) (187) . The presence of islet autoantibodies has been associated with faster progression to insulin deficiency (187) . At the onset of diabetes, DKA occurs in 11% of youth aged 10-19 years with type 2 diabetes (191) . Although uncommon, type 2 diabetes has been observed in prepubertal children under the age of 10 years, thus it should be part of the differential in children with suggestive symptoms (192) . Finally, obesity contributes to the development of type 1 diabetes in some individuals (193) , which further blurs the lines between diabetes types. We must acknowledge that people with type 1 diabetes can also experience weight gain and insulin resistance. However, accurate diagnosis is critical, as treatment plans, educational approaches, nutrition advice, and outcomes differ markedly between individuals with predominantly insulin resistance and absolute insulinopenia phenotypes. The significant diagnostic difficulties posed by maturity-onset diabetes of the young are discussed in Section 2, "Diagnosis and Classification of Diabetes." In addition, there are rare and atypical diabetes cases that represent a challenge for clinicians and researchers. Treatment of youth-onset type 2 diabetes should include lifestyle management, DSMES, and pharmacologic treatment. Initial treatment of youth with obesity and diabetes must consider that diabetes type is often uncertain in the first few weeks of treatment due to overlap in presentation and that a substantial percentage of youth with type 2 diabetes will present with clinically significant ketoacidosis (194) . Therefore, initial therapy should address the hyperglycemia and associated metabolic derangements irrespective of ultimate diabetes type, with adjustment of therapy once metabolic compensation has been established and subsequent information, such as islet autoantibody results, becomes available. Figure 14 .1 provides an approach to the initial treatment of newonset diabetes in youth with overweight or obesity with clinical suspicion of type 2 diabetes.

Glycemic goals should be individualized, taking into consideration the longterm health benefits of more stringent goals and risk for adverse effects, such as hypoglycemia. A lower A1C goal of < 6.5% in youth with type 2 diabetes compared with < 7% recommended in type 1 diabetes is justified by a lower risk of hypoglycemia and higher risk of complications in youth with type 2 diabetes (177, (195) (196) (197) (198) (199) .

Self-management in pediatric diabetes involves both the youth and their parents or adult caregivers. Individuals and their families should receive education and support for healthful nutrition and physical activity, such as a balanced meal plan, achieving and maintaining a healthy weight, and regular physical activity. Physical activity should include aerobic, muscle-strengthening, and bone-strengthening activities (24) . A family-centered approach to nutrition and lifestyle modification is essential in children and adolescents with type 2 diabetes, and nutrition recommendations should be culturally appropriate and sensitive to family resources (see Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes"). Given the complex social and environmental context surrounding youth with type 2 diabetes, individual-level lifestyle interventions may not be sufficient to address the complex interplay of family dynamics, behavioral health, community readiness, and the broader environmental system (3).

An interprofessional diabetes team, including a physician, diabetes care and education specialist (CDCES), registered dietitian nutritionist, and behavioral health specialist or social worker, is essential. In addition to achieving glycemic goals and self-management education (200) (201) (202) , initial treatment must include management of comorbidities such as obesity, dyslipidemia, hypertension, and microvascular complications.

Current pharmacologic treatment options for youth-onset type 2 diabetes are limited to four approved drug classes: insulin, metformin, glucagon-like peptide 1 (GLP-1) receptor agonists, and sodium-glucose cotransporter 2 inhibitors. Presentation with ketoacidosis or marked ketosis requires a period of insulin therapy until fasting and postprandial glycemia have been restored to normal or near-normal levels. Insulin pump therapy may be considered as an option for those on longterm multiple daily injections who are able to safely manage the device. Initial treatment should also be with insulin when the distinction between type 1 diabetes and type 2 diabetes is unclear and in individuals who have random blood glucose concentrations $250 mg/dL ($13.9 mmol/L) and/or A1C $8.5% ($69 mmol/mol) (203) . Metformin therapy should be added after resolution of ketosis or ketoacidosis.

When initial insulin treatment is not required, initiation of metformin is recommended as first-line therapy. The TODAY study found that metformin alone provided durable glycemic management (A1C To date, the TODAY study is the only trial combining lifestyle and metformin therapy in youth with type 2 diabetes; the combination did not perform better than metformin alone in achieving durable glycemic levels (204) .

Randomized controlled trials in youth have shown that GLP-1 receptor agonists are safe and effective for decreasing A1C (206-210) and promoting weight loss at higher doses approved for obesity (211) . Use of GLP-1 receptor agonists can increase the frequency of gastrointestinal side effects and should not be used in individuals with a family history of medullary thyroid cancer.

In addition to GLP-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors are well-studied drugs in adults with type 2 diabetes, and empagliflozin is now approved for use in youth with type 2 diabetes. In a recent multicenter double-blind, placebo-controlled trial, 158 children with type 2 diabetes aged between 10 and 17 years were randomized to 10 mg empagliflozin, 5 mg linagliptin, or placebo. Participants in the empagliflozin group who did not have A1C below 7.0% by week 12 underwent a second double-blinded randomization at week 14 to either remain on 10 mg of empagliflozin or increase their dose to 25 mg. In the empagliflozin pooled group compared with the placebo group, there was a significant reduction in A1C of 0.84% (P = 0.012). There were no episodes of severe hypoglycemia during the study (212) .

Blood glucose monitoring plans should be individualized, taking into consideration the pharmacologic treatment of the person. Although data on CGM in youth with type 2 diabetes are sparse (213, 214) , CGM could be considered in individuals requiring frequent blood glucose monitoring for diabetes management.

Metabolic Surgery

Recommendations 14.70 Metabolic surgery may be considered for the treatment of adolescents with type 2 diabetes who have class 2 obesity or higher (BMI > 35 kg/m 2 or > 120% of 95th percentile for age and sex, whichever is lower) and who have elevated A1C and/or serious comorbidities despite lifestyle and pharmacologic intervention. A 14.71 Metabolic surgery should be performed only by an experienced surgeon working as part of a well-organized and engaged interprofessional team, including a surgeon, endocrinologist, registered dietitian nutritionist, behavioral health specialist, and nurse. A

The results of weight loss and lifestyle interventions for obesity in children and adolescents have been disappointing, and treatment options as adjuncts to lifestyle therapy are limited. Recent U.S. Food and Drug Administration-approved medications for youth ages 12 years and older include phentermine and topiramate extendedrelease capsules and GLP-1 receptor agonists (211, (215) (216) (217) . Over the last decade, weight loss surgery has been increasingly performed in adolescents with obesity. Small retrospective analyses and a prospective multicenter, nonrandomized study suggest that bariatric or metabolic surgery have benefits in adolescents with obesity and type 2 diabetes like those observed in adults. Early follow-up studies indicate that adolescents experience similar degrees of weight loss compared with adults and even higher rates of type 2 diabetes and hypertension remission (218) . A secondary data analysis from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) and TODAY studies suggests surgical treatment of adolescents with severe obesity and type 2 diabetes is associated with improved glycemia compared with the agents used in the TODAY study (219) ; however, no randomized trials have compared the effectiveness and safety of surgery with those of conventional treatment options in adolescents and particularly with the vertical sleeve gastrectomy, which is the most widely performed metabolic surgery in adolescents (220) . The guidelines used as an indication for metabolic surgery in adolescents generally include class 2 obesity or higher (BMI > 35 kg/m 2 or > 120% of 95th percentile for age and sex, whichever is lower, with comorbidities) or BMI > 40 kg/m 2 with or without comorbidities (221) (222) (223) (224) (225) (226) (227) . A number of groups, including the Pediatric Bariatric Study Group and Teen-LABS study, have demonstrated the effectiveness of metabolic surgery in adolescents (221) (222) (223) (224) (225) . However, long-term data on the rates of complications, reoperations, nutritional deficiencies, and diabetes recurrence are still needed. (176, 228) . Therefore, blood pressure measurement, a fasting lipid panel, assessment of random urine albumin-to-creatinine ratio, foot examination for neuropathy, and a dilated eye examination should be performed at diagnosis. Additional medical conditions that may need to be addressed include polycystic ovary disease and other comorbidities associated with pediatric obesity, such as sleep apnea, hepatic steatosis, orthopedic complications, and psychosocial concerns. The ADA position statement "Evaluation and Management of Youth-Onset Type 2 Diabetes" (3) provides guidance on the prevention, screening, and treatment of type 2 diabetes and its comorbidities in children and adolescents.

Youth-onset type 2 diabetes is associated with significant microvascular and macrovascular risk burden and a substantial increase in the risk of cardiovascular morbidity and mortality at an earlier age than in those diagnosed later in life (177, 229). The higher complication risk in earlieronset type 2 diabetes is likely related to prolonged lifetime exposure to hyperglycemia and other atherogenic risk factors, including insulin resistance, dyslipidemia, hypertension, and chronic inflammation. There is a low risk of hypoglycemia in youth with type 2 diabetes, even if they are being treated with insulin (230) , and there are high rates of complications (196) (197) (198) 230) . These diabetes comorbidities also appear to be higher than those in youth with type 1 diabetes despite shorter diabetes duration and lower A1C (228) . In addition, the progression of vascular abnormalities appears to be more pronounced in youthonset type 2 diabetes than with type 1 diabetes of similar duration, including ischemic heart disease and stroke (229) .

In youth with type 2 diabetes and polycystic ovary syndrome, oral contraceptives are appropriate agents.

Psychosocial Factors

Recommendations 14.99 Health care professionals should screen for food insecurity, housing stability, health literacy, financial barriers, and social or community support and apply that information to treatment decisions. E 14.100 Use age-appropriate standardized and validated tools to screen for diabetes distress, depressive symptoms, and behavioral health concerns in youth with type 2 diabetes, with attention to symptoms of depression and disordered eating, and refer to a qualified behavioral health professional when indicated. B 14.101 Starting at puberty, preconception counseling should be incorporated into routine diabetes clinic visits for all individuals of childbearing potential because of the adverse pregnancy outcomes in this population. A Most youth with type 2 diabetes come from historically marginalized communities, have low socioeconomic status, and often experience multiple psychosocial stressors (9, 40, 42, 231) . Consideration of the sociocultural context and efforts to personalize diabetes management are of critical importance to minimize barriers to care, enhance participation, and maximize response to treatment. Screening for food insecurity, housing stability, and other barriers related to the social determinants of health should be part of routine pediatric diabetes care (232) . Please see Section 1, "Improving Care and Promoting Health in Populations," for further information on how to screen and address social determinants of health-related barriers.

Evidence about psychosocial concerns in youth with type 2 diabetes is limited (233) (234) (235) (236) , but given the sociocultural context for many youth, combined with the medical burden and obesity associated with type 2 diabetes, continuous monitoring of behavioral health is recommended. Symptoms of depression and disordered eating are common and associated with higher A1C (41, 233, 237, 238) . Early detection of psychological and behavioral concerns can facilitate effective treatment options to improve psychosocial well-being and support diabetes (42) . When psychological symptoms are identified, referral to a behavioral health professional, ideally with experience in pediatric diabetes, may be warranted. Although far less research has been done on psychological and behavioral interventions for youth with type 2 diabetes than for youth with type 1 diabetes, behavioral professionals can provide behavioral health care services to support youth with type 2 diabetes (50) (51) (52) . Many of the medications prescribed for diabetes and psychiatric disorders are associated with weight gain and can increase concerns about eating, body shape, and weight (239, 240) .

The TODAY study documented high rates of maternal complications during pregnancy and low rates of preconception counseling and contraception use in youth with type 2 diabetes (241) . Preconception counseling tailored for adolescents with diabetes (including type 2 diabetes) has sustained behavioral benefits (65) . The adverse health effects of smoking and use of tobacco products are well recognized with respect to future cancer and CVD risk. Despite this, smoking rates are significantly higher among youth with diabetes than among youth without diabetes (242) . In youth with diabetes, it is important to avoid additional CVD risk factors. Smoking increases the risk of the onset of albuminuria; therefore, smoking avoidance is important to prevent both microvascular and macrovascular complications (150) . Discouraging use of tobacco products, including electronic cigarettes (243, 244) , is an important part of routine diabetes care. Individuals with diabetes should be advised to avoid vaping and using electronic cigarettes, either as a way to stop smoking tobacco or as a recreational drug. In younger children, it is important to assess exposure to cigarette smoke in the home because of the adverse effects of secondhand smoke and to discourage youth from ever smoking.

As alcohol use has implications for glycemic management and safety in youth and young adults with diabetes, efforts are warranted to reduce alcohol use and increase education about the risks of alcohol use and strategies to minimize risks. A psychoeducational intervention for adolescents with chronic medical conditions, including type 1 diabetes, has demonstrated benefits for knowledge, perceived benefits, and reduced use (245) . See also Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes."

Finally, increased legalization and multiple formulations of cannabis products have resulted in increased use of these products among youth and young adults. In 2022, 30.7% of 12th graders reported using cannabis in the past year and 6.3% reported using it daily over the past 30 days (246) . Cannabis users with type 1 diabetes are at increased risk for hyperglycemic ketosis due to cannabis hyperemesis syndrome (severe nausea, abdominal pain, and vomiting) (247) . For youth with type 1 diabetes presenting with a hyperglycemic emergency, health care professionals should consider cannabis hyperemesis syndrome in individuals with pH $7.4 and bicarbonate > 15 mmol/L in the presence of ketosis (247) . Routine diabetes care should discourage the use of recreational cannabis in all forms. See Section 5, "Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes," for more information about smoking cessation, tobacco, electronic cigarettes, and cannabis in people with diabetes.

TRANSITION FROM PEDIATRIC TO ADULT CARE Recommendations 14.106 Diabetes care teams should implement transition preparation programs for youth beginning in early adolescence and, at the latest, at least 1 year before the anticipated transfer from pediatric to adult health care. E 14.107 Interprofessional adult and pediatric health care teams should provide support and resources for adolescents, young adults, and their families prior to and during the transfer process from pediatric to adult health care. C 14.108 Pediatric diabetes specialists should partner with youth with diabetes and their caregivers to engage in shared decision-making for the timing of transfer to an adult diabetes specialist. There is no age-specific cutoff for youth with diabetes to transfer to an adult diabetes specialist. E Care and close supervision of diabetes management are increasingly shifted from parents and other adults to the youth with type 1 or type 2 diabetes throughout childhood and adolescence. The shift from pediatric to adult health care professionals, however, often occurs abruptly as the older teen enters the next developmental stage, referred to as emerging adulthood (248) , which is a critical period for young people who have diabetes. During this period of major life transitions, youth may begin to move out of their parents' or caregivers' homes and become increasingly responsible for their diabetes care. Their new responsibilities include self-management of their diabetes, making medical appointments, and financing health care once they are no longer covered by their parents' health insurance plans (ongoing coverage until age 26 years is currently available under provisions of the U.S. Affordable Care Act). In addition to lapses in health care, this is also a period associated with deterioration in glycemic stability; increased occurrence of acute complications; psychosocial, emotional, and behavioral challenges; and the emergence of chronic complications (249, 250) . The transfer period from pediatric to adult care is prone to fragmentation in health care delivery, which may adversely impact health care quality, cost, and outcomes (251) . Worsening diabetes health outcomes during the transition to adult care and early adulthood have been documented (252, 253) .

Comprehensive and coordinated planning that begins in early adolescence is necessary to facilitate a seamless transition from pediatric to adult health care (249, 254) . Research on effective interventions to promote successful transition to adult care is limited, although there are promising developments that may improve attendance at follow-up appointments and lower hospitalizations (255, 256) . Use of transition coordinators, technology to support communication with young adults, and other interventions may be useful in addressing the identified needs and preferences of young adults for transition (257) and in supporting successful establishment in adult care settings (258) (259) (260) (261) . Given the behavioral, psychosocial, and developmental factors that relate to this transition, diabetes care teams addressing transition should include physicians, certified diabetes care and education specialists, nurses, behavioral health professionals, registered dietitian nutritionists, and social workers (50, 262) . Resources to enhance social and peer support during the transition process may also be valuable (263) . A comprehensive discussion regarding the challenges faced during this period, including specific recommendations, is found in the ADA position statement "Diabetes Care for Emerging Adults: Recommendations for Transition From Pediatric to Adult Diabetes Care Systems" (249) . Ultimately, there is no age cutoff for youth with diabetes to transfer to adult diabetes care. The decision to transfer should be a collaborative process in which the youth with diabetes, their caregivers, and pediatric diabetes specialists discuss their readiness, preferences, and concerns to ensure that the transfer aligns with their needs and circumstances (256) .

The Endocrine Society, in collaboration with the ADA and other organizations, has developed transition tools for clinicians and youth and families (254) . The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

DIABETES IN PREGNANCY

The prevalence of diabetes in pregnancy has been increasing in the U.S. in parallel with the worldwide epidemic of obesity. Not only is the prevalence of type 1 diabetes and type 2 diabetes increasing in individuals of reproductive age but there is also a dramatic increase in the reported rates of gestational diabetes mellitus (GDM). Diabetes confers significantly greater maternal and fetal risk that is largely related to the degree of hyperglycemia but also is related to chronic complications and comorbidities of diabetes. In general, specific risks of diabetes in pregnancy include spontaneous abortion, fetal anomalies, preeclampsia, fetal demise, macrosomia, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal respiratory distress syndrome. In addition, exposure to hyperglycemia in utero increases the risks of obesity, hypertension, and type 2 diabetes in offspring later in life (1, 2) . Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www .diabetesjournals.org/journals/pages/license.

15. MANAGEMENT OF DIABETES IN PREGNANCY

15.4 Individuals with a history of gestational diabetes mellitus (GDM) should seek preconception screening for diabetes and preconception care to identify and treat hyperglycemia and prevent congenital malformations. E Preconception counseling for pregnant people with preexisting type 1 or type 2 diabetes is highly effective in reducing the risk of congenital malformations and decreasing the risk of preterm delivery and admission to neonatal intensive care units. Preconception counseling is also associated with reductions in perinatal mortality and small-for-gestational-age birth weight (3) . A key point is the need to incorporate a question about plans for pregnancy into the routine primary and gynecologic care of people with diabetes.

There are opportunities at any health care visit to educate all adults and adolescents with diabetes and childbearing potential about the risks of unplanned pregnancies and about improved maternal and fetal outcomes with pregnancy planning (4) . Education and counseling should be offered, even when individuals already use contraception or do not intend to conceive (5) . Effective preconception counseling could avert substantial health and associated cost burdens related to the offspring (6) . Family planning should be discussed, including the benefits of long-acting, reversible contraception, and effective contraception should be prescribed and used until the individual is prepared and ready to become pregnant (7) (8) (9) (10) (11) .

All individuals with diabetes and childbearing potential should be informed about the importance of achieving and maintaining as near euglycemia as safely possible prior to conception and throughout pregnancy. Observational studies show an increased risk of diabetic embryopathy, especially anencephaly, microcephaly, congenital heart disease, kidney anomalies, and caudal regression, directly proportional to elevations in A1C during the first 10 weeks of pregnancy (12) . Although observational studies are confounded by the association between elevated periconceptional A1C and other engagement in self-care behaviors, the quantity and consistency of data are convincing and support the recommendation to optimize glycemia prior to conception with an A1C < 6.5% ( < 48 mmol/mol), as this is associated with the lowest risk of congenital anomalies (given that organogenesis occurs primarily at 5-8 weeks of gestation), preeclampsia, and preterm birth (12) (13) (14) (15) (16) . In a systematic review and meta-analysis of observational studies, preconception care for pregnant individuals with preexisting diabetes was associated with lower A1C and reduced risks of birth defects, preterm delivery, perinatal mortality, smallfor-gestational-age births, and neonatal intensive care unit admissions (17) .

To minimize the occurrence of complications, beginning at the onset of puberty or at diagnosis, all adults and adolescents with diabetes of childbearing potential should receive education about 1) the risks of malformations associated with unplanned pregnancies, even with mild hyperglycemia, and 2) the use of effective contraception at all times when trying to prevent a pregnancy. Preconception counseling using developmentally appropriate educational tools enables adolescents with childbearing potential to make well-informed decisions (4). Preconception counseling resources tailored to adolescents are available at no cost through the American Diabetes Association (ADA) (18) .

Individuals with prediabetes or a history of GDM will need preconception evaluation for as long as they have childbearing potential. Individuals with a history of GDM who are planning pregnancy should undergo screening for prediabetes or type 2 diabetes prior to conception, as outlined in Section 2, "Diagnosis and Classification of Diabetes." In the nonpregnant state, evaluation may be performed with any glycemic test recommended in Section 2. If the evaluation reveals euglycemia without prediabetes or type 2 diabetes, then with a subsequent pregnancy the individual with GDM should be screened for abnormal glucose metabolism ( < 15 weeks) or GDM at 24-28 weeks (if abnormal glucose metabolism testing was not previously performed or was not present) as outlined in Section 2. Should prediabetes or type 2 diabetes be diagnosed, the individual should initiate treatment with a goal to achieve and maintain an A1C of < 6.5% ( < 48 mmol/mol) prior to conception using therapies approved for use in pregnancy. Preconception evaluation should assess maternal weight. In a randomized trial of individuals with overweight or obesity and a history of GDM, weight loss prior to a subsequent pregnancy was associated with a lower risk of GDM recurrence, especially when weight loss was $5% (odds ratio [OR] 0.18, 95% CI 0.04-0.88) (19) . Counseling on weight management should include the known benefits and risks of different strategies for achieving and maintaining weight loss. For strategies that include pharmacotherapy, recommendations should be given for when changes in medications should occur prior to pregnancy.

Preconception Care Recommendations 15.5 Individuals with preexisting diabetes who are planning a pregnancy should ideally begin receiving interprofessional care for preconception, which includes an endocrinology health care professional, maternal-fetal medicine specialist, registered dietitian nutritionist, and diabetes care and education specialist, when available. B 15.6 In addition to focused attention on achieving glycemic goals, A standard preconception care should be augmented with extra focus on nutrition, physical activity, diabetes self-care education, and screening for diabetes comorbidities and complications. B 15.7 Individuals with preexisting diabetes who are planning a pregnancy or who have become pregnant should be counseled on the risk of development and/or progression of diabetic retinopathy. Dilated eye examinations should occur ideally before pregnancy as well as in the first trimester, and then pregnant individuals should be monitored every trimester and for 1 year postpartum as indicated by the degree of retinopathy and as recommended by the eye care health care professional. B

The importance of preconception care for all pregnant people is highlighted by American College of Obstetricians and Gynecologists (ACOG) Committee Opinion 762, "Prepregnancy Counseling" (5) . Preconception care for people with prediabetes and diabetes should include the standard screening and care recommended for any person planning pregnancy (5) . Prescription of prenatal vitamins with at least 400-800 mg of folic acid (20) and 150 mg of potassium iodide (21) is recommended prior to conception. Review and counseling on abstaining from nicotine products, alcohol, and recreational drugs, including marijuana, is important. Standard care includes screening for sexually transmitted infections and thyroid disease, recommended vaccinations, routine genetic screening, a careful review of all prescription and nonprescription medications, herbal supplements, and nonherbal supplements used and a review of travel history and plans with special attention on areas known to have relevant endemic viruses, as outlined by ACOG. See Table 15 .1 for additional details on elements of preconception care (5, 20, 22) .

Due to the complexity of insulin management in pregnancy, referral to a specialized center offering team-based care (with team members including a maternalfetal medicine specialist, endocrinologist or other health care professional experienced in managing pregnancy and preexisting diabetes, registered dietitian nutritionist (RDN), diabetes care and education specialist, and social worker, as needed) is recommended if this resource is available. When a single specialized center is not available, providing an interprofessional team approach through interprofessional team members at different centers may still be beneficial.

The most important diabetes-specific component of preconception care is the attainment of glycemic goals prior to conception. Diabetes-specific counseling should include an explanation of the risks to mother and fetus related to pregnancies associated with diabetes and the ways to reduce risks, including glycemic goal setting, lifestyle and behavioral management, and medical nutrition therapy (3) . Risks for GDM are characterized by an increased risk of large-for-gestational-age birth weight and neonatal and pregnancy complications and an increased risk of long-term maternal type 2 diabetes and abnormal glucose metabolism of offspring in childhood. These associations with maternal oral glucose tolerance test (OGTT) results are continuous with no clear inflection points (23, 24) . Offspring with exposure to untreated GDM have reduced insulin sensitivity and b-cell compensation and are more likely to have impaired glucose tolerance in childhood (25) . In other words, short-term and longterm risks increase with progressive maternal hyperglycemia.

Counseling on the specific risks of obesity in pregnancy and lifestyle interventions to prevent and treat obesity, including referral to an RDN, is recommended regardless of diabetes status (26) . The risk for associated hypertension and other comorbidities may be as high or higher with type 2 diabetes as it is with type 1 diabetes, even if diabetes is better managed and of shorter apparent duration, with pregnancy loss appearing to be more prevalent in the third trimester in those with type 2 diabetes compared with the first trimester in those with type 1 diabetes (27, 28) .

For individuals with preexisting diabetes, the presence of microvascular complications is associated with higher risk of disease progression and adverse pregnancy outcomes (29) . Diabetes-specific testing should include A1C, creatinine, and urinary albumin-to-creatinine ratio. Special attention should be paid to the review of the medication list for potentially harmful drugs, e.g., ACE inhibitors (30) , angiotensin receptor blockers (30) , and statins in some cases (31) . For individuals using medications that are not approved for use in pregnancy (such as some glucose-lowering, lipid-lowering, and antihypertensive agents), preconception care should include recommendations for when changes in medications should occur to stabilize the conditions and risk factors managed by these medications (such as glucose levels, weight, lipids, and blood pressure) on alternate therapies prior to pregnancy. A referral for a comprehensive eye exam is recommended. Individuals with preexisting diabetic retinopathy will need close monitoring during pregnancy to assess stability or progression of retinopathy and provide treatment if indicated (32) .

GLYCEMIC GOALS IN PREGNANCY

Recommendations 15.8 Fasting, preprandial, and postprandial blood glucose monitoring are recommended in individuals with diabetes in pregnancy to achieve optimal glucose levels. Glucose goals are fasting plasma glucose < 95 mg/dL ( < 5.3 mmol/L) and either 1-h postprandial glucose < 140 mg/dL ( < 7.8 mmol/L) or 2-h postprandial glucose < 120 mg/dL ( < 6.7 mmol/L). B 15.9 Due to increased red blood cell turnover, A1C is slightly lower during pregnancy in people with and without diabetes. Ideally, the A1C goal in pregnancy is < 6% ( < 42 mmol/mol) if this can be achieved without significant hypoglycemia, but the goal may be relaxed to < 7% ( < 53 mmol/mol) if necessary to prevent hypoglycemia. B 15.10 Continuous glucose monitoring (CGM) can help to achieve glycemic goals (e.g., time in range, time above range) A and A1C goal B in type 1 diabetes and pregnancy and may be beneficial for other types of diabetes in pregnancy. E 15.11 Recommend CGM to pregnant individuals with type 1 diabetes. A In conjunction with aims to achieve traditional pre-and postprandial glycemic goals, real-time CGM can reduce the risk for large-for-gestational-age infants and neonatal hypoglycemia in pregnancy complicated by type 1 diabetes. A 15.12 CGM metrics may be used in combination with blood glucose monitoring to achieve optimal pre-and postprandial glycemic goals. E 15.13 Commonly used estimated A1C and glucose management indicator calculations should not be used in pregnancy as estimates of A1C. C

Insulin Physiology

Pregnancy in people with normal glucose metabolism is characterized by fasting levels of blood glucose that are lower than those in the nonpregnant state due to insulin-independent glucose uptake by the fetus and placenta and by mild postprandial hyperglycemia and carbohydrate intolerance as a result of diabetogenic placental factors. Early pregnancy may be a time of enhanced insulin sensitivity and lower glucose levels and is followed by progressive insulin resistance in the second and third trimesters (33) (34) (35) . Insulin resistance drops rapidly with the delivery of the placenta. In people with normal pancreatic function, insulin production is sufficient to meet the challenge of this physiological insulin resistance and to maintain normal glucose levels. However, in people with diabetes, hyperglycemia occurs if treatment is not adjusted appropriately.

Glucose Monitoring

Reflecting this physiology, fasting and postprandial blood glucose monitoring is recommended to achieve glycemic goals in pregnant people with diabetes. Preprandial testing is also recommended when using insulin pumps or basal-bolus therapy so that the premeal rapid-acting insulin dosage can be adjusted. Postprandial monitoring is associated with better glycemic outcomes and a lower risk of preeclampsia (36) (37) (38) . There are no adequately powered randomized trials comparing different fasting and postmeal glycemic goals for preexisting diabetes in pregnancy.

Similar to the glycemic goals recommended by ACOG (39) , the ADArecommended goals for pregnant people with type 1 or type 2 diabetes are shown in Table 15 .2. Lower limits are based on the mean of normal blood glucose in pregnancy (40) but do not apply to individuals with type 2 diabetes treated with nutrition alone. Hypoglycemia in pregnancy is as defined and discussed in Recommendations 6.10-6.18 (see Section 6, "Glycemic Goals and Hypoglycemia"). The most appropriate hypoglycemia threshold level in pregnancy has not been validated but has ranged from < 60 to < 70 mg/dL ( < 3.3 to < 3.9 mmol/L) in the past. Current recommendations for hypoglycemia thresholds include blood glucose < 70 mg/dL ( < 3.9 mmol/L) and sensor glucose < 63 mg/dL ( < 3.5 mmol/L) (40, 41) . These fasting or premeal and postprandial glucose values represent optimal levels if they can be achieved safely. In practice, it may be challenging for a person with type 1 diabetes to achieve these goals without hypoglycemia, particularly those with a history of recurrent hypoglycemia or impaired awareness of hypoglycemia. If an individual cannot achieve these goals without significant hypoglycemia, aim for less stringent goals based on clinical experience and individualization of care.

For individuals with GDM, glucose monitoring should aim for the goals recommended by the Fifth International Workshop-Conference on Gestational Diabetes Mellitus (42) (Table 15 .2).

A1C in Pregnancy

In studies of individuals without preexisting diabetes, increasing A1C levels within the normal range are associated with adverse outcomes (43) . In the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, increasing levels of glycemia were also associated with worsening outcomes (23) . Observational studies in preexisting diabetes and pregnancy show the lowest rates of adverse fetal outcomes in association with A1C < 6-6.5% ( < 42-48 mmol/mol) early in gestation (13, 14, 16, 44) . Clinical trials have not evaluated the risks and benefits of achieving these goals, and treatment goals should account for the risk of maternal hypoglycemia in setting an individualized goal of < 6% ( < 42 mmol/mol) to < 7% ( < 53 mmol/mol). Due to physiological increases in red blood cell turnover, A1C levels fall during normal pregnancy (45, 46) . Additionally, as A1C represents an integrated measure of glucose, it may not fully capture postprandial hyperglycemia, which drives macrosomia. Thus, although A1C may be useful, it should be used as a secondary measure of glycemic outcomes in pregnancy, after blood glucose monitoring.

In the second and third trimesters, A1C < 6% ( < 42 mmol/mol) has the lowest risk of large-for-gestational-age infants (44, 47, 48) , preterm delivery (49) , and preeclampsia (1, 50) . Taking all of this into account, a goal of < 6% ( < 42 mmol/mol) is optimal during pregnancy if it can be achieved without significant hypoglycemia, which, in addition to the usual adverse sequelae, may increase the risk of low birth weight (51, 52) . Given the alteration in red blood cell kinetics during pregnancy and physiological changes in glycemic parameters, A1C levels may need to be monitored more frequently than usual (e.g., monthly).

Continuous Glucose Monitoring in Pregnancy

The Continuous Glucose Monitoring in Pregnant Women With Type 1 Diabetes Trial (CONCEPTT) was a randomized controlled trial (RCT) of real-time continuous glucose monitoring (CGM) in addition to standard care, including optimization of pre-and postprandial glucose goals versus standard care for pregnant people with type 1 diabetes. It demonstrated the value of using real-time CGM in pregnant individuals with type 1 diabetes by showing a mild improvement in A1C and significant improvements in the maternal glucose time in range (TIR) and time above range (TAR), without an increase in hypoglycemia, and reductions in large-for-gestationalage births, length of infant hospital stays, and severe neonatal hypoglycemia (53) . An observational cohort study that evaluated the glycemic variables reported using CGM systems found that lower mean glucose, lower SD, and higher percentage of TIR were associated with lower risks of large-for-gestational-age births and other adverse neonatal outcomes (54) . Data from one study suggest that the use of the CGMreported mean glucose is superior to the use of estimated A1C, glucose management indicator, and other calculations to estimate A1C, given the changes to A1C that occur in pregnancy (55) . One RCT and two observational studies have found that a 5% increase in CGM TIR was associated with improvements in neonatal morbidity, including large-for-gestational-age births and neonatal intensive care unit admissions (53, 54, 56) . CGM TIR can be used for assessment of glycemic outcomes in people with type 1 diabetes, but it does not provide actionable data to address fasting and postprandial hypoglycemia or hyperglycemia. The cost of CGM use by pregnant individuals with type 1 diabetes is offset by improved maternal and neonatal outcomes (57) .

There are insufficient data to support the use of CGM in all people with type 2 diabetes or GDM (58, 59) . The decision of whether to use CGM in pregnant individuals with type 2 diabetes or GDM should be individualized based on treatment plan, circumstances, preferences, and needs.

The international consensus on TIR (41) endorses pregnancy glucose goal ranges and goals for TIR for people with type 1 diabetes using CGM as reported on the ambulatory glucose profile. The international consensus on TIR (41) endorses the same sensor glucose goal ranges for individuals with type 2 diabetes in pregnancy and GDM but could not quantify the goal of amount of time spent within each category because of insufficient data. However, the consensus does not specify the type or accuracy of the CGM device or need for alarms and alerts. A small prospective, observational study of pregnant people with type 1 diabetes simultaneously monitored with intermittently scanning CGM (isCGM) and real-time CGM for 7 days in early pregnancy demonstrated a higher percentage of time below range (TBR) in the isCGM group. Asymptomatic hypoglycemia measured by isCGM should therefore not necessarily lead to a reduction of insulin dose and/or increased carbohydrate intake at bedtime unless these episodes are confirmed by blood glucose meter measurements (60) . Selection of CGM device should be based on an individual's circumstances, preferences, and needs.

Goals for sensor glucose ranges in pregnancy:

• Goal sensor glucose range 63-140 mg/dL The management of pregnancies associated with diabetes includes appropriate nutrition, lifestyle and behavior management, physical activity goals, and pharmacotherapy to support the maternal, fetal, and placental needs and reach glycemic goals regardless of the diabetes type.

Medical Nutrition Therapy

In people with preexisting diabetes, glycemic goals are usually achieved through a combination of insulin administration and medical nutrition therapy. Because glycemic goals in pregnant individuals are stricter than in nonpregnant individuals, it is important that pregnant people with diabetes eat consistent amounts of carbohydrates to match their insulin dosage and to avoid hyperglycemia or hypoglycemia. Referral to an RDN is important to establish a food plan and insulin-tocarbohydrate ratio and determine weight gain goals. The quality of the carbohydrates should be evaluated. A subgroup analysis of the CONCEPTT study demonstrated that the diets of individuals planning pregnancy and currently pregnant assessed during the run-in phase prior to randomization were characterized by high-fat, low-fiber, and poor-quality carbohydrate intakes. Fruit and vegetable consumption was inadequate, with one in four participants at risk for micronutrient deficiencies, highlighting the importance of medical nutrition therapy ( 61 ). An expert panel on nutrition in pregnancy and the U.S. Department of Health and Human Services recommend a balance of macronutrients. An eating pattern that severely restricts any macronutrient class should be avoided, specifically the ketogenic diet that lacks carbohydrates, the paleo diet because of dairy restriction, and any eating pattern characterized by excess saturated fats (62) . Pregnant individuals with diabetes are recommended to consume whole foods, including fruits, vegetables, legumes, whole grains, lean protein, and healthy fats with n-3 fatty acids, which includes nuts and seeds and fish, which are less likely to promote excessive weight gain (63) . Processed foods, fatty red meat, and sweetened foods and beverages should be limited (62, 63) .

The recommended dietary reference intake for all pregnant people is a minimum of 175 g of carbohydrate ($35% of a 2,000-calorie diet), a minimum of 71 g of protein, and 28 g of fiber (64) . The nutrition plan should emphasize monounsaturated and polyunsaturated fats while limiting saturated fats and avoiding trans fats. As is true for all nutrition therapy in people with diabetes, the amount and type of carbohydrate will impact glucose levels. Promoting higher-quality, nutrient-dense carbohydrates results in ability to meet fasting or postprandial glucose goals, lower free fatty acids, improved insulin action, and vascular benefits and may reduce excess infant adiposity. Individuals who substitute fat for carbohydrates may unintentionally enhance lipolysis, promote elevated free fatty acids, and worsen maternal insulin resistance (65, 66) . Fasting urine ketone testing may be useful to identify those who are severely restricting carbohydrates to manage blood glucose. Carbohydrate restriction can increase the risk of higher dietary fat consumption, which may lead to fetal overgrowth (62) . Simple carbohydrates will result in higher postmeal excursions.

Medical nutrition therapy for GDM is an individualized nutrition plan developed between the pregnant person and an RDN familiar with the management of GDM (67, 68) . The food plan should provide adequate calorie intake to promote fetal, neonatal, and maternal health, achieve glycemic goals, and promote appropriate weight gain, according to the 2009 National Academy of Medicine recommendations (69) . There is no definitive research that identifies a specific optimal calorie intake for people with GDM or suggests that their calorie needs are different from those of pregnant individuals without GDM. The food plan should be based on a nutrition assessment with dietary reference intake guidance from the National Academy of Medicine.

Lifestyle and Behavioral Management

Although there is some heterogeneity, many RCTs and a Cochrane review suggest that the risk of GDM may be reduced by diet, exercise, and lifestyle counseling, particularly when interventions are started during the first trimester or early in the second trimester (70) (71) (72) .

After diagnosis of GDM, treatment starts with medical nutrition therapy, physical activity, and weight management, depending on pregestational weight, as outlined in this section. Depending on the population, studies suggest that 70-85% of people diagnosed with GDM under Carpenter-Coustan criteria can manage GDM with lifestyle modification alone; it is anticipated that this proportion will be even higher if the lower International Association of the Diabetes and Pregnancy Study Groups (73) diagnostic thresholds are used.

It is recommended that generally healthy people do at least 150 min of moderateintensity aerobic activity each week during pregnancy and postpartum, preferably spread throughout the week (74) . Adjustments to a physical activity routine or plan should be done in consultation with a health care professional, especially if someone is considering a big change in physical activity intensity (74) . Such activity improves cardiorespiratory fitness and reduces the risk for excessive gestational weight gain or postpartum weight retention (74) .

With respect to GDM, a systematic review demonstrated improvements in glucose outcomes and reductions in need to start insulin or insulin dose requirements with an exercise intervention. However, there was heterogeneity in the types of effective exercise (aerobic, resistance, or both) and duration of exercise (20-50 min/day, 2-7 days/week of moderate intensity) (75), so there is insufficient evidence about which specific type of exercise program has the biggest impact on these diabetes-related outcomes in pregnancy.

Health Care Delivery for People With Diabetes in Pregnancy

As discussed in the preconception care subsection above, team-based care is recommended either through a single specialized center (when available) or multiple centers with interprofessional team members as part of the care plan during pregnancy. A meta-analysis of 32 RCTs evaluating the effectiveness of telemedicine interventions, which ranged from telemedicine visits to the use of health apps, used in combination with in-person visits for GDM demonstrated reduced incidences of cesarean delivery, premature rupture of membranes, pregnancy-induced hypertension or preeclampsia, preterm birth, neonatal asphyxia, and polyhydramnios compared with standard in-person care alone (76) .

Pharmacologic Therapy

Insulin

Insulin should be used to manage type 1 diabetes in pregnancy and is preferred for the management of type 2 diabetes in pregnancy and GDM. The physiology of pregnancy necessitates frequent titration of insulin to match changing requirements and underscores the importance of daily and frequent blood glucose monitoring. In early pregnancy, many people with type 1 diabetes will have lower insulin requirements and an increased risk for hypoglycemia (33) . At around 16 weeks, insulin resistance begins to increase, and total daily insulin doses increase linearly by $5% per week through week 36. This usually results in a doubling of daily insulin dose compared with the prepregnancy requirement. While there is an increase in both basal and bolus insulin requirements, bolus insulin requirements take up a larger proportion of overall total daily insulin needs in individuals with preexisting diabetes as pregnancy progresses (34, 35) . The insulin requirement levels off toward the end of the third trimester. A rapid and significant reduction in insulin requirements may indicate the development of placental insufficiency (36) , although data are conflicting (77) .

Optimal glycemic goals are often easier to achieve during pregnancy with type 2 diabetes than with type 1 diabetes but can require much higher doses of insulin, sometimes necessitating concentrated insulin formulations. It is recommended that insulin management be performed with interprofessional team members with relevant expertise.

None of the currently available human insulin preparations have been demonstrated to cross the placenta (78) (79) (80) (81) (82) (83) . Insulins studied in RCTs are preferred (84) (85) (86) over those studied in cohort studies (87) , which are preferred over those studied in case reports only.

Both multiple daily insulin injections and continuous subcutaneous insulin infusion are reasonable delivery strategies in pregnancy, with neither showing superiority over the other (82, 88) . Partial closed-loop therapy, such as predictive low-glucose suspend (PLGS) technology, has been shown in nonpregnant people to be better than sensor-augmented insulin pumps (SAP) for reducing low glucose values (89) . It may be suited for pregnancy because predictive low-glucose thresholds for suspending insulin are in the pregnancy ranges of premeal and overnight glucose goals and may allow for more aggressive prandial dosing.

Automated insulin delivery (AID) systems have been studied in pregnancy and postpartum. In one study, 124 pregnant individuals with type 1 diabetes used either an AID system with glucose targets that could be set near or in the pregnancy-specific fasting glucose range or standard of care (CGM use with another insulin delivery strategy). Investigators recommended pump glucose targets of 100 mg/dL in early pregnancy and 81-90 mg/dL from 16 to 20 weeks onward. The AID group had a higher CGM TIR (10.5% difference between groups, P < 0.001), lower TAR (À10.2% [95% CI À13.8 to À6.6]), and lower A1C (À0.31% [À0.50 to À0.12] ), and a subset of participants who were interviewed reported benefits with AID use during pregnancy (e.g., more enjoyment of pregnancy, better sleep, less worry) (90, 91) .

There have been RCTs examining AID systems that do not have either pregnancy-specific pump glucose targets in the algorithms or algorithms that adapt specifically to pregnancy but were used with assistive techniques. In a study with 95 pregnant individuals with type 1 diabetes, participants used an AID system set to a pump glucose target of 100 mg/dL or to standard of care. The 24-h TIR was similar between groups, but the nocturnal TIR was higher (6.58%, P = 0.003), the 24h TBR was lower (À1.34%, P = 0.002), and the nocturnal TBR was lower (À1.86%, P = 0.0005) in the AID group (92) . AID users reported higher diabetes treatment satisfaction and had less hypoglycemia unawareness (per Gold scores) (92) . In a pilot study (n = 23) where participants were randomized in the second trimester to AID with a system whose glucose target is 120 mg/dL or SAP with the same system, time spent in TBR decreased significantly in the AID group from baseline to third trimester (7.5% first trimester vs. 2.8% third trimester, P < 0.05), but the average sensor glucose was higher in the AID group in the third trimester (mean [SE] 119 [4] SAP vs. 132 [4] AID, P = 0.0475) without significant differences between groups in other CGM metrics (93) . These two studies used assistive techniques, such as administration of fake carbohydrate insulin boluses for carbohydrates that were not consumed, and pump management was determined by expert guidance from an experienced interprofessional team (92) (93) (94) . Thus, it may be appropriate to continue or initiate AID therapy with systems that do not have pregnancy-specific glucose targets or algorithms in carefully selected pregnant individuals with type 1 diabetes in the setting of using assistive techniques with expert guidance (92) (93) (94) . Assessments of potential candidates for AID wear in pregnancy should include relevant parameters such as glycemic levels, presence or absence of severe hypoglycemic or hyperglycemic events, ability or comfort in engaging with diabetes technology, psychosocial determinants, cost, individual preference, and other factors as relevant.

Continuous subcutaneous insulin infusion was compared with intravenous insulin infusion in an RCT of 70 participants during labor and delivery. There was no difference between groups in the primary outcome of neonatal hypoglycemia or in secondary outcomes (e.g., mean neonatal glucose in first 24 h of life, severe neonatal hypoglycemia) (95) . In an RCT of 18 participants using AID or sensor-augmented pump therapy for 12 weeks postpartum (96) , those in the AID group had fewer hypoglycemia episodes (96) . See sensoraugmented pumps and automated insulin delivery systems in Section 7, "Diabetes Technology," for more information on these systems.

Treatment of GDM with lifestyle and insulin has been demonstrated to improve perinatal outcomes in two large RCTs, as summarized in a U.S. Preventive Services Task Force review (97) . Insulin is the first-line agent recommended for the treatment of GDM in the U.S. While individual studies support limited efficacy of metformin (98, 99) and glyburide (100) in reducing glucose levels for the treatment of GDM, these agents are not recommended as the first-line treatment of GDM because they are known to cross the placenta and data on long-term safety for offspring is of some concern (39) . Furthermore, in separate RCTs, glyburide and metformin failed to achieve adequate glycemic outcomes in 23% and 25-28% of participants with GDM, respectively (101, 102) .

Sulfonylureas

Sulfonylureas are known to cross the placenta and have been associated with increased neonatal hypoglycemia. Concentrations of glyburide in umbilical cord plasma are approximately 50-70% of maternal levels (101, 102) . In systematic reviews and meta-analyses, compared with insulin or metformin, glyburide was associated with a higher rate of neonatal hypoglycemia and macrosomia and an increased neonatal abdominal circumference (103, 104) .

Glyburide was not found to be noninferior to insulin based on a composite outcome of neonatal hypoglycemia, macrosomia, and hyperbilirubinemia (105) . Long-term safety data for offspring exposed to glyburide are not available (105) .

Metformin was associated with a lower risk of neonatal hypoglycemia and less maternal weight gain than insulin in systematic reviews and RCTs for GDM treatment, but treatment monotherapy failure occurred in 14-46% of individuals (103, (106) (107) (108) (109) . A meta-analysis of 11 RCTs demonstrated that metformin treatment in pregnancy does not reduce the risk of GDM in highrisk individuals with obesity, polycystic ovary syndrome, or preexisting insulin resistance (110) . RCTs of individuals with preexisting type 2 diabetes treated either with insulin alone or insulin plus metformin did not show differences in composite neonatal health outcomes between groups (111, 112) , and one of these also included individuals diagnosed with diabetes early in gestation (112) . Neonatal birth weights were smaller in the metformin groups of these studies, but the metformin group experienced more drug intolerance in one study and there was a doubling of small-for-gestational-age neonates in the other (111, 112) . RCTs comparing metformin with other therapies for ovulation induction in individuals with polycystic ovary syndrome have not demonstrated benefit in preventing spontaneous abortion or GDM (113) , and there is no evidence-based need to continue metformin in these individuals (114) (115) (116) .

Of note, metformin readily crosses the placenta, resulting in umbilical cord blood levels of metformin as high or higher than simultaneous maternal levels (117, 118) . In the Metformin in Gestational Diabetes: The Offspring Follow-Up (MiG TOFU) study's analyses of 7-to 9-year-old offspring, the 9-year-old offspring exposed to metformin for the treatment of GDM in the Auckland cohort (but not the Adelaide cohort) were heavier and had a higher waist-to-height ratio and waist circumference than those exposed to insulin (119) . In one RCT of metformin use in pregnancy for polycystic ovary syndrome, follow-up of 4-year-old offspring demonstrated higher BMI and increased obesity in the offspring exposed to metformin (120) . A follow-up study at 5-10 years showed that the offspring had higher BMI, weight-to-height ratios, and waist circumferences and a borderline increase in fat mass (121, 122) . A meta-analysis demonstrated that metformin exposure resulted in smaller neonates with an acceleration of postnatal growth, resulting in higher BMI in childhood (121) . Follow-up of offspring from the Metformin in Women with Type 2 Diabetes in Pregnancy (MiTy Kids) trial showed no differences in anthropometrics of children at 24 months (123) .

There are some people with GDM requiring medical therapy who may not be able to use insulin safely or effectively during pregnancy due to cost, comprehension, or cultural influences. Oral agents may be an alternative for these individuals after discussing the known risks and the need for more long-term safety data in offspring. However, due to the potential for growth restriction or acidosis in the setting of placental insufficiency, metformin should not be used in pregnant people with hypertension or preeclampsia or those at risk for intrauterine growth restriction (123) (124) (125) .

Special Considerations for Management of Pregnancies With Diabetes

Pregnant individuals with type 1 diabetes have an increased risk of hypoglycemia in the first trimester and after delivery, and like all pregnant people, they have altered counterregulatory response in pregnancy that may decrease hypoglycemia awareness. Education for people with diabetes and family members about the prevention, recognition, and treatment of hypoglycemia is important before, during, and after pregnancy to help prevent and manage hypoglycemia risk.

Pregnancy is a ketogenic state, and people with type 1 diabetes and, to a lesser extent, those with type 2 diabetes are at risk for diabetic ketoacidosis (DKA) at lower blood glucose levels than in the nonpregnant state. Pregnant people with type 1 diabetes should be advised to obtain ketone test strips and receive education on DKA prevention and detection. DKA carries a high risk of stillbirth. Those in DKA who are unable to eat often require 10% dextrose with an insulin drip to adequately meet the higher carbohydrate demands of the placenta and fetus in the third trimester to resolve their ketosis.

Retinopathy is a special concern in pregnancy. The necessary rapid implementation of euglycemia in the setting of retinopathy diabetesjournals.org/care Management of Diabetes in Pregnancy S313

is associated with worsening of retinopathy (126) . Meta-analyses have also demonstrated a high risk of new-onset retinopathy and progression of existing retinopathy in pregnant individuals with type 1 or type 2 diabetes (32, 127) . Therefore, it is recommended that individuals with preexisting diabetes have dilated eye examinations before pregnancy, in each trimester of pregnancy, and for 1 year postpartum as indicated by the degree of retinopathy and as recommended by the eye care health care professional.

Recommended weight gain during pregnancy for people with overweight status is 15-25 lbs (6.8-11.3 kg) and for those with obesity is 10-20 lbs (4.5-9.1 kg) (69) . There are no adequate data on optimal weight gain versus weight maintenance in pregnant people with BMI > 35 kg/m 2 ; however, losing weight is not recommended because of the increased risk of small-for-gestational-age infants (26) .

PREECLAMPSIA AND ASPIRIN

Recommendation 15.23 Pregnant individuals with type 1 or type 2 diabetes should be prescribed low-dose aspirin 100-150 mg/day starting at 12-16 weeks of gestation to lower the risk of preeclampsia. E A dosage of 162 mg/day may be acceptable; E currently, in the U.S., low-dose aspirin is available in 81-mg tablets.

Diabetes in pregnancy is associated with an increased risk of preeclampsia (128) . The U.S. Preventive Services Task Force recommends that blood pressure measurements be obtained throughout gestation to screen for hypertensive disorders of pregnancy (129) . The Task Force also recommends using low-dose aspirin (81 mg/day) as a preventive medication at 12 weeks of gestation in individuals at high risk for preeclampsia, such as those with type 1 or type 2 diabetes (130) . However, a meta-analysis and an additional trial demonstrate that low-dose aspirin < 100 mg is not effective in reducing preeclampsia, so a dose of > 100 mg is required (131) (132) (133) . A cost-benefit analysis has concluded that this approach would reduce morbidity, save lives, and lower health care costs (134) . There are insufficient data about whether the use of aspirin specifically in pregnant people with preexisting diabetes ultimately reduces the incidence of preeclampsia (135, 136) , although a meta-analysis showed that preeclampsia reductions occurred with aspirin administration in high-risk groups overall (128) . Individuals with GDM may be candidates for aspirin therapy for preeclampsia prevention if they have a single high-risk factor, such as chronic hypertension or an autoimmune disease, or multiple moderate risk factors, such as being nulliparous, having obesity, being age $35 years, or other factors per the U.S. Preventive Services Task Force (130) . More studies are needed to assess the long-term effects of prenatal aspirin exposure on offspring (135) .

PREGNANCY AND DRUG CONSIDERATIONS

Recommendations 15.24 In pregnant individuals with diabetes and chronic hypertension, a blood pressure threshold of 140/90 mmHg for initiation or titration of therapy is associated with better pregnancy outcomes than reserving treatment for severe hypertension, with no increase in risk of small-for-gestationalage birth weight. A There are limited data on the optimal lower limit, but therapy should be deintensified for blood pressure < 90/ 60 mmHg. E A blood pressure goal of 110-135/85 mmHg is suggested in the interest of reducing the risk for accelerated maternal hypertension. A 15.25a Potentially harmful medications in pregnancy (e.g., ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists) should be stopped prior to conception and avoided in sexually active individuals of childbearing potential who are not using reliable contraception. B 15.25b In most circumstances, lipidlowering medications should be stopped prior to conception and avoided in sexually active individuals of childbearing potential with diabetes who are not using reliable contraception. B In some circumstances (familial hypercholesterolemia, prior atherosclerotic cardiovascular disease event), statin therapy may be continued when the benefits outweigh risks. E In normal pregnancy, blood pressure is lower than in the nonpregnant state. The Chronic Hypertension and Pregnancy (CHAP) Trial Consortium's RCT on treatment of mild chronic hypertension during pregnancy demonstrated that a blood pressure of 140/90 mmHg, as the threshold for initiation or titration of treatment, reduces the incidence of adverse pregnancy outcomes without compromising fetal growth (137) . The CHAP Consortium's study mitigates concerns about small-for-gestational-age birth weight. Attained mean ± SD blood pressure measurements in the treated versus untreated groups were systolic 129.5 ± 10.0 vs. 132.6 ± 10.1 mmHg (betweengroup difference À3.11 [95% CI À3.95 to 2.28]) and diastolic 79.1 ± 7.4 vs. 81.5 ± 8.0 mmHg (À2.33 [95% CI À2.97 to 0.04] ), respectively (137) . Individuals with diabetes had an even better composite outcome score than those without diabetes (137) .

As a result of the CHAP study, ACOG issued a Practice Advisory recommending a blood pressure of 140/90 mmHg as the threshold for initiation or titration of medical therapy for chronic hypertension in pregnancy (138) rather than their previously recommended threshold of 160/110 mmHg (139) .

Data from the previously published Control of Hypertension in Pregnancy Study (CHIPS) supports a blood pressure goal of 110-135/85 mmHg to reduce the risk of unmanaged maternal hypertension and minimize impaired fetal growth (139) (140) (141) . The 2015 study (140) excluded pregnancies complicated by preexisting diabetes, and only 6% of participants had GDM at enrollment. There was no difference in pregnancy loss, neonatal care, or other neonatal outcomes between the groups with tighter versus less tight management of hypertension (140) .

During pregnancy, treatment with ACE inhibitors and angiotensin receptor blockers is contraindicated because they may cause fetal renal dysplasia, oligohydramnios, pulmonary hypoplasia, and intrauterine growth restriction (30) . A large study found that after adjusting for confounders, first-trimester ACE inhibitor exposure does not appear to be associated with congenital malformations (142) . ACE inhibitors and angiotensin receptor blockers should be stopped prior to pregnancy or as soon as possible in the first trimester to avoid second-and third-trimester fetopathy (142) . Antihypertensive drugs known to be effective and safe in pregnancy include methyldopa, nifedipine, labetalol, and clonidine. Atenolol is not recommended, but other b-blockers may be used, if necessary. Diuretic use during pregnancy is generally not recommended, although it may be used safely when prescribed at lower doses for individuals in certain circumstances (e.g., chronic kidney disease and reduced glomerular filtration rate) (143) .

For most individuals, lipid-lowering medications (e.g., bempedoic acid, PCSK9 therapies, fibrates) should be stopped prior to pregnancy or at the first pregnancy visit (31) . Based on available evidence, statins should also be avoided in pregnancy in most circumstances (31) . The risk of teratogenicity with statins appears to be low, but data are limited (31) . Statins can be considered in a shared decision-making process between pregnant people with diabetes and their health care teams, including discussion of risks and benefits in pregnant individuals at high-risk, such as those with a history of atherosclerotic cardiovascular disease or familial hypercholesterolemia (homozygous or severe heterozygous) (31) . Hydrophilic statins, such as pravastatin, may be associated with less fetal harm than lipophilic statins (144) . Pravastatin has been studied in multiple pregnancy trials administering therapy at various time points in gestation with the aim to reduce preeclampsia risk, and although its ability to do so is inconclusive to date, there does not appear to be increased neonatal mortality or morbidity associated with its use during gestation (31) . See pregnancy and antihypertensive medications in Section 10, "Cardiovascular Disease and Risk Management," for more information on managing blood pressure in pregnancy. For individuals requiring insulin after delivery, insulin sensitivity increases dramatically with the delivery of the placenta. In one study, insulin requirements in the immediate postpartum period are roughly 34% lower than prepregnancy insulin requirements (145) . Insulin sensitivity then returns to prepregnancy levels over the following 1-2 weeks. For individuals taking insulin, particular attention should be directed to hypoglycemia prevention in the setting of breastfeeding and erratic sleep and eating schedules (146) . Individuals with GDM usually do not require diabetes medications in the postpartum period.

018;71:2392-2401 .diabetesjournals.org/journals/pages/license.|

||Visit|| |---|---|---|

|Initial|Every follow-up|Annual|

|1-Continued||| |---|---|---|

||Visit||

|Review insulin pump settings and use and|||

|connected pen and glucose data|||

|Social life assessment|||

|Social network|||

|Identify existing social supports|||

|Identify surrogate decision maker and|||

|advanced care plan|||

|Identify social determinants of health|||

|(e.g., food security, housing stability and|||

|homelessness, transportation access,|||

|financial security, and community safety)|||

|Assess daily routine and environment,|||

|including school or work schedules and|||

|ability to engage in diabetes self-|||

|management|||

|Physical examination|||

|Height, weight, and BMI; growth and|||

|pubertal development in children and|||

|adolescents|||

|Blood pressure determination|||

|Orthostatic blood pressure measures|||

|(when indicated)|||

|Fundoscopic examination (refer to eye|||

|specialist)|||

|Thyroid palpation|||

|Skin examination (e.g., acanthosis|||

|nigricans, insulin injection or insertion|||

|sites, and lipodystrophy)|||

|Comprehensive foot examination|||

|Visual inspection (e.g., skin integrity,|||

|callous formation, foot deformity or ulcer,|||

|and toenails)*|||

|Check pedal pulses and screen for PAD|||

|with ABI testing if a PAD diagnosis would|||

|change management|||

|Determination of temperature, vibration or|||

|pinprick sensation, and 10-g monofilament|||

|exam|||

|Screen for depression, anxiety, diabetes|||

|distress, fear of hypoglycemia, and|||

|disordered eating|||

|Assessment for cognitive performance if|||

|indicated †|||

|Assessment for functional performance if|||

|Consider assessment for bone health (e.g.,|||

|loss of height and kyphosis)|||

|Laboratory evaluation|||

|A1C, if the results are not available within|||

|the past 3 months|||

|Lipid profile, including total, LDL, and HDL|||

|cholesterol and triglycerides ‡|||

|Liver function tests (i.e., FIB-4) ‡|||

|Spot urinary albumin-to-creatinine ratio|||

|Serum creatinine and estimated glomerular|||

|filtration rate §|||

|Thyroid-stimulating hormone in people|||

|with type 1 diabetes ‡|||

|Celiac disease in people with type 1|||

|diabetesjj|||

||Continued on p. S64||

|Vitamin B12 if taking metformin for > 5|||

|years|||

|CBC with platelets|||

|Serum potassium levels in people with|||

|diabetes on ACE inhibitors, ARBs, or|||

|diuretics §|||

|Calcium, vitamin D, and phosphorous for|||

|appropriate people with diabetes|||

|ABI, ankle brachial index; ARBs, angiotensin receptor blockers; CBC, complete blood count;|||

|CGM, continuous glucose monitor; FIB-4: fibrosis-4 index; MASLD, metabolic-associated stea-|||

|totic liver disease; MDI, multiple daily injections; OSA, obstructive sleep apnea; PAD, periph-|||

|eral arterial disease. *Should be performed at every visit in people with diabetes with|||

|sensory loss, previous foot ulcers, or amputations. †At 65 years of age or older.|||

|Assessing risk of diabetes complications| |---|

|ASCVD and heart failure history|

|ASCVD risk factors and 10-year ASCVD risk assessment|

|Staging of chronic kidney disease (see Table 11.2)|

|Hypoglycemia risk (see Section 6, "Glycemic Targets and Hypoglycemia Prevention")|

|Assessment for retinopathy|

|Assessment for neuropathy|

|Assessment for MASLD and MASH|

|Goal setting|

|Set A1C, blood glucose, and time in range goals|

|Set lipid goal|

|If hypertension is present, establish blood pressure goal|

|Weight management and physical activity goals|

|Diabetes self-management goals|

|Therapeutic treatment plans|

|Lifestyle management (e.g., registered dietitian nutritionist)|

|Pharmacologic therapy: glucose lowering|

|Pharmacologic therapy: cardiovascular and kidney disease risk factors|

|Weight management with pharmacotherapy or metabolic surgery, as appropriate|

|Use of glucose monitoring and insulin delivery devices|

|Referral to diabetes education and medical specialists (as needed)|

|Referrals for initial care management|

|Eye care professional for annual dilated eye exam|

|Family planning for individuals of childbearing potential|

|Registered dietitian nutritionist for medical nutrition therapy|

|Diabetes self-management education and support|

|Dentist for comprehensive dental and periodontal examination|

|Behavioral health professional, if indicated|

|Audiology, if indicated|

|Social worker and community resources, if indicated|

|Rehabilitation medicine or another relevant health care professional for physical and|

|cognitive disability evaluation, if indicated|

|Other appropriate health care professionals|

|Assessment and treatment planning are essential components of initial and all follow-up vis-|

|its. ASCVD, atherosclerotic cardiovascular disease; MASH, metabolic dysfunction-associated|

|steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease.|

|Vaccine|Recommended ages|Schedule|GRADE evidence type*|References| |---|---|---|---|---|

||older|and boosters||Prevention, Interim Clinical|

|||||Considerations for Use of COVID-19|

|||||Vaccines in the United States (318)|

|Hepatitis B|Adults with diabetes aged|Adults with diabetes aged|||

||< 60 years; for adults aged|||Vaccination in Adults Aged 19-59|

||$60 years, hepatitis B vaccine|||Years: Updated Recommendations|

||may be administered at the|||of the Advisory Committee on|

||discretion of the treating|discretion of the treating|||

||clinician based on the person's|||States, 2022 (19)|

||likelihood of acquiring|likelihood of acquiring|||

||hepatitis B infection|hepatitis B infection|||

|Influenza|All people with diabetes advised|Annual||Centers for Disease Control and|

||to receive a trivalent influenza|||Prevention, Prevention and Control|

||vaccine and not to receive live|||of Seasonal Influenza with Vaccines:|

||attenuated influenza vaccine|||Recommendations of the Advisory|

|||||Committee on Immunization|

|||||Practices-United States, 2024-25|

|||||Influenza Season (22)|

|[Pneumovax])|with Pneumovax|with Pneumovax|previously received PCV13; if PCV15||

|||was used, follow with PPSV23 $1 year||Recommendations for Prevention of|

|||later; PPSV23 is not indicated after||Invasive Pneumococcal Disease|

|||PCV20; adults who received only||Among Adults Using the 23-Valent|

|||PPSV23 may receive PCV15 or PCV20||Pneumococcal Polysaccharide|

|||$1 year after their last dose||Vaccine (PPSV23) (24,319)|

||$65 years of age|$65 years of age|One dose is recommended for those|2|

|||who previously received PCV13; if||23-Valent Pneumococcal|

|||PCV15 was used, follow with PPSV23||Polysaccharide Vaccine (PPV23)|

|||$1 year later; PPSV23 is not||Against Pneumococcal Disease in|

|||indicated after PCV20; adults who||the Elderly: Systematic Review and|

|||received only PPSV23 may receive||Meta-analysis (24,320)|

|||PCV15 or PCV20 $1 year after their|||

|||last dose|||

|PCV20 or PCV15|Adults 19-64 years of age with|One dose of PCV15 or PCV20 is||Kobayashi et al., Use of 15-Valent|

||an immunocompromising|an immunocompromising|recommended by the Centers for||

||condition (e.g., chronic renal|Disease Control and Prevention||and 20-Valent Pneumococcal|

||failure), cochlear implant, or|||Conjugate Vaccine Among U.S.|

||cerebrospinal fluid leak|cerebrospinal fluid leak|||

||Adults 19-64 years of age,|Adults 19-64 years of age,|For those who have never received any||

||immunocompetent|immunocompetent|pneumococcal vaccine, the Centers||

|||for Disease Control and Prevention||States, 2022 (24, 321)|

|||recommends one dose of PCV15 or|||

|||PCV20|||

||$65 years of age,|$65 years of age,|One dose of PCV15 or PCV20; PCSV23||

||immunocompetent, have|immunocompetent, have|may be given $8 weeks after PCV15;||

||shared decision-making|shared decision-making|PPSV23 is not indicated after PCV20||

||discussion with health care||||

||professionals|professionals|||

|RSV|Older adults $60 years of age|Adults aged $75 years and those aged||Centers for Disease Control and|

||with diabetes appear to be a|$60 years and at high risk may||Prevention, CDC Recommends RSV|

||risk group|risk group|receive a single dose of an RSV||

|||vaccine|||

|pertussis (Tdap)|should have an extra dose||3 for safety|Reduced Diphtheria Toxoid, and|

|||||Acellular Pertussis Vaccines:|

|||||Updated Recommendations of the|

|||||Advisory Committee on|

|||||Immunization Practices-United|

|||||States, 2019 (322)|

|||||Continued on p. S67|

|||vaccinated||the Advisory Committee on|

|||||Immunization Practices for Use of|

|||||Herpes Zoster Vaccines (323)|

|For a comprehensive list of vaccines, refer to the Centers for Disease Control and Prevention web site at cdc.gov/vaccines/. Advisory Commit-|||||

|tee on Immunization Practices recommendations can be found at cdc.gov/vaccines/acip/recommendations. GRADE, Grading of Recommenda-|||||

|tions Assessment, Development, and Evaluation; PCV13, 13-valent pneumococcal conjugate vaccine; PCV15, 15-valent pneumococcal|||||

|conjugate vaccine; PCV 20, 20-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine. *Evidence|||||

|type: 1, randomized controlled trials (RCTs) or overwhelming evidence from observational studies; 2, RCTs with important limitations or excep-|||||

|tionally strong evidence from observational studies; 3, observational studies or RCTs with notable limitations; 4, clinical experience and obser-|||||

|vations, observational studies with important limitations, or RCTs with several major limitations.|vations, observational studies with important limitations, or RCTs with several major limitations.|vations, observational studies with important limitations, or RCTs with several major limitations.|vations, observational studies with important limitations, or RCTs with several major limitations.||

|(Fig.| |---|

|4.2). Given the lack of widespread avail-|

|ability of LSM, the ELF test is a good alter-|

|native (238). Individuals with ELF < 9.8 are|

|considered at low risk for adverse liver|

|outcomes. Individuals with ELF $9.8 are|

|considered at high risk of having MASH|

|with advanced liver fibrosis ($F3-F4) and|

|Diagnostic Algorithm for the Prevention of Cirrhosis in People With|

|Metabolic Dysfunction-Associated Steatotic Liver|

|Lower risk of|

|future cirrhosis|

||• Repeat FIB-4 every 1-2 years| |---|---|

||• Optimize lifestyle and treatment|

||of comorbidities|

|Higher risk of||

|future cirrhosis|• Additional imaging and biomarker|

||risk stratification|

||• Treatment + long-term follow-up|

|||Disease (MASLD)| |---|---|---|

|||No|

||Rule out||

||secondary||

||causes of||

||steatosis|Yes|

||or ↑ ALT|Yes|

|* Consider|vailable. Refer to||

|liver|.8||

|||67|

|Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Treatment Algorithm| |---|

ated Steatotic Liver Disease (MASLD) Treatment Algorithm| |---|

|plasma aminotransferases and steatosis|diabetes and MASLD for glycemic man-|||| |---|---|---|---|---|

|(256) (Fig. 4.3). However, there are few|agement, as clinically indicated. However,||||

|phase 2 RCTs of GLP-1 RAs in individuals|these agents have either failed to im-||||

|with MASH proven by biopsy. A small|prove steatohepatitis in paired-biopsy||||

|RCT reported that liraglutide improved|studies (metformin) or have no RCTs with||||

|some features of MASH and may delay fibrosis progression (276). Subcutaneous|liver histological end points (i.e., sulfonyl-Prefer GLP-1 RA, dual GIP and GLP-1 RA ureas, glitinides, dipeptidyl peptidase 4|Prefer GLP-1 RA, dual GIP and GLP-1 RA, pioglitazone, SGLT2i|Not indicated|Not indicated|

Contraception

A major barrier to effective preconception care is the fact that the majority of pregnancies are unplanned. Planning pregnancy is critical in individuals with preexisting diabetes to achieve the optimal glycemic goals necessary to prevent congenital malformations and reduce the risk of other complications. Therefore, all individuals with diabetes of childbearing potential should have family planning options reviewed at regular intervals to make sure that effective contraception is implemented and maintained. This applies to individuals in the immediate postpartum period. Individuals with diabetes have the same contraception options and recommendations as those without diabetes, although the existence of diabetes complications or other vascular disease may modify recommended options. Long-acting, reversible contraception may be ideal for individuals with diabetes and childbearing potential. The risk of an unplanned pregnancy outweighs the risk of any currently available contraception option.

Lactation

Considering the immediate nutritional and immunological benefits of breastfeeding for the baby, all mothers, including those with diabetes, should be supported in attempts to breastfeed. An analysis of 28 systematic reviews and meta-analyses of associations between breastfeeding and outcomes in children found that breastfeeding was associated with numerous health benefits for children, such as reduced infant mortality due to infectious diseases at < 6 months of age (OR 0.22-0.59 across studies), reduced respiratory infections in children aged < 2 years, and reduced asthma or wheezing in children aged 5-18 years (OR 0.91, 0.85-0.98) (147) . The same analysis found that breastfeeding was associated with improved maternal health outcomes, including reduced risks of breast cancer (OR 0.81 [95% CI 0.77-0.86]), ovarian cancer (OR 0.70 [95% CI 0.64-0.75]), and type 2 diabetes (OR 0.68 [95% CI 0.57-0.82]). Breastfeeding may also confer longer-term metabolic benefits to both mother (148) and offspring (149) . Breastfeeding reduces the risk of developing type 2 diabetes in mothers with previous GDM (148) . It may improve the metabolic risk factors of offspring, but more studies are needed (150) . However, lactation can increase the risk of overnight hypoglycemia, and insulin dosing may need to be adjusted.

Special Postpartum Considerations for Individuals With Gestational Diabetes Mellitus

Because GDM often represents previously undiagnosed prediabetes, type 2 diabetes, maturity-onset diabetes of the young, or even developing type 1 diabetes, individuals with GDM should be tested for persistent diabetes or prediabetes at 4-12 weeks postpartum with a fasting 75-g OGTT using nonpregnancy criteria as outlined in Section 2, "Diagnosis and Classification of Diabetes," specifically Tables 2.1 and 2.2. The OGTT is recommended over A1C at 4-12 weeks postpartum, because A1C may be persistently impacted (lowered) by the increased red blood cell turnover related to pregnancy, by blood loss at delivery, or by the preceding 3-month glucose profile. The OGTT is more sensitive at detecting glucose intolerance, including both prediabetes and diabetes, and has been examined as a screening tool for these conditions in the first 12 weeks after delivery in individuals who had a recent pregnancy with GDM (151, 152) . In the absence of unequivocal hyperglycemia, a positive screen for diabetes requires two abnormal values. If both the fasting plasma glucose ($126 mg/dL [$7.0 mmol/L]) and 2-h plasma glucose ($200 mg/dL [$11.1 mmol/L] ) are abnormal in a single screening test, then the diagnosis of diabetes is made. If only one abnormal value in the OGTT meets diabetes criteria, the test should be repeated to confirm that the abnormality persists. OGTT testing immediately postpartum, while still hospitalized, has demonstrated improved engagement in testing but also variably reduced sensitivity to the diagnosis of impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes (153, 154) .

Individuals with a history of GDM should have ongoing screening for prediabetes or type 2 diabetes every 1-3 years, even if results of the initial 75-g OGTT at 4-12 weeks postpartum are normal. Ongoing evaluation may be performed with any recommended glycemic test (e.g., annual A1C, annual fasting plasma glucose, or triennial 75-g OGTT using thresholds for nonpregnant individuals).

Individuals with a history of GDM have an increased lifetime maternal risk for diabetes estimated at 50-60% (155, 156) , and those with GDM have a 10-fold increased risk of developing type 2 diabetes compared with those without GDM (155) . Absolute risk of developing type 2 diabetes after GDM increases linearly through a person's lifetime, being $20% at 10 years, 30% at 20 years, 40% at 30 years, 50% at 40 years, and 60% at 50 years (156) . Hazard ratios for incident diabetes were significantly elevated for a history of GDM in a single pregnancy but were even higher for a history of two GDM pregnancies in a large retrospective cohort study (hazard ratios ranged from 4.35-to 15.8-fold based on number of pregnancies with GDM and in which pregnancy the individual had GDM (first or second) (157) . In the prospective Nurses' Health Study II (NHS II), subsequent diabetes risk after a history of GDM was significantly lower in those who followed healthy eating patterns (158) .

Adjusting for BMI moderately attenuated this association. Interpregnancy weight gain is associated with increased risk of adverse pregnancy outcomes (159) and higher risk of GDM, while in people with BMI > 25 kg/m 2 , weight loss is associated with lower risk of developing GDM in the subsequent pregnancy (160) . Development of type 2 diabetes is 18% higher per unit of BMI increase from prepregnancy BMI at follow-up, highlighting the importance of effective weight management after GDM (161) . In addition, postdelivery lifestyle interventions are effective in reducing risk of type 2 diabetes (162) .

Both metformin and intensive lifestyle intervention prevent or delay progression to diabetes in individuals with prediabetes and a history of GDM. Only five to six individuals with prediabetes and a history of GDM need to be treated with either intervention to prevent one case of diabetes over 3 years (163) . In these individuals, lifestyle intervention and metformin reduced progression to diabetes by 35% and 40%, respectively, over 10 years compared with placebo (164) . If the pregnancy has motivated the adoption of healthy nutrition, building on these gains to support weight loss is recommended in the postpartum period (see Section 3, "Prevention or Delay of Diabetes and Associated Comorbidities"). The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes .org/SOC. Among hospitalized individuals, hyperglycemia, hypoglycemia, and glucose variability are associated with adverse outcomes, including increased morbidity and mortality (1) . Identification and careful management of people with diabetes and dysglycemia during hospitalization has direct and immediate benefits. Diabetes management in the inpatient setting is facilitated by identification and treatment of hyperglycemia prior to elective procedures, a dedicated inpatient diabetes management service applying validated standards of care, and a proactive transition plan for outpatient diabetes care with timely scheduled follow-up appointments. These steps can improve outcomes, shorten hospital stays, and reduce the need for readmission and emergency department visits. For older hospitalized individuals or for people with diabetes in long-term care facilities, please see Section 13, "Older Adults."

HOSPITAL CARE DELIVERY STANDARDS Recommendations 16.1 Perform an A1C test on all people with diabetes or hyperglycemia (random blood glucose > 140 mg/dL [ > 7.8 mmol/L]) admitted to the hospital if no A1C test result is available from the prior 3 months. B 16.2 Institutions should implement protocols using validated written or computerized provider order entry sets for management of dysglycemia in the hospital that allow for a personalized approach. B

Considerations on Admission

High-quality hospital care for diabetes requires clear and actionable standards for care delivery, which are best implemented using structured order sets and quality improvement strategies for process improvement. Unfortunately, "best practice" protocols, *A complete list of members of the American Diabetes Association Professional Practice Committee can be found at https://doi.org/10.2337/dc25-SINT.

16. DIABETES CARE IN THE HOSPITAL

Diabetes Care Volume 48, Supplement 1, January 2025 reviews, and guidelines are inconsistently implemented within hospitals (2). To correct this, medical centers striving for optimal inpatient diabetes treatment should establish protocols and structured order sets, which include computerized provider order entry (CPOE). Institutions are encouraged to perform audits regularly to monitor proper use and institute educational/training programs to update staff on an ongoing basis.

Initial evaluation should state the type of diabetes (i.e., type 1, type 2, gestational, pancreatogenic, stress hyperglycemia, drug related, or nutrition related [e.g., enteral or parenteral nutrition]) when it is known. Because inpatient treatment and discharge planning are more effective when preadmission glycemia is considered, A1C should be measured for all people with diabetes or dysglycemia admitted to the hospital if no A1C test result is available from the previous 3 months (3, 4) . In addition, diabetes self-management knowledge and behaviors should be assessed on admission, and diabetes self-management education should be provided throughout the hospital stay, especially if a new treatment plan is being considered. Diabetes self-management education should include the knowledge and skills needed after discharge, such as medication dosing and administration, glucose monitoring, and recognition and treatment of hypoglycemia (5) . Evidence supports preadmission treatment of hyperglycemia in people scheduled for elective surgery as an effective means of reducing adverse outcomes (6, 7) .

The National Academy of Medicine recommends CPOE to prevent medicationrelated errors and to increase medication administration efficiency (8) . Systematic reviews of randomized controlled trials using computerized assistance to improve glycemic outcomes in the hospital found significant improvement in the percentage of time individuals spent in the glycemic goal range, lower mean blood glucose levels, and no increase in hypoglycemia (9) . Where feasible, there should be structured order sets that provide computerized guidance for glycemic management. Insulin dosing algorithms using machine learning and data in the electronic health record (EHR) currently in development show promise for predicting insulin requirements during hospitalization (10, 11) .

Diabetes Care Specialists in the Hospital Recommendation 16.3 When caring for hospitalized people with diabetes (with an existing or new diagnosis) or stress hyperglycemia, consult with a specialized diabetes or glucose management team when available. B Care provided by appropriately trained specialists or specialty teams may reduce the length of stay and improve glycemic and other clinical outcomes (12) (13) (14) . In addition, the increased risk of 30-day readmission following hospitalization that has been attributed to diabetes can be reduced, and costs saved, when inpatient care is provided by a specialized diabetes management team (12, 15, 16) . In a crosssectional study comparing usual care to specialists reviewing diabetes cases and making recommendations virtually through the EHR, rates of both hyperglycemia and hypoglycemia were reduced by 30-40% (17) . Providing diabetes self-management education and developing a diabetes discharge plan that includes continued access to diabetes medications and supplies and ongoing education and support are key strategies to improve long-term outcomes (18, 19) . Details of diabetes care team composition and other resources are available from the Joint Commission accreditation program for the hospital care of diabetes, the Society of Hospital Medicine workbook, and the Joint British Diabetes Societies (JBDS) for Inpatient Care Group (20) (21) (22) .

GLYCEMIC GOALS IN HOSPITALIZED ADULTS

Recommendations 16.4a Insulin should be initiated or intensified for treatment of persistent hyperglycemia starting at a threshold of $180 mg/dL ($10.0 mmol/L) (confirmed on two occasions within 24 h) for the majority of critically ill individuals (those in the intensive care unit [ICU]). A 16.4b Insulin and/or other glucoselowering therapies should be initiated or intensified for treatment of persistent hyperglycemia starting at a threshold of $180 mg/dL ($10.0 mmol/L) (confirmed on two occasions within 24 h) for the majority of noncritically ill individuals (those not in the ICU). B 16.5a Once therapy is initiated, a glycemic goal of 140-180 mg/dL (7.8-10.0 mmol/L) is recommended for most critically ill individuals (those in the ICU) with hyperglycemia. A More stringent individualized glycemic goals may be appropriate for selected critically ill individuals if they can be achieved without significant hypoglycemia. B 16.5b For noncritically ill individuals (those not in the ICU), a glycemic goal of 100-180 mg/dL (5.6-10.0 mmol/L) is recommended if it can be achieved without significant hypoglycemia. B

Standard Definitions of Glucose Abnormalities

Hyperglycemia in hospitalized individuals is defined as blood glucose levels > 140 mg/dL ( > 7.8 mmol/L) (23) . An admission A1C value $6.5% ($48 mmol/mol) suggests that the onset of diabetes preceded hospitalization (see Section 2, "Diagnosis and Classification of Diabetes"). Level 1 hypoglycemia is defined as a glucose concentration of 54-69 mg/dL (3.0-3.8 mmol/L). Level 2 hypoglycemia is defined as a glucose concentration < 54 mg/dL ( < 3.0 mmol/L), which is typically the threshold for neuroglycopenic symptoms. Level 3 hypoglycemia is defined as a clinical event characterized by altered mental and/or physical functioning that requires assistance from another person for recovery (Table 6 .4) (24, 25) . Levels 2 and 3 require immediate intervention and correction of low blood glucose. Prompt treatment of level 1 hypoglycemia is recommended for prevention of progression to more significant level 2 and level 3 hypoglycemia.

In a landmark clinical trial conducted in a surgical intensive care unit (ICU), Van den Berghe et al. (26) demonstrated that an intensive intravenous insulin protocol with a glycemic goal of 80-110 mg/dL (4.4-6.1 mmol/L) reduced mortality by 40% compared with a standard approach of a glycemic goal of 180-215 mg/dL (10-12 mmol/L) in critically ill hospitalized individuals with diabetes and/or stress hyperglycemia and recent surgery. This study provided evidence that active treatment to lower blood glucose in hospitalized individuals could have immediate benefits. However, several multicenter studies, including the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial, in critically ill hospitalized individuals in medical and surgical ICUs (27) (28) (29) led to a reconsideration of the optimal glucose lowering goal in critical illness. In these trials, critically ill individuals randomized to intensive glycemic management (80-110 mg/dL [4.4-6.1 mmol/L]) derived no significant treatment advantage compared with a group with more moderate glycemic goals (140-180 mg/dL [7.8-10.0 mmol/L]) and had slightly but significantly higher mortality (27.5% vs. 25%). The intensively treated group had 10-to 15-fold greater rates of hypoglycemia, which may have contributed to the adverse outcomes noted. The findings from the NICE-SUGAR trial, supported by several meta-analyses and a randomized controlled trial, showed higher rates of hypoglycemia and an increase in mortality with more aggressive glycemic management goals compared with moderate glycemic goals (27, 30, 31) . Based on these results, insulin and/or other therapies should be initiated for the treatment of persistent hyperglycemia $180 mg/dL ($10.0 mmol/L). Once therapy is initiated, a glycemic goal of 140-180 mg/dL (7.8-10.0 mmol/L) is recommended for most critically ill individuals with hyperglycemia. Although not as well supported by data from randomized controlled trials, these recommendations have been extended to hospitalized individuals without critical illness. More stringent glycemic goals, such as 110-140 mg/dL (6.1-7.8 mmol/L), may be appropriate for selected individuals (e.g., critically ill individuals undergoing cardiac surgery) if they can be achieved without significant hypoglycemia (32, 33) .

For inpatient management of hyperglycemia in noncritical care settings, a glycemic goal of 100-180 mg/dL (5.6-10.0 mmol/L) is recommended, whether it is hyperglycemia due to newly diagnosed diabetes or stress hyperglycemia or hyperglycemia related to diabetes prior to admission (34) . It has been found that fasting glucose levels < 100 mg/dL ( < 5.6 mmol/L) are predictors of hypoglycemia within the next 24 h (35) . Glycemic levels up to 250 mg/dL (13.9 mmol/L) may be acceptable in selected populations (terminally ill individuals with short life expectancy, advanced kidney failure [and/or on dialysis], high risk for hypoglycemia, and/or labile glycemic excursions). In these individuals, less aggressive treatment goals that would help avoid symptomatic hypoglycemia and/or hyperglycemia are often appropriate. Clinical judgment combined with ongoing assessment of clinical status, including changes in the trajectory of glucose measures, illness severity, nutritional status, or concomitant medications that might affect glucose levels (e.g., glucocorticoids), may be incorporated into the day-to-day decisions regarding treatment goals.

GLUCOSE MONITORING

In hospitalized individuals with diabetes who are eating, point-of-care (POC) blood glucose monitoring should be performed before meals; in those not eating, glucose monitoring is advised every 4-6 h (34). More frequent POC blood glucose monitoring ranging from every 30 min to every 2 h is the required standard for safe use of intravenous insulin therapy.

Hospital blood glucose monitoring should be performed with U.S. Food and Drug Administration (FDA)-approved POC hospital-calibrated glucose monitoring systems (36) . POC blood glucose meters are not as accurate or as precise as laboratory glucose analyzers, and capillary blood glucose readings are subject to artifacts due to perfusion, edema, anemia/ erythrocytosis, and several medications commonly used in the hospital (36) (Table 7 .1). The FDA has established standards for capillary (finger-stick) POC glucose monitoring in the hospital (36) . The balance between analytic requirements (e.g., accuracy, precision, and interference) and clinical requirements (e.g., rapidity, simplicity, and POC) has not been uniformly resolved (36) (37) (38) (39) , and most hospitals have arrived at their own policies to balance these parameters. It is critically important that devices selected for inhospital use, and the workflow through which they are applied, undergo careful analysis of performance and reliability and ongoing quality assessments (39) . Recent studies indicate that POC measures provide adequate information for usual practice, with only rare instances where care has been compromised (37, 38) . Best practice dictates that any glucose result that does not correlate with the individual's clinical status should be confirmed by repeating the test first and measuring a sample in the clinical laboratory if the second result is similar, particularly for asymptomatic hypoglycemic events.

Continuous Glucose Monitoring

Recommendations 16.6 In people with diabetes using a personal continuous glucose monitoring (CGM) device, the use of CGM should be continued during hospitalization if clinically appropriate, with confirmatory point-of-care (POC) blood glucose measurements for insulin dosing decisions and hypoglycemia assessment, if resources and training are available, and according to an institutional protocol. B 16.7 Continue use of insulin pump or automated insulin delivery in people with diabetes who are hospitalized when clinically appropriate, with confirmatory POC blood glucose measurements for insulin dosing decisions and hypoglycemia assessment and treatment. This is contingent upon availability of necessary supplies, resources, and training, ongoing competency assessments, and implementation of institutional diabetes technology protocols. C Several studies have demonstrated that inpatient use of continuous glucose monitoring (CGM) has advantages over POC glucose monitoring in detecting hypoglycemia, particularly nocturnal, prolonged and/or asymptomatic hypoglycemia (40) (41) (42) , and in reducing recurrent hypoglycemia (43, 44) . However, at this time, initiating use of a new CGM device has not been approved by the FDA. During the coronavirus disease 2019 (COVID-19) pandemic, many institutions used CGM in ICU and non-ICU settings, with the aim of minimizing exposure time and saving personal protective equipment, under an FDA policy of enforcement discretion (45, 46) . Data on the safety and efficacy of realtime CGM use in the hospital, particularly with implementation of remote monitoring (e.g., a glucose telemetry system), is growing (44, (46) (47) (48) (49) .

Continuation of personal CGM device use, particularly for people with type 1 or type 2 diabetes treated with intensive insulin therapy and at increased risk for hypoglycemia during hospitalization, is recommended. Confirmatory POC capillary glucose monitoring, using hospital-calibrated glucose meters, is recommended for insulin dosing and hypoglycemia assessment (e.g., hybrid testing protocols) (42, 46, 50) . People with diabetes should be counseled about meaningful use of trend arrows and alarms and the importance of notifying nursing staff for confirmation of these events with POC capillary glucose monitoring. Similarly, continuation of automated insulin delivery systems should be supported during hospitalization, when clinically appropriate, and with proper staff training and supervision (42, 46) . Observational studies have demonstrated improvements in patient satisfaction and improved detection of glycemic excursions (41, 48) . Consultation with the endocrinology/diabetes care team or diabetes care and education specialists, if available, is recommended, especially if the reason for admission is suspected to be related to device malfunction or lack of adequate education/training or use. Hospitals are encouraged to develop institutional policies and have the availability of trained personnel with knowledge of diabetes technology. Recent review articles provide details on accuracy, interferences, precautions, and contraindications of diabetes technology devices in the hospital setting (49, 51) .

For more information on CGM, see Section 7, "Diabetes Technology."

GLUCOSE-LOWERING TREATMENT IN HOSPITALIZED INDIVDIUALS

An individualized approach for glycemic management is encouraged throughout the hospital stay and should take into consideration several predictive factors for achieving glycemic goals, such as prior home use and doses of insulin or noninsulin therapy, expected level of insulin resistance, prior A1C, current glucose levels, oral intake, and duration of diabetes.

Recommendations 16.8a Continuous intravenous insulin infusion is recommended for achieving glycemic goals and avoiding hypoglycemia in critically ill individuals. A 16.8b Basal insulin or a basal plus bolus correction insulin plan is the preferred treatment for noncritically ill hospitalized individuals with poor or no oral intake. A 16.9 An insulin plan with basal, prandial, and correction components is the preferred treatment for most noncritically ill hospitalized individuals with adequate nutritional intake. A 16.10 For most individuals, sole use of a correction or supplemental insulin without basal insulin (formerly referred to as a sliding scale) in the inpatient setting is discouraged. A

Critical Care Setting

Continuous intravenous insulin infusion is the most effective method for achieving specific glycemic goals and avoiding hypoglycemia in the critical care setting. Intravenous insulin infusions should be administered using validated written or computerized protocols that allow for predefined adjustments in the insulin infusion rate based on glycemic fluctuations and immediate past and current insulin infusion rates (52) . For diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) management, continuous intravenous insulin infusion is given for correction of hyperglycemia, hyperketonemia, and acid-base disorder following a fixed-rate intravenous insulin infusion (53) or nurse-driven protocol with a variable rate based on glucose values (54) . Individuals with mild and uncomplicated DKA can be managed with subcutaneous rapid-acting insulin doses given every 1-2 h (55).

Noncritical Care Setting

In most instances, insulin is the preferred treatment for hyperglycemia in hospitalized individuals. In certain circumstances, it may be appropriate to continue home oral glucose-lowering medications or initiate use of agents such as dipeptidyl peptidase 4 inhibitors (DPP-4i) (2, 50) . Several reports indicate that inpatient use of insulin pens is safe and may improve nurse satisfaction when safety protocols, including nursing education, are in place to guarantee single-person use (56) (57) (58) .

Outside of critical care units, scheduled subcutaneous insulin orders are recommended for the management of hyperglycemia in people with diabetes and hyperglycemia. Use of insulin analogs or human insulin results in similar glycemic outcomes in the hospital setting, but regular insulin may increase the risk of hypoglycemic events (59) . The use of subcutaneous rapid-or short-acting insulin before meals, or every 4-6 h if no meals are given or if the individual is receiving continuous enteral or parenteral nutrition, is indicated to correct or prevent hyperglycemia. Basal insulin, or a basal plus bolus correction schedule, is the preferred treatment for noncritically ill hospitalized individuals with inadequate or restricted oral intake. An insulin schedule with basal, prandial, and correction components is the preferred treatment for most noncritically ill hospitalized people with diabetes with adequate nutritional intake.

A randomized controlled trial has shown that basal plus bolus treatment improved glycemic outcomes and reduced hospital complications compared with a correction or supplemental insulin without basal insulin (formerly known as sliding scale) for people with type 2 diabetes admitted for general surgery (60) . Prolonged use of correction or supplemental insulin without basal insulin is strongly discouraged in the inpatient setting, with the exception of that for people with type 2 diabetes in noncritical care with mild hyperglycemia or stress hyperglycemia (61, 62) .

A prospective randomized inpatient study of 70/30 intermediate-acting (NPH)/ regular insulin mixture versus basalbolus therapy showed comparable glycemic outcomes but significantly increased hypoglycemia in the group receiving the insulin mixture (63) . Therefore, insulin mixtures such as 75/25, 70/30, or 50/50 insulins are not routinely recommended for inhospital use.

Data on the use of glargine U-300 and degludec U-100 or U-200 in the inpatient and perioperative settings are limited. A few studies have shown that they demonstrated similar efficacy and safety compared with glargine U-100 (64) (65) (66) .

For people with type 1 diabetes, dosing insulin based solely on premeal glucose levels does not account for basal insulin requirements or caloric intake and increases the risk of both hypoglycemia and hyperglycemia (67) . Typically, basal insulin dosing is based on body weight and expected sensitivity to insulin, and there is some evidence that people with renal insufficiency should be treated with lower insulin doses (68, 69) . An insulin schedule with basal and correction components is necessary for all hospitalized individuals with type 1 diabetes, even for those taking nothing by mouth, with the addition of prandial insulin when individuals are eating. Policies and best practice alerts in the EHR should be put in place to ensure that basal insulin (given subcutaneously, via insulin pump or by insulin infusion) is not held for people with type 1 diabetes, especially during care transitions, and that ongoing prescriber and nursing education is provided (57) .

Transitioning From Intravenous to Subcutaneous Insulin

When discontinuing intravenous insulin, a transition protocol is recommended, as it is associated with less morbidity and lower costs. Subcutaneous basal insulin should be given 2 h before intravenous infusion is discontinued, with the aim of minimizing rebound hyperglycemia while the subcutaneous insulin action rises (70, 71) .

Emerging data from studies in people with hyperglycemia with and without DKA show that the administration of a low dose (0.15-0.3 units/kg) of basal insulin analog in addition to intravenous insulin infusion may reduce the duration of insulin infusion and length of hospital stay and prevent rebound hyperglycemia without increased risk of hypoglycemia (72) (73) (74) .

For transitioning, the total daily dose of subcutaneous insulin may be calculated based on the insulin infusion rate during the prior 6-8 h when stable glycemic goals were achieved, based on prior home insulin dose, or following a weight-based approach (70) . For people being transitioned to concentrated insulin (U-200, U-300, or U-500) in the inpatient setting, it is important to ensure correct dosing by using a separate insulin pen or vial for each individual and by meticulous pharmacy and nursing supervision of the dose administered (64) (65) (66) 75) .

Noninsulin Therapies Recommendation 16.11 For people with type 2 diabetes hospitalized with heart failure, it is recommended that use of a sodiumglucose cotransporter 2 inhibitor be initiated or continued during hospitalization and upon discharge, if there are no contraindications and after recovery from the acute illness. A

The safety and efficacy of noninsulin glucose-lowering therapies in the hospital setting has recently expanded (2, 50, (76) (77) (78) . A randomized trial and an observational study have demonstrated the safety and efficacy of DPP-4i in specific groups of hospitalized people with diabetes (79, 80) . The use of DPP-4i with or without basal insulin may be a safer and simpler plan for people with mild to moderate hyperglycemia on admission (e.g., admission glucose < 180-200 mg/dL), with reduced risk of hypoglycemia (2, 80, 81) . However, the FDA states that health care professionals should consider discontinuing saxagliptin and alogliptin in people who develop heart failure (82) . Data on the inpatient use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are still mostly limited to research studies and select populations that are medically stable (77, 78) .

For people with type 2 diabetes hospitalized with heart failure, it is recommended that use of a sodium-glucose cotransporter 2 (SGLT2) inhibitor be initiated or continued during hospitalization and upon discharge, if there are no contraindications and after recovery from the acute illness (83, 84) . SGLT2 inhibitors should be avoided in cases of severe illness, in people with ketonemia or ketonuria, and during prolonged fasting and surgical procedures (85) (86) (87) (88) . Proactive adjustment of diuretic dosing is recommended during hospitalization and/or discharge, especially in collaboration with a cardiology/heart failure consult team (85) (86) (87) (88) . It is recommended that SGLT2 inhibitors should be stopped 3 days before scheduled surgeries (4 days for ertugliflozin) (89) . HYPOGLYCEMIA Recommendations 16.12 A hypoglycemia management surveillance protocol should be adopted by all health systems. A plan for identifying, treating, and preventing hypoglycemia should be established for each individual. Episodes of hypoglycemia in the hospital should be documented in the health record and tracked to inform quality improvements. C 16.13 Treatment plans should be reviewed and changed as necessary to prevent hypoglycemia and recurrent hypoglycemia when a blood glucose value of < 70 mg/dL ( < 3.9 mmol/L) is documented. C People with or without diabetes may experience hypoglycemia in the hospital setting. While hypoglycemia is associated with increased mortality (90, 91) , in many cases, it is a marker of an underlying disease rather than the cause of fatality. However, hypoglycemia is a severe consequence of dysregulated metabolism and/or diabetes treatment, and it is imperative that it be minimized during hospitalization. Many episodes of inpatient hypoglycemia are preventable. A hypoglycemia prevention and management protocol should be adopted and implemented by each hospital or hospital system. A standardized hospital-wide, nurse-initiated hypoglycemia treatment protocol should be in place to immediately address blood glucose levels < 70 mg/dL ( < 3.9 mmol/L) (92, 93) . In addition, individualized plans for preventing and treating hypoglycemia for each person should also be developed. An American Diabetes Association (ADA) consensus statement recommends that an individual's treatment plan be reviewed any time a blood glucose value of < 70 mg/dL ( < 3.9 mmol/L) occurs, as this level often predicts subsequent level 3 hypoglycemia (94) . Episodes of hypoglycemia in the hospital should be documented in the EHR and tracked (1) . A key strategy is embedding hypoglycemia treatment into all insulin and insulin infusion orders.

Inpatient Hypoglycemia: Risk Factors, Treatment, and Prevention Insulin is one of the most common medications that causes adverse events in hospitalized individuals. Errors in insulin dosing, missed doses, and/or administration errors including incorrect insulin type and/or timing of dose occur relatively frequently (95) (96) (97) and include prescriber (ordering), pharmacy (dispensing), and nursing (administration) errors. Common preventable sources of iatrogenic hypoglycemia are improper prescribing of other glucose-lowering medications and inappropriate management and follow-up of the first episode of hypoglycemia (34) . Kidney failure is an important risk factor for hypoglycemia in the hospital (98) , possibly as a result of decreased insulin clearance. Studies of "bundled" preventive therapies, including proactive surveillance of glycemic outliers and an interprofessional data-driven approach to glycemic management, showed that hypoglycemic episodes in the hospital could be reduced or prevented. Compared with baseline, studies found that hypoglycemic events decreased by 56-80% (93, 99, 100) . The Joint Commission, a global quality improvement and patient safety in health care organization, recommends that all hypoglycemic episodes be evaluated for a root cause and the episodes be aggregated and reviewed to address systemic issues and possible solutions (21) .

In addition to errors with insulin treatment, iatrogenic hypoglycemia may occur after a sudden reduction of corticosteroid dose, reduced oral intake, emesis, inappropriate timing of short-or rapid-acting insulin doses in relation to meals, reduced infusion rate of intravenous dextrose, unexpected interruption of enteral or parenteral feedings, delayed or missed blood glucose checks, and altered ability of the individual to report symptoms (101) .

Recent inpatient studies show promise for CGM to alert of impending hypoglycemia, offering an opportunity to mitigate it before it happens (42, 46, 48) . The use of personal CGM and automated insulin delivery devices, such as insulin pumps that can automatically deliver correction doses and change basal delivery rates in real time, should be supported for ongoing use during hospitalization for individuals who are capable of operating their devices safely and independently when proper oversight supervision is available. Hospitals should be encouraged to develop policies and protocols to support inpatient use of individual-and hospital-owned diabetes technology and have expert staff available for safe implementation and evaluation of continued use during the hospital stay (51) . Hospital information technology teams are beginning to integrate CGM data into the EHR. The ability to download and interpret diabetes device data during hospitalization can inform insulin dosing during hospitalization and care transitions (42) .

Predicting and Preventing Hypoglycemia

In people with diabetes, it is well established that an episode of severe hypoglycemia increases the risk for a subsequent event, partly because of impaired counterregulation (102) . In a study of hospitalized individuals, 84% of people who had an episode of severe hypoglycemia (defined as < 40 mg/dL [ < 2.2 mmol/L]) had a preceding episode of hypoglycemia ( < 70 mg/dL [ < 3.9 mmol/L]) during the same admission (103) . In another study of hypoglycemic episodes (defined as < 50 mg/dL [ < 2.8 mmol/L]), 78% of individuals were taking basal insulin, with the incidence of hypoglycemia peaking between midnight and 6:00 A.M. Despite recognition of hypoglycemia, 75% of individuals did not have their dose of basal insulin changed before the next basal insulin administration (104) . Several groups have developed algorithms to predict episodes of hypoglycemia in the inpatient setting (105, 106) . Models such as these are potentially important and, once validated for general use, could provide a valuable tool to reduce rates of hypoglycemia in the hospital. In one retrospective cohort study, a fasting blood glucose of < 100 mg/dL was shown to be a predictor of next-day hypoglycemia (35) .

MEDICAL NUTRITION THERAPY IN THE HOSPITAL

The goals of medical nutrition therapy in the hospital are to provide adequate calories to meet metabolic demands, optimize glycemic outcomes, address personal food preferences, and facilitate the creation of a discharge plan. The ADA does not endorse any single meal plan or specified percentages of macronutrients. Current nutrition recommendations advise individualization based on treatment goals, physiological parameters, and medication use. Controlled carbohydrate meal plans, where the amount of carbohydrate on each meal tray is calculated, are preferred by many hospitals, as they facilitate matching the prandial insulin dose to the amount of carbohydrate given (107) . Orders should also indicate that the meal delivery and nutritional insulin coverage should be coordinated, as their variability often creates the possibility of hyperglycemic and hypoglycemic events (18) . Some hospitals offer "meals on demand," where individuals may order meals from the menu at any time during the day. This option improves patient satisfaction but complicates glucose monitoring-insulin-meal coordination and can lead to insulin stacking if meals are too close together. Finally, if the hospital food service supports carbohydrate counting, this option should be made available to people with diabetes counting carbohydrates at home, especially people wearing insulin pumps (108, 109) .

SELF-MANAGEMENT IN THE HOSPITAL

Diabetes self-management in the hospital may be appropriate for select individuals who wish to continue to perform self-care while acutely ill (110) (111) (112) . Candidates include children with parental supervision, adolescents, and adults who successfully perform diabetes self-management at home and whose cognitive and physical skills needed to successfully self-administer insulin and perform glucose monitoring are not compromised (5, 42) . In addition, they should have adequate oral intake, be proficient in carbohydrate estimation, take multiple daily insulin injections or wear insulin pumps, have stable insulin requirements, and understand sick-day management. If self-management is supported, a policy should include a requirement that people with diabetes and the care team agree on a daily basis during hospitalization that self-management is appropriate. Hospital personal medication policies may include guidance for people with diabetes who wish to take their own or hospitaldispensed insulin and noninsulin injectable medications during their hospital stay. A hospital policy for personal medication may include a pharmacy exception on a case-by-case basis as determined in consultation with the care team. Pharmacy must verify any home medication and require a prescriber order for the individual to self-administer home or hospitaldispensed medication under the supervision of the registered nurse. If an insulin pump or CGM device is worn, hospital policy and procedures delineating guidelines for wearing an insulin pump and/or CGM device should be developed according to consensus guidelines, including the changing of insulin infusion sites and CGM glucose sensors (42, 113) . As outlined in Recommendations 7.31 and 7.32, people with diabetes wearing diabetes devices should be supported to continue them in an inpatient setting if they are assessed and deemed competent to perform selfcare and proper supervision is available.

STANDARDS FOR SPECIAL SITUATIONS Enteral and Parenteral Feedings

For individuals receiving enteral or parenteral nutrition who require insulin, the insulin orders should include coverage of basal, prandial, and correctional needs (108, 114, 115) . It is essential that people with type 1 diabetes continue to receive basal insulin even if feedings are discontinued.

Most adults receiving basal insulin should continue with their basal dose, while the insulin dose for the total daily nutritional component may be calculated as 1 unit of insulin for every 10-15 g of carbohydrate in the enteral and parenteral formulas. Commercially available cans of enteral nutrition contain variable amounts of carbohydrates and may be infused at different rates (109) .

All of this must be considered when calculating insulin doses to cover the nutritional component of enteral nutrition (109) . Giving NPH insulin two or three times daily (every 8 or 12 h) or regular insulin every 6 h to cover individual requirements are reasonable options. Adjustments in insulin doses should be made frequently. Correctional insulin should also be administered subcutaneously every 6 h with regular human insulin or rapidacting insulin every 4 h. If enteral nutrition is interrupted, a dextrose infusion should be started immediately to prevent hypoglycemia and to allow time to determine more appropriate insulin doses.

For adults receiving enteral bolus feedings, approximately 1 unit of regular human insulin or rapid-acting insulin per every 10-15 g of carbohydrate should be given subcutaneously before each feeding. To mitigate any hyperglycemia, correctional insulin should be added as needed before each feeding.

In individuals receiving nocturnal tube feeding, NPH insulin administered along with the initiation of the feeding to cover this nutritional load is a reasonable approach.

For individuals receiving continuous peripheral or central parenteral nutrition, human regular insulin may be added to the solution, particularly if > 20 units of correctional insulin have been required in the past 24 h. A starting dose of 1 unit of regular human insulin for every 10 g of dextrose has been recommended (1, 108) and should be adjusted daily in the solution. Adding insulin to the parenteral nutrition bag is the safest way to prevent hypoglycemia if the parenteral nutrition is stopped or interrupted. Correctional insulin should be administered subcutaneously to address any hyperglycemia.

Because continuous enteral or parenteral nutrition results in a continuous postprandial state, efforts to bring blood glucose levels to below 140 mg/dL (7.8 mmol/L) substantially increase the risk of hypoglycemia in these individuals. For full enteral and parenteral feeding guidance, please refer to randomized controlled trials detailing this topic (114, 116, 117) .

Glucocorticoid Therapy

The prevalence of consistent use of glucocorticoid therapy in hospitalized individuals can approach 10-15%, and these medications can induce hyperglycemia in 56-86% of these individuals with and without preexisting diabetes (118, 119) . If left untreated, this hyperglycemia increases mortality and morbidity risk, e.g., infections and cardiovascular events. Glucocorticoid type and duration of action must be considered in determining appropriate insulin treatments. Daily-ingested intermediate-acting glucocorticoids such as prednisone reach peak plasma levels in 4-6 h (120) but have pharmacologic actions that can last throughout the day. When monitored by CGM, the typical glycemic pattern for individuals treated with daily prednisone or prednisolone, administered in the morning, is characterized by normal or mild fasting hyperglycemia, with trends of increasing hyperglycemia during the afternoon, and peaking in the evening. These hyperglycemic excursions are more pronounced in individuals with type 2 diabetes than in those without diabetes (121) .

For individuals treated with once-or twice-daily steroids, administering NPH insulin with prednisone or prednisolone dosing is a standard approach, aimed at matching the NPH actions with the steroidinduced hyperglycemic response. NPH may be administered in addition to daily basalbolus insulin or in addition to oral glucoselowering medications, depending on the type of diabetes and recent diabetes medication prior to starting steroids (122) . Because NPH action peaks about 4-6 h after administration, it is recommended that it be administered concomitantly with intermediate-acting steroids (123) . For long-acting glucocorticoids such as dexamethasone and multidose or continuous glucocorticoid use, long-acting basal insulin may be required to manage fasting blood glucose levels (50) . For higher doses of glucocorticoids, increasing doses of prandial (if eating) and correction insulin, sometimes as much as 40-60% or more, are often needed in addition to basal insulin (124, 125) . A retrospective study found that increasing the ratio of insulin to steroids was positively associated with improved time in range (70-180 mg/dL [3.9-10.0 mmol/L]); however, there was an increase in hypoglycemia (118) . If insulin orders are initiated, daily adjustments based on levels of glycemia and anticipated changes in type, dosages, and duration of glucocorticoids, along with POC blood glucose monitoring, are critical to reducing hypoglycemia and hyperglycemia.

Perioperative Care

It is estimated that up to 20% of individuals undergoing general surgery have diabetes, and 23-60% have prediabetes or undiagnosed diabetes. Surgical stress and counterregulatory hormone release increase the risk of hyperglycemia as well as mortality, infection, and length of stay (109, 126, 127) . There is little data available to guide care of people with diabetes through the perioperative period. To reduce surgical risk in these individuals, some institutions (126, 128, 129) have A1C cutoffs for elective surgeries, and some have developed optimization programs to lower A1C prior to surgery (126, (128) (129) (130) .

The following approaches (126, 128, 130 ) may be considered:

1. A preoperative risk assessment should be performed for people with diabetes who are at high risk for ischemic heart disease and those with autonomic neuropathy or renal failure. 2. The A1C goal for elective surgeries should be < 8% ( < 64.0 mmol/L) whenever possible. (128) . 10. Compared with usual dosing, a reduction of 25% of basal insulin dose given the evening before surgery is more likely to achieve perioperative blood glucose goals with a lower risk for hypoglycemia (131) . 11. In individuals undergoing noncardiac general surgery, basal insulin plus premeal short-or rapid-acting insulin (basal-bolus) coverage has been associated with improved glycemic outcomes and lower rates of perioperative complications compared with the reactive, correction-only short-or rapid-acting insulin coverage alone with no basal insulin dosing (60, 126) . 12. There is little data on the safe use and/or influence of GLP-1 RAs on glycemia and delayed gastric emptying in the perioperative period. With increasing use of GLP-1 RA and dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA medications for diabetes and/or weight loss, there are concerns about the safety of these drugs in the perioperative period. These drugs may be associated with nausea, vomiting, and delayed gastric emptying and have the potential to increase the risk of pulmonary aspiration during general anesthesia and deep sedation. The American Society of Anesthesiologists recommends holding GLP-1 RAs on the day of the procedure or surgery for daily dose agents and for at least 7 days prior to the procedures or surgery for once-weekly dose agents (132) . Despite the safety concerns around the use of GLP-1 RA and dual GIP and GLP-1 RA drugs in the perioperative setting, there is a need for guidance for individual risk assessment and mitigation strategies. While waiting for more definitive evidence, an interprofessional and personalized approach for perioperative management of individuals taking a GLP-1 RA or a dual GIP and GLP-1 RA is suggested. Factors such as the primary indication of these medications (e.g., diabetes or weight loss), current glycemic management, type of surgery or procedure and its urgency, type of anesthesia, consideration of preoperative gastric ultrasound to quantify gastric contents, and implementation of full stomach precautions will determine an individualized approach based on clinical judgement. If worsening of glycemic outcomes due to holding a GLP-1 RA or a dual GIP and GLP-1 RA is anticipated, an alternative strategy for perioperative glycemic management (e.g., insulin) should be considered. The discharge planning process should include education on the recognition, prevention, and management of DKA and/or HHS for all individuals affected by or at high risk for these events to prevent recurrence and readmission. B There is considerable variability in the presentation of DKA and HHS, including euglycemic DKA (defined as plasma glucose levels < 200 mg/dL [ < 11.1 mmol/L] in the presence of ketosis and metabolic acidosis), mild to moderate hyperglycemia and acidosis, or severe hyperglycemia, dehydration, and coma; therefore, individualization of treatment based on a careful clinical and laboratory assessment is needed (70, 73, 133, 134) .

Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State

Management goals include restoration of circulatory volume and tissue perfusion, resolution of ketoacidosis, and correction of electrolyte imbalance and acidosis. It is also essential to treat any correctable underlying cause of DKA, such as sepsis, myocardial infarction, or stroke. In critically ill and mentally obtunded individuals with DKA or HHS, continuous intravenous insulin is the standard of care. Successful transition from intravenous to subcutaneous insulin requires administration of basal insulin 2-4 h before the intravenous insulin is stopped to prevent recurrence of ketoacidosis and rebound hyperglycemia while the subcutaneous insulin action rises (71, 133, 135) . Studies have reported that the administration of a low dose of basal insulin analog in addition to intravenous insulin infusion may prevent rebound hyperglycemia without increased risk of hypoglycemia (72) (73) (74) 133) . There is no significant difference in outcomes for intravenous human regular insulin versus subcutaneous rapid-acting analogs when combined with aggressive fluid management for treating mild or moderate DKA (136) . Individuals with uncomplicated DKA may sometimes be treated with subcutaneous rapid-acting insulin analogs in the emergency department or step-down units (137) . This approach may be safer and more cost-effective than treatment with intravenous insulin. If subcutaneous insulin administration is used, it is important to provide an adequate fluid replacement, frequent POC blood glucose monitoring, treatment of any concurrent infections, and appropriate follow-up to avoid recurrent DKA. Several studies have shown that the use of bicarbonate in people with DKA made no difference in the resolution of acidosis or time to discharge, and its use is generally not recommended (138) . For further treatment information and in-depth review, refer to the recently updated ADA consensus report (70) . A structured discharge plan tailored to the individual may reduce the length of hospital stay and readmission rates and increase satisfaction with the hospital experience (139, 140) . Multiple strategies are key, including diabetes selfmanagement education prior to discharge, diabetes medication reconciliation with attention to access, and scheduled virtual and/or face-to-face follow-up visits after discharge. Discharge planning should begin at admission and be updated as individual needs change (141, 142) . Individualization and shared decision-making is key when creating a safe and effective discharge plan.

TRANSITION FROM THE HOSPITAL TO THE AMBULATORY SETTING

The transition from the acute care setting presents risks for all people with diabetes. Individuals may be discharged to varied settings, including home (with or without visiting nurse services), assisted living, rehabilitation, or skilled nursing facilities. For individuals discharged to home or assisted living, the optimal discharge plan will need to consider diabetes type and severity, effects of the illness on blood glucose levels, and the individual's circumstances, capabilities, and preferences (19, 143, 144) . See Section 13, "Older Adults," for more information.

An outpatient follow-up visit with primary care, endocrinology, or a diabetes care and education specialist within 1 month of discharge is advised for all individuals experiencing hyperglycemia and/or hypoglycemia in the hospital. If glycemic management medications are changed or glucose management is not optimal at discharge, an earlier appointment (in 1-2 weeks) is preferred, and frequent contact to consider therapy adjustments may be needed to avoid hyperglycemia and hypoglycemia. A discharge algorithm for glycemic medication adjustment, based on admission A1C, diabetes medications before admission, and insulin usage during hospitalization was found useful to guide treatment decisions and significantly improve A1C after discharge (4).

Clear communication with outpatient health care professionals directly or via hospital discharge summaries facilitates safe transitions to outpatient care. Providing information regarding the root cause of hyperglycemia (or the plan for determining the cause), related complications and comorbidities, and recommended treatments can assist outpatient health care professionals as they assume ongoing care.

The Agency for Healthcare Research and Quality recommends that, at a minimum, discharge plans include the following (145):

Medication Reconciliation

• Home and hospital medications must be cross-checked to ensure that no chronic medications are stopped and to ensure the safety of new and old prescriptions.

• Prescriptions for new or changed medication should be filled and reviewed with the individual and care partners at or before discharge whenever possible.

Structured Discharge Communication

• Information on medication changes, pending tests and studies, and follow-up needs must be accurately and promptly communicated to outpatient health care professionals. • Discharge summaries should be transmitted to the primary care health care professional as soon as possible after discharge. • Scheduling follow-up appointments prior to discharge with people with diabetes agreeing to the time and place increases the likelihood that they will attend. It is recommended that the following areas of knowledge be reviewed and addressed before hospital discharge:

• Identification of the health care professionals who will provide diabetes care after discharge. † Some have recommended that insulin be withheld until glucose has stopped dropping with fluid administration alone. • Level of understanding related to the diabetes diagnosis, glucose monitoring, home glucose goals, and when to call a health care professional. • Definition, recognition, treatment, and prevention of hyperglycemia and hypoglycemia. • Information on choosing healthy food at home and referral to an outpatient registered dietitian nutritionist or diabetes care and education specialist to guide individualization of the meal plan, if needed. • When and how to take blood glucose-lowering medications, including insulin administration and noninsulin injectables. • Sick-day management (19, 144) .

• Proper use and disposal of diabetes supplies, e.g., insulin pens, pen needles, syringes, glucose meters, and lancets.

People with diabetes must be provided with appropriate durable medical equipment, medications, supplies (e.g., blood glucose test strips or CGM sensors), prescriptions, and appropriate education at the time of discharge to avoid a potentially dangerous hiatus in care.

PREVENTING ADMISSIONS AND READMISSIONS

In people with diabetes, the hospital readmission rate is between 14% and 20%, which is nearly twice that in people without diabetes (141, 146) . This may result in increased diabetes distress and has significant financial implications. Of people with diabetes who are hospitalized, 30% have two or more hospital stays, and these admissions account for over 50% of hospital costs for diabetes (147) . Factors contributing to readmission include male sex, longer duration of prior hospitalization, number of previous hospitalizations, number and severity of comorbidities, and lower socioeconomic and/or educational status; factors that may reduce readmission rates include scheduled home health visits and timely ambulatory follow-up care (141, 146) . While there is no standardized protocol to prevent readmissions, several successful strategies have been reported that identify high-risk individuals and offer some possible solutions (141) . To prevent readmissions, monitor insulin adjustments for individuals admitted with A1C > 9% ( > 75 mmol/ mol) (148) or DKA (149, 150) and follow a transitional care model (151) . For individuals hospitalized with severe hypoglycemia, impaired awareness of hypoglycemia, or high risk for hypoglycemia (end-stage kidney disease, intensive insulin management, frailty, etc.), consider prescribing glucagon to treat any future severe hypoglycemia events (152, 153) . For people with diabetes and chronic kidney disease, collaborative person-centered medical homes may decrease risk-adjusted readmission rates (154) . Since recent studies have shown that use of CGM may prevent emergency department visits and hospital admission in people with type 1 and type 2 diabetes, it may be beneficial to initiate CGM just prior to discharge to facilitate follow-up and possibly prevent acute diabetes-related complications and readmission (155) .

Age is also an important risk factor in hospitalization and readmission among people with diabetes (refer to Section 13, "Older Adults," for detailed criteria). Successful proactive care transitions from inpatient to outpatient is a key strategy for preventing readmission and emergency department visits.

THE FUTURE

Inpatient diabetes management is challenging for hospitals, health care professionals, and people with diabetes, as acute illness increases the risk of both hypoglycemia and hyperglycemia. The use of decision support tools and best practice advisories in the EHR has facilitated health care professionals following the recommendations in this standard of care. In addition, personal and hospital-owned diabetes devices and dosing algorithms are changing the way we provide care. Future enhancements will likely continue to improve the quality of care we deliver in hospitals and in transitions from inpatient to outpatient. The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Managing the daily health demands of diabetes can be challenging. People living with diabetes should not have to face discrimination due to diabetes. By advocating for the rights of those with diabetes at all levels, the American Diabetes Association (ADA) can help to ensure that they live a healthy and productive life. A strategic goal of the ADA is for more children and adults with diabetes to live free from the burden of discrimination. The ADA is also focused on making sure cost is not a barrier to successful diabetes management.

One tactic for achieving these goals has been to implement the ADA Standards of Care through advocacy-oriented statements. The ADA publishes evidence-based, peer-reviewed statements on topics such as diabetes and employment, diabetes and driving, insulin access and affordability, and diabetes management in certain settings such as schools, childcare programs, and detention facilities. In addition to the ADA's clinical documents, these advocacy statements are important tools in educating schools, employers, licensing agencies, policymakers, and others about the intersection of diabetes management and the law and for providing scientifically supported policy recommendations.

ADVOCACY STATEMENTS

The following is a partial list of advocacy statements ordered by publication date, with the most recent statement appearing first. A comprehensive list of advocacy statements is available at professional.diabetes.org/content/key-statements-and-reports.

Diabetes Care in the School Setting

A sizable portion of a child's day is spent in school, so close communication with and training and cooperation of school personnel are essential to optimize diabetes management, safety, and access to all school-sponsored opportunities. Additionally, the updated statement further details optimal use of technologies, management of diabetes, behavioral health considerations, and guidance for diabetes care in special situations (e.g., emergency situations or clinical trial participation). Refer to the *A complete list of members of the American Diabetes Association Professional Practice Committee can be found at https://doi.org/10.2337/dc25-SINT.

Duality of interest information for each author is available at https://doi.org/10.2337/dc25-SDIS. Suggested citation: American Diabetes Association Professional Practice Committee. 17 Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www .diabetesjournals.org/journals/pages/license. published ADA statement for diabetes management information for students with diabetes in elementary and secondary school settings (1) .

Diabetes and Driving

People with diabetes who wish to operate on-road motor vehicles are subject to various licensing requirements applied by both state and federal jurisdictions. For an overview of existing licensing rules for people with diabetes, factors that impact driving for this population, diabetes technology use, and general guidelines for assessing driver fitness and determining appropriate licensing restrictions, refer to the published ADA statement (2).

Diabetes Management in Detention Facilities

People with diabetes who are in detention facilities deserve equitable care that meets national standards. As many facilities differ and have unique challenges, written policies and procedures are essential to create a solid foundation and infrastructure for diabetes management and the training of medical and security staff. Policies should address considerations such as security needs, transfers, access to medical personnel, needed supplies and equipment, and empowering diabetes self-management. For a comprehensive discussion on these considerations, refer to the published ADA statement (3).

Care of Young Children With Diabetes in the Childcare and Community Setting

Very young children (aged < 5 years) with diabetes have legal protections and can be safely cared for by childcare professionals with appropriate training, access to resources, and a communication system with parents or guardians and the child's diabetes health care professional. Refer to the published ADA advocacy statement for information on young children aged < 5 years in settings such as childcare centers, preschools, camps, and other programs (4).

Insulin Access and Affordability

The ADA's Insulin Access and Affordability Working Group compiled public information and convened a series of meetings with stakeholders throughout the insulin supply chain to learn how each entity affects the cost of insulin for the consumer. Their conclusions and recommendations are published in an ADA statement (5) .

Diabetes and Employment

Any person with diabetes, whether insulin treated or noninsulin treated, should be eligible for any employment for which they are otherwise qualified. Employment decisions should never be based on generalizations or stereotypes regarding the effects of diabetes. For a general set of guidelines for evaluating individuals with diabetes for employment, including how an assessment should be performed and what changes (accommodations) in the workplace may be needed for an individual with diabetes, refer to the published ADA statement (6) . UK Prospective Diabetes Study (UKPDS), S131, S133, S134, S135, S226 ulcers, foot, S1, S64, S102, S104, S255, S258, S259, S260 ultra-rapid-acting insulin analogs, S182, S184, S192 ultrasound wound debridement, S261, S262 urinary tract infections, S7, S72, S276 urine albumin-to-creatinine ratio (UCAR), S239 vaccines. see immunizations. vagus nerve stimulator, S175 vaping, S104-S105 vascular disease, S11, S71, S104, S133-S134, S210, S222, S223, S224, S225, S259, S315 prevention of, in prediabetes, S54-S55 vertical sleeve gastrectomy, S175, S296 VERTIS CV trial, S225 Veterans Affairs Diabetes Trial (VADT), S69, S132, S133, S134, S268 visual rehabilitation, S255 vitamin D supplementation, S7, S53-S54, S64, S67-S68, S95, S170 VOYAGER PAD trial, S222 weight gain, S39 weight loss surgery. see metabolic surgery. weight loss/management, S7, S8, S9-S10, S96-S97, S167-S180 assessment and monitoring, S167-S169 in children/adolescents, S291, S296 in diabetes prevention, S9-S10, S51-S53, S54, S55, S96-S97, S167-S180 in older adults, S272 in prediabetes, S96-S97 in pregnancy, S307, S315 in type 1 diabetes, S96 in type 2 diabetes, S31, S96, S188, S192, S194 medical devices for weight loss, S175 metabolic surgery, S8, S10, S62, S65, S67, S75, S77, S90, S96, S99-S100, S102, S107, S167, S168, S171, S175-S177, S188, S194, S257, S286, S287 nutrition, physical activity, and behavioral therapy, S169-S170 pharmacotherapy, S170-S174 with MASH and MASLD, S75-S77 with neuropathy, S257 unexplained, S27, S28, S30, S32, S36, S168, S186, S274, S288 weight stigma, S9, S168 well-being, S15, S17, S60, S71, S72, S86-S87, S96, S101, S102, S106, S113, S186, S255, S288, S289, S298 white coat hypertension, S209, S214 whites, non-Hispanic, S15, S30, S36, S129 WISDM trial, S268 wound therapy, advanced, S261-S262 We're stronger together.

|Subpopulation of a person with diabetes|Team members to engage in care|Unique care considerations| |---|---|---|

|All adults with diabetes|Primary care clinician, CDCES, RDN, and other|Assess for and address social determinants|

||specialists as available and appropriate to|of health.|

||treat comorbidities (Table 4.1)|treat comorbidities (Table 4.1)|

|Adults treated with intensive insulin therapy,|Clinicians and other health care team|Clinicians and other health care team|

|including multiple daily injections of|members experienced in advanced diabetes||

|insulin and insulin pump therapy|management, including technology use|management, including technology use|

|All youth with diabetes|Primary care clinician, pediatric|Primary care clinician, pediatric|

||endocrinologist, CDCES, RDN, other|endocrinologist, CDCES, RDN, other|

||specialists as available and appropriate to|and academic performance in school.|

||treat comorbidities (Table 14.1), daycare|Engage professionals within the school and|

||or school nurse or other professional,|or school nurse or other professional,|

||behavioral health professional (as needed),|ensure safe diabetes management. An|

||and parent(s) or caregiver(s)|and parent(s) or caregiver(s)|

|||management plan should be developed in|

|||collaboration with school professionals|

|||and parent(s) or caregiver(s).|

|||Support gradual developmentally appropriate|

|||transfer of self-management from|

|||caregivers to the youth with diabetes.|

|Individuals with diabetes and|Specialist referrals as appropriate and|Specialist referrals as appropriate and|

|diabetes-related complications or|available (e.g., behavioral health|available (e.g., behavioral health|

|comorbidities|professional, cardiologist, eye specialist,|evidence that self-care demands exceed|

||gastroenterologist or hepatologist,|gastroenterologist or hepatologist,|

||neurologist, nephrologist, obesity medicine|support systems.|

||specialist, or podiatrist), care coordinator/||

||navigator or case manager, and clinical|navigator or case manager, and clinical|

||pharmacist (for those with polypharmacy||

||or complex medication plans)|or complex medication plans)|

|Individuals with social and/or structural|Care coordinator/navigator, social services|Care coordinator/navigator, social services|

|barriers to care|professional, insurance specialist/navigator,|available resources, and support systems.|

||peer-to-peer support (as available),|peer-to-peer support (as available),|

||community health worker and/or community||

||paramedic (as available), public health|paramedic (as available), public health|

||professional, and interpreter (as applicable)||

|Older adults|Geriatric medicine specialist, social services|Consider the older adult's nutritional status,|

||professional, case manager, community|including ability to afford (financial|

||services provider, and physical and/or|services provider, and physical and/or|

||occupational therapist as available and|occupational therapist as available and|

||appropriate based on functional status|appropriate based on functional status|

||and independence|and independence|

|||vision, hearing, dexterity, cognition,|

|||mobility, and other challenges.|

|Individuals in long-term care settings|Long-term care facility clinicians, nurses, other|Engage professionals within the long-term|

||health care professionals, physical and|health care professionals, physical and|

||occupational therapists, and RDN|occupational therapists, and RDN|

|Pregnant individuals with diabetes|Maternal-fetal medicine specialist or obstetrician|Ensure appropriate postpartum follow-up and|

||experienced in the care of pregnant|experienced in the care of pregnant|

||individuals with diabetes (particularly for|individuals with diabetes (particularly for|

||individuals with type 1 diabetes or requiring||

||intensive insulin therapy), CDCES, RDN, eye||

||specialist (particularly for individuals with||

||preexisting type 1 or type 2 diabetes), other||

||specialists as appropriate, and lactation|specialists as appropriate, and lactation|

||consultant as appropriate|consultant as appropriate|

|OR| |---|

|FPG $126 mg/dL ($7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.*|

|OR|

|2-h PG $200 mg/dL ($11.1 mmol/L) during OGTT. The test should be performed as|

|described by the WHO, using a glucose load containing the equivalent of 75 g anhydrous|

|glucose dissolved in water.*|

|In an individual|

||Stage 1|Stage 2|Stage 3| |---|---|---|---|

||• Normoglycemia|• Normoglycemia|• Dysglycemia|

||• Presymptomatic|• Presymptomatic|• Presymptomatic|

|Diagnostic criteria • Multiple islet autoantibodies||||

||• No IGT or IFG, normal A1C|||

|factors:| |---|

|First-degree relative with diabetes|

|High-risk race, ethnicity, and ancestry (e.g., African American, Latino, Native American,|

|Asian American)|

|History of cardiovascular disease|

|Hypertension ($130/80 mmHg or on therapy for hypertension)|

|HDL cholesterol level < 35 mg/dL ( < 0.9 mmol/L) and/or triglyceride level > 250 mg/dL|

|( > 2.8 mmol/L)|

|Individuals with polycystic ovary syndrome|

|Physical inactivity|

|Other clinical conditions associated with insulin resistance (e.g., severe obesity,|

|acanthosis nigricans, metabolic dysfunction-associated steatotic liver disease)|

|2. People with prediabetes (A1C $5.7% [$39 mmol/mol], IGT, or IFG) should be tested yearly.|

|6-Risk-based screening for type 2 diabetes or prediabetes in| |---|

|asymptomatic children and adolescents in a clinical setting|

|Screening should be considered in youth* who have overweight ($85th percentile) or|

|obesity ($95th percentile) and who have one or more additional risk factors:|

|Maternal history of diabetes or GDM during the child's gestation|

|Family history of type 2 diabetes in first-or second-degree relative|

|diabetesjournals.org/care Diagnosis and Classification of Diabetes Foot Care"). In the National Institutes of|||||| |---|---|---|---|---|---|

|Health (NIH) Diabetes Prevention Program||||||

|Outcomes Study (DPPOS) report, preven-||||||

|tion of progression from prediabetes to di-||||||

|abetes (101) resulted in lower rates of||||||

|developing retinopathy and nephropathy (102). Similar impact on diabetes com-Are you at risk for type 2 diabetes? plications was reported with screening,||||||

|diagnosis, and comprehensive risk factor||||||

|management in the U.K. Clinical Prac-|WRITE YOUR SCORE IN THE BOX.|||||

|tice Research Datalink database||Height||Weight (lbs.)||

|||4´ 10˝119-142|4´ 10˝119-142|143-190|191+|

|||4´ 11˝|124-147|148-197|198+|

|||5´ 0˝128-152|5´ 0˝128-152|153-203|204+|

|||5´ 1˝|132-157|158-210|211+|

|||5´ 2˝|136-163|164-217|218+|

|||5´ 3˝|141-168|169-224|225+|

|||5´ 4˝|145-173|174-231|232+|

|||5´ 5˝|150-179|180-239|240+|

|||5´ 6˝|155-185|186-246|247+|

|||5´ 7˝|159-190|191-254|255+|

|||5´ 8˝|164-196|197-261|262+|

|||5´ 9˝|169-202 203-269|169-202 203-269|270+|

|||5´ 10˝|174-208|209-277|278+|

|||5´ 11˝|179-214|215-285|286+|

|||6´ 0˝|184-220|221-293|294+|

|||6´ 1˝|189-226|227-301|302+|

|||6´ 2˝|194-232 233-310|194-232 233-310|311+|

|||6´ 3˝|200-239 240-318|200-239 240-318|319+|

|||6´ 4˝|205-245 246-327|205-245 246-327|328+|

||||1 point|2 points|3 points|

||||If you weigh less than the amount|||

||ADD UP YOUR SCORE|in the left column: 0 The good news is you can manage|in the left column: 0 The good news is you can manage|||

|||your risk for type 2 diabetes. Small|your risk for type 2 diabetes. Small|your risk for type 2 diabetes. Small|your risk for type 2 diabetes. Small|

|||steps make a big difference in helping|steps make a big difference in helping|steps make a big difference in helping|steps make a big difference in helping|

|||you live a longer, healthier life.||||

|||If you are at high risk, your first step is|If you are at high risk, your first step is|If you are at high risk, your first step is|If you are at high risk, your first step is|

|Type 2 diabetes is more common in African Americans,||to visit your doctor to see if additional|to visit your doctor to see if additional|to visit your doctor to see if additional|to visit your doctor to see if additional|

|Hispanic/Latino individuals, Native Americans, Asian||testing is needed.|testing is needed.|||

|Americans, and Native Hawaiians and Pacific Islanders.||Visit diabetes.org or call|Visit diabetes.org or call|Visit diabetes.org or call||

|Higher body weight increases diabetes risk for everyone. Asian Americans are at increased diabetes risk at lower body weight than the rest of the general||1-800-DIABETES (800-342-2383) for information, tips on getting started, and ideas for simple, small steps you can take to help lower your risk|1-800-DIABETES (800-342-2383) for information, tips on getting started, and ideas for simple, small steps you can take to help lower your risk|1-800-DIABETES (800-342-2383) for information, tips on getting started, and ideas for simple, small steps you can take to help lower your risk|1-800-DIABETES (800-342-2383) for information, tips on getting started, and ideas for simple, small steps you can take to help lower your risk|

|public (about 15 pounds lower).||||||

|diabetesjournals.org/care|diabetesjournals.org/care||Diagnosis and Classification of Diabetes| |---|---|---|---|

||Gene|Inheritance|Clinical features|

||||adolescence or early adulthood; lowered renal threshold for glucosuria;|

||||large rise in 2-h PG level on OGTT ( > 90 mg/dL [ > 5 mmol/L]); low|

||||hs-CRP; sensitive to sulfonylureas|

||HNF4A|AD|HNF4A-MODY: progressive insulin secretory defect with presentation in|

||||adolescence or early adulthood; may have large birth weight|

||||(macrosomia) and transient neonatal hypoglycemia; sensitive to|

||||sulfonylureas|

||HNF1B|AD|HNF1B-MODY: developmental renal disease (typically cystic); genitourinary|

||||abnormalities; atrophy of the pancreas; hyperuricemia; gout|

||GCK|AD|GCK-MODY: higher glucose threshold (set point) for glucose-stimulated|

||||insulin secretion, causing stable, nonprogressive elevated fasting blood|

||||glucose; typically does not require treatment; microvascular|

||||complications are rare; small rise in 2-h PG level on OGTT ( < 54 mg/dL|

||||[ < 3 mmol/L])|

|Neonatal diabetes KCNJ11|AD|Permanent or transient: IUGR; possible developmental delay and seizures;||

||||responsive to sulfonylureas|

||INS|AD|Permanent: IUGR; insulin requiring|

||ABCC8|AD|Permanent or transient: IUGR; rarely developmental delay; responsive to|

||6q24 (PLAGL1,|AD for paternal|Transient: IUGR; macroglossia; umbilical hernia; mechanisms include|

||HYMA1)|duplications|UPD6, paternal duplication, or maternal methylation defect; may be|

||||treatable with medications other than insulin|

||GATA6|AD|Permanent: pancreatic hypoplasia; cardiac malformations; pancreatic|

||||exocrine insufficiency; insulin requiring|

||EIF2AK3|AR|Permanent: Wolcott-Rallison syndrome: epiphyseal dysplasia; pancreatic|

||EIF2B1|AD|Permanent diabetes: can be associated with fluctuating liver function|

||||(154)|

||FOXP3|X-linked|Permanent: immunodysregulation, polyendocrinopathy, enteropathy|

|exceeded:| |---|

|Fasting: 92 mg/dL (5.1 mmol/L)|

|1 h: 180 mg/dL (10.0 mmol/L)|

|2 h: 153 mg/dL (8.5 mmol/L)|

|Two-step strategy|

|Step 1:|

|Annu Rev Public Health 2021;42:59-77 9. Chadha C, Pittas AG, Lary CW, et al.; D2d Research Group. Reproducibility of a prediabetes classification in a contemporary population. Metabol Open 2020;6:100031 10. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997;20:1183-1197 11. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2003;26(Suppl 1):S5-S20 12. Klein KR, Walker CP, McFerren AL, Huffman H, Frohlich F, Buse JB. Carbohydrate intake prior to oral glucose tolerance testing. J Endocr Soc 2021;5:bvab049 13. Conn JW. Interpretation of the glucose tolerance test. The necessity of a standard preparatory diet. Am J Med Sci 1940;199: 555-563 14. Wilkerson HL, Butler FK, Francis JO. The effect of prior carbohydrate intake on the oral glucose tolerance test. Diabetes 1960;9:386-391 15. Lenters-Westra E, Slingerland RJ. Six of eight hemoglobin A1c point-of-care instruments do not meet the general accepted analytical performance criteria. Clin Chem 2010;56:44-52 16. Hirst JA, McLellan JH, Price CP, et al. Performance of point-of-care HbA1c test devices: implications for use in clinical practice-a sys-tematic review and meta-analysis. Clin Chem Lab Med 2017;55:167-180 17. Nathan DM, Griffin A, Perez FM, Basque E, Do L, Steiner B. Accuracy of a point-of-care hemoglobin A1c assay. J Diabetes Sci Technol 2019;13:1149-1153 18. Centers for Medicare & Medicaid Services. CLIA Brochures. Accessed 5 August 2024. Available from https://www.cms.gov/Regulations-and-Guidance/ Legislation/CLIA/CLIA_Brochures 19. Eckhardt BJ, Holzman RS, Kwan CK, Baghdadi J, Aberg JA. Glycated hemoglobin A(1c) as screening for diabetes mellitus in HIV-infected individuals. AIDS Patient Care STDS 2012;26: 197-201 20. Kim PS, Woods C, Georgoff P, et al. A1C underestimates glycemia in HIV infection. Diabetes Care 2009;32:1591-1593 21. Wheeler E, Leong A, Liu C-T, et al.; Lifelines Cohort Study. Impact of common genetic determinants of hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: a transethnic genome-wide meta-analysis. PLoS Med 2017;14:e1002383 22. Bergenstal RM, Gal RL, Connor CG, et al.; T1D Exchange Racial Differences Study Group. Racial differences in the relationship of glucose concentrations and hemoglobin A1c levels. Ann Intern Med 2017;167:95-102 23. Prevention Program. Diabetes Care 2007;30: consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2021;44:2589-2625 37. Zhong VW, Juhaeri J, Mayer-Davis EJ. Trends in hospital admission for diabetic ketoacidosis 2453-2457 24. Saaddine JB, Fagot-Campagna A, Rolka D, et al. Distribution of HbA(1c) levels for children and young adults in the U.S.: Third National Health and Nutrition Examination Survey. Diabetes Care 2002;25:1326-1330 25. Selvin E, Steffes MW, Ballantyne CM, Hoogeveen RC, Coresh J, Brancati FL. Racial differences in glycemic markers: a cross-sectional analysis of community-based data. Ann Intern Med 2011;154:303-309 26. Landry LG, Ali N, Williams DR, Rehm HL, Bonham VL. Lack of diversity in genomic databases is a barrier to translating precision medicine research into practice. Health Aff (Millwood) 2018;37:780-785 27. Wojcik GL, Graff M, Nishimura KK, et al. Genetic analyses of diverse populations improves discovery for complex traits. Nature 2019;570: 514-518 28. Selvin E, Rawlings AM, Bergenstal RM, Coresh J, Brancati FL. No racial differences in the association of glycated hemoglobin with kidney disease and cardiovascular outcomes. Diabetes Care 2013;36:2995-3001 29. Selvin E, Wang D, Matsushita K, Grams ME, Coresh J. Prognostic implications of single-sample confirmatory testing for undiagnosed diabetes: a prospective cohort study. Ann Intern Med 2018; 169:156-164 30. Umpierrez GE, Davis GM, ElSayed NA, et al. Hyperglycemic crises in adults with diabetes: a consensus report. Diabetes Care 2024;47:1257-1275 31. Alonso GT, Coakley A, Pyle L, Manseau K, Thomas S, Rewers A. Diabetic ketoacidosis at diagnosis of type 1 diabetes in Colorado children, 2010-2017. Diabetes Care 2020;43:117-121 32. Jensen ET, Stafford JM, Saydah S, et al. Increase in prevalence of diabetic ketoacidosis at diagnosis among youth with type 1 diabetes: the SEARCH for Diabetes in Youth Study. Diabetes Care 2021;44:1573-1578 33. Humphreys A, Bravis V, Kaur A, et al. Individual and diabetes presentation characteristics associated with partial remission status in children and adults evaluated up to 12months following diagnosis of type 1 diabetes: an ADDRESS-2 (After Diagnosis Diabetes Research Support System-2) study analysis. Diabetes Res Clin Pract 2019;155:107789 34. Thomas NJ, Lynam AL, Hill AV, et al. Type 1 diabetes defined by severe insulin deficiency occurs after 30 years of age and is commonly treated as type 2 diabetes. Diabetologia 2019; 62:1167-1172 35. Hope SV, Wienand-Barnett S, Shepherd M, et al. Practical Classification Guidelines for Diabetes in patients treated with insulin: a cross-sectional study of the accuracy of diabetes diagnosis. Br J Gen Pract 2016;66:e315-e322 36. Holt RIG, DeVries JH, Hess-Fischl A, et al. The management of type 1 diabetes in adults. A diabetesjournals.org/care Diagnosis and Classification of Diabetes early childhood diabetes: The Environmental 2006;49:1989-1995 52. Schwartz SS, Epstein S, Corkey BE, Grant 38. Skyler JS, Bakris GL, Bonifacio E, et al. Differentiation of diabetes by pathophysiology, natural history, and prognosis. Diabetes 2017;66: 241-255 39. Williams DM, Jones H, Stephens JW. Personalized type 2 diabetes management: an update on recent advances and recommendations. Diabetes Metab Syndr Obes 2022;15:281-295 40. Ziegler AG, Rewers M, Simell O, et al. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 2013;309:2473-2479 41. Ziegler A-G, Bonifacio E, BABYDIAB-BABYDIET Study Group. Age-related islet autoantibody incidence in offspring of patients with type 1 diabetes. Diabetologia 2012;55:1937-1943 42. Parikka V, N€ ant€ o-Salonen K, Saarinen M, et al. Early seroconversion and rapidly increasing autoantibody concentrations predict prepubertal manifestation of type 1 diabetes in children at genetic risk. Diabetologia 2012;55:1926-1936 43. Krischer JP, Lynch KF, Schatz DA, et al.; TEDDY Study Group. The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study. Diabetologia 2015;58:980-987 44. Bogun MM, Bundy BN, Goland RS, Greenbaum CJ. C-peptide levels in subjects followed longitudinally before and after type 1 diabetes diagnosis in TrialNet. Diabetes Care 2020;43:1836-1842 45. Insel RA, Dunne JL, Atkinson MA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care 2015;38:1964-1974 46. Zhu Y, Qian L, Liu Q, et al. Glutamic acid decarboxylase autoantibody detection by el-ectrochemiluminescence assay identifies latent autoimmune diabetes in adults with poor islet function. Diabetes Metab J 2020;44:260-266 47. Lynam A, McDonald T, Hill A, et al. Development and validation of multivariable clinical diagnostic models to identify type 1 diabetes requiring rapid insulin therapy in adults aged 18-50 years. BMJ Open 2019;9:e031586 48. Jones AG, McDonald TJ, Shields BM, Hagopian W, Hattersley AT. Latent autoimmune diabetes of adults (LADA) is likely to represent a mixed population of autoimmune (type 1) and nonautoimmune (type 2) diabetes. Diabetes Care 2021;44:1243-1251 49. Lynam AL, Dennis JM, Owen KR, et al. Logistic regression has similar performance to optimised machine learning algorithms in a clinical setting: application to the discrimination between type 1 and type 2 diabetes in young adults. Diagn Progn Res 2020;4:6 50. Chung WK, Erion K, Florez JC, et al. Precision medicine in diabetes: a consensus report from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2020;43:1617-1635 51. Gale EAM. Declassifying diabetes. Diabetologia Determinants of Diabetes in the Young (TEDDY). Diabetes Care 2015;38:808-813 54. McKeigue PM, Spiliopoulou A, McGurnaghan S, et al. Persistent C-peptide secretion in type 1 diabetes and its relationship to the genetic architecture of diabetes. BMC Med 2019;17:165 55. Sosenko JM, Palmer JP, Rafkin-Mervis L, et al.; Diabetes Prevention Trial-Type 1 Study Group. Incident dysglycemia and progression to type 1 diabetes among participants in the Diabetes Prevention Trial-Type 1. Diabetes Care 2009;32: 1603-1607 56. Krischer JP; Type 1 Diabetes TrialNet Study Group. The use of intermediate endpoints in the design of type 1 diabetes prevention trials. Diabetologia 2013;56:1919-1924 57. Phillip M, Achenbach P, Addala A, et al. Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes. Diabetes Care 2024;47:1276-1298 58. Greenbaum CJ, Beam CA, Boulware D, et al.; Type 1 Diabetes TrialNet Study Group. Fall in C-peptide during first 2 years from diagnosis: evidence of at least two distinct phases from composite type 1 diabetes TrialNet data. Diabetes 2012;61:2066-2073 59. Mishra R, Hodge KM, Cousminer DL, Leslie RD, Grant SFA. A global perspective of latent autoimmune diabetes in adults. Trends Endocrinol Metab 2018;29:638-650 60. Buzzetti R, Zampetti S, Maddaloni E. Adult-onset autoimmune diabetes: current knowledge and implications for management. Nat Rev Endocrinol 2017;13:674-686 61. Ben-Skowronek I. IPEX syndrome: genetics and treatment options. Genes (Basel) 2021;12:323 62. Frommer L, Kahaly GJ. Autoimmune poly-endocrinopathy. J Clin Endocrinol Metab 2019; 104:4769-4782 63. Smith CJ, Almodallal Y, Jatoi A. Rare adverse events with programmed death-1 and programmed death-1 ligand inhibitors: justification and rationale for a systematic review. Curr Oncol Rep 2021;23:86 64. Zhao Z, Wang X, Bao X-Q, Ning J, Shang M, Zhang D. Autoimmune polyendocrine syndrome induced by immune checkpoint inhibitors: a systematic review. Cancer Immunol Immunother 2021;70:1527-1540 65. Chen X, Affinati AH, Lee Y, et al. Immune checkpoint inhibitors and risk of type 1 diabetes. Diabetes Care 2022;45:1170-1176 66. Stamatouli AM, Quandt Z, Perdigoto AL, et al. Collateral damage: insulin-dependent diabetes induced with checkpoint inhibitors. Diabetes 2018; 67:1471-1480 67. Wu L, Tsang V, Menzies AM, et al. Risk factors and characteristics of checkpoint inhibitor-associated autoimmune diabetes mellitus (CIADM): a systematic review and delineation from type 1 diabetes. Diabetes Care 2023;46:1292-1299 68. modelling study. Lancet Diabetes Endocrinol 2022;10:741-760 71. McQueen RB, Geno Rasmussen C, Waugh K, et al. Cost and cost-effectiveness of large-scale screening for type 1 diabetes in Colorado. Dia-betes Care 2020;43:1496-1503 72. Ziegler A-G, Kick K, Bonifacio E, et al.; Fr1da Study Group. Yield of a public health screening of children for islet autoantibodies in Bavaria, Germany. JAMA 2020;323:339-351 73. Hagopian WA, Erlich H, Lernmark A, et al.; TEDDY Study Group. The Environmental Deter-minants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. Pediatr Diabetes 2011;12:733-743 74. Orban T, Sosenko JM, Cuthbertson D, et al.; Diabetes Prevention Trial-Type 1 Study Group. Pancreatic islet autoantibodies as predictors of type 1 diabetes in the Diabetes Prevention Trial-Type 1. Diabetes Care 2009;32:2269-2274 75. Sosenko JM, Skyler JS, Palmer JP, et al.; Diabetes Prevention Trial-Type 1 Study Group. The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients. Diabetes Care 2013;36:2615-2620 76. Jacobsen LM, Larsson HE, Tamura RN, et al.; TEDDY Study Group. Predicting progression to type 1 diabetes from ages 3 to 6 in islet autoantibody positive TEDDY children. Pediatr Diabetes 2019;20:263-270 77. Barker JM, Goehrig SH, Barriga K, et al.; DAISY Study. Clinical characteristics of children diagnosed with type 1 diabetes through intensive screening and follow-up. Diabetes Care 2004;27: 1399-1404 78. Elding Larsson H, Vehik K, Gesualdo P, et al.; TEDDY Study Group. Children followed in the TEDDY study are diagnosed with type 1 diabetes at an early stage of disease. Pediatr Diabetes 2014;15:118-126 79. Kimpim€ aki T, Kulmala P, Savola K, et al. Natural history of beta-cell autoimmunity in young children with increased genetic susceptibility to type 1 diabetes recruited from the general population. J Clin Endocrinol Metab 2002;87:4572-4579 80. Vehik K, Lynch KF, Schatz DA, et al.; TEDDY Study Group. Reversion of b-cell autoimmunity changes risk of type 1 diabetes: TEDDY study. Diabetes Care 2016;39:1535-1542 81. Sharp SA, Rich SS, Wood AR, et al. Development and standardization of an improved type 1 diabetes genetic risk score for use in newborn screening and incident diagnosis. Diabetes Care 2019;42:200-207 82. Luckett AM, Weedon MN, Hawkes G, Leslie RD, Oram RA, Grant SFA. Utility of genetic risk scores in type 1 diabetes. Diabetologia 2023;66: 1589-1600 83. 86. Zhang X, Gregg EW, Williamson DF, et al. A1C level and future risk of diabetes: a systematic review. Diabetes Care 2010;33:1665-1673 87. Selvin E, Steffes MW, Zhu H, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med 2010;362: 800-811 88. Ackermann RT, Cheng YJ, Williamson DF, Gregg EW. Identifying adults at high risk for diabetes and cardiovascular disease using hemoglobin A1c National Health and Nutrition Examination Survey 2005-2006. Am J Prev Med 2011;40: 11-17 89. Umpierrez G, Korytkowski M. Diabetic emergencies-ketoacidosis, hyperglycaemic hyper-osmolar state and hypoglycaemia. Nat Rev Endocrinol 2016;12:222-232 90. Fadini GP, Bonora BM, Avogaro A. SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event Reporting System. Dia-betologia 2017;60:1385-1389 91. Taheri S, Zaghloul H, Chagoury O, et al. Effect of intensive lifestyle intervention on bodyweight and glycaemia in early type 2 diabetes (DIADEM-I): an open-label, parallel-group, randomised con-trolled trial. Lancet Diabetes Endocrinol 2020;8: 477-489 92. Obes Surg 2020;30:4810-4820 94. Cresci B, Cosentino C, Monami M, Mannucci E. Metabolic surgery for the treatment of type 2 diabetes: a network meta-analysis of randomized controlled trials. Diabetes Obes Metab 2020;22: 1378-1387 95. U.S. Centers for Disease Control and Prevention. National Diabetes Statistics Report. Estimates of Diabetes and Its Burden in the United States. Accessed 11 September 2024. Available from https://www.cdc.gov/diabetes/ php/data-research/index.html 96. International Diabetes Federation. IDF Diabetes Atlas, 10th edition. Brussels, Belgium, International Diabetes Federation, 2021. Accessed 5 August 2024. Available from https://www.diabetesatlas.org/atlas/ tenth-edition/ 97. Mei Z, Wang F, Bhosle A, et al. Strain-specific gut microbial signatures in type 2 diabetes identified in a cross-cohort analysis of 8,117 metagenomes. Nat Med 2024;30:2265-2276 98. Bardenheier BH, Wu W-C, Zullo AR, Gravenstein S, Gregg EW. Progression to diabetes by baseline glycemic status among middle-aged and older adults in the United States, 2006-2014. Diabetes Prevention Program Research Group. Exploring residual risk for diabetes and micro-vascular disease in the Diabetes Prevention Program Outcomes Study (DPPOS). Diabet Med 2017;34:1747-1755 102. Nathan DM, Bennett PH, Crandall JP, et al.; DPP Research Group. Does diabetes prevention translate into reduced long-term vascular com-plications of diabetes? Diabetologia 2019;62: 1319-1328 103. Chung S, Azar KMJ, Baek M, Lauderdale DS, Palaniappan LP. Reconsidering the age thresholds for type II diabetes screening in the U.S. Am J Prev Med 2014;47:375-381 104. Mansi IA, Sumithran P, Kinaan M. Risk of diabetes with statins. BMJ 2023;381:e071727 105. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Asso-ciation for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004; 27:596-601 106. Schambelan M, Benson CA, Carr A, et al.; International AIDS Society-USA. Management of metabolic complications associated with anti-retroviral therapy for HIV-1 infection: recommendations of an International AIDS Society-USA panel . J Acquir Immune Defic Syndr 2002;31:257-275 107. Monroe AK, Glesby MJ, Brown TT. Diag-nosing and managing diabetes in HIV-infected patients: current concepts. Clin Infect Dis 2015; 60:453-462 108. Wohl DA, McComsey G, Tebas P, et al. Current concepts in the diagnosis and man-agement of metabolic complications of HIV infection and its therapy. Clin Infect Dis 2006;43: 645-653 109. Johnson SL, Tabaei BP, Herman WH. The efficacy and cost of alternative strategies for systematic screening for type 2 diabetes in the U.S. population 45-74 years of age. Diabetes Care 2005;28:307-311 110. Tabaei BP, Burke R, Constance A, et al. Community-based screening for diabetes in Michigan. Diabetes Care 2003;26:668-670 111. Lalla E, Cheng B, Kunzel C, Burkett S, Lamster IB. Dental findings and identification of undiagnosed hyperglycemia. J Dent Res 2013;92: 888-892 112. Herman WH, Taylor GW, Jacobson JJ, Burke R, Brown MB. Screening for prediabetes and type 2 diabetes in dental offices. J Public Health Dent 2015;75:175-182 113. Cowie CC, Rust KF, Byrd-Holt DD, et al. Prevalence of diabetes and high risk for diabetes using A1C criteria in the U.S. population in 1988-2006. Diabetes Care 2010;33:562-568 114. 116. Ewald N, Bretzel RG. Diabetes mellitus secondary to pancreatic diseases (type 3c)-are we neglecting an important disease? Eur J Intern Med 2013;24:203-206 117. Hines OJ, Pandol SJ. Management of chronic pancreatitis. BMJ 2024;384:e070920 118. Hardt PD, Brendel MD, Kloer HU, Bretzel RG. Is pancreatic diabetes (type 3c diabetes) underdiagnosed and misdiagnosed? Diabetes Care 2008;31(Suppl 2):S165-S169 119. Woodmansey C, McGovern AP, McCullough KA, et al. Incidence, demographics, and clinical characteristics of diabetes of the exocrine pancreas (type 3c): a retrospective cohort study. Diabetes Care 2017;40:1486-1493 120. Makuc J. Management of pancreatogenic diabetes: challenges and solutions. Diabetes Metab Syndr Obes 2016;9:311-315 121. Andersen DK, Korc M, Petersen GM, et al. Diabetes, pancreatogenic diabetes, and pancreatic cancer. Diabetes 2017;66:1103-1110 122. Petrov MS, Basina M. Diagnosis of endocrine disease: diagnosing and classifying diabetes in diseases of the exocrine pancreas. Eur J Endocrinol 2021;184:R151-R163 123. Bellin MD, Gelrud A, Arreaza-Rubin G, et al. Total pancreatectomy with islet autotrans-Glycemic predictors of insulin independence after total pancreatectomy with islet autotrans-plantation. J Clin Endocrinol Metab 2017;102: 801-809 126. Putman MS, Norris AW, Hull RL, et al. Cystic fibrosis-related diabetes workshop: research priorities spanning disease pathophysiology, diagnosis, and outcomes. Diabetes Care 2023;46: 1112-1123 127. Ode KL, Ballman M, Battezzati A, et al. ISPAD Clinical Practice Consensus Guidelines 2022: management of cystic fibrosis-related diabetes in children and adolescents. Pediatr Diabetes 2022;23:1212-1228 128. Cystic Fibrosis Foundation. Patient Registry 2022 Annual Data Report. Bethesda, MD, Cystic Fibrosis Foundation, 2022. Accessed 5 August 2024. Available from https://www.cff.org/media/ 31216/download 129. Gilmour JA. Response to the letter to the editor from Dr. Boudreau et al, "Validation of a stepwise approach using glycated hemoglobin levels to reduce the number of required oral glucose tolerance tests to screen for cystic fibrosis-related diabetes in adults." Can J Diabetes 2019;43:163 130. Gilmour JA, Sykes J, Etchells E, Tullis E. on clinical outcomes by center: a CF patient registry study. J Cyst Fibros 2020;19:316-320 133. Olesen HV, Drevinek P, Gulmans VA, et al.; ECFSPR Steering Group. Cystic fibrosis related diabetes in Europe: prevalence, risk factors and outcome. J Cyst Fibros 2020;19:321-327 134. Mainguy C, Bellon G, Delaup V, et al. Sensitivity and specificity of different methods for cystic fibrosis-related diabetes screening: is the oral glucose tolerance test still the standard? J Pediatr Endocrinol Metab 2017;30:27-35 135. Moran A, Pekow P, Grover P, et al.; Cystic Fibrosis Related Diabetes Therapy Study Group. Insulin therapy to improve BMI in cystic fibrosis-related diabetes without fasting hyperglycemia: results of the cystic fibrosis related diabetes therapy trial. Diabetes Care 2009;32:1783-1788 136. Moran A, Brunzell C, Cohen RC, et al.; CFRD Guidelines Committee. Clinical care guidelines for cystic fibrosis-related diabetes: a position statement of the American Diabetes Association and a clinical practice guideline of the Cystic Fibrosis Foundation, endorsed by the Pediatric Endocrine Society. Diabetes Care 2010; 33:2697-2708 137. Shivaswamy V, Boerner B, Larsen J. Post-transplant diabetes mellitus: causes, treatment, and impact on outcomes. Endocr Rev 2016;37: 37-61 138. Sharif A, Hecking M, de Vries APJ, et al. Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions. Am J Transplant 2014;14:1992-2000 139. Hecking M, Werzowa J, Haidinger M, et al.; European-New-Onset Diabetes After Trans-plantation Working Group. Novel views on new-onset diabetes after transplantation: development, prevention and treatment. Nephrol Dial Transplant 2013;28:550-566 140. Montero N, Oliveras L, Soler MJ, Cruzado JM. Management of post-transplant diabetes mellitus: an opportunity for novel therapeutics. Clin Kidney J 2022;15:5-13 141. Ramirez SC, Maaske J, Kim Y, et al. The association between glycemic control and clinical outcomes after kidney transplantation. Endocr Pract 2014;20:894-900 142. Thomas MC, Moran J, Mathew TH, Russ GR, Rao MM. Early peri-operative hyperglycaemia and renal allograft rejection in patients without diabetes. BMC Nephrol 2000;1:1 143. Chakkera HA, Weil EJ, Castro J, et al. Hyperglycemia during the immediate period after kidney transplantation. Clin J Am Soc Nephrol 2009;4:853-859 144. Wallia A, Illuri V, Molitch ME. Diabetes care after transplant: definitions, risk factors, and clinical management. Med Clin North Am 2016; 100:535-550 Diagnosis and Classification of Diabetes 145. diabetesjournals.org/care 147. Gulsoy Kirnap N, Bozkus Y, Haberal M. Analysis of risk factors for posttransplant diabetes mellitus after kidney transplantation: single-center experience. Exp Clin Transplant 2020;18:36-40 148. Sharif A, Moore RH, Baboolal K. The use of oral glucose tolerance tests to risk stratify for new-onset diabetes after transplantation: an underdiagnosed phenomenon. Transplantation 2006;82:1667-1672 149. Galindo RJ, Fried M, Breen T, Tamler R. Hyperglycemia management in patients with posttransplantation diabetes. Endocr Pract 2016;22: 454-465 150. Jenssen T, Hartmann A. Emerging treatments for post-transplantation diabetes mellitus. Nat Rev Nephrol 2015;11:465-477 151. Thomas MC, Mathew TH, Russ GR, Rao MM, Moran J. Early peri-operative glycaemic control and allograft rejection in patients with diabetes mellitus: a pilot study. Transplantation 2001;72:1321-1324 152. Greeley SAW, Polak M, Njølstad PR, et al. ISPAD Clinical Practice Consensus Guidelines 2022: the diagnosis and management of mono-genic diabetes in children and adolescents. an international cohort study. Lancet 2015;386: 957-963 155. Sanyoura M, Letourneau L, Knight Johnson AE, et al. GCK-MODY in the US Monogenic Diabetes Registry: description of 27 unpublished variants. Diabetes Res Clin Pract 2019;151: 231-236 156. Carmody D, Naylor RN, Bell CD, et al. GCK-MODY in the US National Monogenic Diabetes Registry: frequently misdiagnosed and unnecessarily treated. Acta Diabetol 2016;53:703-708 157. Timsit J, Saint-Martin C, Dubois-Laforgue D, Bellann e-Chantelot C. Searching for maturity-onset diabetes of the young (MODY): when and what for? Can J Diabetes 2016;40:455-461 158. Awa WL, Schober E, Wiegand S, et al. Reclassification of diabetes type in pediatric patients initially classified as type 2 diabetes mellitus: 15 years follow-up using routine data from the German/Austrian DPV database. Dia-betes Res Clin Pract 2011;94:463-467 159. Shields BM, Hicks S, Shepherd MH, Colclough K, Hattersley AT, Ellard S. Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia 2010;53: 2504-2508 160. Accessed 5 August 2024. Available from https:// www.diabetesgenes.org/exeter-diabetes-app/ ModyCalculator 163. Huvinen E, Koivusalo SB, Meinil€ a J, et al. Effects of a lifestyle intervention during pregnancy and first postpartum year: findings from the RADIEL study. J Clin Endocrinol Metab 2018;103: 1669-1677 164. Feig DS, Hwee J, Shah BR, Booth GL, Bierman AS, Lipscombe LL. Trends in incidence of diabetes in pregnancy and serious perinatal outcomes: a large, population-based study in Ontario, Canada, 1996-2010. Diabetes Care 2014; 37:1590-1596 165. Peng TY, Ehrlich SF, Crites Y, et al. Trends and racial and ethnic disparities in the prevalence of pregestational type 1 and type 2 diabetes in Northern California: 1996-2014. Am J Obstet Gynecol 2017;216:177.e171-177.e178 166. Jovanovi c L, Liang Y, Weng W, Hamilton M, Chen L, Wintfeld N. Trends in the incidence of diabetes, its clinical sequelae, and associated costs in pregnancy. Diabetes Metab Res Rev 2015;31:707-716 167. Poltavskiy E, Kim DJ, Bang H. Comparison of screening scores for diabetes and prediabetes. Disparities in preconception health indicators-Behavioral Risk Factor Surveillance System, 2013-2015, and Pregnancy Risk Assessment Monitoring System, 2013-2014. MMWR Surveill Summ 2018; 67:1-16 172. Yuen L, Wong VW, Simmons D. Ethnic disparities in gestational diabetes. Curr Diab Rep 2018;18:68 173. Wahabi HA, Fayed A, Esmaeil S, et al. Systematic review and meta-analysis of the effectiveness of pre-pregnancy care for women with diabetes for improving maternal and perinatal outcomes. PLoS One 2020;15:e0237571 174. Zhu W-W, Yang H-X, Wei Y-M, et al. Evaluation of the value of fasting plasma glucose in the first prenatal visit to diagnose gestational diabetes mellitus in China. Diabetes Care 2013;36: 586-590 175. comes: a population-based study. Am J Perinatol 2019;36:1045-1053 178. Osmundson SS, Zhao BS, Kunz L, et al. First trimester hemoglobin A1c prediction of gestational diabetes. Am J Perinatol 2016;33:977-982 179. McIntyre HD, Sacks DA, Barbour LA, et al. Issues with the diagnosis and classification of hyperglycemia in early pregnancy. Diabetes Care 2016;39:53-54 180. Simmons D, Immanuel J, Hague WM, et al.; TOBOGM Research Group. Treatment of gestational diabetes mellitus diagnosed early in pregnancy. N Engl J Med 2023;388:2132-2144 181. Cavagnolli G, Pimentel AL, Freitas PAC, Gross JL, Camargo JL. Factors affecting A1C in non-diabetic individuals: review and meta-analysis. Clin Chim Acta 2015;445:107-114 182. Buchanan TA, Xiang A, Kjos SL, Watanabe R. What is gestational diabetes? Diabetes Care 2007;30(Suppl 2):S105-S111 183. Noctor E, Crowe C, Carmody LA, et al.; ATLANTIC-DIP Investigators. Abnormal glucose tolerance post-gestational diabetes mellitus as defined by the International Association of Diabetes and Pregnancy Study Groups criteria. Endocrine 2023;82:498-512 186. Ratner RE, Christophi CA, Metzger BE, et al.; Diabetes Prevention Program Research Group. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab 2008;93:4774-4779 187. Aroda VR, Christophi CA, Edelstein SL, et al.; Diabetes Prevention Program Research Group. The effect of lifestyle intervention and metformin on preventing or delaying diabetes among women with and without gestational diabetes: the Diabetes Prevention Program out-comes study 10-year follow-up. J Clin Endocrinol Metab 2015;100:1646-1653 188. Vounzoulaki E, Khunti K, Abner SC, Tan BK, Davies MJ, Gillies CL. Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis. BMJ 2020;369:m1361 189. Metzger BE, Lowe LP, Dyer AR, et al.; HAPO Study Cooperative Research Group. Hyper-glycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991-2002 190. O'Sullivan JB, Mahan CM. Criteria for the oral glucose tolerance test in pregnancy. Diabetes 1964;13:278-285 191. Curr Diab Rep 2017;17:85 193. Lowe WL, Scholtens DM, Lowe LP, et al.; HAPO Follow-up Study Cooperative Research Group. Association of gestational diabetes with maternal disorders of glucose metabolism and childhood adiposity. JAMA 2018;320:1005-1016 194. Landon MB, Spong CY, Thom E, et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A multicenter, rando-mized trial of treatment for mild gestational diabetes. N Engl J Med 2009;361:1339-1348 195. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS, Australian Carbo-hydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005;352:2477-2486 196. Hillier TA, Pedula KL, Ogasawara KK, et al. A pragmatic, randomized clinical trial of gestational diabetes screening. N Engl J Med 2021;384:895-904 197. Coustan DR, Dyer AR, Metzger BE. One-step or 2-step testing for gestational diabetes: which is better? Am J Obstet Gynecol 2021;225: 634-644 198. Lowe WL, Scholtens DM, Kuang A, et al.; HAPO Follow-up Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): maternal gestational diabetes mellitus and childhood glucose metabolism. Diabetes Care 2019;42: 372-380 199. Scholtens DM, Kuang A, Lowe LP, et al.; HAPO Follow-Up Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): maternal glycemia and childhood glucose metabolism. Diabetes Care 2019;42:381-392 200. Josefson JL, Scholtens DM, Kuang A, et al.; HAPO Follow-up Study Cooperative Research Group. Newborn adiposity and cord blood C-peptide as mediators of the maternal metabolic environment and childhood adiposity. Diabetes Care 2021;44:1194-1202 201. Landon MB, Rice MM, Varner MW, et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. Mild gestational diabetes mellitus and long-term child health. Diabetes Care 2015;38:445-452 202. Tam WH, Ma RCW, Ozaki R, et al. In utero exposure to maternal hyperglycemia increases childhood cardiometabolic risk in offspring. Diabetes Care 2017;40:679-686 203. Vandorsten JP, Dodson WC, Espeland MA, et al. NIH consensus development conference: diagnosing gestational diabetes mellitus. NIH Consens State Sci Statements 2013;29:1-31 204. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol 2018;131:e49-e64 205. Pillay J, Donovan L, Guitard S, et al. Screening for gestational diabetes mellitus: a systematic review to update the 2014 U.S. Preventive Services Task Force Recommendation. In US Preventative Services Task Force Evidence Syntheses, formerly Systematic Evidence Reviews. Treatments for gestational diabetes: a systematic review and meta-analysis. BMJ Open 2017;7: e015557 208. Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982;144:768-773 209. National Diabetes Data Group. Classifi-cation and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979;28:1039-1057 3. Prevention or Delay of Diabetes and Associated Comorbidities: Standards of Care in Diabetes-2025 Diabetes Care 2025;48(Suppl. 1):S50-S58 | https://doi.org/10.2337/dc25-S003 American Diabetes Association Professional Practice Committee* Recommendations 3.1 In people with prediabetes, monitor for the development of type 2 diabetes at least annually; modify frequency of testing based on individual risk assess-ment. E 3.2 In people with presymptomatic type 1 diabetes, monitor for disease pro-gression using A1C approximately every 6 months and 75-g oral glucose toler-ance test (i.e., fasting and 2-h plasma glucose) annually; modify frequency of monitoring based on individual risk assessment based on age, number and vene. Once identified, several effective therapeutic approaches exist that can de-lay type 2 diabetes in those with prediabe-tes with an A1C 5.7-6.4% (39-47 mmol/ mol), impaired glucose tolerance (IGT) on 75-g oral glucose tolerance test (OGTT), or impaired fasting glucose (IFG). The util-ity of screening with A1C for prediabe-tes and diabetes may be limited in the presence of certain hemoglobinopa-thies and conditions that affect red blood cell turnover (Table 2.3). See Sec-tion 2, "Diagnosis and Classification of Diabetes," and Section 6, "Glycemic Goals and Hypoglycemia," for additional details on the appropriate use and limitations of type of autoantibodies, and glycemic metrics. complications during which one can inter-A1C testing.|S47| |---|---|

|in adults with type 1 and type 2 diabetes in||

|England, 1998-2013: a retrospective cohort study.||

|Diabetes Care 2018;41:1870-1877||

|diabetesjournals.org/care|Prevention or Delay of Diabetes|S57| |---|---|---|

|in autoantibody positive children. J Clin Endocrinol Metab 2019;104:3337-3344 3. Ylescupidez A, Speake C, Pietropaolo SL, et al. OGTT metrics surpass continuous glucose moni-toring data for T1D prediction in multiple-autoantibody-positive individuals. J Clin Endocrinol Metab 2023;109:57-67 4. Phillip M, Achenbach P, Addala A, et al. Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes. Diabetes Care 2024;47:1276-1298 5. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403 6. Lindstr€ om J, Ilanne-Parikka P, Peltonen M, et al. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet 2006; 368:1673-1679 7. Li G, Zhang P, Wang J, et al. Cardiovascular mortality, all-cause mortality, and diabetes in-cidence after lifestyle intervention for people with impaired glucose tolerance in the Da Qing Diabetes Prevention Study: a 23-year follow-up study. Lancet Diabetes Endocrinol 2014;2:474-480 8. Nathan DM, Bennett PH, Crandall JP, et al. Does diabetes prevention translate into reduced long-term vascular complications of diabetes? Diabetologia 2019;62:1319-1328 9. Gong Q, Zhang P, Wang J, et al. Morbidity and mortality after lifestyle intervention for people with impaired glucose tolerance: 30-year results of the Da Qing Diabetes Prevention Outcome Study. Lancet Diabetes Endocrinol 2019;7: 452-461 10. Knowler WC, Fowler SE, Hamman RF, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet 2009;374:1677-1686 11. Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or met-formin on diabetes development and micro-vascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol 2015;3:866-875 12. Diabetes Prevention Program (DPP) Research Group. The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes Care 2002;25:2165-2171 13. Hamman RF, Wing RR, Edelstein SL, et al. Effect of weight loss with lifestyle intervention on risk of diabetes. Diabetes Care 2006;29:2102-2107 14. Goldberg RB, Orchard TJ, Crandall JP, et al. Effects of long-term metformin and lifestyle interventions on cardiovascular events in the Diabetes Prevention Program and its outcome study. Circulation 2022;145:1632-1641 15. Evert AB, Dennison M, Gardner CD, et al. Nutrition therapy for adults with diabetes or prediabetes: a consensus report. Diabetes Care 2019;42:731-754 16. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 48. The Community Guide. Diabetes Prevention: 93. de Jager J, Kooy A, Lehert P, et al. Long term 33. Association for the Study of Diabetes (EASD). Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med 2018;378:e34 19. Stentz FB, Brewer A, Wan J, et al. Remission of pre-diabetes to normal glucose tolerance in obese adults with high protein versus high carbohydrate diet: randomized control trial. BMJ Open Diabetes Res Care 2016;4:e000258 20. Jardine MA, Kahleova H, Levin SM, Ali Z, Trapp CB, Barnard ND. Perspective: plant-based eating pattern for type 2 diabetes prevention and treatment: efficacy, mechanisms, and practical considerations. Adv Nutr 2021;12:2045-2055 21. Lee Y, Park K. Adherence to a vegetarian diet and diabetes risk: a systematic review and meta-analysis of observational studies. Nutrients 2017; 9:603 22. Qian F, Liu G, Hu FB, Bhupathiraju SN, Sun Q. Association between plant-based dietary patterns and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA Intern Med 2019;179: 1335-1344 23. Esposito K, Chiodini P, Maiorino MI, Bellastella G, Panagiotakos D, Giugliano D. Which diet for prevention of type 2 diabetes? A meta-analysis of prospective studies. Endocrine 2014; 47:107-116 24. Yau JW, Thor SM, Ramadas A. Nutritional strategies in prediabetes: a scoping review of recent evidence. Nutrients 2020;12:2990 25. Ley SH, Hamdy O, Mohan V, Hu FB. Prevention and management of type 2 diabetes: dietary components and nutritional strategies. Lancet 2014;383:1999-2007 26. Parker AR, Byham-Gray L, Denmark R, Winkle PJ. The effect of medical nutrition therapy by a registered dietitian nutritionist in patients with prediabetes participating in a randomized controlled clinical research trial. J Acad Nutr Diet 2014;114:1739-1748 27. Fedewa MV, Gist NH, Evans EM, Dishman RK. Exercise and insulin resistance in youth: a meta-analysis. Pediatrics 2014;133:e163-e174 28. Davis CL, Pollock NK, Waller JL, et al. Exercise dose and diabetes risk in overweight and obese children: a randomized controlled trial. JAMA 2012;308:1103-1112 29. Dai X, Zhai L, Chen Q, et al. Two-year-supervised resistance training prevented dia-betes incidence in people with prediabetes: a randomised control trial. Diabetes Metab Res Rev 2019;35:e3143 30. Thorp AA, Kingwell BA, Sethi P, Hammond L, Owen N, Dunstan DW. Alternating bouts of sitting and standing attenuate postprandial glucose res-ponses. Med Sci Sports Exerc 2014;46:2053-2061 31. Russo LM, Nobles C, Ertel KA, Chasan-Taber L, Whitcomb BW. Physical activity interventions in pregnancy and risk of gestational diabetes mellitus: a systematic review and meta-analysis. Obstet Gynecol 2015;125:576-582 32. Henson J, Covenant A, Hall AP, et al. Waking up to the importance of sleep in type 2 diabetes management: a narrative review. Diabetes Care 2024;47:331-343 79. Demay MB, Pittas AG, Bikle DD, et al. review with pairwise, network, and dose-"Facilitating Positive Health Behaviors Diabetes Care 2022;45:2753-2786 34. Mostafa SA, Mena SC, Antza C, Balanos G, Nirantharakumar K, Tahrani AA. Sleep behaviours and associated habits and the progression of pre-diabetes to type 2 diabetes mellitus in adults: a systematic review and meta-analysis. Diab Vasc Dis Res 2022;19:14791641221088824 35. Nelson KL, Davis JE, Corbett CF. Sleep quality: an evolutionary concept analysis. Nurs Forum 2022;57:144-151 36. Anothaisintawee T, Reutrakul S, Van Cauter E, Thakkinstian A. Sleep disturbances compared to traditional risk factors for diabetes de-velopment: systematic review and meta-analysis. Sleep Med Rev 2016;30:11-24 37. Merikanto I, Lahti T, Puolijoki H, et al. Associations of chronotype and sleep with cardiovascular diseases and type 2 diabetes. Chronobiol Int 2013;30:470-477 38. Herman WH, Hoerger TJ, Brandle M, et al. The cost-effectiveness of lifestyle modification or metformin in preventing type 2 diabetes in adults with impaired glucose tolerance. Ann Intern Med 2005;142:323-332 39. Chen F, Su W, Becker SH, et al. Clinical and economic impact of a digital, remotely-delivered intensive behavioral counseling program on Medi-care beneficiaries at risk for diabetes and cardiovascular disease. PLoS One 2016;11:e0163627 40. Diabetes Prevention Program Research Group. The 10-year cost-effectiveness of lifestyle intervention or metformin for diabetes pre-vention: an intent-to-treat analysis of the DPP/ DPPOS. Diabetes Care 2012;35:723-730 41. Alva ML, Hoerger TJ, Jeyaraman R, Amico P, Rojas-Smith L. Impact of the YMCA of the USA Diabetes Prevention Program on Medicare spending and utilization. Health Aff (Millwood) 2017;36:417-424 42. Zhou X, Siegel KR, Ng BP, et al. Cost-effectiveness of diabetes prevention interventions targeting high-risk individuals and whole po-pulations: a systematic review. Diabetes Care 2020;43:1593-1616 43. Balk EM, Earley A, Raman G, Avendano EA, Pittas AG, Remington PL. Combined diet and physical activity promotion programs to prevent type 2 diabetes among persons at increased risk: a systematic review for the Community Pre-ventive Services Task Force. Ann Intern Med 2015;163:437-451 44. Ackermann RT, Kang R, Cooper AJ, et al. Effect on health care expenditures during nation-wide implementation of the Diabetes Prevention Program as a health insurance benefit. Diabetes Care 2019;42:1776-1783 45. Ely EK, Gruss SM, Luman ET, et al. A national effort to prevent type 2 diabetes: participant-level evaluation of CDC's National Diabetes Prevention Program. Diabetes Care 2017;40:1331-1341 46. Lanza A, Soler R, Smith B, Hoerger T, Neuwahl S, Zhang P. The Diabetes Prevention Impact Tool Kit: an online tool kit to assess the cost-effectiveness of preventing type 2 diabetes. J Public Health Manag Pract 2019;25:E1-E5 47. Cannon MJ, Masalovich S, Ng BP, et al. Retention among participants in the National Diabetes Prevention Program lifestyle change program, 2012-2017. Diabetes Care 2020;43: Interventions Engaging Community Health Workers, 2016. Accessed 7 August 2024. Available from https://www.thecommunityguide.org/findings/ diabetes-prevention-interventions-engaging-community-health-workers 49. Zare H, Delgado P, Spencer M, et al. Using community health workers to address barriers to participation and retention in Diabetes Prevention Program: a concept paper. J Prim Care Community Health 2022;13:21501319221134563 50. Raynor HA, Davidson PG, Burns H, et al. Medical nutrition therapy and weight loss questions for the Evidence Analysis Library prevention of type 2 diabetes project: systematic reviews. J Acad Nutr Diet 2017;117:1578-1611 51. Lau KHK. Nutrition therapy for adults with diabetes or prediabetes. ADCES Pract 2022;10: 34-38 52. Briggs Early K, Stanley K. Position of the Academy of Nutrition and Dietetics: the role of medical nutrition therapy and registered dietitian nutritionists in the prevention and treatment of prediabetes and type 2 diabetes. J Acad Nutr Diet 2018;118:343-353 53. Powers MA, Bardsley JK, Cypress M, et al. Diabetes self-management education and support in adults with type 2 diabetes: a consensus report of the American Diabetes Association, the Asso-ciation of Diabetes Care & Education Specialists, the Academy of Nutrition and Dietetics, the American Academy of Family Physicians, the American Academy of PAs, the American Association of Nurse Practitioners, and the American Pharmacists Association. Diabetes Care 2020;43:1636-1649 54. Hudspeth BD. Power of prevention: the pharmacist's role in prediabetes management. Diabetes Spectr 2018;31:320-323 55. Grock S, Ku JH, Kim J, Moin T. A review of technology-assisted interventions for diabetes prevention. Curr Diab Rep 2017;17:107 56. Bian RR, Piatt GA, Sen A, et al. The effect of technology-mediated diabetes prevention inter-ventions on weight: a meta-analysis. J Med Internet Res 2017;19:e76 57. Moin T, Damschroder LJ, AuYoung M, et al. Results from a trial of an online Diabetes Prevention Program intervention. Am J Prev Med 2018;55:583-591 58. Michaelides A, Major J, Pienkosz E, Jr., Wood M, Kim Y, Toro-Ramos T. Usefulness of a novel mobile Diabetes Prevention Program delivery platform with human coaching: 65-week observational follow-up. JMIR Mhealth Uhealth 2018;6:e93 59. Michaud TL, Almeida FA, Porter GC, et al. Effects of a digital diabetes prevention program on cardiovascular risk among individuals with prediabetes. Prim Care Diabetes 2023;17:148-154 60. Kim SE, Castro Sweet CM, Cho E, Tsai J, Cousineau MR. Evaluation of a digital diabetes prevention program adapted for low-income patients, 2016-2018. Prev Chronic Dis 2019;16: E155 61. Vadheim LM, Patch K, Brokaw SM, et al. Telehealth delivery of the diabetes prevention program to rural communities. Transl Behav Med 2017;7:286-291 outcomes in dysglycemia. N Engl J Med 2012; 367:319-328 64. DeFronzo RA, Tripathy D, Schwenke DC, et al. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med 2011;364: 1104-1115 65. Gerstein HC, Yusuf S, Bosch J, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised con-trolled trial. Lancet 2006;368:1096-1105 66. le Roux CW, Astrup A, Fujioka K, et al. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Vitamin D for the prevention of disease: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2024;109:1907-1947 80. Jorde R, Sollid ST, Svartberg J, et al. Vitamin D 20,000 IU per week for five years does not prevent progression from prediabetes to diabetes. J Clin Endocrinol Metab 2016;101:1647-1655 81. Pittas AG, Dawson-Hughes B, Sheehan P, et al. Vitamin D supplementation and prevention of type 2 diabetes. N Engl J Med 2019;381: 520-530 82. Kawahara T, Suzuki G, Mizuno S, et al. Effect of active vitamin D treatment on development of type 2 diabetes: DPVD randomised controlled trial in Japanese population. BMJ 2022;377:e066222 83. Pittas AG, Kawahara T, Jorde R, et al. Vitamin treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ 2010; 340:c2181 94. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int 2022;102: S1-S127 95. Ali MK, Bullard KM, Saydah S, Imperatore G, Gregg EW. Cardiovascular and renal burdens of prediabetes in the USA: analysis of data from serial cross-sectional surveys, 1988-2014. Lancet Diabetes Endocrinol 2018;6:392-403 96. Pan Y, Chen W, Wang Y. Prediabetes and outcome of ischemic stroke or transient ischemic response meta-analyses. BMJ 2021;374:n1537 108. Kernan WN, Viscoli CM, Furie KL, et al. Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med 2016;374:1321-1331 109. Inzucchi SE, Viscoli CM, Young LH, et al. Pioglitazone prevents diabetes in patients with insulin resistance and cerebrovascular disease. Diabetes Care 2016;39:1684-1692 110. Spence JD, Viscoli CM, Inzucchi SE, et al. Pioglitazone therapy in patients with stroke and prediabetes: a post hoc analysis of the IRIS randomized clinical trial. JAMA Neurol 2019;76: 526-535 111. Spence JD, Viscoli C, Kernan WN, et al. Efficacy of lower doses of pioglitazone after stroke or transient ischaemic attack in patients 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes-2025 Diabetes Care 2025;48(Suppl. 1):S59-S85 | https://doi.org/10.2337/dc25-S004 American Diabetes Association Professional Practice Committee* and Well-being to Improve Health Outcomes") and pharmacotherapy, as appropriate. The goals of treatment for diabetes are to prevent or delay complications and optimize quality of life (Fig. 4.1). Treatment goals and plans should be co-created by the care team and people with diabetes based on their individual preferences, values, and goals. This indi-vidualized management plan should take into account the person's age, cognitive abilities, school/work schedule and condi-62. Basal insulin and cardiovascular and other Lancet 2017;389:1399-1409 67. Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM ran-domised trial. Lancet 2002;359:2072-2077 68. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021;384:989-1002 69. Holman RR, Haffner SM, McMurray JJ, et al. Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med 2010; 362:1463-1476 70. Dennison RA, Chen ES, Green ME, et al. The absolute and relative risk of type 2 diabetes after gestational diabetes: a systematic review and meta-analysis of 129 studies. Diabetes Res Clin Pract 2021;171:108625 71. Torgerson JS, Hauptman J, Boldrin MN, in Obese Subjects (XENDOS) study: a randomized for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004;27:155-161 with phentermine and topiramate extended release. Diabetes Care 2014;37:912-921 73. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Testosterone treatment to prevent or revert type 2 (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial. Lancet Diabetes Endocrinol 2021;9:32-45 and cardiovascular events. N Engl J Med 2010; 362:1477-1490 76. Bosch J, Yusuf S, Gerstein HC, et al. Effect of ramipril on the incidence of diabetes. N Engl J Med 2006;355:1551-1562 77. Ray KK, Colhoun HM, Szarek M, et al. Effects of alirocumab on cardiovascular and metabolic controlled trial. Lancet Diabetes Endocrinol 2019; 7:618-628 78. Everett BM, Donath MY, Pradhan AD, et al. Anti-inflammatory therapy with canakinumab for the prevention and management of diabetes. J Metformin in non-diabetic hyperglycaemia: the GLINT feasibility RCT. Health Technol Assess 2018;22:1-64 107. Cai T, Abel L, Langford O, et al. Associations between statins and adverse events in primary prevention of cardiovascular disease: systematic More information is available at https://www diabetes, their family or support group, and the health care team together formu-and not for profit, and the work is not altered. and values of the person with diabetes, elicited by the care team, the person with work is properly cited, the use is educational type 1 diabetes. N Engl J Med 2019;381:603-613 care partners must assume an active role in their care. Based on the preferences Readers may use this article as long as the CD3 antibody, teplizumab, in relatives at risk for health workers and community paramedics. Individuals with diabetes and their © 2024 by the American Diabetes Association. 121. Herold KC, Bundy BN, Long SA, et al. An anti-analysis of the ODYSSEY OUTCOMES randomised 92. Griffin SJ, Bethel MA, Holman RR, et al. Lancet 2012;380:565-571 1037822 behavioral health professionals, and community partners such as community Research. patients with or without diabetes: a prespecified diabetes. Medicine (Baltimore) 2019;98:e17918 prevention: an analysis from the JUPITER trial. NOD mice. Front Endocrinol (Lausanne) 2022;13: tered dietitian nutritionists, exercise specialists, pharmacists, dentists, podiatrists, from the American Society for Bone and Mineral outcomes after acute coronary syndrome in 90. Aroda VR, Edelstein SL, Goldberg RB, et al. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab 2016; 101:1754-1761 91. Kim J, Ahn CW, Fang S, Lee HS, Park JS. Association between metformin dose and vitamin B12 deficiency in patients with type 2 105. Mansi IA, Chansard M, Lingvay I, Zhang S, Halm EA, Alvarez CA. Association of statin therapy initiation with diabetes progression: a retrospective matched-cohort study. JAMA Intern Med 2021;181:1562-1574 106. Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary 119. Lamb MM, Frederiksen B, Seifert JA, Kroehl immunity to type 1 diabetes: the Diabetes Autoimmunity Study in the Young. Diabetologia glucose intake accelerates type 1 diabetes in The BONE HEALTH subsection has received endorsement and education specialists, primary care and subspecialty clinicians, nurses, regis-120. Li X, Wang L, Meng G, et al. Sustained high nated interprofessional team that may include but is not limited to diabetes care Diabetes Care 2025;48(Suppl. 1):S59-S85 2015;58:2027-2034 orbidities: Standards of Care in Diabetes-2025. ment planning. People with diabetes should receive health care from a coordi-medical evaluation and assessment of com-relationship between the person with diabetes and clinicians involved in treat-Professional Practice Committee. 4. Comprehensive associated with progression from islet auto-Populations") is a person-centered approach to care that requires a close working Suggested citation: American Diabetes Association M, Rewers M, Norris JM. Sugar intake is Care Model (2-4) (see Section 1, "Improving Care and Promoting Health in available at https://doi.org/10.2337/dc25-SDIS. Effect of valsartan on the incidence of diabetes 2006;49:289-297 Open Diabetes Res Care 2017;5:e000438 Metab 2008;93:3936-3942 dination between the person with diabetes and the care team (1). The Chronic Duality of interest information for each author is 75. McMurray JJ, Holman RR, Haffner SM, et al. Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia coepidemiol Drug Saf 2016;25:1131-1149 104. Crandall JP, Mather K, Rajpathak SN, et al. Statin use and risk of developing diabetes: results from the Diabetes Prevention Program. BMJ diabetes in young children. J Clin Endocrinol A successful medical evaluation depends on beneficial interactions and care coor-can be found at https://doi.org/10.2337/dc25-SINT. immunity, and subsequent progression to type 1 Diabetes Association Professional Practice Committee glycemic index, development of islet auto-*A complete list of members of the American 118. Lamb MM, Yin X, Barriga K, et al. Dietary diabetes in men enrolled in a lifestyle programme 89. Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay V. The Indian Malik A. Statin use and the risk of developing diabetes: a network meta-analysis. Pharma-Care 2023;46:1409-1416 ioral health professionals. C children followed in the TEDDY study. Diabetes 74. Wittert G, Bracken K, Robledo KP, et al. Diabetes Care 2019;42:601-608 103. Thakker D, Nair S, Pagada A, Jamdade V, immunity and type 1 diabetes in 5-to 15-year-old nutritionists, exercise specialists, pharmacists, dentists, podiatrists, and behav-obesity. N Engl J Med 2022;387:205-216 Diabetes Prevention Program Outcomes Study. Guidelines. Circulation 2019;140:e596-e646 activity and the development of islet auto-cialists, primary care and subspecialty clinicians, nurses, registered dietitian Tirzepatide once weekly for the treatment of 88. Diabetes Prevention Program Research Group. Long-term effects of metformin on diabetes pre-vention: identification of subgroups that benefited most in the Diabetes Prevention Program and 2019 ACC/AHA guideline on the primary preventio n of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice 117. Liu X, Johnson SB, Lynch KF, et al. Physical team that may include but is not limited to diabetes care and education spe-2021;64:1279-1287 4.2 People with diabetes can benefit from a coordinated interprofessional Diabetes Prevention Outcome Study. Diabetologia used to optimize health outcomes and health-related quality of life. B secondary analysis of the 30 year Da Qing prediabetes and metabolic syndrome treated 2015;100:1646-1653 102. Arnett DK, Blumenthal RS, Albert MA, et al. people with impaired glucose tolerance: a beliefs; and assesses literacy, numeracy, and potential barriers to care should be Prevention of type 2 diabetes in subjects with 10-year follow-up. J Clin Endocrinol Metab Trial. Diabetes Care 2019;42:777-788 cardiovascular and microvascular disease among strength-based language and active listening; elicits individual preferences and 72. Garvey WT, Ryan DH, Henry R, et al. with and without gestational diabetes: the Diabetes Prevention Program outcomes study with energy-restricted mediterranean diet and exercise on weight loss and cardiovascular risk factors: one-year results of the PREDIMED-Plus 116. Chen Y, Zhang P, Wang J, et al. Associations normal glucose tolerance with development of 4.1 A communication style that uses person-centered, culturally sensitive, and of progression to diabetes and regression to Recommendations on preventing or delaying diabetes among women study of orlistat as an adjunct to lifestyle changes 87. Aroda VR, Christophi CA, Edelstein SL, et al. The effect of lifestyle intervention and metformin M, et al. Effect of a lifestyle intervention program Outcomes Study (DPPOS). Diabetes Care 2019; 42:1809-1815 PERSON-CENTERED COLLABORATIVE CARE 101. Salas-Salvad o J, D ıaz-L opez A, Ruiz-Canela Sj€ ostr€ om L. XENical in the prevention of Diabetes D and risk for type 2 diabetes in people with prediabetes: a systematic review and meta-analysis of individual participant data from 3 randomized clinical trials. Ann Intern Med 2023; 176:355-363 84. Shah VP, Nayfeh T, Alsawaf Y, et al. A systematic review supporting the Endocrine Society clinical practice guidelines on vitamin D. J Clin Endocrinol Metab 2024;109:1961-1974 85. Diabetes Prevention Program Research Group. Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care 2012;35:731-737 86. Ratner RE, Christophi CA, Metzger BE, et al. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab 2008;93:4774-4779 attack: a systematic review and meta-analysis. J Stroke Cerebrovasc Dis 2019;28:683-692 97. Huang Y, Cai X, Mai W, Li M, Hu Y. Association between prediabetes and risk of cardiovascular disease and all cause mortality: systematic review and meta-analysis. BMJ 2016; 355:i5953 98. Yeh HC, Duncan BB, Schmidt MI, Wang NY, Brancati FL. Smoking, smoking cessation, and risk for type 2 diabetes mellitus: a cohort study. Ann Intern Med 2010;152:10-17 99. Hu Y, Zong G, Liu G, et al. Smoking cessation, weight change, type 2 diabetes, and mortality. N Engl J Med 2018;379:623-632 100. Orchard TJ, Temprosa M, Barrett-Connor E, et al. Long-term effects of the Diabetes Prevention Program interventions on cardiovascular risk factors: a report from the DPP Outcomes Study. Diabet Med 2013;30:46-55 with insulin resistance. Diabetes Obes Metab tions, health beliefs, support systems, eating 2022;24:1150-1158 112. Nadeau KJ, Anderson BJ, Berg EG, et al. Youth-onset type 2 diabetes consensus report: current status, challenges, and priorities. Diabetes Care 2016;39:1635-1642 113. Rooney MR, Rawlings AM, Pankow JS, et al. Risk of progression to diabetes among older adults with prediabetes. JAMA Intern Med 2021; 181:511-519 114. Lachin JM, Christophi CA, Edelstein SL, et al. Factors associated with diabetes onset during metformin versus placebo therapy in the Diabetes Prevention Program. Diabetes 2007;56: 1153-1159 115. Perreault L, Pan Q, Schroeder EB, et al. Regression from prediabetes to normal glucose regulation and prevalence of microvascular disease in the Diabetes Prevention Program The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Com-mittee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes .org/SOC. patterns, physical activity, social situation, fi-nancial concerns, cultural factors, literacy and numeracy (mathematical literacy), dia-betes history (duration, complications, and current use of medications), comorbidities, disabilities, health priorities, other medical conditions, preferences for care, access to health care services, and life expectancy.|4. MEDICAL EVALUATION AND COMORBIDITIES||

|2042-2049 late the management plan, which includes lifestyle management (see Section 5,|Am Coll Cardiol 2018;71:2392-2401 .diabetesjournals.org/journals/pages/license.|Am Coll Cardiol 2018;71:2392-2401 .diabetesjournals.org/journals/pages/license.|

|the following: tes) led to resolution of steatohepatitis||pharmacotherapy|pharmacotherapy|pharmacotherapy|

|• Adoption of a healthy lifestyle without worsening of fibrosis in 59% of • Weight loss (if indicated) individuals at the higher dose (equiva-||Prefer GLP-1 RA, dual GIP and GLP-1 RA|Prefer GLP-1 RA, dual GIP and GLP-1 RA, pioglitazone|Resmetirom|

|• Optimal diabetes lent to 2.4 mg/week semaglutide) com-|||||

|management pared with 17% in the placebo group • Cardiovascular risk reduction (P < 0.001) (262). Cumulatively, sema-||Obesity pharmacotherapy|Diabetes pharmacotherapy|MASH pharmacotherapy|

|• Need for metabolic glutide did not significantly affect the surgery (as recommended by guidelines) stage of liver fibrosis in this group of|MASLD|As with F2-F3 with caution*|As with F2-F3 with caution*| AVOID|

|people but, over 72 weeks, slowed the|||||

|progression of liver fibrosis (4.9% with the GLP-1 RA at the highest dose com-||Obesity pharmacotherapy|Diabetes pharmacotherapy|MASH pharmacotherapy|

|pared with 18.8% on placebo). Tirzepa-|| AVOID|Only use insulin| AVOID|

|tide is a dual GIP and GLP-1 RA known|||||

|to reduce liver steatosis in MASLD|||||

|*Individualized care and close monitoring needed in compensated cirrhosis given limited safety data available. (277), and a phase 2 paired-biopsy study|||||

|of 190 adults with overweight or obesity|||||

|Figure 4.3-Metabolic dysfunction-associated steatotic liver disease (MASLD) treatment algorithm. F0-F1, no to minimal fibrosis; F2-F3, moderate with MASH (50-60% of whom had type 2 fibrosis; F4, cirrhosis; GIP, glucose-dependent insulinotropic polypeptide; GLP-1 RA, glucagon-like peptide 1 receptor agonist; MASH, metabolic diabetes) recently reported that doses of 5, dysfunction-associated steatohepatitis; SGLT2i, sodium-glucose cotransporter 2 inhibitor. 10, and 15 mg/day resulted in resolution|||||

|of steatohepatitis without worsening of fi-|||||

|brosis in 44%, 56%, and 62% of partici-|||||

|pants, respectively, compared with 10% of|||||

|participants receiving placebo (P < 0.001|||||

|for all three comparisons) (278). Improve-|||||

|ment of at least one fibrosis stage without|||||

|worsening of MASH occurred in 55%, 51%,|||||

|and 61% of participants, respectively, com-|||||

|pared with 30% of participants receiving|||||

|placebo. Survodutide is a dual GLP-1 and|||||

|glucagon RA that is in development, and a|||||

|phase 2 paired-biopsy trial recently re-|||||

|ported benefit in MASH (279). In summary,|||||

|GLP-1-based therapies and/or pioglitazone is|||||

|recommended to treat type 2 diabetes in|||||

|adults with MASH based on histological|||||

|benefit for steatohepatitis in several|||||

|phase 2 RCTs (278,279) compared|||||

|with no benefit with metformin or|||||

|other glucose-lowering or weight loss|||||

|medications. Within the context of their|||||

|approved indication (e.g., obesity or type 2|||||

|diabetes), these medications are cost-|||||

|effective to treat the comorbidity, while|||||

|potentially improving MASH, which be-|||||

|comes an added benefit.|||||

|SGLT2 inhibitors (280-282) and insulin|||||

|(258) reduce hepatic steatosis, but their ef-|||||

|fects on steatohepatitis remain unknown.|||||

|The use of glucose-lowering agents other|||||

|than pioglitazone or GLP-1 RAs may be|||||

|continued in individuals with type 2|||||

|diabetesjournals.org/care||Comprehensive Medical Evaluation and Assessment of Comorbidities|S81| |---|---|---|---|

|diabetes mellitus and risk of fracture. Am J biomarkers in patients with type 2 diabetes 139. Selvarajah D, Kar D, Khunti K, et al. Diabetic and nonalcoholic fatty liver disease. Obesity assessing steatosis and fibrosis in patients with trial of subcutaneous semaglutide in nonalcoholic A scoping review. J Nutr Health Aging 2017;21: observational evidence. J Periodontol 2013;84: 60. Schwartz AV, Chen H, Ambrosius WT, et al. the Action to Control Cardiovascular Risk in 155. Grossmann M. Low testosterone in men function based on international index of erectile with chronic kidney disease: a systematic review||||

|Effects of TZD use and discontinuation on Diabetes-Memory in Diabetes (ACCORD-MIND) trial. with type 2 diabetes: significance and treatment. S135-S152 527-538 function scores. Eur Urol 2017;72:1000-1011 and meta-analysis. PLoS Med 2014;11:e1001680 steatohepatitis. N Engl J Med 2021;384:1113-1124|Epidemiol 2007;166:495-505 treated with canagliflozin. J Clin Endocrinol Metab peripheral neuropathy: advances in diagnosis (Silver Spring) 2021;29:1950-1960 nonalcoholic fatty liver disease. Gastroenterology|||

|fracture rates in ACCORD bone study. J Clin Diabetes Care 2009;32:221-226 J Clin Endocrinol Metab 2011;96:2341-2353||46. Napoli N, Conte C, Pedone C, et al. Effect of 2016;101:44-51 and strategies for screening and early inter-76. National Institutes of Health. Calcium-fact 124. Simpson TC, Clarkson JE, Worthington HV, 170. Lindau ST, Tang H, Gomero A, et al. 185. Younossi ZM, Golabi P, Price JK, et al. The 214. Song D, Li C, Wang Z, Zhao Y, Shen B, Zhao 2019;156:1717-1730 263. National Library of Medicine, National||

|insulin resistance on BMD and fracture risk in older 92. Watts NB, Bilezikian JP, Usiskin K, et al. vention. Lancet Diabetes Endocrinol 2019;7: Sexuality among middle-aged and older adults sheet for health professionals. Accessed 19 et al. Treatment of periodontitis for glycaemic 156. Bhasin S, Cunningham GR, Hayes FJ, et al.; Endocrinol Metab 2015;100:4059-4066 110. Launer LJ, Miller ME, Williamson JD, et al.; global epidemiology of nonalcoholic fatty liver W. Association of non-alcoholic fatty liver disease 229. M ozes FE, Lee JA, Selvaraj EA, et al.; Center for Biotechnology Information. Research||||

|61. Hidayat K, Du X, Wu M-J, Shi B-M. The use ACCORD MIND Investigators. Effects of intensive Task Force, Endocrine Society. Testosterone||August 2024. Available from https://ods.od.nih. control in people with diabetes mellitus. with diagnosed and undiagnosed diabetes: a with diabetic retinopathy in type 2 diabetic Study on Whether Semaglutide Works in People|August 2024. Available from https://ods.od.nih. control in people with diabetes mellitus. with diagnosed and undiagnosed diabetes: a with diabetic retinopathy in type 2 diabetic Study on Whether Semaglutide Works in People|

|of metformin, insulin, sulphonylureas, and glucose lowering on brain structure and function in therapy in men with androgen deficiency Cochrane Database Syst Rev 2022;4:CD004714 gov/factsheets/Calcium-HealthProfessional national, population-based study. Diabetes Care patients: a meta-analysis of observational studies. With Non-Alcoholic Steatohepatitis (NASH)|47. Napoli N, Schwartz AV, Schafer AL, et al.; with type 2 diabetes mellitus. J Clin Endocrinol 140. Fatma S, Noohu MM. Classification of patients with type 2 diabetes. Clin Gastroenterol non-invasive tests for advanced fibrosis in|||

|thiazolidinediones and the risk of fracture: people with type 2 diabetes (ACCORD MIND): a syndromes: an Endocrine Society clinical practice|Osteoporotic Fractures in Men (MrOS) Study Metab 2016;101:157-166 functionality of people with diabetic peripheral Hepatol 2024;22:1999-2010.e8 patients with NAFLD: an individual patient data (ESSENCE). Accessed 23 September 2024. 77. Rosen CJ, Abrams SA, Aloia JF, et al. IOM 125. D'Aiuto F, Gkranias N, Bhowruth D, et al.; 2010;33:2202-2210 J Diabetes Investig 2021;12:1471-1479|||

|Research Group. Vertebral fracture risk in diabetic committee members respond to Endocrine 93. Perkovic V, Jardine MJ, Neal B, et al.; TASTE Group. Systemic effects of periodontitis neuropathy based on international classification 171. Maiorino MI, Bellastella G, Esposito K. 186. Stefan N, Cusi K. A global view of the 215. Arab JP, Dirchwolf M, systematic review and meta-analysis of obser-randomised open-label substudy. Lancet Neurol guideline. J Clin Endocrinol Metab 2010;95: Alvares-da-Silva MR, meta-analysis. Gut 2022;71:1006-1019 Available from https://clinicaltrials.gov/study/||||

|vational studies. Obes Rev 2019;20:1494-1503 2011;10:969-977 2536-2559|Society vitamin D guideline. J Clin Endocrinol treatment in patients with type 2 diabetes: a Diabetes and sexual dysfunction: current et al. Latin American Association for the Study of NCT04822181|Society vitamin D guideline. J Clin Endocrinol treatment in patients with type 2 diabetes: a Diabetes and sexual dysfunction: current et al. Latin American Association for the Study of NCT04822181|Society vitamin D guideline. J Clin Endocrinol treatment in patients with type 2 diabetes: a Diabetes and sexual dysfunction: current et al. Latin American Association for the Study of NCT04822181|

|2018;33:63-69 renal outcomes in type 2 diabetes and nephro-CS) of diabetes mellitus. J Diabetes Metab Disord and diabetes. Lancet Diabetes Endocrinol 2022; Compensated advanced chronic liver disease in 264. Belfort R, Harrison SA, Brown K, et al. A Metab 2012;97:1146-1152 12 month, single-centre, investigator-masked, ran-perspectives. Diabetes Metab Syndr Obes 2014;7: the Liver (ALEH) practice guidance for the 157. Bhasin S, Brito JP, Cunningham GR, et al. 62. Piccoli A, Cannata F, Strollo R, et al. Sclerostin 111. McCoy RG, Galindo RJ, Swarna KS, et al.||||

|48. Koromani F, Oei L, Shevroja E, et al. pathy. N Engl J Med 2019;380:2295-2306 2020;19:213-221 78. National Institutes of Health. Vitamin D-domised trial. Lancet Diabetes Endocrinol 2018;6: Testosterone therapy in men with hypogonadism: regulation, microarchitecture, and advanced Sociodemographic, clinical, and treatment-95-105 10:284-296 diagnosis and treatment of non-alcoholic fatty nonalcoholic fatty liver disease: two-step strategy placebo-controlled trial of pioglitazone in||||

|Vertebral fractures in individuals with type 2 94. Neal B, Perkovic V, Matthews DR. Can-141. Zhang Y, Lazzarini PA, McPhail SM, van fact sheet for health professionals. Accessed 19 954-965 an Endocrine Society clinical practice guideline. J glycation end-products in the bone of elderly related factors associated with hyperglycemic 172. Pontiroli AE, Cortelazzi D, Morabito A. 187. Song SJ, Lai JC-T, Wong GL-H, Wong VW-S, liver disease. Ann Hepatol 2020;19:674-690 is better than Baveno criteria. Dig Dis Sci 2023; subjects with nonalcoholic steatohepatitis. N||||

|women with type 2 diabetes. J Bone Miner Res crises among adults with type 1 or type 2 Clin Endocrinol Metab 2018;103:1715-1744|diabetes: more than skeletal complications alone. agliflozin and cardiovascular and renal events in Netten JJ, Armstrong DG, Pacella RE. Global Female sexual dysfunction and diabetes: a August 2024. Available from https://ods.od.nih 126. Elangovan S, Hertzman-Miller R, Karimbux Yip TC-F. Can we use old NAFLD data under the 216. Eslam M, Sarin SK, Wong VW-S, et al. The 68:1016-1025 Engl J Med 2006;355:2297-2307|||

|Diabetes Care 2020;43:137-144 type 2 diabetes. N Engl J Med 2017;377:2099 disability burdens of diabetes-related lower-systematic review and meta-analysis. J Sex Med .gov/factsheets/VitaminD-HealthProfessional N, Giddon D. A framework for physician-dentist 158. Shindel AW, Lue TF, Anawalt B, et al. Medical 2020;35:2415-2422 diabetes in the US from 2014 to 2020. JAMA new MASLD definition? J Hepatol 2024;80: Asian Pacific Association for the Study of the 231. Wong VWS, Zelber-Sagi S, Cusi K, et al. 265. Cusi K, Orsak B, Bril F, et al. Long-term||||

|63. Leanza G, Cannata F, Faraj M, et al. Bone Netw Open 2021;4:e2123471 and surgical therapy of erectile dysfunction. In|49. Faraj M, Schwartz AV, Burghardt AJ, et al. Risk 79. Eastell R, Vittinghoff E, Lui L-Y, et al. Diabetes 95. Li X, Li T, Cheng Y, et al. Effects of SGLT2 collaboration in diabetes and periodontitis. Clin extremity complications in 1990 and 2016. 2013;10:1044-1051 e54-e56 Liver clinical practice guidelines for the diagnosis Management of NAFLD in primary care settings. pioglitazone treatment for patients with|||

|factors for bone microarchitecture impairments in inhibitors on fractures and bone mineral density Diabetes Care 2020;43:964-974 173. Van Cauwenberghe J, Enzlin P, Nefs G, et al. mellitus and the benefit of antiresorptive therapy Diabetes 2014;32:188-192 Endotext. Feingold KR, Anawalt B, Blackman MR, canonical Wnt signaling is downregulated in type 2 112. Mair ML, Athavale R, Abdelhafiz AH. Practical 188. Younossi ZM, Paik JM, Stepanova M, Ong J, and management of metabolic associated fatty Liver Int 2022;42:2377-2389 nonalcoholic steatohepatitis and prediabetes or||||

|older men with type 2 diabetes -the MrOS study. J in type 2 diabetes: an updated meta-analysis. 142. Tsai Y-H, Chuang L-L, Lee Y-J, Chiu C-J. How Prevalence of and risk factors for sexual on fracture risk. J Bone Miner Res 2022;37: 127. Herrera D, Sanz M, Shapira L, et al. Alqahtani S, Henry L. Clinical profiles and mortality liver disease. Hepatol Int 2020;14:889-919 et al., Eds. South Dartmouth, MA, MDText.com, diabetes and associates with higher advanced considerations for managing patients with diabetes 232. Lazarus JV, Anstee QM, Hagstr€ om H, et al. type 2 diabetes mellitus: a randomized trial. Ann||||

|glycation end-products (AGEs) content and and dementia. Expert Rev Endocrinol Metab 2017; 2000. Available from https://www.ncbi.nlm.nih|Clin Endocrinol Metab. 12 July 2024 [Epub ahead Diabetes Metab Res Rev 2019;35:e3170 does diabetes accelerate normal aging? An dysfunctions in adults with type 1 or type 2 2121-2131 Association between periodontal diseases and rates are similar for metabolic dysfunction-217. European Association for the Study of the Defining comprehensive models of care for Intern Med 2016;165:305-315|||

|reduced bone strength. Elife 2024;12:RP90437 12:429-440 .gov/pubmed/25905163|of print]. DOI: 10.1210/clinem/dgae452 96. Suh S, Kim KW. Diabetes and cancer: cancer examination of ADL, IADL, and mobility disability 80. Langdahl BL, Silverman S, Fujiwara S, et al. cardiovascular diseases, diabetes and respiratory diabetes: results from Diabetes MILES -Flanders. associated steatotic liver disease and non-alcoholic Liver (EASL); European Association for the Study of NAFLD. Nat Rev Gastroenterol Hepatol 2021;18: 266. Sanyal AJ, Chalasani N, Kowdley KV, et al.;|||

|50. Schwartz AV, Vittinghoff E, Bauer DC, et al.; Real-world effectiveness of teriparatide on should be screened in routine diabetes assessment. diseases: consensus report of the Joint Workshop in middle-aged and older adults with and without 159. Allen MS, Walter EE. Erectile dysfunction: 64. Tramontana F, Napoli N, Litwack-Harrison S, 113. Punthakee Z, Miller ME, Launer LJ, et al.; Diabet Med 2022;39:e14676 fatty liver disease. J Hepatol 2024;80:694-701 Diabetes (EASD); European Association for the 717-729 NASH CRN. Pioglitazone, vitamin E, or placebo for||||

|Osteoporotic Fractures (SOF) Research Group; Diabetes Metab J 2019;43:733-743 diabetes. Diabetes Res Clin Pract 2021;182: fracture reduction in patients with osteoporosis by the European Federation of Periodontology et al. More rapid bone mineral density loss in ACCORD-MIND Investigators. Poor cognitive an umbrella review of meta-analyses of risk-174. Pyrgidis N, Mykoniatis I, Tishukov M, et al. 189. Harrison SA, Gawrieh S, Roberts K, et al. Study of Obesity (EASO); European Association for 233. Cusi K, Budd J, Johnson E, Shubrook J. nonalcoholic steatohepatitis. N Engl J Med 2010;||||

|Osteoporotic Fractures in Men (MrOS) Research Group; Health, Aging, and Body Composition (Health ABC) Research Group. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 2011;305: 2184-2192 51. Hidayat K, Fang Q-L, Shi B-M, Qin L-Q. Influence of glycemic control and hypoglycemia on the risk of fracture in patients with diabetes mellitus: a systematic review and meta-analysis of observational studies. Osteoporos Int 2021;32: 1693-1704 52. Wang B, Wang Z, Poundarik AA, et al. Unmasking fracture risk in type 2 diabetes: the association of longitudinal glycemic hemoglobin level and medications. J Clin Endocrinol Metab 2022;107:e1390-e1401 53. Komorita Y, Iwase M, Fujii H, et al. Both hypo-and hyperglycaemia are associated with increased fracture risk in Japanese people with type 2 diabetes: the Fukuoka Diabetes Registry. Diabet Med 2020;37:838-847 54. Majumdar SR, Leslie WD, Lix LM, et al. Longer duration of diabetes strongly impacts fracture risk assessment: the Manitoba BMD cohort. J Clin Endocrinol Metab 2016;101:4489-4496 55. Vavanikunnel J, Charlier S, Becker C, et al. Association between glycemic control and risk of fracture in diabetic patients: a nested case-97. Giovannucci E, Harlan DM, Archer MC, et al. 109114 Sexual dysfunction in women with end-stage and comorbidities or risk factors for fractures: (EFP) and the European arm of the World Prospective evaluation of the prevalence of non-the Study of the Liver (EASL). EASL-EASD-EASO Making sense of the nonalcoholic fatty liver 362:1675-1685 older men with diabetes: the Osteoporotic function and risk of severe hypoglycemia in type 2 factors, treatment, and prevalence outcomes. J Fractures in Men (MrOS) study. J Clin Endocrinol Metab. 24 February 2024 [Epub ahead of print]. DOI: 10.1210/clinem/dgae045 65. Ferrari SL, Abrahamsen B, Napoli N, et al.; Bone and Diabetes Working Group of IOF. Diagnosis and management of bone fragility in diabetes: an emerging challenge. Osteoporos Int 2018;29:2585-2596 66. Leslie WD, Johansson H, McCloskey EV, Harvey NC, Kanis JA, Hans D. Comparison of methods for improving fracture risk assessment in diabetes: the Manitoba BMD registry. J Bone Miner Res 2018;33:1923-1930 67. Ferrari S, Eastell R, Napoli N, et al. Denosumab in postmenopausal women with osteoporosis and diabetes: subgroup analysis of FREEDOM and FREEDOM extension. Bone 2020; 134:115268 68. LeBoff MS, Greenspan SL, Insogna KL, et al.The clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int 2022;33:2049-2102 69. Napoli N, Conte C, Eastell R, et al. Bone turnover markers do not predict fracture risk in type 2 diabetes. J Bone Miner Res 2020;35: 2363-2371 70. International Society for Pediatric and Adolescent Diabetes. ISPAD Clinical Practice Consensus Guidelines 2022. Accessed 19 August 2024. Available from https://www.ispad.org/ integrated analysis of 4 prospective obser-vational studies. Bone 2018;116:58-66 81. Schwartz AV, Pavo I, Alam J, et al. Teriparatide in patients with osteoporosis and type 2 diabetes. Bone 2016;91:152-158 82. Napoli N, Pannacciulli N, Vittinghoff E, et al. Effect of denosumab on fasting glucose in women with diabetes or prediabetes from the FREEDOM trial. Diabetes Metab Res Rev 2018; 34:e2991 83. Langdahl BL, Hofbauer LC, Forfar JC. Cardiovascular safety and sclerostin inhibition. J Clin Endocrinol Metab 2021;106:1845-1853 84. Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med 2016; 375:1532-1543 85. Conley RB, Adib G, Adler RA, et al. Secondary fracture prevention: consensus clinical recom-mendations from a multistakeholder coalition. J Bone Miner Res 2020;35:36-52 86. Hofbauer LC, Rachner TD. More DATA to guide sequential osteoporosis therapy. Lancet 2015;386:1116-1118 87. Napoli N, Strotmeyer ES, Ensrud KE, et al. Fracture risk in diabetic elderly men: the MrOS study. Diabetologia 2014;57:2057-2065 88. Hidayat K, Du X, Shi B-M. Risk of fracture with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-Diabetes and cancer: a consensus report. CA Cancer J Clin 2010;60:207-221 98. Aggarwal G, Kamada P, Chari ST. Prevalence of diabetes mellitus in pancreatic cancer compared to common cancers. Pancreas 2013;42:198-201 99. Cho J, Scragg R, Petrov MS. Postpancreatitis diabetes confers higher risk for pancreatic cancer than type 2 diabetes: results from a nationwide cancer registry. Diabetes Care 2020;43:2106-2112 100. Ninomiya I, Yamazaki K, Oyama K, et al. Pioglitazone inhibits the proliferation and metastasis of human pancreatic cancer cells. Oncol Lett 2014; 8:2709-2714 101. Hendriks AM, Schrijnders D, Kleefstra N, et al. Sulfonylurea derivatives and cancer, friend or foe? Eur J Pharmacol 2019;861:172598 102. Hua Y, Zheng Y, Yao Y, Jia R, Ge S, Zhuang A. Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing. J Transl Med 2023;21:403 103. Wang L, Xu R, Kaelber DC, Berger NA. Glucagon-like peptide 1 receptor agonists and 13 obesity-associated cancers in patients with type 2 diabetes. JAMA Netw Open 2024;7:e2421305 104. Xue M, Xu W, Ou Y-N, et al. Diabetes mellitus and risks of cognitive im pairment and dementia: a systematic review and meta-analysis of 144 prospective studies. Ageing Res Rev 2019; 55:100944 105. Ohara T, Doi Y, Ninomiya T, et al. Glucose diabetes: post hoc epidemiologic analysis of the ACCORD trial. Diabetes Care 2012;35:787-793 114. Lacy ME, Gilsanz P, Eng C, Beeri MS, Karter AJ, Whitmer RA. Severe hypoglycemia and cognitive function in older adults with type 1 diabetes: the Study of Longevity in Diabetes (SOLID). Diabetes Care 2020;43:541-548 115. Lee AK, Rawlings AM, Lee CJ, et al. Severe hypoglycaemia, mild cognitive impairment, dementia and brain volumes in older adults with type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) cohort study. Diabetologia 2018;61:1956-1965 116. Ye M, Yang Q, Zhang L, et al. Effect of hypoglycemic events on cognitive function in individuals with type 2 diabetes mellitus: a dose-response meta-analysis. Front Neurol 2024;15: 1394499 117. Mattishent K, Loke YK. Bi-directional interaction between hypoglycaemia and cognitive impairment in elderly patients treated with glucose-lowering agents: a systematic review and meta-analysis. Diabetes Obes Metab 2016;18: 135-141 118. Giorda CB, Ozzello A, Gentile S, et al.; HYPOS-1 Study Group of AMD. Incidence and risk factors for severe and symptomatic hypoglycemia in type 1 diabetes. Results of the HYPOS-1 study. Acta Diabetol 2015;52:845-853 Organization of Family Doctors (WONCA Europe). J Clin Periodontol 2023;50:819-841 128. Lalla E, Papapanou PN. Diabetes mellitus and periodontitis: a tale of two common interrelated diseases. Nat Rev Endocrinol 2011;7:738-748 129. Christgau M, Palitzsch KD, Schmalz G, Kreiner U, Frenzel S. Healing response to non-surgical periodontal therapy in patients with diabetes mellitus: clinical, microbiological, and immunologic results. J Clin Periodontol 1998;25: 112-124 130. Retzepi M, Donos N. The effect of diabetes mellitus on osseous healing. Clin Oral Implants Res 2010;21:673-681 131. United States Code. Americans with Disabilities Act of 1990. Pub. L. No. 101-336 42 U.S.C. § 2. 104 Stat. 328. p. 101-336. 132. United States Code. Americans with Disabilities Act Amendments Act of 2008. Pub. L. No. 110-325 42 U.S.C.A. § 12101 et seq. 133. Wong E, Backholer K, Gearon E, et al. Diabetes and risk of physical disability in adults: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2013;1:106-114 134. Tomic D, Shaw JE, Magliano DJ. The burden and risks of emerging complications of diabetes mellitus. Nat Rev Endocrinol 2022;18:525-539 135. Lisy K, Campbell JM, Tufanaru C, Moola S, 143. Streckmann F, Balke M, Cavaletti G, et al. Exercise and neuropathy: systematic review with meta-analysis. Sports Med 2022;52:1043-1065 144. Jing X, Chen J, Dong Y, et al. Related factors of quality of life of type 2 diabetes patients: a systematic review and meta-analysis. Health Qual Life Outcomes 2018;16:189 145. Yoon S-J, Kim K-I. Frailty and disability in diabetes. Ann Geriatr Med Res 2019;23:165-169 146. World Health Organization. WHO Disability Assessment Schedule 2.0 (WHODAS 2.0). Accessed 26 September 2024. Available from https://www.who.int/standards/classifications/ international-classification-of-functioning-disability-and-health/who-disability-assessment-schedule 147. Diabetes Distress Assessment and Resource Center. Diabetes Distress Scale (DDS). Accessed 26 September 2024. Available from https:// diabetesdistress.org/take-dd-survey/ 148. Hill-Briggs F, Adler NE, Berkowitz SA, et al. Social determinants of health and diabetes: a scientific review. Diabetes Care 2020;44:258-279 149. Tan T-W, Shih C-D, Concha-Moore KC, et al. Disparities in outcomes of patients admitted with diabetic foot infections. PLoS One 2019;14: e0215532 150. Skrepnek GH, Mills JL, Armstrong DG. A diabetic emergency one million feet long: disparities and burdens of illness among diabetic renal disease: a systematic review and meta-alcoholic fatty liver disease and steatohepatitis in Clinical Practice Guidelines on the management of disease clinical practice guidelines: what clinicians 267. Aithal GP, Thomas JA, Kaye PV, et al. Sex Med 2019;16:531-541 analysis. J Sex Med 2021;18:936-945 a large middle-aged US cohort. J Hepatol 2021; metabolic dysfunction-associated steatotic liver need to know. Diabetes Spectr 2024;37:29-38 Randomized, placebo-controlled trial of pioglitazone 160. Kouidrat Y, Pizzol D, Cosco T, et al. High 175. Haugstvedt A, Jørgensen J, Strandberg RB, 75:284-291 disease (MASLD). J Hepatol 2024;81:492-542 234. Anstee QM, Lawitz EJ, Alkhouri N, et al. in nondiabetic subjects with nonalcoholic steato-prevalence of erectile dysfunction in diabetes: a et al. Sexual dysfunction in women with type 1 190. Castera L, Laouenan C, Vallet-Pichard A, 218. Portillo-Sanchez P, Bril F, Maximos M, et al. Noninvasive tests accurately identify advanced hepatitis. Gastroenterology 2008;135:1176-1184 systematic review and meta-analysis of 145 diabetes in Norway: a cross-sectional study on et al.; QUID-NASH Investigators. High prevalence High prevalence of nonalcoholic fatty liver fibrosis due to NASH: baseline data from the 268. Huang J-F, Dai C-Y, Huang C-F, et al. First-in-studies. Diabet Med 2017;34:1185-1192 the prevalence and associations with physical of NASH and advanced fibrosis in type 2 diabetes: disease in patients with type 2 diabetes mellitus STELLAR trials. Hepatology 2019;70:1521-1530 Asian double-blind randomized trial to assess the 161. Araujo AB, Mohr BA, McKinlay JB. Changes and psychosocial complications. Diabet Med 2022; a prospective study of 330 outpatients undergoing and normal plasma aminotransferase levels. J 235. Lee J, Vali Y, Boursier J, et al. Prognostic efficacy and safety of insulin sensitizer in in sexual function in middle-aged and older men: 39:e14704 liver biopsies for elevated ALT, using a low Clin Endocrinol Metab 2015;100:2231-2238 accuracy of FIB-4, NAFLD fibrosis score and APRI nonalcoholic steatohepatitis patients. Hepatol Int longitudinal data from the Massachusetts Male 176. Buskoven MEH, Kjørholt EKH, Strandberg threshold. Diabetes Care 2023;46:1354-1362 219. Maximos M, Bril F, Portillo Sanchez P, et al. for NAFLD-related events: a systematic review. 2021;15:1136-1147 Aging Study. J Am Geriatr Soc 2004;52:1502-RB, Søfteland E, Haugstvedt A. Sexual dysfunction 191. Paik JM, Golabi P, Younossi Y, Mishra A, The role of liver fat and insulin resistance as Liver Int 2021;41:261-270 269. Sathyanarayana P, Jogi M, Muthupillai R, 1509 in women with type 1 diabetes in Norway: a Younossi ZM. Changes in the global burden of determinants of plasma aminotransferase elevation 236. Chan W-K, Treeprasertsuk S, Goh GB-B, Krishnamurthy R, Samson SL, Bajaj M. Effects of 162. Grover SA, Lowensteyn I, Kaouache M, qualitative study of women's experiences. Diabet chronic liver diseases from 2012 to 2017: the in nonalcoholic fatty liver disease. Hepatology 2015; et al. Optimizing use of nonalcoholic fatty liver combined exenatide and pioglitazone therapy on et al. The prevalence of erectile dysfunction in Med 2022;39:e14856 growing impact of NAFLD. Hepatology 2020;72: 61:153-160 disease fibrosis score, fibrosis-4 score, and liver hepatic fat content in type 2 diabetes. Obesity the primary care setting: importance of risk 177. Hendrieckx C, Halliday JA, Russell-Green S, 1605-1616 220. Kwo PY, Cohen SM, Lim JK. ACG clinical stiffness measurement to identify patients with (Silver Spring) 2011;19:2310-2315 factors for diabetes and vascular disease. Arch et al. Adults with diabetes distress often want to 192. Simon TG, Roelstraete B, Khalili H, Hagstr€ om guideline: evaluation of abnormal liver chemistries. advanced fibrosis. Clin Gastroenterol Hepatol 270. Abdul-Ghani M, Migahid O, Megahed A, Intern Med 2006;166:213-219 talk with their health professionals about it: H, Ludvigsson JF. Mortality in biopsy-confirmed Am J Gastroenterol 2017;112:18-35 2019;17:2570-2580.e2537 DeFronzo RA, Al-Ozairi E, Jayyousi A. Combination 163. Ma RC-W, So W-Y, Yang X, et al. Erectile findings from an audit of 4 Australian specialist nonalcoholic fatty liver disease: results from a 221. Younossi ZM, Anstee QM, Wai-Sun Wong V, 237. Petta S, Wai-Sun Wong V, Bugianesi E, et al. therapy with pioglitazone/exenatide improves dysfunction predicts coronary heart disease in diabetes clinics. Can J Diabetes 2020;44:473-480 nationwide cohort. Gut 2021;70:1375-1382 et al. The association of histologic and noninvasive Impact of obesity and alanine aminotransferase beta-cell function and produces superior glycaemic type 2 diabetes. J Am Coll Cardiol 2008;51:2045-178. Di Stasi V, Maseroli E, Vignozzi L. Female 193. Burra P, Becchetti C, Germani G. NAFLD tests with adverse clinical and patient-reported levels on the diagnostic accuracy for advanced control compared with basal/bolus insulin in 2050 sexual dysfunction in diabetes: mechanisms, and liver transplantation: disease burden, current outcomes in patients with advanced fibrosis due liver fibrosis of noninvasive tools in patients with poorly controlled type 2 diabetes: a 3-year follow-164. Gazzaruso C, Solerte SB, Pujia A, et al. Erectile diagnosis and treatment. Curr Diabetes Rev management and future challenges. JHEP Rep to nonalcoholic steatohepatitis. Gastroenterology nonalcoholic fatty liver disease. Am J Gastroenterol up of the Qatar study. Diabetes Obes Metab dysfunction as a predictor of cardiovascular events 2022;18:e171121198002 2020;2:100192 2021;160:1608-1619.e1613 2019;114:916-928 2020;22:2287-2294 and death in diabetic patients with angiographically 179. Wing RR, Bond DS, Gendrano IN, 3rd, et al.; 194. Corbin KD, Driscoll KA, Pratley RE, Smith SR, 222. Siddiqui MS, Yamada G, Vuppalanchi R, 238. Vali Y, Lee J, Boursier J, et al.; LITMUS 271. Lavynenko O, Abdul-Ghani M, Alatrach M, proven asymptomatic coronary artery disease: Sexual Dysfunction Subgroup of the Look AHEAD Maahs DM, Mayer-Davis EJ; Advancing Care for et al.; NASH Clinical Research Network. Diagnostic Systematic Review Team. Enhanced liver fibrosis et al. Combination therapy with pioglitazone/ a potential protective role for statins and Research Group. Effect of intensive lifestyle Type 1 Diabetes and Obesity Network (ACT1ON). accuracy of noninvasive fibrosis models to detect test for the non-invasive diagnosis of fibrosis in exenatide/metformin reduces the prevalence of 5-phosphodiesterase inhibitors. J Am Coll Cardiol intervention on sexual dysfunction in women Obesity in type 1 diabetes: pathophysiology, change in fibrosis stage. Clin Gastroenterol Hepatol patients with NAFLD: a systematic review and hepatic fibrosis and steatosis: the efficacy and 2008;51:2040-2044 with type 2 diabetes: results from an ancillary clinical impact, and mechanisms. Endocr Rev 2018; 2019;17:1877-1885.e1875 meta-analysis. J Hepatol 2020;73:252-262 durability of initial combination therapy for type 2 165. Kalter-Leibovici O, Wainstein J, Ziv A, et al.; Look AHEAD study. Diabetes Care 2013;36: 39:629-663 239. Srivastava A, Gailer R, Tanwar S, et al. diabetes (EDICT). Diabetes Obes Metab 2022;24: 223. Unalp-Arida A, Ruhl CE. Liver fibrosis scores Israel Diabetes Research Group (IDRG) Investigators. 2937-2944 195. de Vries M, Westerink J, Kaasjager KHAH, predict liver disease mortality in the United Prospective evaluation of a primary care referral 899-907 Lockwood C. The prevalence of disability among foot ulcer cases within emergency departments Clinical, socioeconomic, and lifestyle parameters 180. Rinella ME, Lazarus JV, Ratziu V, et al. A de Valk HW. Prevalence of nonalcoholic fatty liver States population. Hepatology 2017;66:84-95 pathway for patients with non-alcoholic fatty 272. Ahr en B, Masmiquel L, Kumar H, et al.||||

|control study. J Clin Endocrinol Metab 2019; tolerance status and risk of dementia in the in the United States, 2006-2010. PLoS One 2015; multisociety Delphi consensus statement on new glucose cotransporter-2 inhibitors in real-world people with cancer, cardiovascular disease, associated with erectile dysfunction among diabetic page/ISPADGuidelines2022 119. Jacobson AM, Ryan CM, Braffett BH, et al.; disease (NAFLD) in patients with type 1 diabetes 224. Qadri S, Ahlholm N, Lønsmann I, et al. liver disease. J Hepatol 2019;71:371-378 Efficacy and safety of once-weekly semaglutide||||

|104:1645-1654 56. Strotmeyer ES, Cauley JA, Schwartz AV, et al. use: systematic review and meta-analysis of observational studies. Osteoporos Int 2019;30: community: the Hisayama study. Neurology 2011; 77:1126-1134 chronic respiratory disease and/or diabetes: a 71. Armamento-Villareal R, Aguirre L, Napoli N, et al. Changes in thigh muscle volume predict DCCT/EDIC Research Group. Cognitive performance declines in older adults with type 1 diabetes: results systematic review. Int J Evid Based Healthc 10:e0134914 151. Lecube A, Hern andez C, Genesc a J, Sim o R. men. Diabetes Care 2005;28:1739-1744 fatty liver disease nomenclature. Hepatology 2023; mellitus: a systematic review and meta-analysis. J 240. Saarinen K, F€ arkkil€ a M, Jula A, et al. versus once-daily sitagliptin as an add-on to Obesity modifies the performance of fibrosis 166. De Berardis G, Pellegrini F, Franciosi M, 78:1966-1986 Clin Endocrinol Metab 2020;105:3842-3853 biomarkers in nonalcoholic fatty liver disease. J Enhanced liver fibrosis test predicts liver-related metformin, thiazolidinediones, or both, in patients||||

|bone mineral density response to lifestyle from 32 years of follow-up in the DCCT and EDIC 2018;16:154-166 1923-1940 et al.; QuED (Quality of Care and Outcomes in 181. Rinella ME, Neuschwander-Tetri BA, Clin Endocrinol Metab 2022;107:e2008-e2020 with type 2 diabetes (SUSTAIN 2): a 56-week,|Nontraumatic fracture risk with diabetes mellitus and 106. Hanyu H. Diabetes-related dementia. Adv Proinflammatory cytokines, insulin resistance, and 196. Cusi K, Sanyal AJ, Zhang S, et al. Non-outcomes in the general population. JHEP Rep|||

|therapy in frail, obese older adults. Osteoporos study. Lancet Diabetes Endocrinol 2021;9:436-445 Type 2 Diabetes) Study Group. Longitudinal|89. Chai S, Liu F, Yang Z, et al. Risk of fracture 136. Gregg EW, Menke A. Diabetes and Siddiqui MS, et al. AASLD practice guidance on 225. Bril F, McPhaul MJ, Caulfield MP, et al. double-blind, phase 3a, randomised trial. Lancet|89. Chai S, Liu F, Yang Z, et al. Risk of fracture 136. Gregg EW, Menke A. Diabetes and Siddiqui MS, et al. AASLD practice guidance on 225. Bril F, McPhaul MJ, Caulfield MP, et al. double-blind, phase 3a, randomised trial. Lancet|89. Chai S, Liu F, Yang Z, et al. Risk of fracture 136. Gregg EW, Menke A. Diabetes and Siddiqui MS, et al. AASLD practice guidance on 225. Bril F, McPhaul MJ, Caulfield MP, et al. double-blind, phase 3a, randomised trial. Lancet|

|adults: the health, aging, and body composition with dipeptidyl peptidase-4 inhibitors, glucagon-107. Gudala K, Bansal D, Schifano F, Bhansali A. disability. In Diabetes in America, 3rd ed. Cowie a case-control study. Diabetes Care 2006;29: assessment of quality of life in patients with Int 2014;25:551-558 120. Khader YS, Dauod AS, El-Qaderi SS, the clinical assessment and management of and its metabolic associations in patients with Performance of plasma biomarkers and diagnostic 241. Kjaergaard M, Lindvig KP, Thorhauge KH, Diabetes Endocrinol 2017;5:341-354||||

|study. Arch Intern Med 2005;165:1612-1617 like peptide-1 receptor agonists, or sodium-Diabetes mellitus and risk of dementia: a meta-CC, Casagrande SS, Menke A, et al., Eds. 72. Sinclair AJ, Abdelhafiz A, Dunning T, et al. Alkafajei A, Batayha WQ. Periodontal status of 1096-1101 type 2 diabetes and self-reported erectile nonalcoholic fatty liver disease. Hepatology 2023; type 1 diabetes and type 2 diabetes. Diabetes panels for nonalcoholic steatohepatitis and et al. Using the ELF test, FIB-4 and NAFLD fibrosis 273. Noureddin M, Jones C, Alkhouri N, Gomez||||

|57. Schwartz AV, Vittinghoff E, Sellmeyer DE, analysis of prospective observational studies. J 152. Hum J, Jou JH, Green PK, et al. Improvement Obes Metab 2017;19:1630-1634 score to screen the population for liver disease. J EV, Dieterich DT, Rinella ME; NASHNET. Screening glucose cotransporter-2 inhibitors in patients Bethesda, MD, National Institute of Diabetes and An international position statement on the diabetics compared with nondiabetics: a meta-dysfunction. Diabetes Care 2005;28:2637-2643 77:1797-1835 advanced fibrosis in patients with type 2 diabetes.||||

|management of frailty in diabetes mellitus: analysis. J Diabetes Complications 2006;20:59-68 167. Navaneethan SD, Vecchio M, Johnson DW,|et al.; Health, Aging, and Body Composition with type 2 diabetes mellitus: a systematic Diabetes Investig 2013;4:640-650 Digestive and Kidney Diseases, 2018. Available in glycemic control of type 2 diabetes after 182. Lomonaco R, Godinez Leiva E, Bril F, et al. 197. Ciardullo S, Perseghin G. Prevalence of Diabetes Care 2020;43:290-297 Hepatol 2023;79:277-286 for nonalcoholic fatty liver disease in persons|||

|Study. Diabetes-related complications, glycemic review and network meta-analysis combining 108. Tang X, Cardoso MA, Yang J, Zhou J-B, Sim o from https://www.ncbi.nlm.nih.gov/pubmed/ summary of recommendations. J Frailty Aging 121. Casanova L, Hughes FJ, Preshaw PM. successful treatment of hepatitis C virus. Diabetes et al. Prevalence and correlates of self-reported Advanced liver fibrosis is common in patients elevated liver stiffness in patients with type 1 and 226. McPherson S, Hardy T, Dufour J-F, et al. Age 242. Zoncap e M, Liguori A, Tsochatzis EA. Non-with type 2 diabetes in the United States is cost-||||

|2017;7:10-20 Diabetes and periodontal disease: a two-way sexual dysfunction in CKD: a meta-analysis of|control, and falls in older adults. Diabetes Care 177 randomized controlled trials with a median R. Impact of intensive glucose control on brain 33651544 Care 2017;40:1173-1180 with type 2 diabetes followed in the outpatient type 2 diabetes: a systematic review and meta-as a confounding factor for the accurate non-invasive testing and risk-stratification in patients|||

|73. Ebeling PR, Adler RA, Jones G, et al. relationship. Br Dent J 2014;217:433-437 137. Khan KS, Andersen H. The impact of follow-up of 26 weeks. Front Pharmacol 2022; observational studies. Am J Kidney Dis 2010; setting: the need for systematic screening. Diabetes invasive diagnosis of advanced NAFLD fibrosis.|2008;31:391-396 health: meta-analysis of cumulative data from 153. Carnovale C, Pozzi M, Dassano A, et al. The analysis. Diabetes Res Clin Pract 2022;190:109981 with MASLD. Eur J Intern Med 2024;122:11-19|||

|Management of endocrine disease: therapeutics of 122. Eke PI, Thornton-Evans GO, Wei L, 56:670-685|13:825417 diabetic neuropathy on activities of daily living, Care 2021;44:399-406 Am J Gastroenterol 2017;112:740-751|58. Loke YK, Singh S, Furberg CD. Long-term use 16,584 patients with type 2 diabetes mellitus. impact of a successful treatment of hepatitis C 198. Cusi K. Nonalcoholic fatty liver disease in 243. Andersson A, Kelly M, Imajo K, et al. Clinical||

|of thiazolidinediones and fractures in type 2 90. Rosenstock J, Wysham C, Fr ıas JP, et al. Diabetes Ther 2021;12:765-779 postural balance and risk of falls -a systematic virus on glyco-metabolic control in diabetic 168. Hackett G, Kirby M, Wylie K, et al. British vitamin D. Eur J Endocrinol 2018;179:R239-R259 Borgnakke WS, Dye BA, Genco RJ. Periodontitis 183. Ciardullo S, Monti T, Perseghin G. High diabetes: a call to action. Diabetes Spectr 2024; 227. Castera L, Friedrich-Rust M, Loomba R. utility of magnetic resonance imaging biomarkers||||

|diabetes: a meta-analysis. CMAJ 2009;180:32-39 Efficacy and safety of a novel dual GIP and GLP-1 109. Cukierman-Yaffe T, Gerstein HC, Williamson review. J Diabetes Sci Technol 2022;16:289-294 74. Maddaloni E, Cavallari I, Napoli N, Conte C. in US adults: National Health and Nutrition patients: a systematic review and meta-analysis. society for sexual medicine guidelines on the prevalence of advanced liver fibrosis assessed by 37:5-7 Noninvasive assessment of liver disease in for identifying nonalcoholic steatohepatitis patients||||

|Vitamin D and diabetes mellitus. Front Horm Res Examination Survey 2009-2014. J Am Dent Assoc 138. Elafros MA, Andersen H, Bennett DL, et al. receptor agonist tirzepatide in patients with type 2 management of erectile dysfunction in men-transient elastography among U.S. adults with patients with nonalcoholic fatty liver disease.|59. Dormandy J, Bhattacharya M, van JD, et al.; Action to Control Cardiovascular Risk in Acta Diabetol 2019;56:341-354 199. Younossi ZM, Ong JP, Takahashi H, et al.; at high risk of progression: a multicenter pooled|||

|2018;50:161-176 2018;149:576-588.e576 2017. J Sex Med 2018;15:430-457|diabetes (SURPASS-1): a double-blind, randomised, Towards prevention of diabetic peripheral type 2 diabetes. Diabetes Care 2021;44:519-525 Gastroenterology 2019;156:1264-1281.e1264|diabetes (SURPASS-1): a double-blind, randomised, Towards prevention of diabetic peripheral type 2 diabetes. Diabetes Care 2021;44:519-525 Gastroenterology 2019;156:1264-1281.e1264|diabetes (SURPASS-1): a double-blind, randomised, Towards prevention of diabetic peripheral type 2 diabetes. Diabetes Care 2021;44:519-525 Gastroenterology 2019;156:1264-1281.e1264|

|75. Iolascon G, Gimigliano R, Bianco M, et al. Are 123. Borgnakke WS, Yl€ ostalo PV, Taylor GW, neuropathy: clinical presentation, pathogenesis, phase 3 trial. Lancet 2021;398:143-155 169. Corona G, Rastrelli G, Morgentaler A, 184. Barb D, Repetto EM, Stokes ME, Shankar 228. Eddowes PJ, Sasso M, Allison M, et al.|Safety and tolerability of pioglitazone in high-risk vestigators. Relationship between baseline glycemic Testosterone concentrations in diabetic and non-global survey of physicians knowledge about 2022;20:2451-2461|||

|patients with type 2 diabetes: an overview of data control and cognitive function in individuals with diabetic obese men. Diabetes Care 2010;33: SS, Cusi K. Type 2 diabetes mellitus increases the 91. Bilezikian JP, Watts NB, Usiskin K, et al. and new treatments. Lancet Neurol 2022;21: Sforza A, Mannucci E, Maggi M. Meta-analysis of dietary supplements and nutraceuticals effective Genco RJ. Effect of periodontal disease on nonalcoholic fatty liver disease. Clin Gastroenterol Accuracy of FibroScan controlled attenuation 244. Long MT, Noureddin M, Lim JK. AGA clinical||||

|for musculoskeletal health and cognitive function? diabetes: systematic review of epidemiologic results of testosterone therapy on sexual 922-936 Evaluation of bone mineral density and bone risk of hepatic fibrosis in individuals with obesity parameter and liver stiffness measurement in|from PROactive. Drug Saf 2009;32:187-202 type 2 diabetes and other cardiovascular risk factors: 1186-1192 Hepatol 2022;20:e1456-e1468 practice update: diagnosis and management of|||

|Encourage healthy, evidence-based|5.13| |---|---|

|eating patterns||

|Nutrition Therapy Goals for All|| |---|---|

|People With Diabetes|Carbohydrates|

|1. To promote and support healthful eat-||

|ing patterns, emphasizing a variety of||

|nutrient-dense foods in appropriate||

|portion sizes, contributing to im-||

|proved overall health, and to:||

|• achieve and maintain body weight||

|goals||

|• attain individualized glycemic, blood||

|Risk element| |---|

|PSYCHOSOCIAL CARE| |---|

|Such care should be integrated with|

|routine medical care and delivered by|

|trained health care professionals using|

|a collaborative, person-centered, cul-|

|turally informed approach. A|

|5.45 Implement screening protocols|

|for psychosocial concerns, including|

|diabetes distress, depression, anxi-|

|ety, fear of hypoglycemia, and dis-|

|ordered eating behaviors. Screen at|

|least annually or when there is a|

|change in disease, treatment, or life|

|circumstances. C|

|5.46 When indicated, refer to behav-|

|ioral health professionals or other|

|trained health care professionals, ide-|

|ally those with experience in diabetes,|

|for further assessment and treatment|

|for symptoms of diabetes distress, de-|

|pression, suicidality, anxiety, treatment-|

|related fear of hypoglycemia, disordered|

|eating, and/or cognitive capacities. Such|

|specialized psychosocial care should|

|use age-appropriate standardized and|

|validated tools and treatment ap-|

|proaches. B|

|5.47 Consider developmental factors|

|and use age-appropriate validated|

|tools for psychosocial screening in|

|people with diabetes.|

||Increased|mortality|?||+++|||?|+++|||+++|||||| |---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

||Decreased|quality of life|+++||+++|||+++|+++|||?||||||

|Comorbid|psychosocial|concerns|+++||+++|||+++|+++|||+++|||+++|||

|Decreased|self-care|behaviors|+++||+++|||+++|+++|||?|||11|||

|Increased|microvascular|complications|+++||+++|||?|+++|||+++|||+++|||

|Increased|macrovascular|complications|+++||+++|||?|?|||+++|||+++|||

||Increased|cholesterol|+||+++|||?|?|||+|||+++|||

||Increased|blood pressure|?||?|||?|?|||?|||+++|||

||Increased|A1C|+++||+++|||+++|+++|||+++|||+++|||

||||Diabetes distress|(406,528-530)|Depression and depressive|symptoms|(528,529,531,532)|Anxiety (359,533,534)|Disordered eating|behaviors (insulin|omission) (535,536)|Serious mental illness|(schizophrenia,|personality disorders)|(537-539)|Cognitive impairment|(540-544)|

|diabetesjournals.org/care|||||||||Facilitating Positive Health Behaviors and Well-being|S109|||| |---|---|---|---|---|---|---|---|---|---|---|---|---|---|

||Increased|mortality|+++|+++||+++|?|||+++||||

|Decreased|quality|of life|+++|+++||+++|+++|||+++|+++|||

|Comorbid|psychosocial|concerns|+++|+++||+++|+++|||+++|+++|||

|Decreased|self-care|behaviors|+++|+++||+++|+|||+++|+++|||

|Increased|microvascular|complications|+++|+++||+|?|||+++|+++|||

|Increased|macrovascular|complications|+++|+++||+++|?|||+++|+++|||

||Increased|dyslipidemia|+|+++||+|?|||?|+++|||

||Increased|blood pressure|+|++||++|?|||?|+++|||

||Increased|A1C|+++|+++||+++|+/-|||+/-|+++|||

||||Diabetes distress (545-551)|Depression and depressive|symptoms (552-559)|Anxiety (358,408,553,560-563)|Disordered eating behaviors|(binge eating disorder, night|eating syndrome) (564-567)|Serious mental illness|(schizophrenia, bipolar|disorder) (568-575)|Cognitive impairment (576-583)|

||diabetesjournals.org/care diabetesjournals.org/care diabetesjournals.org/care diabetesjournals.org/care diabetesjournals.org/care diabetesjournals.org/care|Facilitating Positive Health Behaviors and Well-being Facilitating Positive Health Behaviors and Well-being Facilitating Positive Health Behaviors and Well-being Facilitating Positive Health Behaviors and Well-being Facilitating Positive Health Behaviors and Well-being Facilitating Positive Health Behaviors and Well-being|S115 S117 S119 S121 S123 S125| |---|---|---|---|

|6. GLYCEMIC GOALS AND HYPOGLYCEMIA|References 1. Young-Hyman D, de Groot M, Hill-Briggs F, Gonzalez JS, Hood K, Peyrot M. Psychosocial care for people with diabetes: a position statement of the American Diabetes Association. Diabetes Care 2016;39:2126-2140 2. Powers MA, Bardsley JK, Cypress M, et al. Diabetes self-management education and support in adults with type 2 diabetes: a consensus report of the American Diabetes Association, the Association of Diabetes Care & Education Specialists, the Academy of Nutrition and Dietetics, the American Academy of Family Physicians, the American Academy of PAs, the American Association of Nurse Practitioners, and the American Pharmacists Association. Diabetes Care 2020;43:1636-1649 3. Rutten GEHM, Alzaid A. Person-centred type 2 diabetes care: time for a paradigm shift. Lancet Diabetes Endocrinol 2018;6:264-266 4. Dickinson JK, Guzman SJ, Maryniuk MD, et al. The use of language in diabetes care and education. Diabetes Care 2017;40:1790-1799 5. Fisher L, Hessler D, Polonsky WH, et al. T1-REDEEM: a randomized controlled trial to reduce diabetes distress among adults with type 1 diabetes. Diabetes Care 2018;41:1862-1869 6. van der Feltz-Cornelis C, Allen SF, Holt RIG, Roberts R, Nouwen A, Sartorius N. Treatment for comorbid depressive disorder or subthreshold depression in diabetes mellitus: systematic review and meta-analysis. Brain Behav 2021;11:e01981 7. Fitzpatrick SL, Schumann KP, Hill-Briggs F. Problem solving interventions for diabetes self-management and control: a systematic review of the literature. Diabetes Res Clin Pract 2013;100: 145-161 8. Greenwood DA, Howell F, Scher L, et al. A framework for optimizing technology-enabled diabetes and cardiometabolic care and education: the role of the diabetes care and education specialist. Diabetes Educ 2020;46:315-322 9. Davis J, Fischl AH, Beck J, et al. 2022 National standards for diabetes self-management education and support. Diabetes Care 2022;45:484-494 10. Fitzpatrick SL, Golden SH, Stewart K, et al. Effect of DECIDE (Decision-making Education for Choices In Diabetes Everyday) program delivery modalities on clinical and behavioral outcomes in urban african americans with type 2 diabetes: a randomized trial. Diabetes Care 2016;39: 2149-2157 11. Brunisholz KD, Briot P, Hamilton S, et al. Diabetes self-management education improves quality of care and clinical outcomes determined by a diabetes bundle measure. J Multidiscip Healthc 2014;7:533-542 12. Woodard L, Amspoker AB, Hundt NE, et al. Comparison of collaborative goal setting with enhanced education for managing diabetes-associated distress and hemoglobin A1c levels: a randomized clinical trial. JAMA Netw Open 2022; 5:e229975 13. Cheng L, Sit JWH, Choi K-C, et al. The effects of an empowerment-based self-management inter-vention on empowerment level, psychological and meta-analysis of randomised controlled trials. Lancet Digit Health 2023;5:e125-e143 44. Anderson A, O'Connell SS, Thomas C, Chimmanamada R. Telehealth interventions to improve diabetes management among Black and Hispanic patients: a systematic review and meta-analysis. J Racial Ethn Health Disparities 2022;9: 2375-2386 45. Sherifali D, Brozic A, Agema P, et al. Effect of diabetes health coaching on glycemic control and quality of life in adults living with type 2 diabetes: a community-based, randomized, controlled trial. Can J Diabetes 2021;45:594-600 46. Gershkowitz BD, Hillert CJ, Crotty BH. Digital coaching strategies to facilitate behavioral change in type 2 diabetes: a systematic review. J Clin Endocrinol Metab 2021;106:e1513-e1520 47. Lee M-K, Lee DY, Ahn H-Y, Park C-Y. A novel user utility score for diabetes management using tailored mobile coaching: secondary analysis of a randomized controlled trial. JMIR Mhealth Uhealth 2021;9:e17573 48. van Eikenhorst L, Taxis K, van Dijk L, de Gier H. Pharmacist-led self-management interventions to improve diabetes outcomes. a systematic literature review and meta-analysis. Front Pharmacol 2017; 8:891 49. Tshiananga JKT, Kocher S, Weber C, Erny-Albrecht K, Berndt K, Neeser K. The effect of nurse-led diabetes self-management education on glycosylated hemoglobin and cardiovascular risk factors: a meta-analysis. Diabetes Educ 2012; 38:108-123 50. Evert AB, Dennison M, Gardner CD, et al. Nutrition therapy for adults with diabetes or prediabetes: a consensus report. Diabetes Care 2019;42:731-754 51. Scalzo P. From the Association of Diabetes Care & Education Specialists: the role of the diabetes care and education specialist as a champion of technology integration. Sci Diabetes Self Manag Care 2021;47:120-123 52. Rodriguez K, Ryan D, Dickinson JK, Phan V. Improving quality outcomes: the value of diabetes care and education specialists. Clin Diabetes 2022; 40:356-365 53. Litchman ML, Oser TK, Hodgson L, et al. In-person and technology-mediated peer support in diabetes care: a systematic review of reviews and gap analysis. Diabetes Educ 2020;46:230-241 54. Evans J, White P, Ha H. Evaluating the effectiveness of community health worker inter-ventions on glycaemic control in type 2 diabetes: a systematic review and meta-analysis. Lancet 2023;402(Suppl. 1):S40 55. Mendez I, Lundeen EA, Saunders M, Williams A, Saaddine J, Albright A. Diabetes self-management education and association with diabetes self-care and clinical preventive care practices. Sci Diabetes Self Manag Care 2022; 48:23-34 56. Horigan G, Davies M, Findlay-White F, Chaney D, Coates V. Reasons why patients referred to diabetes education programmes choose not to attend: a systematic review. Diabet Med 2017;34: 14-26 57. Roth SE, Gronowski B, Jones KG, et al. Evaluation of an integrated intervention to address clinical care and social needs among patients with type 2 diabetes. J Gen Intern Med 2023;38:38-44 toolkit. Accessed 13 August 2024. Available from https://www.eatrightpro.org/referrals-to-an-rdn-primary-care-provider-toolkit 84. Evert AB, Chomko M. Nutrition therapy. In The Art and Science of Diabetes Care and Education. 6th ed. Cornell S, Miller K, Urbanski P, Eds. Association of Diabetes Care & Education Specialists, 2023, p. 455-484 85. Salvia MG, Quatromoni PA. Behavioral approaches to nutrition and eating patterns for managing type 2 diabetes: A review. Am J Med Open 2023;9:100034 86. Schwingshackl L, Schwedhelm C, Hoffmann G, et al. Food groups and risk of all-cause mortality: a systematic review and meta-analysis of prospective studies. Am J Clin Nutr 2017;105:1462-1473 87. Benson G, Hayes J. An update on the Mediterranean, vegetarian, and DASH eating patterns in people with type 2 diabetes. Diabetes Spectr 2020;33:125-132 88. Ge L, Sadeghirad B, Ball GDC, et al. Comparison of dietary macronutrient patterns of 14 popular named dietary programmes for weight and cardiovascular risk factor reduction in adults: systematic review and network meta-analysis of randomised trials. BMJ 2020;369: m696 89. of carbohydrate counting versus other forms of dietary advice in patients with type 1 diabetes mellitus: a systematic review and meta-analysis of randomised clinical trials. J Hum Nutr Diet 2022;35:1030-1042 91. Witkow S, Liberty IF, Goloub I, et al. Sim-plifying carb counting: a randomized controlled study -feasibility and efficacy of an individualized, simple, patient-centred carb counting tool. Endo-crinol Diabetes Metab 2023;6:e411 92. Haidar A, Legault L, Raffray M, et al. A randomized crossover trial to compare automated insulin delivery (the artificial pancreas) with carbo-hydrate counting or simplified qualitative meal-size estimation in type 1 diabetes. Diabetes Care 2023; 46:1372-1378 93. Joubert M, Meyer L, Doriot A, Dreves B, Jeandidier N, Reznik Y. Prospective independent evaluation of the carbohydrate counting accuracy of two smartphone applications. Diabetes Ther 2021;12:1809-1820 94. Vasiloglou MF, Mougiakakou S, Aubry E, et al. A comparative study on carbohydrate estimation: GoCARB vs. dietitians. Nutrients 2018; 10:741 95. Bowen ME, Cavanaugh KL, Wolff K, et al. The diabetes nutrition education study randomized controlled trial: a comparative effectiveness study of approaches to nutrition in diabetes self-management education. Patient Educ Couns 2016;99:1368-1376 96. American Diabetes Association. systematic review on definitions of nutrition distress, and quality of life in patients with poorly controlled type 2 diabetes: a randomized con-trolled trial. Int J Nurs Stud 2021;116:103407 14. Okeyo HM, Biddle M, Williams LB. Impact of diabetes self-management education on A1C levels among Black/African Americans: a syste-matic review. Sci Diabetes Self Manag Care 2024;50:87-95 15. Rutten GEHM, Van Vugt H, de Koning E. Person-centered diabetes care and patient acti-vation in people with type 2 diabetes. BMJ Open Diabetes Res Care 2020;8 16. Li R, Shrestha SS, Lipman R, et al.; Centers for Disease Control and Prevention (CDC). Diabetes self-management education and training among privately insured persons with newly diagnosed diabetes-United States, 2011-2012. MMWR Morb Mortal Wkly Rep 2014;63:1045-1049 17. Hildebrand JA, Billimek J, Lee J-A, et al. Effect of diabetes self-management education on gly-cemic control in Latino adults with type 2 diabetes: a systematic review and meta-analysis. Patient Educ Couns 2020;103:266-275 18. Rosland A-M, Piette JD, Trivedi R, et al. Effectiveness of a health coaching intervention for patient-family dyads to improve outcomes among adults with diabetes: a randomized clinical trial. JAMA Netw Open 2022;5:e2237960 19. Chrvala CA, Sherr D, Lipman RD. Diabetes self-management education for adults with type 2 diabetes mellitus: a systematic review of the effect on glycemic control. Patient Educ Couns 2016;99: 926-943 20. Bekele BB, Negash S, Bogale B, et al. Effect of diabetes self-management education (DSME) on glycated hemoglobin (HbA1c) level among patients with T2DM: systematic review and meta-analysis of randomized controlled trials. Diabetes Metab Syndr 2021;15:177-185 21. Nkhoma DE, Soko CJ, Bowrin P, et al. Digital interventions self-management education for type 1 and 2 diabetes: a systematic review and meta-analysis. Comput Methods Programs Biomed 2021;210:106370 22. Odgers-Jewell K, Ball LE, Kelly JT, Isenring EA, Reidlinger DP, Thomas R. Effectiveness of group-based self-management education for individuals with Type 2 diabetes: a systematic review with meta-analyses and meta-regression. Diabet Med 2017;34:1027-1039 23. Winkley K, Upsher R, Stahl D, et al. Psychological interventions to improve self-management of type 1 and type 2 diabetes: a systematic review. Health Technol Assess 2020; 24:1-232 24. Davidson P, LaManna J, Davis J, et al. The effects of diabetes self-management education on quality of life for persons with type 1 diabetes: a systematic review of randomized controlled trials. Sci Diabetes Self Manag Care 2022;48: 111-135 25. He X, Li J, Wang B, et al. Diabetes self-management education reduces risk of all-cause mortality in type 2 diabetes patients: a sys-tematic review and meta-analysis. Endocrine 2017;55:712-731 26. Thorpe CT, Fahey LE, Johnson H, Deshpande and-medicaid-programs-cy-2025-payment-policies-and hospitalization rates and charges: the Urban Diabetes Study. Diabetes Care 2008;31:655-660 28. Duncan I, Ahmed T, Li QE, et al. Assessing the value of the diabetes educator. Diabetes Educ 2011;37:638-657 29. Strawbridge LM, Lloyd JT, Meadow A, Riley GF, Howell BL. One-year outcomes of diabetes self-management training among medicare bene-ficiaries newly diagnosed with diabetes. Med Care 2017;55:391-397 30. Al Harbi SS, Alajmi MM, Algabbas SM, Alharbi MS. The comparison of self-management group education and the standard care for patients with type 2 diabetes mellitus: an updated systematic review and meta-analysis. J Family Med Prim Care 2022;11:4299-4309 31. Cruz-Cobo C, Santi-Cano MJ. Efficacy of diabetes education in adults with diabetes mellitus type 2 in primary care: a systematic review. J Nurs Scholarsh 2020;52:155-163 32. Dallosso H, Mandalia P, Gray LJ, et al. The effectiveness of a structured group education programme for people with established type 2 diabetes in a multi-ethnic population in primary care: a cluster randomised trial. Nutr Metab Cardiovasc Dis 2022;32:1549-1559 33. Lu JB, Danko KJ, Elfassy MD, Welch V, Grimshaw JM, Ivers NM. Do quality improvement initiatives for diabetes care address social inequities? Secondary analysis of a systematic review. BMJ Open 2018;8:e018826 34. Attridge M, Creamer J, Ramsden M, Cannings-John R, Hawthorne K. Culturally appropriate health education for people in ethnic minority groups with type 2 diabetes mellitus. Cochrane Database Syst Rev 2014;2014:CD006424 35. Chodosh J, Morton SC, Mojica W, et al. Meta-analysis: chronic disease self-management programs for older adults. Ann Intern Med 2005; 143:427-438 36. Sarkisian CA, Brown AF, Norris KC, Wintz RL, Mangione CM. A systematic review of diabetes self-care interventions for older, African American, or Latino adults. Diabetes Educ 2003;29:467-479 37. Peyrot M, Rubin RR. Behavioral and psy-chosocial interventions in diabetes: a con-ceptual review. Diabetes Care 2007;30:2433-2440 38. Naik AD, Palmer N, Petersen NJ, et al. Comparative effectiveness of goal setting in diabetes mellitus group clinics: randomized clinical trial. Arch Intern Med 2011;171:453-459 39. Mannucci E, Giaccari A, Gallo M, et al. Self-management in patients with type 2 diabetes: group-based versus individual education. A sys-tematic review with meta-analysis of randomized trails. Nutr Metab Cardiovasc Dis 2022;32:330-336 40. Almutairi N, Hosseinzadeh H, Gopaldasani V. The effectiveness of patient activation intervention on type 2 diabetes mellitus glycemic control and self-management behaviors: a systematic review of RCTs. Prim Care Diabetes 2020;14:12-20 41. Seo Y-C, Yong SY, Choi WW, Kim SH. Meta-analysis of studies on the effects of digital therapeutics. J Pers Med 2024;14 42. Eberle C, Stichling S. Clinical improvements by telemedicine interventions managing type 1 and type 2 diabetes: systematic meta-review. J Med Internet Res 2021;23:e23244 43. Moschonis G, Siopis G, Jung J, et al.; DigiCare4You Consortium. Effectiveness, reach, uptake, and feasibility of digital health interventions for adults with type 2 diabetes: a systematic review under-the-physician-fee-schedule-and-other 71. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care 1989;12:365-368 72. Lichtenstein AH, Appel LJ, Vadiveloo M, et al. 2021 Dietary guidance to improve cardiovascular health: a scientific statement from the American Heart Association. Circulation 2021;144:e472-e487 73. Levin A, Ahmed SB, Carrero JJ, et al. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. Kidney Int 2024; 105:684-701 74. Holt RIG, DeVries JH, Hess-Fischl A, et al. The management of type 1 diabetes in adults. a consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2021;44:2589-2625 75. Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycemia in type 2 dia-betes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2022;45:2753-2786 76. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th ed. 2020. Accessed 13 August 2024. Available from https://www.dietaryguidelines.gov/sites/default/ files/2021-03/Dietary_Guidelines_for_Americans-2020-2025.pdf 77. Forouhi NG. Embracing complexity: making sense of diet, nutrition, obesity and type 2 diabetes. Diabetologia 2023;66:786-799 78. Franz MJ, MacLeod J, Evert A, et al. Academy of Nutrition and Dietetics Nutrition practice guideline for type 1 and type 2 diabetes in adults: systematic review of evidence for medical nutrition therapy effectiveness and recommendations for integration into the nutrition care process. J Acad Nutr Diet 2017;117:1659-1679 79. Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018;41:2669-2701 80. Marincic PZ, Salazar MV, Hardin A, et al. Diabetes self-management education and medical nutrition therapy: a multisite study documenting the efficacy of registered dietitian nutritionist interventions in the management of glycemic control and diabetic dyslipidemia through retro-spective chart review. J Acad Nutr Diet 2019;119: 449-463 81. Briggs Early K, Stanley K. Position of the Academy of Nutrition and Dietetics: the role of medical nutrition therapy and registered dietitian nutritionists in the prevention and treatment of prediabetes and type 2 diabetes. J Acad Nutr Diet 2018;118:343-353 82. Dobrow L, Estrada I, Burkholder-Cooley N, Miklavcic J. Potential effectiveness of registered dietitian nutritionists in healthy behavior inter-ventions for managing type 2 diabetes in older adults: a systematic review. Front Nutr 2021;8: 737410 83. Academy of Nutrition and Dietetics Eat Right PRO. Referrals to an RDN: primary care provider literacy and food literacy. Health Promot Int 2018;33:378-389 98. Food Literacy Center. What is food literacy? Accessed 13 August 2024. Available from https:// www.foodliteracycenter.org/about 99. Walker GS, Chen JY, Hopkinson H, Sainsbury CAR, Jones GC. Structured education using Dose Adjustment for Normal Eating (DAFNE) reduces long-term HbA1c and HbA1c variability. Diabet Med 2018;35:745-749 100. Delahanty LM, Nathan DM, Lachin JM, et al.; Diabetes Control and Complications Trial/ Epidemiology of Diabetes. Association of diet with glycated hemoglobin during intensive treatment of type 1 diabetes in the Diabetes Control and Complications Trial. Am J Clin Nutr 2009;89: 518-524 101. Kirkpatrick CF, Bolick JP, Kris-Etherton PM, et al. Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: a scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force. J Clin Lipidol 2019;13:689-711.e1 e681 102. Goldenberg JZ, Day A, Brinkworth GD, et al. Efficacy and safety of low and very low car-bohydrate diets for type 2 diabetes remission: systematic review and meta-an alysis of published and unpublished randomized trial data. BMJ 2021;372:m4743 103. Schwingshackl L, Chaimani A, Hoffmann G, Schwedhelm C, Boeing H. A network meta-analysis on the comparative efficacy of different dietary approaches on glycaemic control in patients with type 2 diabetes mellitus. Eur J Epidemiol 2018;33:157-170 104. Sacks FM, Bray GA, Carey VJ, et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 2009;360:859-873 105. Gardner CD, Landry MJ, Perelman D, et al. Effect of a ketogenic diet versus Mediterranean diet on glycated hemoglobin in individuals with prediabetes and type 2 diabetes mellitus: The interventional Keto-Med randomized crossover trial. Am J Clin Nutr 2022;116:640-652 106. Chiavaroli L, Lee D, Ahmed A, et al. Effect of low glycaemic index or load dietary patterns on glycaemic control and cardiometabolic risk factors in diabetes: systematic review and meta-analysis of randomised controlled trials. BMJ 2021;374: n1651 107. Athinarayanan SJ, Adams RN, Hallberg SJ, et al. Long-term effects of a novel continuous remote care intervention including nutritional ketosis for the management of type 2 diabetes: a 2-year non-randomized clinical trial. Front Endo-crinol (Lausanne) 2019;10:348 108. Accessed 14 August 2024. Available from https:// www.fda.gov/drugs/drug-safety-and-availability/ fda-revises-labels-sglt2-inhibitors-diabetes-include-warnings-about-too-much-acid-blood-and-serious #:$:text=To%20lessen%20the%20risk%20of, issued%20on%20May%2015%2C%202015%20 111. Ozoran H, Matheou M, Dyson P, Karpe F, Tan GD. Type 1 diabetes and low carbohydrate diets-defining the degree of nutritional ketosis. Diabet Med 2023;40:e15178 112. Attaye I, Warmbrunn MV, Boot ANAF, et al. A systematic review and meta-analysis of dietary interventions modulating gut microbiota and cardiometabolic diseases-striving for new standards in microbiome studies. Gastroenterology 2022; 162:1911-1932 113. Partula V, Deschasaux M, Druesne-Pecollo N, et al.; Milieu Int erieur Consortium. Associations between consumption of dietary fibers and the risk of cardiovascular diseases, cancers, type 2 diabetes, and mortality in the prospective NutriNet-Sant e cohort. Am J Clin Nutr 2020;112: 195-207 114. Reynolds AN, Akerman AP, Mann J. Dietary fibre and whole grains in diabetes management: systematic review and meta-analyses. PLoS Med 2020;17:e1003053 115. Qi X, Chiavaroli L, Lee D, et al. Effect of important food sources of fructose-containing sugars on inflammatory biomarkers: a systematic review and meta-analysis of controlled feeding trials. Nutrients 2022;14:14 116. Zafar MI, Mills KE, Zheng J, et al. Low-glycemic index diets as an intervention for diabetes: a systematic review and meta-analysis. Am J Clin Nutr 2019;110:891-902 117. Vega-L opez S, Venn BJ, Slavin JL. Relevance of the glycemic index and glycemic load for body weight, diabetes, and cardiovascular disease. Nutrients 2018;10:1361 118. Jenkins DJA, Willett WC, Yusuf S, et al.; Clinical Nutrition & Risk Factor Modification Centre Collaborators. Association of glycaemic index and glycaemic load with type 2 diabetes, cardiovascular disease, cancer, and all-cause mortality: a meta-analysis of mega cohorts of more than 100000 participants. Lancet Diabetes Endocrinol 2024;12:107-118 119. Thomas D, Elliott EJ. Low glycaemic index, or low glycaemic load, diets for diabetes mellitus. Cochrane Database Syst Rev 2009:CD006296 120. Smith TA, Smart CE, Howley PP, Lopez PE, King BR. For a high fat, high protein breakfast, preprandial administration of 125% of the insulin dose improves postprandial glycaemic excursions in people with type 1 diabetes using multiple daily injections: A cross-over trial. Diabet Med 2021;38:e14512 121. Nutrients 2021;13:3558 123. Al Balwi R, Al Madani W, Al Ghamdi A. Efficacy of insulin dosing algorithms for high-fat high-protein mixed meals to control postprandial glycemic excursions in people living with type 1 diabetes: a systematic review and meta-analysis. Pediatr Diabetes 2022;23:1635-1646 124. Bell KJ, Toschi E, Steil GM, Wolpert HA. Optimized mealtime insulin dosing for fat and protein in type 1 diabetes: application of a model-based approach to derive insulin doses for open-loop diabetes management. Diabetes Care 2016;39:1631-1634 125. Metwally M, Cheung TO, Smith R, Bell KJ. Insulin pump dosing strategies for meals varying in fat, protein or glycaemic index or grazing-style meals in type 1 diabetes: a systematic review. Diabetes Res Clin Pract 2021;172:108516 126. Phillip M, Nimri R, Bergenstal RM, et al. Consensus recommendations for the use of automated insulin delivery technologies in clinical practice. Endocr Rev 2023;44:254-280 127. Lesser LI. In adults at CV risk, Medi-terranean-style or low-fat dietary programs vs. minimal interventions reduce all-cause mortality. Ann Intern Med 2023;176:JC78 128. Ley SH, Hamdy O, Mohan V, Hu FB. Prevention and management of type 2 diabetes: dietary components and nutritional strategies. Lancet 2014;383:1999-2007 129. Jiang S, Fang J, Li W. Protein restriction for diabetic kidney disease. Cochrane Database Syst Rev 2023;1:CD014906 130. Viguiliouk E, Stewart SE, Jayalath VH, et al. Effect of replacing animal protein with plant protein on glycemic control in diabetes: a systematic review and meta-analysis of randomized controlled trials. Nutrients 2015;7:9804-9824 131. Lamberg-Allardt C, B€ arebring L, Arnesen EK, et al. Animal versus plant-based protein and risk of cardiovascular disease and type 2 diabetes: a systematic review of randomized controlled trials and prospective cohort studies. Food Nutr Res 2023;67 132. Sullivan VK, Kim H, Caulfield LE, Steffen LM, Selvin E, Rebholz CM. Plant-based dietary patterns and incident diabetes in the Atherosclerosis Risk in Communities (ARIC) study. Diabetes Care 2024;47: 803-809 133. Willett W, Rockstr€ om J, Loken B, et al. Food in the Anthropocene: the EAT-Lancet Commission on healthy diets from sustainable food systems. Lancet 2019;393:447-492 134. Estruch R, Ros E, Salas-Salvad o J, et al.; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med 2018;378:e34 135. Forouhi NG, Imamura F, Sharp SJ, et al. Association of plasma phospholipid n-3 and n-6 polyunsaturated fatty acids with type 2 diabetes: the EPIC-InterAct case-cohort study. PLoS Med 2016;13:e1002094 136. a clinical perspective from the National Lipid Association. J Clin Lipidol 2023;17:428-451 139. Karam G, Agarwal A, Sadeghirad B, et al. Comparison of seven popular structured dietary programmes and risk of mortality and major cardiovascular events in patients at increased cardiovascular risk: systematic review and network meta-analysis. BMJ 2023;380:e072003 140. Rosqvist F, Kullberg J, Ståhlman M, et al. Overeating saturated fat promotes fatty liver and ceramides compared with polyunsaturated fat: a randomized trial. J Clin Endocrinol Metab 2019; 104:6207-6219 141. Schwab U, Reynolds AN, Sallinen T, Rivellese AA, Ris erus U. Dietary fat intakes and cardiovascular disease risk in adults with type 2 diabetes: a systematic review and meta-analysis. Eur J Nutr 2021;60:3355-3363 142. Sacks FM, Lichtenstein AH, Wu JHY, et al.; American Heart Association. Dietary fats and cardiovascular disease: a presidential advisory from the American Heart Association. Circulation 2017;136:e1-e23 143. Bosch J, Gerstein HC, Dagenais GR, et al.; ORIGIN Trial Investigators. n-3 fatty acids and cardiovascular outcomes in patients with dys-glycemia. N Engl J Med 2012;367:309-318 144. Wheeler ML, Dunbar SA, Jaacks LM, et al. Macronutrients, food groups, and eating patterns in the management of diabetes: a systematic review of the literature, 2010. Diabetes Care 2012;35:434-445 145. Brown TJ, Brainard J, Song F, Wang X, Abdelhamid A, Hooper L, PUFAH Group. Omega-3, omega-6, and total dietary polyunsaturated fat for prevention and treatment of type 2 diabetes mellitus: systematic review and meta-analysis of randomised controlled trials. BMJ 2019;366:l4697 146. Bowman L, Mafham M, Wallendszus K, et al.; ASCEND Study Collaborative Group. Effects of n-3 fatty acid supplements in diabetes mellitus. N Engl J Med 2018;379:1540-1550 147. Bhatt DL, Steg PG, Miller M, et al.; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380:11-22 148. Hodson EM, Cooper TE. Altered dietary salt intake for preventing diabetic kidney disease and its progression. Cochrane Database Syst Rev 2023;1:CD006763 149. Han S, Cheng D, Liu N, Kuang H. The relationship between diabetic risk factors, diabetic complications and salt intake. J Diabetes Complications 2018;32:531-537 150. Morales-Alvarez MC, Nissaisorakarn V, Appel LJ, et al. Effects of reduced dietary sodium and the DASH diet on GFR: the DASH-sodium trial. Kidney360 2024;5:569-576 151. Hannon BA, Fairfield WD, Adams B, Kyle T, Crow M, Thomas DM. Use and abuse of dietary supplements in persons with diabetes. Nutr Diabetes 2020;10:14 152. supplements 154. U.S. Food and Drug Administration. Dietary supplements. Accessed 13 August 2024. Available from https://www.fda.gov/food/dietary-supplements 155. Dwyer JT, Coates PM, Smith MJ. Dietary supplements: regulatory challenges and research resources. Nutrients 2018;10:10 156. U.S. Food and Drug Administration. Dietary supplement ingredient directory. Accessed 13 August 2024. Available from https://www.fda. gov/food/dietary-supplements/dietary-supplement-ingredient-directory 157. Mangione CM, Barry MJ, Nicholson WK, et al.; US Preventive Services Task Force. Vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer: US Preventive Services Task Force recommendation statement. JAMA 2022;327:2326-2333 158. Pittas AG, Kawahara T, Jorde R, et al. Vitamin D and risk for type 2 diabetes in people with prediabetes: a systematic review and meta-analysis of individual participant data from 3 randomized clinical trials. Ann Intern Med 2023; 176:355-363 159. Dawson-Hughes B, Staten MA, Knowler WC, et al. Intratrial exposure to vitamin D and new-onset diabetes among adults with prediabetes: a secondary analysis from the Vitamin D and Type 2 Diabetes (D2d) study. Diabetes Care 2020;43:2916-2922 160. Barbarawi M, Zayed Y, Barbarawi O, et al. Effect of vitamin D supplementation on the incidence of diabetes mellitus. J Clin Endocrinol Metab 2020;105:dgaa335 161. Barbarawi M, Kheiri B, Zayed Y, et al. Vitamin D supplementation and cardiovascular disease risks in more than 83,000 individuals in 21 randomized clinical trials: a meta-analysis. JAMA Cardiol 2019;4:765-776 162. Jayedi A, Daneshvar M, Jibril AT, et al. Serum 25(OH)D concentration, vitamin D supplementation, and risk of cardiovascular disease and mortality in patients with type 2 diabetes or prediabetes: a systematic review and dose-response meta-analysis. Am J Clin Nutr 2023;118:697-707 163. Dadon Y, Hecht Sagie L, Mimouni FB, Arad I, Mendlovic J. Vitamin D and insulin-dependent diabetes: a systematic review of clinical trials. Nutrients 2024;16 164. Moridpour AH, Kavyani Z, Khosravi S, et al. The effect of cinnamon supplementation on glycemic control in patients with type 2 diabetes mellitus: an updated systematic review and dose-response meta-analysis of randomized controlled trials. Phytother Res 2024;38:117-130 165. Khattab R, Albannawi M, Alhajjmohammed D, et al. Metformin-induced vitamin B12 deficiency among type 2 diabetes mellitus' patients: a systematic review. Curr Diabetes Rev 2023;19: e180422203716 166. National Institutes of Health Office of Dietary Supplements. Multivitamin/mineral supplements: levels of alcohol consumption. Lancet Public Health 2023;8:e6-e7 169. de Souza ABC, Correa-Giannella MLC, Gomes MB, Negrato CA, Nery M. Epidemiology and risk factors of hypoglycemia in subjects with type 1 diabetes in Brazil: a cross-sectional, multi-center study. Arch Endocrinol Metab 2022;66: 784-791 170. Llamosas-Falc on L, Rehm J, Bright S, et al. The relationship between alcohol consumption, BMI, and type 2 diabetes: a systematic review and dose-response meta-analysis. Diabetes Care 2023;46:2076-2083 171. Krittanawong C, Isath A, Rosenson RS, et al. Alcohol consumption and cardiovascular health. Am J Med 2022;135:1213-1230.e3 172. Weitzman ER, Wisk LE, Minegishi M, et al. Effects of a patient-centered intervention to reduce alcohol use among youth with chronic medical conditions. J Adolesc Health 2022;71:S24-S33 173. National Agricultural Library, U.S. Department of Agriculture. Nutritive and nonnutritive sweetener. Accessed 13 August 2024. Available from https:// www.nal.usda.gov/human-nutrition-and-food-safety/ food-composition/sweeteners 174. Arnett DK, Blumenthal RS, Albert MA, et al. ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;140:e596-e646 175. Lohner S, Kuellenberg de Gaudry D, Toews I, Ferenci T, Meerpohl JJ. Non-nutritive sweeteners for diabetes mellitus. Cochrane Database Syst Rev 2020;5:CD012885 176. Zhang R, Noronha JC, Khan TA, et al. The effect of non-nutritive sweetened beverages on postprandial glycemic and endocrine responses: a systematic review and network meta-analysis. Nutrients 2023;15:15 177. Sylvetsky AC, Chandran A, Talegawkar SA, Welsh JA, Drews K, El Ghormli L. Consumption of beverages containing low-calorie sweeteners, diet, and cardiometabolic health in youth with type 2 diabetes. J Acad Nutr Diet 2020;120: 1348-1358.e6 178. Golzan SA, Movahedian M, Haghighat N, Asbaghi O, Hekmatdoost A. Association between non-nutritive sweetener consumption and liver enzyme levels in adults: a systematic review and meta-analysis of randomized clinical trials. Nutr Rev 2023;81:1105-1117 179. Miller PE, Perez V. Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies. Am J Clin Nutr 2014; 100:765-777 180. Rogers PJ, Hogenkamp PS, de Graaf C, et al. Does low-energy sweetener consumption affect energy intake and body weight? A systematic randomized controlled trials and prospective cohort studies. CMAJ 2017;189:E929-E939 183. Lee JJ, Khan TA, McGlynn N, et al. Relation of change or substitution of low-and no-calorie sweetened beverages with cardiometabolic outcomes: a systematic review and meta-analysis of prospective cohort studies. Diabetes Care 2022; 45:1917-1930 184. Mattes RD, Popkin BM. Nonnutritive sweetener consumption in humans: effects on appetite and food intake and their putative mechanisms. Am J Clin Nutr 2009;89:1-14 185. McGlynn ND, Khan TA, Wang L, et al. Association of low-and no-calorie sweetened beverages as a replacement for sugar-sweetened beverages with body weight and cardiometabolic risk: a systematic review and meta-analysis. JAMA Netw Open 2022;5:e222092 186. Gostoli S, Raimondi G, Popa AP, Giovannini M, Benasi G, Rafanelli C. Behavioral lifestyle interventions for weight loss in overweight or obese patients with type 2 diabetes: a systematic review of the literature. Curr Obes Rep 2024; 13:224-241 187. Balk EM, Earley A, Raman G, Avendano EA, Pittas AG, Remington PL. Combined diet and physical activity promotion programs to prevent type 2 diabetes among persons at increased risk: a systematic review for the community pre-ventive services task force. Ann Intern Med 2015;163:437-451 188. Garvey WT, Ryan DH, Bohannon NJV, et al. Weight-loss therapy in type 2 diabetes: effects of phentermine and topiramate extended release. Diabetes Care 2014;37:3309-3316 189. Kahan S, Fujioka K. Obesity pharmacotherapy in patients with type 2 diabetes. Diabetes Spectr 2017;30:250-257 190. Jeon CY, Lokken RP, Hu FB, van Dam RM. Physical activity of moderate intensity and risk of type 2 diabetes: a systematic review. Diabetes Care 2007;30:744-752 191. Rebello CJ, Zhang D, Kirwan JP, et al. Effect of exercise training on insulin-stimulated glucose disposal: a systematic review and meta-analysis of randomized controlled trials. Int J Obes (Lond) 2023;47:348-357 192. Singh N, Stewart RAH, Benatar JR. Intensity and duration of lifestyle interventions for long-term weight loss and association with mortality: a meta-analysis of randomised trials. BMJ Open 2019;9:e029966 193. Lean ME, Leslie WS, Barnes AC, et al. Primary care-led weight management for re-mission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet 2018;391: 541-551 194. Wing RR, Lang W, Wadden TA, et al.; Look AHEAD Research Group. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 197. Garvey WT. Long-term health benefits of intensive lifestyle intervention in the Look AHEAD study. Obesity (Silver Spring) 2021;29:1242-1243 198. Davies M, Faerch L, Jeppesen OK, et al.; STEP 2 Study Group. Semaglutide 2•4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet 2021;397:971-984 199. Jastreboff AM, Aronne LJ, Ahmad NN, et al.; SURMOUNT-1 Investigators. Tirzepatide once weekly for the treatment of obesity. N Engl J Med 2022;387:205-216 200. Garvey WT, Frias JP, Jastreboff AM, et al.; SURMOUNT-2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2023;402:613-626 201. Sj€ ostr€ om L, Peltonen M, Jacobson P, et al. Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications. JAMA 2014;311: 2297-2304 202. Cefalu WT, Leiter LA, de Bruin TWA, Gause-Nilsson I, Sugg J, Parikh SJ. Dapagliflozin's effects on glycemia and cardiovascular risk factors in high-risk patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled study with a 28-week extension. Diabetes Care 2015;38:1218-1227 203. Perreault L, Kramer ES, Smith PC, Schmidt D, Argyropoulos C. A closer look at weight loss interventions in primary care: a systematic review and meta-analysis. Front Med (Lausanne) 2023;10:1204849 204. Farhat G, Mellor DD, Sattar N, Harvie M, Issa B, Rutter MK. Effectiveness of lifestyle interventions/culturally bespoke programmes in South Asian ethnic groups targeting weight loss for prevention and/or remission of type 2 diabetes: a systematic review and meta-analysis of intervention trials. J Hum Nutr Diet 2024; 37:550-563 205. Prinz N, Schwandt A, Becker M, et al. Trajectories of body mass index from childhood to young adulthood among patients with type 1 diabetes-a longitudinal group-based modeling approach based on the DPV Registry. J Pediatr 2018;201:78-85.e4 e74 206. Lipman TH, Levitt Katz LE, Ratcliffe SJ, et al. Increasing incidence of type 1 diabetes in youth: twenty years of the Philadelphia Pediatric Diabetes Registry. Diabetes Care 2013;36:1597-1603 207. Park J, Ntelis S, Yunasan E, et al. Glucagon-like peptide 1 analogues as adjunctive therapy for patients with type 1 diabetes: an updated sys-tematic review and meta-analysis. J Clin Endocrinol Metab 2023;109:279-292 208. Franz MJ, Boucher JL, Rutten-Ramos S, VanWormer JJ. Lifestyle weight-loss intervention a subsequent 12-month weight maintenance intervention but is predicted by adaption of adipose atrial natriuretic peptide system: 48-month results of a randomized controlled trial. BMC Med 2022;20:238 211. Tomah S, Zhang H, Al-Badri M, et al. Long-term effect of intensive lifestyle intervention on cardiometabolic risk factors and microvascular complications in patients with diabetes in real-world clinical practice: a 10-year longitudinal study. BMJ Open Diabetes Res Care 2023;11 212. Ekong G, Kavookjian J. Motivational inter-viewing and outcomes in adults with type 2 diabetes: a systematic review. Patient Educ Couns 2016;99:944-952 213. Nip ASY, Reboussin BA, Dabelea D, et al.; SEARCH for Diabetes in Youth Study Group. Disordered eating behaviors in youth and young adults with type 1 or type 2 diabetes receiving insulin therapy: the SEARCH for Diabetes in Youth study. Diabetes Care 2019;42:859-866 214. Jamshed H, Steger FL, Bryan DR, et al. Effectiveness of early time-restricted eating for weight loss, fat loss, and cardiometabolic health in adults with obesity: a randomized clinical trial. JAMA Intern Med 2022;182:953-962 215. Lowe DA, Wu N, Rohdin-Bibby L, et al. Effects of time-restricted eating on weight loss and other metabolic parameters in women and men with overweight and obesity: the TREAT randomized clinical trial. JAMA Intern Med 2020; 180:1491-1499 216. Schroor MM, Joris PJ, Plat J, Mensink RP. Effects of intermittent energy restriction compared with those of continuous energy restriction on body composition and cardiometabolic risk markers -a systematic review and meta-analysis of randomized controlled trials in adults. Adv Nutr 2024;15:100130 217. Pappachan JM. In T2DM with obesity, time-restricted eating increased weight loss and reduced HbA1c level at 6 mo. Ann Intern Med 2024;177:JC16 218. Varady KA, Cienfuegos S, Ezpeleta M, Gabel K. Clinical application of intermittent fasting for weight loss: progress and future directions. Nat Rev Endocrinol 2022;18:309-321 219. Ye W, Xu L, Ye Y, et al. The efficacy and safety of meal replacement in patients with type 2 diabetes: a systematic review and meta-analysis. J Clin Endocrinol Metab 2023; 220. Murphy E, Finucane FM. Structured lifestyle modification as an adjunct to obesity pharmacotherapy: there is much to learn. Int J Obes (Lond) 2024; 221. Lean MEJ, Leslie WS, Barnes AC, et al. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol 2019;7:344-355 222. Raben A, Vestentoft PS, Brand-Miller J, on weight loss and metabolic health. J Clin Endocrinol Metab 2023;108:1824-1834 225. Wang L, Ma Q, Fang B, et al. Shift work is associated with an increased risk of type 2 diabetes and elevated RBP4 level: cross sectional analysis from the OHSPIW cohort study. BMC Public Health 2023;23:1139 226. Al-Arouj M, Assaad-Khalil S, Buse J, et al. Recommendations for management of diabetes during Ramadan: update 2010. Diabetes Care 2010;33:1895-1902 227. Grajower MM. Management of diabetes mellitus on Yom Kippur and other Jewish fast days. Endocr Pract 2008;14:305-311 228. Gupta N, Gusdorf J. Guidance for physicians on the Yom Kippur fast. Georgetown Medical Review 2023;7 229. Saboo B, Joshi S, Shah SN, et al. Management of diabetes during fasting and feasting in India. J Assoc Physicians India 2019; 67:70-77 230. Hassanein M, Afandi B, Yakoob Ahmedani M, et al. Diabetes and Ramadan: practical guidelines 2021. Diabetes Res Clin Pract 2022;185:109185 231. Deeb A, Babiker A, Sedaghat S, et al. ISPAD Clinical Practice Consensus Guidelines 2022: Ramadan and other religious fasting by young people with diabetes. Pediatr Diabetes 2022;23: 1512-1528 232. Noor SK, Alutol MT, FadAllah FSA, et al. Risk factors associated with fasting during Ramadan among individuals with diabetes according to IDF-DAR risk score in Atbara city, Sudan: cross-sectional hospital-based study. Diabetes Metab Syndr 2023;17:102743 233. Mohammed N, Buckley A, Siddiqui M, et al. Validation of the new IDF-DAR risk assessment tool for Ramadan fasting in patients with diabetes. Diabetes Metab Syndr 2023;17:102754 234. Alfadhli EM, Alharbi TS, Alrotoie AM, et al. Validity of the International Diabetes Federation risk stratification score of Ramadan fasting in individuals with diabetes mellitus. Saudi Med J 2024;45:86-92 235. Shamsi N, Naser J, Humaidan H, et al. Verification of 2021 IDF-DAR risk assessment tool for fasting Ramadan in patients with diabetes attending primary health care in the Kingdom of Bahrain: the DAR-BAH study. Diabetes Res Clin Pract 2024;211:111661 236. Hassanein M, Hussein Z, Shaltout I, et al. The DAR 2020 global survey: Ramadan fasting during COVID 19 pandemic and the impact of older age on fasting among adults with type 2 diabetes. Diabetes Res Clin Pract 2021;173: 108674 237. Yousuf S, Syed A, Ahmedani MY. To explore the association of Ramadan fasting with sym-ptoms of depression, anxiety, and stress in people with diabetes. Diabetes Res Clin Pract 2021;172:108545 238. 240. Afandi B, Hassanein M, Roubi S, Nagelkerke N. The value of continuous glucose monitoring and self-monitoring of blood glucose in patients with gestational diabetes mellitus during Ramadan fasting. Diabetes Res Clin Pract 2019;151:260-264 241. World Health Organization. Malnutrition. Accessed 13 August 2024. Available from https:// www.who.int/news-room/fact-sheets/detail/ malnutrition 242. Yuan S, Larsson SC. Epidemiology of sarcopenia: Prevalence, risk factors, and con-sequences. Metabolism 2023;144:155533 243. Feng L, Gao Q, Hu K, et al. Prevalence and risk factors of sarcopenia in patients with diabetes: a meta-analysis. J Clin Endocrinol Metab 2022; 107:1470-1483 244. Today's Dietitian: The Magazine for Nutrition Professionals. The new weight management meds. Accessed 13 August 2024. Available from https:// www.todaysdietitian.com/newarchives/1123p24. shtml 245. Neeland IJ, Linge J, Birkenfeld AL. Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. Dia-betes Obes Metab 2024;26 Suppl 4:16-27 246. Jawara D, Ufearo DM, Murtha JA, et al. Racial disparities in selected micronutrient defi-ciencies after bariatric surgery: a systematic review. Surg Obes Relat Dis 2024;20:283-290 247. Mellen RH, Girotto OS, Marques EB, et al. Insights into pathogenesis, nutritional and drug approach in sarcopenia: a systematic review. Biomedicines 2023;11:11 248. Locatelli JC, Costa JG, Haynes A, et al. Incretin-based weight loss pharmacotherapy: can resistance exercise optimize changes in body composition? Diabetes Care 2024;47;1718-1730 249. BAPEN. Introducing 'MUST'. Accessed 13 September 2024. Available from https://www. bapen.org.uk/must-and-self-screening/introducing-must/ 250. Lau S, Pek K, Chew J, et al. The Simplified Nutritional Appetite Questionnaire (SNAQ) as a screening tool for risk of malnutrition: optimal cutoff, factor structure, and validation in healthy community-dwelling older adults. Nutrients 2020; 12:12 251. Yu SCY, Khow KSF, Jadczak AD, Visvanathan R. Clinical screening tools for sarcopenia and its management. Curr Gerontol Geriatr Res 2016; 2016:5978523 252. Economic Research Service, U.S. Department of Agriculture. Household Food Security in the United States in 2022 (Economic Research Report No. ERR-325). Accessed 13 August 2024. Available from https://www.ers.usda.gov/publications/pub-details/?pubid=107702 253. Whitehouse CR, Akyirem S, Petoskey C, et al. A systematic review of interventions that address food insecurity for persons with prediabetes or Services, 2018 256. Bazargan-Hejazi S, Arroyo JS, Hsia S, Brojeni NR, Pan D. A racial comparison of differences between self-reported and objectively measured physical activity among US adults with diabetes. Ethn Dis 2017;27:403-410 257. Khunti K, Griffin S, Brennan A, et al. Behavioural interventions to promote physical activity in a multiethnic population at high risk of diabetes: PROPELS three-arm RCT. Health Technol Assess 2021;25:1-190 258. Bootwong P, Intarut N. The effects of text messages for promoting physical activities in prediabetes: a randomized controlled trial. Telemed J E Health 2022;28:896-903 259. Sluik D, Buijsse B, Muckelbauer R, et al. Physical activity and mortality in individuals with diabetes mellitus: a prospective study and meta-analysis. Arch Intern Med 2012;172:1285-1295 260. Tikkanen-Dolenc H, Wad en J, Forsblom C, et al.; FinnDiane Study Group. Physical activity reduces risk of premature mortality in patients with type 1 diabetes with and without kidney disease. Diabetes Care 2017;40:1727-1732 261. Peters AL, Laffel L. The American Diabetes Association/JDRF Type 1 Diabetes Sourcebook. Arlington, VA, American Diabetes Association, 2013 262. Ostman C, Jewiss D, King N, Smart NA. Clinical outcomes to exercise training in type 1 diabetes: a systematic review and meta-analysis. Diabetes Res Clin Pract 2018;139:380-391 263. Boul e NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA 2001;286:1218-1227 264. Martland R, Mondelli V, Gaughran F, Stubbs B. Can high-intensity interval training improve physical and mental health outcomes? A meta-review of 33 systematic reviews across the lifespan. J Sports Sci 2020;38:430-469 265. Pandey A, Patel KV, Bahnson JL, et al.; Look AHEAD Research Group. Association of intensive lifestyle intervention, fitness, and body mass index with risk of heart failure in overweight or obese adults with type 2 diabetes mellitus: an analysis from the Look AHEAD trial. Circulation 2020;141:1295-1306 266. Rejeski WJ, Ip EH, Bertoni AG, et al.; Look AHEAD Research Group. Lifestyle change and mobility in obese adults with type 2 diabetes. N Engl J Med 2012;366:1209-1217 267. Colberg SR, Sigal RJ, Yardley JE, et al. Physical activity/exercise and diabetes: a position statement of the American Diabetes Association. Diabetes Care 2016;39:2065-2079 268. Frediani JK, Bienvenida AF, Li J, Higgins MK, Lobelo F. Physical fitness and activity changes after a 24-week soccer-based adaptation of the U.S diabetes prevention program intervention in Hispanic men. Prog Cardiovasc Dis 2020;63: 775-785 269. in school-aged children and youth. Int J Behav Nutr Phys Act 2010;7:40 271. Savoye M, Caprio S, Dziura J, et al. Reversal of early abnormalities in glucose metabolism in obese youth: results of an intensive lifestyle randomized controlled trial. Diabetes Care 2014; 37:317-324 272. Patience M, Janssen X, Kirk A, et al. 24-Hour movement behaviours (physical activity, sedentary behaviour and sleep) association with glycaemic control and psychosocial outcomes in adolescents with type 1 diabetes: a systematic review of quantitative and qualitative studies. Int J Environ Res Public Health 2023;20:4363 273. Riddell MC, Gallen IW, Smart CE, et al. Exercise management in type 1 diabetes: a consensus statement. Lancet Diabetes Endocrinol 2017;5:377-390 274. Anderson BJ, Laffel LM, Domenger C, et al. Factors associated with diabetes-specific health-related quality of life in youth with type 1 diabetes: the global TEENs study. Diabetes Care 2017;40:1002-1009 275. Adolfsson P, Riddell MC, Taplin CE, et al. ISPAD Clinical Practice Consensus Guidelines 2018: exercise in children and adolescents with diabetes. Pediatr Diabetes 2018;19 Suppl 27:205-226 276. Gortmaker SL, Must A, Sobol AM, Peterson K, Colditz GA, Dietz WH. Television viewing as a cause of increasing obesity among children in the United States, 1986-1990. Arch Pediatr Adolesc Med 1996;150:356-362 277. de Jong E, Visscher TLS, HiraSing RA, Heymans MW, Seidell JC, Renders CM. Association between TV viewing, computer use and over-weight, determinants and competing activities of screen time in 4-to 13-year-old children. Int J Obes (Lond) 2013;37:47-53 278. Armstrong M, Colberg SR, Sigal RJ. Where to start? Physical assessment, readiness, and exercise recommendations for people with type 1 or type 2 diabetes. Diabetes Spectr 2023;36: 105-113 279. Jelleyman C, Yates T, O'Donovan G, et al. The effects of high-intensity interval training on glucose regulation and insulin resistance: a meta-analysis. Obes Rev 2015;16:942-961 280. Little JP, Gillen JB, Percival ME, et al. Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes. J Appl Physiol (1985) 2011;111:1554-1560 281. Bohn B, Herbst A, Pfeifer M, et al.; DPV Initiative. Impact of physical activity on glycemic control and prevalence of cardiovascular risk factors in adults with type 1 diabetes: a cross-sectional multicenter study of 18,028 patients. Diabetes Care 2015;38:1536-1543 282. U.S. Department of Health and Human Services. Physical Activity Guidelines for Americans. Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial. EClinicalMedicine 2024 ;69:102475 286. Katzmarzyk PT, Church TS, Craig CL, Bouchard C. Sitting time and mortality from all causes, cardiovascular disease, and cancer. Med Sci Sports Exerc 2009;41:998-1005 287. Dempsey PC, Larsen RN, Sethi P, et al. Benefits for type 2 diabetes of interrupting prolonged sitting with brief bouts of light walking or simple resistance activities. Diabetes Care 2016;39:964-972 288. Campbell MD, Alobaid AM, Hopkins M, et al. Interrupting prolonged sitting with frequent short bouts of light-intensity activity in people with type 1 diabetes improves glycaemic control without increasing hypoglycaemia: the SIT-LESS randomised controlled trial. Diabetes Obes Metab 2023;25:3589-3598 289. Wang Y, Lee D-C, Brellenthin AG, et al. Leisure-time running reduces the risk of incident type 2 diabetes. Am J Med 2019;132:1225-1232 290. Schellenberg ES, Dryden DM, Vandermeer Effects of yoga in adults with type 2 diabetes mellitus: a meta-analysis. J Diabetes Investig 2017; 8:201-209 293. Lee MS, Jun JH, Lim H-J, Lim H-S. A systematic review and meta-analysis of tai chi for treating type 2 diabetes. Maturitas 2015;80:14-23 294. Rees JL, Johnson ST, Boul e NG. Aquatic exercise for adults with type 2 diabetes: a meta-analysis. Acta Diabetol 2017;54:895-904 295. Mohammad Rahimi GR, Aminzadeh R, Azimkhani A, Saatchian V. The effect of exercise interventions to improve psychosocial aspects and glycemic control in type 2 diabetic patients: a systematic review and meta-analysis of randomized controlled trials. Biol Res Nurs 2022;24:10-23 296. Church TS, Blair SN, Cocreham S, et al. Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial. JAMA 2010;304:2253-2262 297. Kanaley JA, Colberg SR, Corcoran MH, et al. Exercise/physical activity in individuals with type 2 diabetes: a consensus statement from the 300. Grace A, Chan E, Giallauria F, Graham PL, Smart NA. Clinical outcomes and glycaemic responses to different aerobic exercise training intensities in type II diabetes: a systematic review and meta-analysis. Cardiovasc Diabetol 2017;16:37 301. Aronson R, Brown RE, Li A, Riddell MC. Optimal insulin correction factor in post-high-intensity exercise hyperglycemia in adults with type 1 diabetes: the FIT study. Diabetes Care 2019;42:10-16 302. Bax JJ, Young LH, Frye RL, Bonow RO, Steinberg HO, Barrett EJ, ADA. Screening for coronary artery disease in patients with diabetes. Diabetes Care 2007;30:2729-2736 303. Moser O, Riddell MC, Eckstein ML, et al. Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA). Diabetologia 2020;63:2501-2520 304. Rietz M, Lehr A, Mino E, et al. Physical activity and risk of major diabetes-related complications in individuals with diabetes: a systematic review and meta-analysis of observational studies. Diabetes Care 2022;45:3101-3111 305. Colberg SR. Exercise and Diabetes: A Clinician's Guide to Prescribing Physical Activity. Arlington, VA, American Diabetes Association, 2013 306. Hulshof CM, van Netten JJ, Pijnappels M, Bus SA. The role of foot-loading factors and their associations with ulcer development and ulcer healing in people with diabetes: a systematic review. J Clin Med 2020;9 307. Lemaster JW, Reiber GE, Smith DG, Heagerty PJ, Wallace C. Daily weight-bearing activity does not increase the risk of diabetic foot ulcers. Med Sci Sports Exerc 2003;35:1093-1099 308. Smith AG, Russell J, Feldman EL, et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care 2006;29:1294-1299 309. Spallone V, Ziegler D, Freeman R, et al.; Toronto Consensus Panel on Diabetic Neuropathy. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and man-agement. Diabetes Metab Res Rev 2011;27:639-653 310. Pop-Busui R, Evans GW, Gerstein HC, et al.; Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Diabetes Care 2010;33:1578-1584 311. National Center for Chronic Disease Prevention and Health Promotion (US) Office on Smoking and Health. Reports of the Surgeon General. In The Health Consequences of Smoking-Relationship of cardiometabolic parameters in non-smokers, current smokers, and quitters in diabetes: a systematic review and meta-analysis. Cardiovasc Diabetol 2016;15:158 315. Pan A, Wang Y, Talaei M, Hu FB. Relation of smoking with total mortality and cardiovascular events among patients with diabetes mellitus: a meta-analysis and systematic review. Circulation 2015;132:1795-1804 316. Pan A, Wang Y, Talaei M, Hu FB, Wu T. Relation of active, passive, and quitting smoking with incident type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2015;3:958-967 317. U.S. Department of Health and Human Services. Smoking cessation: a report of the Surgeon General. 2020. Accessed 13 August 2024. Available from https://www.hhs.gov/sites/ default/files/2020-cessation-sgr-full-report.pdf 318. Loretan CG, Cornelius ME, Jamal A, Cheng YJ, Homa DM. Cigarette smoking among US adults with selected chronic diseases associated with smoking, 2010-2019. Prev Chronic Dis 2022;19:E62 319. Rigotti NA, Kruse GR, Livingstone-Banks J, Hartmann-Boyce J. Treatment of tobacco smoking: a review. JAMA 2022;327:566-577 320. Krist AH, Davidson KW, Mangione CM, et al.; US Preventive Services Task Force. Interventions for tobacco smoking cessation in adults, including pregnant persons: US Pre-ventive Services Task Force recommendation statement. JAMA 2021;325:265-279 US 321. Rojewski AM, Palmer AM, Baker NL, Toll BA. Smoking cessation pharmacotherapy efficacy in comorbid medical populations: secondary analysis of the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) randomized clinical trial. Nicotine Tob Res 2024; 26:31-38 322. Leone FT, Zhang Y, Evers-Casey S, et al. Initiating pharmacologic treatment in tobacco-dependent adults. an official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med 2020;202:e5-e31 323. Tian J, Venn A, Otahal P, Gall S. The association between quitting smoking and weight gain: a systematic review and meta-analysis of prospective cohort studies. Obes Rev 2015;16: 883-901 324. Voulgari C, Katsilambros N, Tentolouris N. Smoking cessation predicts amelioration of microalbuminuria in newly diagnosed type 2 diabetes mellitus: a 1-year prospective study. Metabolism 2011;60:1456-1464 325. Asthana S, Labani S, Kailash U, Sinha DN, Mehrotra R. Association of smokeless tobacco use and oral cancer: a systematic global review and meta-analysis. Nicotine Tob Res 2019;21: 1162-1171 326. perceived harmfulness in the U.S. Am J Prev Med 2017;52:339-346 328. Kiernan E, Click ES, Melstrom P, et al.; Lung Injury Response Clinical Task Force; Lung Injury Response Clinical Working Group. A brief over-view of the national outbreak of e-cigarette, or vaping, product use-associated lung injury and the primary causes. Chest 2021;159:426-431 329. Darville A, Hahn EJ. E-cigarettes and ather-osclerotic cardiovascular disease: what clinicians and researchers need to know. Curr Atheroscler Rep 2019;21:15 330. Pierce JP, Benmarhnia T, Chen R, et al. Role of e-cigarettes and pharmacotherapy during attempts to quit cigarette smoking: the PATH study 2013-16. PLoS One 2020;15:e0237938 331. Chen R, Pierce JP, Leas EC, et al. Use of electronic cigarettes to aid long-term smoking cessation in the United States: prospective evidence from the PATH cohort study. Am J Epidemiol 2020;189:1529-1537 332. Assaf RD, Gorbach PM, Cooper ZD. Changes in medical and non-medical cannabis use among United States adults before and during the COVID-19 pandemic. Am J Drug Alcohol Abuse 2022;48:321-327 333. Hasin D, Walsh C. Trends over time in adult cannabis use: a review of recent findings. Curr Opin Psychol 2021;38:80-85 334. Jadoon KA, Ratcliffe SH, Barrett DA, et al. Efficacy and safety of cannabidiol and tetra-hydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group pilot Study. Diabetes Care 2016; 39:1777-1786 335. Freeman TP, Craft S, Wilson J, et al. Changes in delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations in cannabis over time: systematic review and meta-analysis. Addiction 2021;116:1000-1010 336. U.S. Food and Drug Administration. 5 things to know about delta-8 tetrahydrocannabinol-delta-8 THC. 2022. Accessed 13 August 2024. Available from https://www.fda.gov/consumers/ consumer-updates/5-things-know-about-delta-8-tetrahydrocannabinol-delta-8-thc 337. Akturk HK, Taylor DD, Camsari UM, Rewers A, Kinney GL, Shah VN. Association between cannabis use and risk for diabetic ketoacidosis in adults with type 1 diabetes. JAMA Intern Med 2019;179:115-118 338. Kinney GL, Akturk HK, Taylor DD, Foster NC, Shah VN. Cannabis use is associated with increased risk for diabetic ketoacidosis in adults with type 1 diabetes: findings from the T1D Exchange clinic registry. Diabetes Care 2020;43: 247-249 339. Akturk HK, Snell-Bergeon J, Kinney GL, Champakanath A, Monte A, Shah VN. Differentiating of their impact on glycemic control. Diabetes Care 2010;33:1658-1664 342. Asche C, LaFleur J, Conner C. A review of diabetes treatment adherence and the asso-ciation with clinical and economic outcomes. Clin Ther 2011;33:74-109 343. Berhe KK, Gebru HB, Kahsay HB. Effect of motivational interviewing intervention on HgbA1C and depression in people with type 2 diabetes mellitus (systematic review and meta-analysis). PLoS One 2020;15:e0240839 344. Liang W, Lo SHS, Tola YO, Chow KM. The effectiveness of self-management programmes for people with type 2 diabetes receiving insulin injection: a systematic review and meta-analysis. Int J Clin Pract 2021;75:e14636 345. Gray KE, Hoerster KD, Taylor L, Krieger J, Nelson KM. Improvements in physical activity and some dietary behaviors in a community health worker-led diabetes self-management intervention for adults with low incomes: results from a randomized controlled trial. Transl Behav Med 2021;11:2144-2154 346. Van Rhoon L, Byrne M, Morrissey E, Murphy J, McSharry J. A systematic review of the behaviour change techniques and digital features in technology-driven type 2 diabetes prevention interventions. Digit Health 2020;6:2055207620914427 347. Patton SR, Cushing CC, Lansing AH. Applying behavioral economics theories to inter-ventions for persons with diabetes. Curr Diab Rep 2022;22:219-226 348. Avery L, Flynn D, van Wersch A, Sniehotta FF, Trenell MI. Changing physical activity behavior in type 2 diabetes: a systematic review and meta-analysis of behavioral interventions. Diabetes Care 2012;35:2681-2689 349. Hilliard ME, Powell PW, Anderson BJ. Evidence-based behavioral interventions to promote diabetes management in children, adolescents, and families. Am Psychol 2016;71:590-601 350. Lake AJ, Bo A, Hadjiconstantinou M. Developing and evaluating behaviour change interventions for people with younger-onset type 2 diabetes: lessons and recommendations from existing programmes. Curr Diab Rep 2021;21:59 351. Berlin KS, Klages KL, Banks GG, et al. Toward the development of a culturally humble intervention to improve glycemic control and quality of life among adolescents with type-1 diabetes and their families. Behav Med 2021; 47:99-110 352. Nicolucci A, Haxhi J, D'Errico V, et al.; Italian Diabetes and Exercise Study 2 (IDES_2) Investi-gators. Effect of a behavioural intervention for adoption and maintenance of a physically active lifestyle on psychological well-being and quality of life in patients with type 2 diabetes: the IDES_2 randomized clinical trial. Sports Med 2022;52:643-654 353. Crowley MJ, Tarkington PE, Bosworth HB, healthcare practitioners in motivational inter-viewing: a systematic review. Health Psychol Rev 2022;16:430-449 356. Bell KJ, Barclay AW, Petocz P, Colagiuri S, Brand-Miller JC. Efficacy of carbohydrate counting in type 1 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2014;2:133-140 357. McVoy M, Hardin H, Fulchiero E, et al. Mental health comorbidity and youth onset type 2 diabetes: a systematic review of the literature. Int J Psychiatry Med 2023;58:37-55 358. Naicker K, Johnson JA, Skogen JC, et al. Type 2 diabetes and comorbid symptoms of depression and anxiety: longitudinal associations with mortality risk. Diabetes Care 2017;40:352-358 359. Anderson RJ, Grigsby AB, Freedland KE, et al. Anxiety and poor glycemic control: a meta-analytic review of the literature. Int J Psychiatry Med 2002;32:235-247 360. Anderson RJ, Freedland KE, Clouse RE, Lustman PJ. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care 2001;24:1069-1078 361. Nicolucci A, Kovacs Burns K, Holt RIG, et al.; DAWN2 Study Group. Diabetes Attitudes, Wishes and Needs second study (DAWN2): cross-national benchmarking of diabetes-related psy-chosocial outcomes for people with diabetes. Diabet Med 2013;30:767-777 362. Guerrero Fern andez de Alba I, Gimeno-Miguel A, Poblador-Plou B, et al. Association between mental health comorbidity and health outcomes in type 2 diabetes mellitus patients. Sci Rep 2020;10:19583 363. Gonzalvo JD, Hamm J, Eaves S, et al. A practical approach to mental health for the diabetes educator. AADE in Practice 2019;7:29-44 364. Robinson DJ, Coons M, Haensel H, Vallis M, Yale J-F; Diabetes Canada Clinical Practice Guidelines Expert Committee. Diabetes and mental health. Can J Diabetes 2018;42 Suppl 1:S130-S141 365. Cho M-K, Kim MY. Self-management nursing intervention for controlling glucose among diabetes: a systematic review and meta-analysis. Int J Environ Res Public Health 2021; 18:12750 366. Majidi S, Reid MW, Fogel J, et al. Psychosocial outcomes in young adolescents with type 1 diabetes participating in shared medical appointments. Pediatr Diabetes 2021;22: 787-795 367. Phillips S, Culpepper J, Welch M, et al. A multidisciplinary diabetes clinic improves clinical and behavioral outcomes in a primary care setting. J Am Board Fam Med 2021;34:579-589 368. Ali MK, Chwastiak L, Poongothai S, et al.; INDEPENDENT Study Group. Effect of a colla-borative care model on depressive symptoms and outcomes among adults with type 2 diabetes: a systematic review. BMJ Open 2022;12:e054650 371. Harkness E, Macdonald W, Valderas J, Coventry P, Gask L, Bower P. Identifying psy-chosocial interventions that improve both physical and mental health in patients with diabetes: a systematic review and meta-analysis. Diabetes Care 2010;33:926-930 372. Radcliff TA, Côt e MJ, Whittington MD, et al. Cost-effectiveness of three doses of a behavioral intervention to prevent or delay type 2 diabetes in rural areas. J Acad Nutr Diet 2020;120: 1163-1171 373. Corathers S, Williford DN, Kichler J, et al. Implementation of psychosocial screening into diabetes clinics: experience from the Type 1 Diabetes Exchange Quality Improvement Network. Curr Diab Rep 2023;23:19-28 374. Mulvaney SA, Mara CA, Kichler JC, et al. A retrospective multisite examination of depression screening practices, scores, and correlates in pediatric diabetes care. Transl Behav Med 2021; 11:122-131 375. Monaghan M, Mara CA, Kichler JC, et al. Multisite examination of depression screening scores and correlates among adolescents and young adults with type 2 diabetes. Can J Diabetes 2021;45:411-416 376. Brodar KE, Davis EM, Lynn C, et al. Comprehensive psychosocial screening in a pediatric diabetes clinic. Pediatr Diabetes 2021;22: 656-666 377. Myers AK, Grannemann BD, Lingvay I, Trivedi MH. Brief report: depression and history of suicide attempts in adults with new-onset type 2 diabetes. Psychoneuroendocrinology 2013;38:2810-2814 378. Majidi S, O'Donnell HK, Stanek K, Youngkin E, Gomer T, Driscoll KA. Suicide risk assessment in youth and young adults with type 1 diabetes. Diabetes Care 2020;43:343-348 379. Barnard-Kelly KD, Naranjo D, Majidi S, et al. Suicide and self-inflicted injury in diabetes: a balancing act. J Diabetes Sci Technol 2020;14: 1010-1016 380. Hill RM, Gallagher KAS, Eshtehardi SS, Uysal S, Hilliard ME. Suicide risk in youth and young adults with type 1 diabetes: a review of the literature and clinical recommendations for prevention. Curr Diab Rep 2021;21:51 381. Huang C-J, Huang Y-T, Lin P-C, Hsieh H-M, Yang Y-H. Mortality and suicide related to major depressive disorder before and after type 2 diabetes mellitus. J Clin Psychiatry 2022;83 382. Barry MJ, Nicholson WK, Silverstein M, et al.; US Preventive Services Task Force. Screening for depression and suicide risk in adults: US Preventive Services Task Force recommendation statement. JAMA 2023;329:2057-2067 383. Mangione CM, Barry MJ, Nicholson WK, et al.; US Preventive Services Task Force. Screening for depression and suicide risk in children and adolescents: US Preventive Services Task Force recommendation statement. JAMA 2022;328:1534-1542 US 384. among youth with chronic illness. Pediatr Ann 2017;46:e182-e187 386. O'Gurek DT, Henke C. A practical approach to screening for social determinants of health. Fam Pract Manag 2018;25:7-12 387. Zhang H, Zhang Q, Luo D, et al. The effect of family-based intervention for adults with diabetes on HbA1c and other health-related outcomes: systematic review and meta-analysis. J Clin Nurs 2022;31:1488-1501 388. Oyedeji AD, Ullah I, Weich S, Bentall R, Booth A. Effectiveness of non-specialist delivered psychological interventions on glycemic control and mental health problems in individuals with type 2 diabetes: a systematic review and meta-analysis. Int J Ment Health Syst 2022;16:9 389. Beverly EA, Hultgren BA, Brooks KM, Ritholz MD, Abrahamson MJ, Weinger K. Understanding physicians' challenges when treating type 2 diabetic patients' social and emotional difficulties: a qualitative study. Diabetes Care 2011;34: 1086-1088 390. Li Y, Storch EA, Ferguson S, Li L, Buys N, Sun J. The efficacy of cognitive behavioral therapy-based intervention on patients with diabetes: a meta-analysis. Diabetes Res Clin Pract 2022;189: 109965 391. Vlachou E, Ntikoudi A, Owens DA, Nikolakopoulou M, Chalimourdas T, Cauli O. Effectiveness of cognitive behavioral therapy-based interventions on psychological symptoms in adults with type 2 diabetes mellitus: an update review of randomized controlled trials. J Diabetes Complications 2022;36:108185 392. Ni Y-X, Ma L, Li J-P. Effects of mindfulness-based intervention on glycemic control and psychological outcomes in people with diabetes: a systematic review and meta-analysis. J Diabetes Investig 2021;12:1092-1103 393. Hood KK, Iturralde E, Rausch J, Weissberg-Benchell J. Preventing diabetes distress in adole-scents with type 1 diabetes: results 1 year after participation in the STePS program. Diabetes Care 2018;41:1623-1630 394. Weissberg-Benchell J, Shapiro JB, Bryant FB, Hood KK. Supporting Teen Problem-Solving (STEPS) 3 year outcomes: preventing diabetes-specific emotional distress and depressive symptoms in adolescents with type 1 diabetes. J Consult Clin Psychol 2020;88:1019-1031 395. Laffel LMB, Vangsness L, Connell A, Goebel-Fabbri A, Butler D, Anderson BJ. Impact of ambulatory, family-focused teamwork intervention on glycemic control in youth with type 1 diabetes. J Pediatr 2003;142:409-416 396. Wysocki T, Harris MA, Buckloh LM, et al. Effects of behavioral family systems therapy for diabetes on adolescents' family relationships, treatment adherence, and metabolic control. J Pediatr Psychol 2006;31:928-938 397. 399. Hagger V, Hendrieckx C, Sturt J, Skinner TC, Speight J. Diabetes distress among adolescents with type 1 diabetes: a systematic review. Curr Diab Rep 2016;16:9 400. Fisher L, Hessler D, Polonsky W, Strycker L, Masharani U, Peters A. Diabetes distress in adults with type 1 diabetes: prevalence, incidence and change over time. J Diabetes Complications 2016; 30:1123-1128 401. Hagger V, Hendrieckx C, Cameron F, Pouwer F, Skinner TC, Speight J. Diabetes distress is more strongly associated with HbA1c than depressive symptoms in adolescents with type 1 diabetes: results from Diabetes MILES Youth-Australia. Pediatr Diabetes 2018;19:840-847 402. Wasserman RM, Eshtehardi SS, Anderson BJ, Weissberg-Benchell JA, Hilliard ME. Profiles of depressive symptoms and diabetes distress in preadolescents with type 1 diabetes. Can J Diabetes 2021;45:436-443 403. Fisher L, Hessler DM, Polonsky WH, Mullan J. When is diabetes distress clinically meaningful? Establishing cut points for the Diabetes Distress Scale. Diabetes Care 2012;35:259-264 404. Fisher L, Polonsky WH, Perez-Nieves M, Desai U, Strycker L, Hessler D. A new perspective on diabetes distress using the type 2 diabetes distress assessment system (T2-DDAS): prevalence and change over time. J Diabetes Complications 2022;36:108256 405. Aikens JE. Prospective associations between emotional distress and poor outcomes in type 2 diabetes. Diabetes Care 2012;35:2472-2478 406. Hernar I, Cooper JG, Nilsen RM, et al. Diabetes distress and associations with demographic and clinical variables: a nationwide population-based registry study of 10,186 adults with type 1 diabetes in Norway. Diabetes Care 2024;47:126-131 407. Gonzalez JS, Krause-Steinrauf H, Bebu I, et al.; GRADE Research Group. Emotional distress, self-management, and glycemic control among participants enrolled in the glycemia reduction approaches in diabetes: a comparative effectiveness (GRADE) study. Diabetes Res Clin Pract 2023;196:110229 408. Liu X, Haagsma J, Sijbrands E, et al. Anxiety and depression in diabetes care: longitudinal associations with health-related quality of life. Sci Rep 2020;10:8307 409. Guo X, Wu S, Tang H, et al. The relationship between stigma and psychological distress among people with diabetes: a meta-analysis. BMC Psychol 2023;11:242 410. Akyirem S, Ekpor E, Namumbejja Abwoye D, Batten J, Nelson LE. Type 2 diabetes stigma and its association with clinical, psychological, and behavioral outcomes: a systematic review and meta-analysis. Diabetes Res Clin Pract 2023;202: 110774 411. Hamilton K, Forde R, Due-Christensen M, 13591053241241841 413. Fisher L, Polonsky WH, Hessler D. Addressing diabetes distress in clinical care: a practical guide. Diabet Med 2019;36:803-812 414. Sturt J, Dennick K, Hessler D, Hunter BM, Oliver J, Fisher L. Effective interventions for reducing diabetes distress: systematic review and meta-analysis. International Diabetes Nursing 2015;12:40-55 415. Ngan HY, Chong YY, Chien WT. Effects of mindfulness-and acceptance-based interventions on diabetes distress and glycaemic level in people with type 2 diabetes: Systematic review and meta-analysis. Diabet Med 2021;38:e14525 416. Roddy MK, Spieker AJ, Nelson LA, et al. Well-being outcomes of a family-focused intervention for persons with type 2 diabetes and support persons: main, mediated, and subgroup effects from the FAMS 2.0 RCT. Diabetes Res Clin Pract 2023;204:110921 417. Hessler DM, Fisher L, Guzman S, et al. EMBARK: a randomized, controlled trial comparing three approaches to reducing diabetes distress and improving HbA1c in adults with type 1 diabetes. Diabetes Care 2024;47:1370-1378 418. Wicaksana AL, Apriliyasari RW, Tsai P-S. Effectiveness of lay-led, group-based self-management interventions to improve glycated hemoglobin (HbA1c), self-efficacy, and emergency visit rates among adults with type 2 diabetes: a systematic review and meta-analysis. Int J Nurs Stud 2021;113:103779 421. DiNardo MM, Greco C, Phares AD, et al. Effects of an integrated mindfulness intervention for veterans with diabetes distress: a randomized controlled trial. BMJ Open Diabetes Res Care 2022;10 422. Lutes LD, Cummings DM, Littlewood K, et al. A tailored cognitive-behavioural intervention produces comparable reductions in regimen-related distress in adults with type 2 diabetes regardless of insulin use: 12-month outcomes from the COMRADE trial. Can J Diabetes 2020;44: 530-536 423. Friis AM, Johnson MH, Cutfield RG, Consedine NS. Kindness matters: a randomized controlled trial of a mindful self-compassion intervention improves depression, distress, and HbA1c among patients with diabetes. Diabetes Care 2016;39:1963-1971 424. Godoi A, Reis Marques I, Padrão EMH, et al. Glucose control and psychosocial outcomes with use of automated insulin delivery for 12 to 96 weeks in type 1 diabetes: a meta-analysis of randomised controlled trials. Diabetol Metab Syndr 2023;15:190 e10073 2014. Int J Diabetes Res 2014;3:15-21 514. Itani O, Kaneita Y, Tokiya M, et al. Short sleep duration, shift work, and actual days taken off work are predictive life-style risk factors for new-onset metabolic syndrome: a seven-year cohort study of 40,000 male workers. Sleep Med 2017;39:87-94 425. 881 427. Gonder-Frederick LA, Schmidt KM, Vajda KA, et al. Psychometric properties of the hypoglycemia fear survey-ii for adults with type 1 diabetes. Diabetes Care 2011;34:801-806 428. Wild D, von Maltzahn R, Brohan E, Christensen T, Clauson P, Gonder-Frederick L. A critical review of the literature on fear of hypo-glycemia in diabetes: implications for diabetes management and patient education. Patient Educ Couns 2007;68:10-15 429. Alazmi A, Bashiru MB, Viktor S, Erjavec M. Psychological variables and lifestyle in children with type1 diabetes and their parents: a systematic review. Clin Child Psychol Psychiatry 2023;29:1174-1194 430. Zhang L, Xu H, Liu L, et al. Related factors associated with fear of hypoglycemia in parents of children and adolescents with type 1 diabetes -a systematic review. J Pediatr Nurs 2022;66:125-135 431. Zambanini A, Newson RB, Maisey M, Feher MD. Injection related anxiety in insulin-treated diabetes. Diabetes Res Clin Pract 1999;46:239-246 432. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. Washington, DC, American Psychiatric Association, 2013 433. Effect of a collaborative care model on anxiety symptoms among patients with depression and diabetes in India: the INDEPENDENT randomized clinical trial. Gen Hosp Psychiatry 2022;74:39-45 435. Abbas Q, Latif S, Ayaz Habib H, et al. Cognitive behavior therapy for diabetes distress, depression, health anxiety, quality of life and treatment adherence among patients with type-II diabetes mellitus: a randomized control trial. BMC Psychiatry 2023;23:86 436. Visser MM, Charleer S, Fieuws S, et al. Effect of switching from intermittently scanned to real-time continuous glucose monitoring in adults with type 1 diabetes: 24-month results from the randomised ALERTT1 trial. Lancet Diabetes Endocrinol 2023;11:96-108 437. Talbo MK, Katz A, Hill L, Peters TM, Yale J-F, Brazeau A-S. Effect of diabetes technologies on the fear of hypoglycaemia among people living with type 1 diabetes: a systematic review and meta-analysis. EClinicalMedicine 2023;62:102119 438. Martyn-Nemeth P, Duffecy J, Quinn L, et al. FREE: A randomized controlled feasibility trial of a cognitive behavioral therapy and technology-assisted intervention to reduce fear of hypo-glycemia in young adults with type 1 diabetes. J Psychosom Res 2024;181:111679 439. de Groot M, Crick KA, Long M, Saha C, Shubrook JH. Lifetime duration of depressive disorders in patients with type 2 diabetes. children/adolescents with type 1 diabetes: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2023;14:1095729 442. Clouse RE, Lustman PJ, Freedland KE, Griffith LS, McGill JB, Carney RM. Depression and coronary heart disease in women with diabetes. Psychosom Med 2003;65:376-383 443. Rosas CE, Talavera GA, Roesch SC, et al. Randomized trial of an integrated care intervention among Latino adults: sustained effects on diabetes management. Transl Behav Med 2024;14:310-318 444. Cannon A, Handelsman Y, Heile M, Shannon M. Burden of illness in type 2 diabetes mellitus. J Manag Care Spec Pharm 2018;24: S5-S13 445. Atlantis E, Fahey P, Foster J. Collaborative care for comorbid depression and diabetes: a systematic review and meta-analysis. BMJ Open 2014;4:e004706 446. Lu X, Yang D, Liang J, et al. Effectiveness of intervention program on the change of glycaemic control in diabetes with depression patients: a meta-analysis of randomized controlled studies. Prim Care Diabetes 2021;15:428-434 447. Ellis D, Carcone AI, Templin T, et al. Moderating effect of depression on glycemic control in an ehealth intervention among Black youth with type 1 diabetes: findings from a multicenter randomized controlled trial. JMIR Diabetes 2024;9:e55165 448. Li Y, Buys N, Ferguson S, et al. The evaluation of cognitive-behavioral therapy-based intervention on type 2 diabetes patients with comorbid metabolic syndrome: a randomized controlled trial. Diabetol Metab Syndr 2023;15:158 449. Fisher V, Li WW, Malabu U. The effectiveness of mindfulness-based stress reduction (MBSR) on the mental health, HbA1C, and mindfulness of diabetes patients: a systematic review and meta-analysis of randomised controlled trials. Appl Psychol Health Well Being 2023;15:1733-1749 450. Varela-Moreno E, Carreira Soler M, Guzm an-Parra J, J odar-S anchez F, Mayoral-Cleries F, Anarte-Ort ız MT. Effectiveness of ehealth-based psychological interventions for depression treatment in patients with type 1 or type 2 diabetes mellitus: a systematic review. Front Psychol 2021;12:746217 451. Tavares Franquez R, Del Grossi Moura M, Cristina Ferreira McClung D, et al. E-health technologies for treatment of depression, anxiety and emotional distress in person with diabetes mellitus: a systematic review and meta-analysis. Diabetes Res Clin Pract 2023;203:110854 452. Stewart JC, Patel JS, Polanka BM, et al. Effect of modernized collaborative care for depression on depressive symptoms and cardio-vascular disease risk biomarkers: eIMPACT ran-domized controlled trial. Brain Behav Immun 2023;112:18-28 453. 455. Saha CK, Shubrook JH, Guyton Hornsby W, et al. Program ACTIVE II: 6-and 12-month outcomes of a treatment approach for major depressive disorder in adults with type 2 diabetes. J Diabetes Complications 2024;38:108666 456. Chen X, Zhao P, Wang W, Guo L, Pan Q. The antidepressant effects of GLP-1 receptor agonists: a systematic review and meta-analysis. Am J Geriatr Psychiatry 2024;32:117-127 457. Pinhas-Hamiel O, Hamiel U, Levy-Shraga Y. Eating disorders in adolescents with type 1 diabetes: challenges in diagnosis and treatment. World J Diabetes 2015;6:517-526 458. Papelbaum M, Appolin ario JC, Moreira RdO, Ellinger VCM, Kupfer R, Coutinho WF. Prevalence of eating disorders and psychiatric comorbidity in a clinical sample of type 2 dia-betes mellitus patients. Braz J Psychiatry 2005; 27:135-138 459. Niemel€ a PE, Lepp€ anen HA, Voutilainen A, et al. Prevalence of eating disorder symptoms in people with insulin-dependent-diabetes: a systematic review and meta-analysis. Eat Behav 2024;53:101863 460. Dean YE, Motawea KR, Aslam M, et al. Association between type 1 diabetes mellitus and eating disorders: a systematic review and meta-Analysis. Endocrinol Diabetes Metab 2024; 7:e473 461. Weinger K, Beverly EA. Barriers to achieving glycemic targets: who omits insulin and why? Diabetes Care 2010;33:450-452 462. Hudson JI, Hiripi E, Pope HG, Kessler RC. The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. Biol Psychiatry 2007;61:348-358 463. Martyn-Nemeth P, Quinn L, Hacker E, Park H, Kujath AS. Diabetes distress may adversely affect the eating styles of women with type 1 diabetes. Acta Diabetol 2014;51:683-686 464. Marks KP, Aalders J, Liu S, et al. Associations between disordered eating behaviors and HbA1c in young people with type 1 diabetes: a systematic review and meta-analysis. Curr Diabetes Rev 2024;20:e220823220144 465. Peterson CM, Fischer S, Young-Hyman D. Topical review: a comprehensive risk model for disordered eating in youth with type 1 diabetes. J Pediatr Psychol 2015;40:385-390 466. Jones CJ, Read R, O'Donnell N, et al. PRIORITY trial: results from a feasibility randomised controlled trial of a psychoeducational intervention for parents to prevent disordered eating in children and young people with type 1 diabetes. Diabet Med 2024;41:e15263 467. Wisting L, Haugvik S, Wennersberg AL, et al. A pilot study of a virtually delivered dissonance-based eating disorder prevention program for young women wit h type 1 diabetes: within-subject changes over 6-month follow-up. Eat Disord 2024:1-17 468. 470. Banting R, Randle-Phillips C. A systematic review of psychological interventions for comorbid type 1 diabetes mellitus and eating disorders. Diabetes Management 2018;8:1-18 471. Priesterroth L, Grammes J, Clauter M, Kubiak T. Diabetes technologies in people with type 1 diabetes mellitus and disordered eating: a systematic review on continuous subcutaneous insulin infusion, continuous glucose monitoring and automated insulin delivery. Diabet Med 2021;38:e14581 472. van Bloemendaal L, IJzerman RG, Ten Kulve JS, et al. GLP-1 receptor activation modulates appetite-and reward-related brain areas in humans. Diabetes 2014;63:4186-4196 473. Aoun L, Almardini S, Saliba F, et al. GLP-1 receptor agonists: a novel pharmacotherapy for binge eating (binge eating disorder and bulimia nervosa)? A systematic review. J Clin Transl Endocrinol 2024;35:100333 474. Suvisaari J, Per€ al€ a J, Saarni SI, et al. Type 2 diabetes among persons with schizophrenia and other psychotic disorders in a general population survey. Eur Arch Psychiatry Clin Neurosci 2008; 258:129-136 475. American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Asso-ciation for the Study of Obesity. Consensus devel-opment conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004;27: 596-601 476. Mulligan K, McBain H, Lamontagne-Godwin F, et al. Barriers to effective diabetes management -a survey of people with severe mental illness. BMC Psychiatry 2018;18:165 477. Kruse J, Schmitz N, Thefeld W, German National Health Interview and Examination Survey. On the association between diabetes and mental disorders in a community sample: results from the German National Health Interview and Examination Survey. Diabetes Care 2003;26: 1841-1846 478. Ojo O, Kalocs anyiov a E, McCrone P, Elliott H, Milligan W, Gkaintatzi E. Non-pharmacological interventions for type 2 diabetes in people living with severe mental illness: results of a systematic review and meta-analysis. Int J Environ Res Public Health 2024;21 479. Schnitzer K, Cather C, Zvonar V, et al. Patient experience and predictors of improvement in a group behavioral and educational intervention for individuals with diabetes and serious mental illness: mixed methods case study. J Particip Med 2021;13:e21934 480. Biessels GJ, Whitmer RA. Cognitive dys-function in diabetes: how to implement emerging guidelines. Diabetologia 2020;63:3-9 481. Brands AMA, Biessels GJ, de Haan EHF, Kappelle LJ, Kessels RPC. The effects of type 1 484. Biessels GJ, Despa F. Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications. Nat Rev Endocrinol 2018; 14:591-604 485. Munshi MN. Cognitive dysfunction in older adults with diabetes: what a clinician needs to know. Diabetes Care 2017;40:461-467 486. Garcia-Argibay M, Li L, Du Rietz E, et al. The association between type 2 diabetes and attention-deficit/hyperactivity disorder: a systematic review, meta-analysis, and population-based sibling study. Neurosci Biobehav Rev 2023;147:105076 487. Ding K, Reynolds CM, Driscoll KA, Janicke DM. The relationship between executive functioning, type 1 diabetes self-management behaviors, and glycemic control in adolescents and young adults. Curr Diab Rep 2021;21:10 488. Miller AL, Albright D, Bauer KW, et al. Self-regulation as a protective factor for diabetes distress and adherence in youth with type 1 diabetes during the COVID-19 pandemic. J Pediatr Psychol 2022;47:873-882 489. Feinkohl I, Aung PP, Keller M, et al.; Edinburgh Type 2 Diabetes Study (ET2DS) Investigators. Severe hypoglycemia and cognitive decline in older people with type 2 diabetes: the Edinburgh type 2 diabetes study. Diabetes Care 2014;37:507-515 490. Impact of type 1 diabetes in the developing brain in children: a longitudinal study. Diabetes Care 2021;44:983-992 492. Tilvis RS, K€ ah€ onen-V€ are MH, Jolkkonen J, Valvanne J, Pitkala KH, Strandberg TE. Predictors of cognitive decline and mortality of aged people over a 10-year period. J Gerontol A Biol Sci Med Sci 2004;59:268-274 493. Chi H, Song M, Zhang J, Zhou J, Liu D. Relationship between acute glucose variability and cognitive decline in type 2 diabetes: a systematic review and meta-analysis. PLoS One 2023;18:e0289782 494. Jacobson AM, Ryan CM, Cleary PA, et al.; Diabetes Control and Complications Trial/EDIC Research Group. Biomedical risk factors for decreased cognitive functioning in type 1 diabetes: an 18 year follow-up of the Diabetes Control and Complications Trial (DCCT) cohort. Diabetologia 2011;54:245-255 495. West RK, Ravona-Springer R, Schmeidler J, et al. The association of duration of type 2 diabetes with cognitive performance is modulated by long-term glycemic control. Am J Geriatr Psychiatry 2014;22:1055-1059 496. Tian S, Jiang J, Wang J, et al. Comparison on cognitive outcomes of antidiabetic agents for type 2 diabetes: a systematic review and network meta-analysis. Diabetes Metab Res Rev 2023; 39:e3673 Impact of shift work on glycemic control in insulin treated diabetics Dar El Chefa Hospital, Egypt 497. systematic review and meta-analysis. Sleep Med Rev 2016;30:11-24 499. Cappuccio FP, D'Elia L, Strazzullo P, Miller MA. Quantity and quality of sleep and incidence of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care 2010;33:414-420 500. Zhang X, Zhang R, Cheng L, et al. The effect of sleep impairment on gestational diabetes mellitus: a systematic review and meta-analysis of cohort studies. Sleep Med 2020;74:267-277 501. Monzon AD, Patton SR, Koren D. Childhood diabetes and sleep. Pediatr Pulmonol 2022;57: 1835-1850 502. Lee SWH, Ng KY, Chin WK. The impact of sleep amount and sleep quality on glycemic control in type 2 diabetes: a systematic review and meta-analysis. Sleep Med Rev 2017;31:91-101 503. Al-Gadi IS, Streisand R, Tully C, et al. Up all night? Sleep disruption in parents of young children newly diagnosed with type 1 diabetes. Pediatr Diabetes 2022;23:815-819 504. Macaulay GC, Boucher SE, Yogarajah A, Galland BC, Wheeler BJ. Sleep and night-time caregiving in parents of children and adolescents with type 1 diabetes mellitus -a qualitative study. Behav Sleep Med 2020;18:622-636 505. Reutrakul S, Thakkinstian A, Anothaisintawee T, et al. Sleep characteristics in type 1 diabetes and associations with glycemic control: systematic review and meta-analysis. Sleep Med 2016; 23:26-45 506. Barone MTU, Menna-Barreto L. Diabetes and sleep: a complex cause-and-effect relationship. Diabetes Res Clin Pract 2011;91:129-137 507. Denic-Roberts H, Costacou T, Orchard TJ. Subjective sleep disturbances and glycemic control in adults with long-standing type 1 diabetes: the Pittsburgh's Epidemiology of Diabetes Complications study. Diabetes Res Clin Pract 2016;119:1-12 508. Ogilvie RP, Patel SR. The epidemiology of sleep and diabetes. Curr Diab Rep 2018;18:82 509. Schipper SBJ, Van Veen MM, Elders PJM, et al. Sleep disorders in people with type 2 diabetes and associated health outcomes: a review of the literature. Diabetologia 2021;64: 2367-2377 510. Bener A, Al-Hamaq AOAA, A gan AF, € Ozt€ urk M, € Omer A. The prevalence of restless legs syndrome and comorbid condition among patient with type 2 diabetic mellitus visiting primary healthcare. J Family Med Prim Care 2019; 8:3814-3820 511. Modarresnia L, Golgiri F, Madani NH, Emami Z, Tanha K. Restless legs syndrome in Iranian people with type 2 diabetes mellitus: the role in quality of life and quality of sleep. J Clin Sleep Med 2018;14:223-228 512. Manodpitipong A, Saetung S, Nimitphong H, et al. Night-shift work is associated with poorer glycaemic control in patients with type 2 diabetes. J Sleep Res 2017;26:764-772 513. El Tayeb IM, El Saghier EOA, Ramadan BK. 515. Lecube A, Sim o R, Pallayova M, et al. Pulmonary function and sleep breathing: two new targets for type 2 diabetes care. Endocr Rev 2017;38:550-573 516. Herth J, Sievi NA, Schmidt F, Kohler M. Effects of continuous positive airway pressure therapy on glucose metabolism in patients with obstructive sleep apnoea and type 2 diabetes: a systematic review and meta-analysis. Eur Respir Rev 2023;32 517. O'Donnell C, Crilly S, O'Mahony A, et al. Continuous positive airway pressure but not GLP1-mediated weight loss improves early cardiovascular disease in obstructive sleep apnea: a randomized proof-of-concept study. Ann Am Thorac Soc 2024; 21:464-473 518. Malhotra A, Grunstein RR, Fietze I, et al.; SURMOUNT-OSA Investigators. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med 2024; 519. Tan X, van Egmond L, Chapman CD, Cedernaes J, Benedict C. Aiding sleep in type 2 diabetes: therapeutic considerations. Lancet Diabetes Endocrinol 2018;6:60-68 520. Carreon SA, Cao VT, Anderson BJ, Thompson DI, Marrero DG, Hilliard ME. 'I don't sleep through the night': qualitative study of sleep in type 1 diabetes. Diabet Med 2022;39: e14763 521. Hood KK, Schneider-Utaka AK, Reed ZW, et al.; PEDAP Trial Study Group. Patient reported outcomes (PROs) and user experiences of young children with type 1 diabetes using t:slim X2 insulin pump with control-IQ technology. Diabetes Res Clin Pract 2024;208:111114 522. Cobry EC, Hamburger E, Jaser SS. Impact of the hybrid closed-loop system on sleep and quality of life in youth with type 1 diabetes and their parents. Diabetes Technol Ther 2020;22: 794-800 523. Franceschi R, Mozzillo E, Di Candia F, et al. A systematic review on the impact of commercially available hybrid closed loop systems on psy-chological outcomes in youths with type 1 diabetes and their parents. Diabet Med 2023;40:e15099 524. Kothari V, Cardona Z, Chirakalwasan N, Anothaisintawee T, Reutrakul S. Sleep interventions and glucose metabolism: systematic review and meta-analysis. Sleep Med 2021;78:24-35 525. Groeneveld L, Beulens JW, Blom MT, et al. The effect of cognitive behavioral therapy for insomnia on sleep and glycemic outcomes in people with type 2 diabetes: a randomized controlled trial. Sleep Med 2024;120:44-52 526. Li M, Li D, Tang Y, et al. Effect of diabetes sleep education for T2DM who sleep after midnight: a pilot study from China. Metab Syndr Relat Disord 2018;16:13-19 527. Khandelwal D, Dutta D, Chittawar S, Kalra S. Sleep disorders in type 2 diabetes. Indian J Endocrinol Metab 2017;21:758-761 528. hypoglycaemia on quality of life among adults with type 1 diabetes: results from "YourSAY: Hypoglycaemia." J Diabetes Complications 2023; 37:108232 531. Trief PM, Xing D, Foster NC, et al.; T1D Exchange Clinic Network. Depression in adults in the T1D Exchange Clinic Registry. Diabetes Care 2014;37:1563-1572 532. Schram MT, Baan CA, Pouwer F. Depression and quality of life in patients with diabetes: a systematic review from the European depression in diabetes (EDID) research consortium. Curr Diabetes Rev 2009;5:112-119 533. Schmitt A, McSharry J, Speight J, et al. Symptoms of depression and anxiety in adults with type 1 diabetes: associations with self-care behaviour, glycaemia and incident complications over four years -results from Diabetes MILES-Australia. J Affect Disord 2021;282:803-811 534. Stahl-Pehe A, Selinski S, B€ achle C, et al. Screening for generalized anxiety disorder (GAD) and associated factors in adolescents and young adults with type 1 diabetes: cross-sectional results of a Germany-wide population-based study. Diabetes Res Clin Pract 2022;184:109197 535. Goebel-Fabbri AE, Fikkan J, Franko DL, Pearson K, Anderson BJ, Weinger K. Insulin restriction and associated morbidity and mortality in women with type 1 diabetes. Diabetes Care 2008;31:415-419 536. Araia E, King RM, Pouwer F, Speight J, Hendrieckx C. Psychological correlates of disordered eating in youth with type 1 diabetes: results from Diabetes MILES Youth-Australia. Pediatr Diabetes 2020;21:664-672 537. Galler A, Bollow E, Meusers M, et al.; German Federal Ministry of Education and Research (BMBF) Competence Network Diabetes Mellitus. Comparison of glycemic and metabolic control in youth with type 1 diabetes with and without antipsychotic medication: analysis from the nationwide German/Austrian Diabetes Survey (DPV). Diabetes Care 2015;38:1051-1057 538. Cooper MN, Lin A, Alvares GA, de Klerk NH, Jones TW, Davis EA. Psychiatric disorders during early adulthood in those with childhood onset type 1 diabetes: rates and clinical risk factors from population-based follow-up. Pediatr Diabetes 2017; 18:599-606 539. Chan JKN, Wong CSM, Or PCF, Chen EYH, Chang WC. Risk of mortality and complications in patients with schizophrenia and diabetes mellitus: population-based cohort study. Br J Psychiatry 2021;219:375-382 540. Jacobson AM, Ryan CM, Braffett BH, et al.; DCCT/EDIC Research Group. Cognitive performance declines in older adults with type 1 diabetes: results from 32 years of follow-up in the DCCT and EDIC Study. Lancet Diabetes Endocrinol 2021;9:436-445 541. Ryan CM, Geckle MO, Orchard TJ. Cognitive efficiency declines over time in adults with type 1 cognition, mild cognitive impairment and dementia in persons with diabetes mellitus: a systematic review and meta-analysis. Diabetes Res Clin Pract 2022;185:109227 544. Matsunaga M, Tanihara S, He Y, Yatsuya H, Ota A. Impact of diabetes on mortality and hospitalization after dementia diagnosis: health insurance claims data analysis. Geriatr Gerontol Int 2024;24:773-781 545. Fisher L, Mullan JT, Arean P, Glasgow RE, Hessler D, Masharani U. Diabetes distress but not clinical depression or depressive symptoms is associated with glycemic control in both cross-sectional and longitudinal analyses. Diabetes Care 2010;33:23-28 546. Khashayar P, Shirzad N, Zarbini A, Esteghamati A, Hemmatabadi M, Sharafi E. Diabetes-related distress and its association with the complications of diabetes in Iran. J Diabetes Metab Disord 2022;21:1569-1575 547. Park H-S, Cho Y, Seo DH, et al. Impact of diabetes distress on glycemic control and diabetic complications in type 2 diabetes mellitus. Sci Rep 2024;14:5568 548. Young CF, Mullin R, Moverley JA, Shubrook JH. Associations between diabetes-related distress and predicted cardiovascular complication risks in patients with type 2 diabetes. J Osteopath Med 2022;122:319-326 549. Hayashino Y, Okamura S, Tsujii S, Ishii H, Care Registry at Tenri Study G. Diabetes distress is associated with future risk of progression of diabetic nephropathy in adults with type 2 diabetes: a prospective cohort study (Diabetes Distress and Care Registry at Tenri [DDCRT23] ). Can J Diabetes 2023;47:519-524 550. Bruno BA, Choi D, Thorpe KE, Yu CH. Relationship among diabetes distress, decisional conflict, quality of life, and patient perception of chronic illness care in a cohort of patients with type 2 diabetes and other comorbidities. Diabetes Care 2019;42:1170-1177 551. Hayashino Y, Okamura S, Tsujii S, Ishii H, Care Registry at Tenri Study G. Association between diabetes distress and all-cause mortality in Japanese individuals with type 2 diabetes: a prospective cohort study (Diabetes Distress and Care Registry in Tenri [DDCRT 18]). Diabetologia 2018;61:1978-1984 552. Lustman PJ, Anderson RJ, Freedland KE, de Groot M, Carney RM, Clouse RE. Depression and poor glycemic control: a meta-analytic review of the literature. Diabetes Care 2000;23:934-942 553. Khuwaja AK, Lalani S, Dhanani R, Azam IS, Rafique G, White F. Anxiety and depression among outpatients with type 2 diabetes: a multi-centre study of prevalence and associated factors. Diabetol Metab Syndr 2010;2:72 554. Chourpiliadis C, Zeng Y, Lovik A, et al. Metabolic profile and long-term risk of depression, anxiety, and stress-related disorders. JAMA Netw Open 2024;7:e244525 2010;33:1034-1036 558. Ali S, Stone M, Skinner TC, Robertson N, Davies M, Khunti K. The association between depression and health-related quality of life in people with type 2 diabetes: a systematic literature review. Diabetes Metab Res Rev 2010; 26:75-89 559. Park M, Katon WJ, Wolf FM. Depression and risk of mortality in individuals with diabetes: a meta-analysis and systematic review. Gen Hosp Psychiatry 2013;35:217-225 560. Lee LO, Grimm KJ, SA, 3rd, Kubzansky LD. Neuroticism, worry, and cardiometabolic risk trajectories: findings from a 40-year study of men. J Am Heart Asso c 2022;11:e022006 561. Deschênes SS, Burns RJ, Schmitz N. Trajectories of anxiety symptoms and asso-ciations with incident cardiovascular disease in adults with type 2 diabetes. J Psychosom Res 2018;104:95-100 562. Karpha K, Biswas J, Nath S, Dhali A, Sarkhel S, Dhali GK. Factors affecting depression and anxiety in diabetic patients: a cross sectional study from a tertiary care hospital in Eastern India. Ann Med Surg (Lond) 2022;84:104945 563. Deschênes SS, Burns RJ, Schmitz N. Binge eating disorder and night eating syndrome 565. Papelbaum M, de Oliveira Moreira R, Coutinho WF, et al. Does binge-eating matter for glycemic control in type 2 diabetes patients? J Eat Disord 2019;7:30 566. Pekin C, McHale M, Seymour M, et al. Psychopathology and eating behaviour in people with type 2 diabetes referred for bariatric surgery. Eat Weight Disord 2022;27:3627-3635 567. TODAY Study Group. Longitudinal association of depressive symptoms, binge eating, and quality of life with cardiovascular risk factors in young adults with youth-onset type 2 diabetes: the TODAY2 study. Diabetes Care 2022;45:1073-1081 568. Wykes TL, Lee AA, McKibbin CL, Laurent SM. Self-efficacy and hemoglobin A1C among adults with serious mental illness and type 2 diabetes: the roles of cognitive functioning and psychiatric symptom severity. Psychosom Med 2016;78:263-270 569. Dixon LB, Kreyenbuhl JA, Dickerson FB, et al. A comparison of type 2 diabetes outcomes among persons with and without severe mental illnesses. Psychiatr Serv 2004;55:892-900 570. McEvoy JP, Meyer JM, Goff DC, et al. Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Inter-vention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr Res 2005;80:19-32 571. Kim H, Lee K-N, Shin DW, Han K, Jeon HJ. Association of comorbid mental disorders with cardiovascular disease risk in patients with type 2 among Ment Health Nurs 2024;31:364-375 574. Bajor LA, Gunzler D, Einstadter D, et al. Associations between comorbid anxiety, diabetes control, and overall medical burden in patients with serious mental illness and diabetes. Int J Psychiatry Med 2015;49:309-320 575. Dickerson F, Brown CH, Fang L, et al. Quality of life in individuals with serious mental illness and type 2 diabetes. Psychosomatics 2008; 49:109-114 576. Munshi M, Grande L, Hayes M, et al. Cognitive dysfunction is associated with poor diabetes control in older adults. Diabetes Care 2006;29:1794-1799 577. Lee S-H, Han K, Cho H, et al. Variability in metabolic parameters and risk of dementia: a nationwide population-based study. Alzheimers Res Ther 2018;10:110 578. Olesen KKW, Thrane PG, Gyldenkerne C, et al. Diabetes and coronary artery disease as risk factors for dementia. Eur J Prev Cardiol 2024; 579. Cheng D, Zhao X, Yang S, Wang G, Ning G. Association between diabetic retinopathy and cognitive impairment: a systematic review and meta-analysis. Front Aging Neurosci 2021;13: 692911 580. Sinclair AJ, Girling AJ, Bayer AJ. Cognitive dysfunction in older subjects with diabetes mellitus: impact on diabetes self-management and use of care services. All Wales Research into Elderly (AWARE) study. Diabetes Res Clin Pract 2000;50:203-212 581. Katon W, Lyles CR, Parker MM, Karter AJ, Huang ES, Whitmer RA. Association of depression with increased risk of dementia in patients with type 2 diabetes: the Diabetes and Aging Study. Arch Gen Psychiatry 2012;69:410-417 582. Janssen J, Koekkoek PS, Biessels G-J, Kappelle JL, Rutten GEHM, Cog-ID study group. Depressive symptoms and quality of life after screening for cognitive impairment in patients 583. Titcomb TJ, Richey P, Casanova R, et al. Association of type 2 diabetes mellitus with dementia-related and non-dementia-related mor-tality among postmenopausal women: a secondary competing risks analysis of the women's health initiative. Alzheimers Dement 2024;20:234-242 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes-2025 Diabetes Care 2025;48(Suppl. 1):S128-S145 | https://doi.org/10.2337/dc25-S006 American Diabetes Association Professional Practice Committee* Individuals on a variety of insulin treatment plans can benefit from CGM with im-proved glucose levels, decreased hypoglycemia, and enhanced self-efficacy (Section 7, "Diabetes Technology") (1). *A complete list of members of the American Diabetes Association Professional Practice Committee can be found at https://doi.org/10.2337/dc25-SINT. Duality of interest information for each author is available at https://doi.org/10.2337/dc25-SDIS. Glycemic Assessment by A1C The A1C test is the primary tool for assess-ing glycemic status in both clinical practice and clinical trials, and it is strongly linked to diabetes complications (2-4). A1C reflects average glycemia over approxi-mately 2-3 months. The performance of laboratory tests for A1C is generally excellent for National Glycohemoglobin Standardization Program (NGSP)-certified assays (ngsp.org). Thus, A1C testing should be performed routinely in all people with diabetes at initial assessment and as part of continuing care. Measurement ap-proximately every 3 months determines whether glycemic goals have been reached and maintained. Adults with type 1 or type 2 diabetes who have achieved and are maintaining glucose levels within their target range may only need A1C testing or other glucose assessments twice a year. Individuals with less stable glucose levels, those with intensive care plans, or those not meet-ing their treatment goals may require more frequent testing, typically every 3 months, with additional assessments as needed. Poin-t-of-care A1C testing can offer timely oppor-tunities for treatment adjustments during 555. patients with type 2 diabetes. Diabetes Care in adults with type 2 diabetes: a systematic cross-sectional correlational study. J Psychiatr ID cohort study. BMJ Open 2019;9:e024696 review. J Eat Disord 2018;6:36 people diagnosed with serious mental illness: a with type 2 diabetes: observations from the Cog-appointments with health care professionals.|||

||1-Equivalent A1C levels and|| |---|---|---|

|estimated average glucose (eAG)|estimated average glucose (eAG)|estimated average glucose (eAG)|

|A1C (%)|mg/dL*|mmol/L|

|5|97 (76-120)|5.4 (4.2-6.7)|

|6|126 (100-152)|7.0 (5.5-8.5)|

|7|154 (123-185) 8.6 (6.8-10.3)||

|8|183 (147-217) 10.2 (8.1-12.1)||

|9|212 (170-249) 11.8 (9.4-13.9)||

|10|240 (193-282) 13.4 (10.7-15.7)||

|11|269 (217-314) 14.9 (12.0-17.5)||

|12|298 (240-347) 16.5 (13.3-19.3)||

|Data in parentheses are 95% CI. A calcula-|||

|3,| |---|

|diabetesjournals.org/care||Glycemic Goals and Hypoglycemia|S131| |---|---|---|---|

|Metric|Interpretation|Goals||

|Metrics for valid CGM wear||||

|Glycemic metrics||||

|Mean glucose|Mean of glucose values|*||

|Glucose management indicator (GMI)|Calculated value approximating A1C|*||

||(not always equivalent)|||

|Glucose coefficient of variation (CV)|Spread of glucose values|#36% †||

|TBR < 54 mg/dL ( < 3.0 mmol/L)|Percent of time in level 2 hypoglycemia|< 1%||

|3-Summary of glycemic goals for many nonpregnant adults with|| |---|---|

|diabetes||

|A1C|< 7.0% ( < 53 mmol/mol)* †|

|Preprandial capillary plasma glucose|80-130 mg/dL* (4.4-7.2 mmol/L)|

|Peak postprandial capillary plasma glucose ‡|< 180 mg/dL* ( < 10.0 mmol/L)|

||Glycemic criteria/description|| |---|---|---|

|Level 1|Glucose < 70 mg/dL ( < 3.9 mmol/L) and $54 mg/dL ($3.0 mmol/L)||

|Level 2|Glucose < 54 mg/dL ( < 3.0 mmol/L)||

|Level 3|A severe event characterized by altered mental and/or physical status||

||requiring assistance for treatment of hypoglycemia, irrespective of||

||glucose level||

|Adapted from Agiostratidou et al. (72).|||

||Table 6.5-Assessment of hypoglycemia risk among individuals treated with|Table 6.5-Assessment of hypoglycemia risk among individuals treated with|

||insulin, sulfonylureas, or meglitinides||

|||Social, cultural, and economic|

||Clinical and biological risk factors|risk factors|

||Major risk factors|Major risk factors|

||• Recent (within the past 3-6 months) level 2|Food insecurity|

||or 3 hypoglycemia|Low-income status §|

||• Intensive insulin therapy*|Housing insecurity|

||• Impaired hypoglycemia awareness|Fasting for religious or cultural|

||• End-stage kidney disease|reasons|

||• Cognitive impairment or dementia|Underinsurance|

||Other risk factors|Other risk factors|

||• Multiple recent episodes of level 1 hypoglycemia|Low health literacy|

||• Basal insulin therapy*|Alcohol or substance use disorder|

||• Age $75 years †||

||• Female sex||

||• High glycemic variability ‡||

||• Polypharmacy||

||• Cardiovascular disease||

||• Chronic kidney disease (eGFR < 60 mL/min/||

||1.73 m 2 or albuminuria)||

||• Neuropathy||

||• Retinopathy||

||• Major depressive disorder||

||• Severe mental illness||

|||Median AWP*|Median NADAC*|| |---|---|---|---|---|

|Glucagon|Injection powder|$206 ($194, $337) $235 ($199, $295)|$206 ($194, $337) $235 ($199, $295)|$206 ($194, $337) $235 ($199, $295)|

||with diluent for||||

||reconstitution||||

|Glucagon|Nasal powder|$347|$269|3 mg|

||prefilled syringe||||

|Dasiglucagon|Prefilled pen,|$371|$298|0.6 mg|

||Initial|Every|Annual| |---|---|---|---|

|Hypoglycemia history assessment||||

|Hypoglycemia awareness assessment||||

|Cognitive function and other hypoglycemia risk factor||||

|assessment||||

|Structured patient education for hypoglycemia||*|*|

|prevention and treatment||||

|Consideration of continuous glucose monitoring||||

|needs||||

|Reevaluation of diabetes treatment plan with||†|†|

|deintensification, simplification, or agent||||

|modification as appropriate||||

|Glucagon prescription and training for close contacts||||

|for insulin-treated individuals or those at high||||

|hypoglycemic risk||||

|diabetesjournals.org/care|Glycemic Goals and Hypoglycemia|S139| |---|---|---|

|8-Diagnostic criteria for DKA and HHS|||

|DKA|||

|Diabetes/hyperglycemia|Glucose $200 mg/dL (11.1 mmol/L) or prior history of|Glucose $200 mg/dL (11.1 mmol/L) or prior history of|

||diabetes||

|Ketosis|b-Hydroxybutyrate concentration $3.0 mmol/L or urine|b-Hydroxybutyrate concentration $3.0 mmol/L or urine|

||ketone strip 21 or greater|ketone strip 21 or greater|

|Metabolic acidosis|pH < 7.3 and/or bicarbonate concentration < 18 mmol/L|pH < 7.3 and/or bicarbonate concentration < 18 mmol/L|

|HHS|||

|Hyperglycemia|Plasma glucose $600 mg/dL (33.3 mmol/L)|Plasma glucose $600 mg/dL (33.3 mmol/L)|

|Type 1 diabetes/absolute insulin deficiency| |---|

|Younger age|

|Prior history of hyperglycemic crises|

|Prior history of hypoglycemic crises|

|Presence of other diabetes complications|

|Presence of other chronic health conditions (particularly in people with type 2 diabetes)|

|Presence of behavioral health conditions (e.g., depression, bipolar disorder, and eating|

|disorders)|

|Alcohol and/or substance use|

|High A1C level|

|Social determinants of health|

|DKA| |---|

|Setting|FDA*|ISO 15197:2013*| |---|---|---|

|Hospital use|95% within 12% for BG $75 mg/dL|95% within 15% for BG $100 mg/dL|

||95% within 12 mg/dL for BG < 75 mg/dL|95% within 15 mg/dL for BG < 100 mg/dL|

||98% within 15% for BG $75 mg/dL|99% in A or B region of consensus error grid ‡|

||98% within 15 mg/dL for BG < 75 mg/dL||

|Home use|95% within 15%||

|CONTINUOUS GLUCOSE| |---|

|MONITORING DEVICES|

|See|

|Recommendations| |---|

|7.15 Recommend real-time CGM|

|(rtCGM) A or intermittently scanned|

|CGM (isCGM) for diabetes manage-|

|ment to youth C and adults B with dia-|

|betes on any type of insulin therapy.|

|The choice of CGM device should be|

|made based on the individual's circum-|

|stances, preferences, and needs.|

|7.16 Consider using rtCGM and isCGM|

|in adults with type 2 diabetes treated|

|with glucose-lowering medications other|

|than insulin to achieve and maintain indi-|

|vidualized glycemic goals. The choice of|

|device should be made based on the in-|

|dividual's circumstances, preferences,|

|and needs. B|

|7.17 In people with diabetes on insulin|

|therapy, rtCGM devices should be used|

|as close to daily as possible for maximal|

|benefit. A isCGM devices should be|

|scanned frequently, at minimum once|

|every 8 h, to avoid gaps in data. A Peo-|

|ple with diabetes should have unin-|

|terrupted access to their supplies to|

|minimize gaps in CGM. A|

|7.18 CGM can help achieve glycemic|

|goals (e.g., time in range and time|

|above range) A and A1C goal B in type 1|

|diabetes and pregnancy and may be|

|beneficial for other types of diabetes in|

|pregnancy. E|

|7.19 In circumstances when consistent|

|use of CGM is not feasible, consider pe-|

|riodic use of personal or professional|

|CGM to adjust medication and/or life-|

|style. C|

|7.20|

|Substance or condition|Effects on glucose values measured by blood glucose meters| |---|---|

|Maltose*|Falsely higher blood glucose values|

|Galactose|Falsely higher blood glucose values|

|Xylose|Falsely higher blood glucose values|

|N-Acetylcysteine †|Falsely higher blood glucose values|

|Acetaminophen|Falsely higher blood glucose values at low blood glucose levels|

|Dopamine|Falsely higher blood glucose values at low blood glucose levels|

|Furosemide|Falsely lower blood glucose values|

|Vitamin C|Falsely lower or higher blood glucose values|

|Uric acid|Falsely higher blood glucose values at very low or|

||very high glucose levels|

|Hematocrit (high)|Falsely higher blood glucose values|

|Hematocrit (low)|Falsely lower blood glucose values|

|(MDI), insulin pens are preferred in| |---|

|most cases. Still, insulin syringes may|

|be used for insulin delivery considering|

|individual and caregiver preference, in-|

|sulin type, availability in vials, dosing|

|therapy, cost, and self-management ca-|

|pabilities. C|

|7.23 Insulin pens or insulin injection aids|

|are recommended for people with|

|dexterity issues or vision impairment|

|or when decided by shared decision-|

|making to facilitate the accurate dos-|

|ing and administration of insulin. C|

|7.24 Offer connected insulin pens for|

|people with diabetes taking multiple|

|daily insulin injections. B|

|7.25 FDA-approved insulin dose calcula-|

|tors/decision support systems may be|

|helpful for calculating insulin doses. B|

|INSULIN DELIVERY|

|Insulin Syringes and Pens|

|Recommendations|

|7.22 For people with insulin-requiring|

|diabetes on multiple daily injections|

|Medication|Systems affected|Effect| |---|---|---|

|Acetaminophen|||

|> 4 g/day|Dexcom G6, Dexcom G7|Dexcom G6, Dexcom G7|

|Any dose|Medtronic Guardian|Medtronic Guardian|

|Ascorbic acid (vitamin C), > 500 mg/day|FreeStyle Libre 14 day, FreeStyle Libre 2,|Higher sensor readings than actual glucose|

||FreeStyle Libre 3|FreeStyle Libre 3|

|Ascorbic acid (vitamin C), > 1,000 mg/day|FreeStyle Libre 2 Plus, FreeStyle Libre 3 Plus|Higher sensor readings than actual glucose|

|Hydroxyurea|Dexcom G6, Dexcom G7, Medtronic Guardian|Higher sensor readings than actual glucose|

|Mannitol (intravenously or as peritoneal|Senseonics Eversense|Senseonics Eversense|

|dialysis solution)|||

|Sorbitol (intravenously or as peritoneal|Senseonics Eversense|Senseonics Eversense|

|||Possible safety concerns and considerations|||• Contraindicated for use in combination with monoamine oxidase|inhibitors|• Caution with cardiovascular disease|• Do not use if at high risk for glaucoma due to risk of acute angle-|closure glaucoma|• Potential malabsorption of fat-soluble vitamins (A, D, E, K) and of|certain medications (e.g., cyclosporine, thyroid hormone,|anticonvulsants)|• Rare cases of severe liver injury reported|• Cholelithiasis|• Nephrolithiasis||• Contraindicated for use in combination with monoamine oxidase|inhibitors|• Birth defects|• Cognitive impairment|• Caution with cardiovascular disease|• Do not use if at high risk for glaucoma due to risk of acute angle-|closure glaucoma||• Contraindicated in people with unmanaged hypertension and/or|seizure disorders|• Contraindicated for use with chronic opioid therapy|• Acute angle-closure glaucoma|Black box warning:|• Risk of suicidal behavior/ideation in people younger than 24 years|old who have depression|• Hypoglycemia (with concomitant use of insulin or sulfonylurea)|• Pancreatitis has been reported in clinical trials, but causality has not|been established; discontinue if pancreatitis is suspected.|• Use caution in people with kidney disease when initiating or increas-|ing dose due to increased risk of gastrointestinal side effects and|potential risk of acute kidney injury from dehydration|Continued on p. S173| |---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

|||Common side effects|||Dry mouth, insomnia,|dizziness, irritability,|increased blood pressure,|elevated heart rate||Abdominal pain, flatulence,|fecal urgency||||||Constipation, paresthesia,|insomnia,|nasopharyngitis,|xerostomia, increased|blood pressure,|nephrolithiasis|||Constipation, nausea,|headache, xerostomia,|insomnia, elevated heart|rate and blood pressure||||Gastrointestinal side effects|(nausea, vomiting,|diarrhea, esophageal|reflux)||||

|Time frame|for weight loss|(weeks)*|||28|||||52|||||||56||||||||56|||||||56|||||||

|1-Weight management pharmacotherapy|Treatment arm; weight loss|Medication name from baseline|Sympathomimetic amine anorectic:|approved for short-term use only|Phentermine (160,161) † • 15 mg q.d.; 7.4%|• 7.5 mg q.d.; 6.6%|• Placebo; 2.3%||Lipase inhibitor|Orlistat (4,162) ‡ • 120 mg t.i.d.; 9.6%|• Placebo; 5.6%||||Sympathomimetic amine anorectic/|antiepileptic combination|Phentermine/topiramate ER (49,163) § • 15 mg/92 mg q.d.; 9.8%|• 7.5 mg/46 mg q.d.; 7.8%|• Placebo; 1.2%||||Opioid antagonist/antidepressant|combination|Naltrexone/bupropion ER (13,164) • 16 mg/180 mg b.i.d.; 5%|• Placebo; 1.8%|||||Glucagon-like peptide 1 receptor agonist|Liraglutide (14,51,165)jj • 3.0 mg q.d.; 6%|4.7% • 1.8 mg q.d.;|• Placebo; 2%|||||

||Typical adult|AWP (median and range|NADAC (median and| |---|---|---|---|

|Sympathomimetic amine anorectic: approved||||

|for short-term use only||||

|Phentermine|8-37.5 mg q.d.|$43 ($9-$98)*|$3 ($3, $79)*|

|Lipase inhibitor||||

|Orlistat|60 mg t.i.d. (OTC)|$58 ($41-$82)|NA|

||120 mg t.i.d. (Rx)|$843 ($781-$904)|$677 ($629-$724)|

|Sympathomimetic amine anorectic/||||

|antiepileptic combination||||

|Phentermine/topiramate ER|7.5 mg/46 mg q.d.|$237|NA|

|Opioid antagonist/antidepressant combination||||

|Naltrexone/bupropion ER|16 mg/180 mg b.i.d.|$750|NA|

|Glucagon-like peptide 1 receptor agonist||||

|Liraglutide †|3 mg q.d.|$1,619|$1,296|

|Semaglutide|2.4 mg once weekly|$1,619|$1,296|

|Dual glucose-dependent insulinotropic||||

|polypeptide and glucagon-like peptide 1||||

|receptor agonist||||

|Tirzepatide|5, 10, or 15 mg once weekly|$1,272|$1,017|

|References 1. Narayan KMV, Boyle JP, Thompson TJ, Gregg EW, Williamson DF. Effect of BMI on lifetime risk for diabetes in the U.S. Diabetes Care 2007;30: 1562-1566 2. Knowler WC, Barrett-Connor E, Fowler SE, et al.; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403 3. Garvey WT, Ryan DH, Henry R, et al. Prevention of type 2 diabetes in subjects with prediabetes and metabolic syndrome treated with phentermine and topiramate extended release. Diabetes Care 2014;37:912-921 4. Torgerson JS, Hauptman J, Boldrin MN, Sj€ ostr€ om L. XENical in the Prevention of Diabetes in Obese Subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004;27:155-161 5. Le Roux CW, Astrup A, Fujioka K, et al.; SCALE Obesity Prediabetes NN8022-1839 Study Group. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet 2017;389:1399-1409 6. Booth H, Khan O, Prevost T, et al. Incidence of type 2 diabetes after bariatric surgery: population-based matched cohort study. Lancet Diabetes Endocrinol 2014;2:963-968 7. Pastors JG, Warshaw H, Daly A, Franz M, Kulkarni K. The evidence for the effectiveness of medical nutrition therapy in diabetes management. Diabetes Care 2002;25:608-613 8. Galaviz KI, Weber MB, Suvada K, et al. Interventions for reversing prediabetes: a systematic review and meta-analysis. Am J Prev Med 2022; 62:614-625 9. Jackness C, Karmally W, Febres G, et al. Very low-calorie diet mimics the early beneficial effect of Roux-en-Y gastric bypass on insulin sensitivity and b-cell function in type 2 diabetic patients. Diabetes 2013;62:3027-3032 10. Rothberg AE, McEwen LN, Kraftson AT, Fowler CE, Herman WH. Very-low-energy diet for type 2 diabetes: an underutilized therapy? J Diabetes Complications 2014;28:506-510 11. Hollander PA, Elbein SC, Hirsch IB, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study. Diabetes Care 1998;21:1288-1294 12. Garvey WT, Ryan DH, Bohannon NJV, et al. Weight-loss therapy in type 2 diabetes: effects of phentermine and topiramate extended release. Diabetes Care 2014;37:3309-3316 13. Hollander P, Gupta AK, Plodkowski R, et al.; COR-Diabetes Study Group. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care 2013;36:4022-diabetesjournals.org/care Obesity and Weight Management cardiovascular outcomes in obesity without dia-15. Rubino F, Nathan DM, Eckel RH, et al.; Delegates of the 2nd Diabetes Surgery Summit. Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by international diabetes organizations. Obes Surg 2017;27:2-21 16. UKPDS Group. UK Prospective Diabetes Study 7: response of fasting plasma glucose to diet therapy in newly presenting type II diabetic patients. Metabolism 1990;39:905-912 17. Goldstein DJ. Beneficial health effects of modest weight loss. Int J Obes Relat Metab Disord 1992;16:397-415 18. Steven S, Hollingsworth KG, Al-Mrabeh A, et al. Very low-calorie diet and 6 months of weight stability in type 2 diabetes: pathophysiological changes in responders and nonresponders. Diabetes Care 2016;39:808-815. Diabetes Care 2016;41:1321 19. Jensen MD, Ryan DH, Apovian CM, et al.; Obesity Society. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol 2014;63:2985-3023 20. Lean ME, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet 2018;391:541-551 21. Lean MEJ, Leslie WS, Barnes AC, et al. Durability of a primary care-led weight-management inter-vention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol 2019;7:344-355 22. Kahan S, Fujioka K. Obesity pharmacotherapy in patients with type 2 diabetes. Diabetes Spectr 2017;30:250-257 23. Wiggins T, Guidozzi N, Welbourn R, Ahmed AR, Markar SR. Association of bariatric surgery with all-cause mortality and incidence of obesity-related disease at a population level: a sys-tematic review and meta-analysis. PLoS Med 2020;17:e1003206 24. Aminian A, Wilson R, Zajichek A, et al. Cardiovascular outcomes in patients with type 2 diabetes and obesity: comparison of gastric bypass, sleeve gastrectomy, and usual care. Diabetes Care 2021;44:2552-2563 25. World Health Organization. Obesity. 2023. Accessed 21 August 2024. Available from https:// www.who.int/health-topics/obesity#tab=tab_1 26. WHO Expert Consultation. Appropriate body-mass index for Asian populations and its imp-lications for policy and intervention strategies. Lancet 2004;363:157-163 27. Araneta MRG, Kanaya AM, Hsu WC, et al. Optimum BMI cut points to screen Asian Americans for type 2 diabetes. Diabetes Care 2015;38:814-820 28. Aggarwal R, Bibbins-Domingo K, Yeh RW, et al. Diabetes screening by race and ethnicity in the United States: equivalent body mass index and age thresholds. Ann Intern Med 2022;175:765-773 29. Rubino F, Batterham RL, Koch M, et al. Lancet Diabetes & Endocrinology Commission on the Definition and Diagnosis of Clinical Obesity. Lancet Diabetes Endocrinol 2023;11:226-228 30. Klein S, Gastaldelli A, Yki-J€ arvinen H, Scherer 32. Moore CH, Oliver TL, Randolph J, Dowdell EB. Interventions for reducing weight bias in healthcare providers: an interprofessional systematic review and meta-analysis. Clin Obes 2022;12:e12545 33. American Medical Association. AMA Manual of Style: a Guide for Authors and Editors. Oxford University Press, 2019 34. American Medical Association. Person-First Language for Obesity H-440.821. Accessed 21 August 2024. Available from https://policysearch. ama-assn.org/policyfinder/detail/obesity?uri=% 2FAMADoc%2FHOD.xml-H-440.821.xml 35. Kushner RF, Batsis JA, Butsch WS, et al. Weight history in clinical practice: the state of the science and future directions. Obesity (Silver Spring) 2020;28:9-17 36. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol 2017; 70:776-803 37. Bosch X, Moncl us E, Escoda O, et al. Unintentional weight loss: clinical characteristics and outcomes in a prospective cohort of 2677 patients. PLoS One 2017;12:e0175125 38. Wilding JPH. The importance of weight management in type 2 diabetes mellitus. Int J Clin Pract 2014;68:682-691 39. Van Gaal L, Scheen A. Weight management in type 2 diabetes: current and emerging approaches to treatment. Diabetes Care 2015;38:1161-1172 40. Warren J, Smalley B, Barefoot N. Higher motivation for weight loss in African American than Caucasian rural patients with hypertension and/or diabetes. Ethn Dis 2016;26:77-84 41. Stoops H, Dar M. Equity and obesity treatment-expanding Medicaid-covered interventions. N Engl J Med 2023;388:2309-2311 42. Rothberg AE, McEwen LN, Kraftson AT, et al. Impact of weight loss on waist circumference and the components of the metabolic syndrome. BMJ Open Diabetes Res Care 2017;5:e000341 43. Wing RR, Bolin P, Brancati FL, et al.; Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013;369:145-154 44. Look AHEAD Research Group. Eight-year weight losses with an intensive lifestyle inter-vention: the Look AHEAD study. Obesity (Silver Spring) 2014;22:5-13 45. Gregg E, Jakicic J, Blackburn G, et al.; Look AHEAD Research Group. Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial. Lancet Diabetes Endocrinol 2016;4:913-921 46. Baum A, Scarpa J, Bruzelius E, Tamler R, Basu S, Faghmous J. Targeting weight loss interventions to reduce cardiovascular complications of type 2 diabetes: a machine learning-based post-hoc analysis of heterogeneous treatment effects in the betes. N Engl J Med 2023;389:2221-2232 96. Neeland IJ, Linge J, Birkenfeld AL. Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. Diabetes Obes Metab 2024;26(Suppl 4):16-27 97. Locatelli JC, Costa JG, Haynes A, et al. Incretin-based weight loss pharmacotherapy: can resistance exercise optimize changes in body composition? Diabetes Care 2024;47:1718-1730 98. Lau S, Pek K, Chew J, et al. The Simplified Nutritional Appetite Questionnaire (SNAQ) as a screening tool for risk of malnutrition: optimal cutoff, factor structure, and validation in healthy community-dwelling older adults. Nutrients 2020; 12:2885 99. Yu SCY, Khow KSF, Jadczak AD, Visvanathan R. Clinical screening tools for sarcopenia and its management. Curr Gerontol Geriatr Res 2016; 2016:5978523 100. BAPEN. Introducing 'MUST.' Accessed 17 September 2024. Available from https://www. bapen.org.uk/must-and-self-screening/introducing-must/ 101. Fujioka K, O'Neil PM, Davies M, et al. Early weight loss with liraglutide 3.0 mg predicts 1-year weight loss and is associated with im-provements in clinical markers. Obesity (Silver Spring) 2016;24:2278-2288 102. Fujioka K, Plodkowski R, O'Neil PM, Gilder K, Walsh B, Greenway FL. The relationship between early weight loss and weight loss at 1 year with naltrexone ER/bupropion ER combination therapy. Int J Obes (Lond)2016;40:1369-1375 103. Wilding JPH, Batterham RL, Davies M, et al.; STEP 1 Study Group. Weight regain and cardio-metabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab 2022;24:1553-1564 104. Rubino D, Abrahamsson N, Davies M, et al.; STEP 4 Investigators. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA 2021;325:1414-1425 105. Aronne LJ, Sattar N, Horn DB, et al.; SURMOUNT-4 Investigators. Continued treatment with tirzepatide for maintenance of weight redu-ction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA 2024;331:38-48 106. Sullivan S. Endoscopic medical devices for primary obesity treatment in patients with diabetes. Diabetes Spectr 2017;30:258-264 107. Kahan S, Saunders KH, Kaplan LM. Combining obesity pharmacotherapy with endoscopic bariatric and metabolic therapies. Techniques Innovations Gastrointest Endosc 2020;22:154-158 108. Eisenberg D, Shikora SA, Aarts E, et al. 2022 American Society for Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO): indications for metabolic and bariatric surgery. Surg Obes Relat Dis 2022;18:1345-1356 386:964-973 111. Sj€ ostr€ om L, Peltonen M, Jacobson P, et al. Association of bariatric surgery with long-term remission of type 2 diabetes and with micro-vascular and macrovascular complications. JAMA 2014;311:2297-2304 112. Sj€ ostr€ om L, Lindroos A-K, Peltonen M, et al.; Swedish Obese Subjects Study Scientific Group. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004;351:2683-2693 113. Adams TD, Davidson LE, Litwin SE, et al. Health benefits of gastric bypass surgery after 6 years. JAMA 2012;308:1122-1131 114. Sj€ ostr€ om L, Gummesson A, Sj€ ostr€ om CD, et al.; Swedish Obese Subjects Study. Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial. Lancet Oncol 2009;10:653-662 115. Sj€ ostr€ om L, Peltonen M, Jacobson P, et al. Bariatric surgery and long-term cardiovascular events. JAMA 2012;307:56-65 116. Arterburn DE, Olsen MK, Smith VA, et al. Association between bariatric surgery and long-term survival. JAMA 2015;313:62-70 117. Sheng B, Truong K, Spitler H, Zhang L, Tong X, Chen L. The long-term effects of bariatric surgery on type 2 diabetes remission, microvascular and macrovascular complications, and mortality: a systematic review and meta-analysis. Obes Surg 2017;27:2724-2732 118. Fisher DP, Johnson E, Haneuse S, et al. Association between bariatric surgery and macro-vascular disease outcomes in patients with type 2 diabetes and severe obesity. JAMA 2018;320: 1570-1582 119. Billeter AT, Scheurlen KM, Probst P, et al. Meta-analysis of metabolic surgery versus medical treatment for microvascular complications in patients with type 2 diabetes mellitus. Br J Surg 2018;105:168-181 120. Sj€ ostr€ om L, Narbro K, Sj€ ostr€ om CD, et al.; Swedish Obese Subjects Study. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357:741-752 121. Aminian A, Zajichek A, Arterburn DE, et al. Association of metabolic surgery with major adverse cardiovascular outcomes in patients with type 2 diabetes and obesity. JAMA 2019;322: 1271-1282 122. Syn NL, Cummings DE, Wang LZ, et al. Association of metabolic-bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174 772 participants. Lancet 2021;397:1830-1841 123. Verrastro O, Panunzi S, Castagneto-Gissey L, et al. Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-of nonalcoholic steatohepatitis and regression of fibrosis. Gastroenterology 2020;159:1290-1301 126. Li Y, Gu Y, Jin Y, Mao Z. Is bariatric surgery effective for Chinese patients with type 2 diabetes mellitus and body mass index < 35 kg/m 2 ? A systematic review and meta-analysis. Obes Surg 2021;31:4083-4092 127. McTigue KM, Wellman R, Nauman E, et al.; PCORnet Bariatric Study Collaborative. Comparing the 5-year diabetes outcomes of sleeve gastrectomy and gastric bypass: the national Patient-Centered Clinical Research Network (PCORNet) bariatric study. JAMA Surg 2020;155:e200087 128. Sj€ oholm K, Pajunen P, Jacobson P, et al. Incidence and remission of type 2 diabetes in relation to degree of obesity at baseline and 2 year weight change: the Swedish Obese Subjects (SOS) study. Diabetologia 2015;58:1448-1453 129. Arterburn DE, Bogart A, Sherwood NE, et al. A multisite study of long-term remission and relapse of type 2 diabetes mellitus following gastric bypass. Obes Surg 2013;23:93-102 130. Brethauer SA, Aminian A, Romero-Talam as H, et al. Can diabetes be surgically cured? Long-term metabolic effects of bariatric surgery in obese patients with type 2 diabetes mellitus. Ann Surg 2013;258:628-636 131. Hariri K, Guevara D, Jayaram A, Kini SU, Herron DM, Fernandez-Ranvier G. Preoperative insulin therapy as a marker for type 2 diabetes remission in obese patients after bariatric surgery. Surg Obes Relat Dis 2018;14:332-337 132. Yu H, Di J, Bao Y, et al. Visceral fat area as a new predictor of short-term diabetes remission after Roux-en-Y gastric bypass surgery in Chinese patients with a body mass index less than 35 kg/m2. Surg Obes Relat Dis 2015;11:6-11 133. Kirwan JP, Aminian A, Kashyap SR, Burguera B, Brethauer SA, Schauer PR. Bariatric surgery in obese patients with type 1 diabetes. Diabetes Care 2016;39:941-948 134. Fouse T, Schauer P. The socioeconomic impact of morbid obesity and factors affecting access to obesity surgery. Surg Clin North Am 2016;96:669-679 135. Lauren BN, Lim F, Krikhely A, et al. Estimated cost-effectiveness of medical therapy, sleeve gastrectomy, and gastric bypass in patients with severe obesity and type 2 diabetes. JAMA Netw Open 2022;5:e2148317 136. Young MT, Gebhart A, Phelan MJ, Nguyen NT. Use and outcomes of laparoscopic sleeve gas-trectomy vs laparoscopic gastric bypass: analysis of the American College of Surgeons NSQIP. J Am Coll Surg 2015;220:880-885 137. Aminian A, Brethauer SA, Kirwan JP, Kashyap SR, Burguera B, Schauer PR. How safe is metabolic/diabetes surgery? Diabetes Obes Metab 2015;17:198-201 138. Arterburn DE, Courcoulas AP. Bariatric surgery for obesity and metabolic conditions in adults. BMJ 2014;349:g3961 Obesity and Weight Management 139. diabetesjournals.org/care Bariatric Surgery Center Network: laparoscopic sleeve gastrectomy has morbidity and effectiveness positioned between the band and the bypass. Ann Surg 2011;254:410-420 142. Nguyen NT, Slone JA, Nguyen X-MT, Hartman JS, Hoyt DB. A prospective randomized trial of laparoscopic gastric bypass versus laparo-scopic adjustable gastric banding for the treatment of morbid obesity: outcomes, quality of life, and costs. Ann Surg 2009;250:631-641 143. Courcoulas AP, King WC, Belle SH, et al. Seven-year weight trajectories and health out-comes in the Longitudinal Assessment of Bariatric Surgery (LABS) study. JAMA Surg 2018;153: 427-434 144. Birkmeyer JD, Finks JF, O'Reilly A, et al.; Michigan Bariatric Surgery Collaborative. Surgical skill and complication rates after bariatric surgery. N Engl J Med 2013;369:1434-1442 145. Mechanick JI, Apovian C, Brethauer S, et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures-2019 update: cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists-executive summary. Endocr Pract 2019;25:1346-1359 146. Service GJ, Thompson GB, Service FJ, Andrews JC, Collazo-Clavell ML, Lloyd RV. Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery. N Engl J Med 2005;353:249-254 147. Sheehan A, Patti ME. Hypoglycemia after upper gastrointestinal surgery: clinical approach to assessment, diagnosis, and treatment. Diabetes Metab Syndr Obes 2020;13:4469-4482 148. Lee D, Dreyfuss JM, Sheehan A, Puleio A, Mulla CM, Patti ME. Glycemic patterns are distinct in post-bariatric hypoglycemia after gastric bypass (PBH-RYGB). J Clin Endocrinol Metab 2021; 106:2291-2303 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2025 Diabetes Care 2025;48(Suppl. 1):S181-S206 | https://doi.org/10.2337/dc25-S009 American Diabetes Association Professional Practice Committee* A 9.3 Early use of continuous glucose monitoring is recommended for adults with type 1 diabetes to improve glycemic outcomes and quality of life and to minimize hypoglycemia. B 9.4 Automated insulin delivery systems should be offered to all adults with type 1 diabetes. A 9.5 To improve glycemic outcomes and quality of life and to minimize hypogly-cemia risk, most adults with type 1 diabetes should receive education on how to match mealtime insulin doses to carbohydrate intake and fat and protein in-take. They should also be taught how to modify the insulin dose (correction dose) based on concurrent glycemia, glycemic trends (if available), sick-day man-agement, and anticipated physical activity. B 9.6 Insulin treatment plan and insulin-taking behavior should be reevaluated A complete list of members of the American Diabetes Association Professional Practice Committee can be found at https://doi.org/10.2337/dc25-SINT. Duality of interest information for each author is available at https://doi.org/10.2337/dc25-SDIS. Suggested citation: American Diabetes Association Professional Practice Committee. 9. Pharmacologic approaches to glycemic treatment: Standards of Care in Diabetes-2025. Diabetes Care 2025;48 109. centre, randomised controlled trial. Lancet 2015; (Suppl. 1):S181-S206|S179|| |---|---|---|

|4029|PE. Why does obesity cause diabetes? Cell Metab|Look AHEAD trial. Lancet Diabetes Endocrinol|

|14. Davies MJ, Bergenstal R, Bode B, et al.;|2022;34:11-20|2017;5:808-815|

|NN8022-1922 Study Group. Efficacy of liraglutide|31. Lawrence BJ, Kerr D, Pollard CM, et al.|47. Schauer PR, Bhatt DL, Kirwan JP, et al.;|

|for weight loss among patients with type 2|Weight bias among health care professionals: a|STAMPEDE Investigators. Bariatric surgery versus|

|diabetes: the SCALE diabetes randomized clinical|systematic review and meta-analysis. Obesity|intensive medical therapy for diabetes-5-year|

|trial. JAMA 2015;314:687-699|(Silver Spring) 2021;29:1802-1812|outcomes. N Engl J Med 2017;376:641-651|

|diabetesjournals.org/care|diabetesjournals.org/care|diabetesjournals.org/care|diabetesjournals.org/care|||||||||||||||||||||||Pharmacologic Approaches to Glycemic Treatment|S183||||||||||||| |---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

|Adjusting doses||Mealtime insulin: if carbohydrate|counting is accurate, change ICR if|glucose after meal consistently out|of target.|Correction insulin: adjust ISF and/or|target glucose if correction does|not consistently bring glucose into|range.|Basal rates: adjust based on overnight,|fasting or daytime glucose outside|of activity of URAA/RAA bolus.|AID systems: carbohydrate ratio, insulin|on board, targets, and/or ISF may|be adjusted, depending on the|system. Make sure to review and|adjust manual mode settings, if|available.|Mealtime insulin: if carbohydrate|counting is accurate, change ICR|if glucose after meal consistently|out of target.|Correction insulin: adjust ISF and/or|target glucose if correction does|not consistently bring glucose|into range.|LAA: based on overnight or fasting|glucose or daytime glucose|outside of activity time course, or|URAA or RAA injections.|Pre-breakfast RAA: based on BGM after|breakfast or before lunch.|Pre-lunch RAA: based on BGM after|lunch or before dinner.|Pre-dinner RAA: based on BGM after|dinner or at bedtime.|Evening N: based on fasting or|overnight BGM.|Continued on p. S184|

|Disadvantages||Most expensive plan.|Must continuously wear one or more|devices.|Risk of rapid development of ketosis or|DKA with interruption of insulin|delivery.|Potential reactions to adhesives and|site infections.|Most technically complex approach|(harder for people with lower|numeracy or literacy skills).|||||||At least four daily injections.|Most costly insulins.|Smallest increment of insulin is 1 unit|(0.5 unit with some pens).|LAAs may not cover strong dawn|phenomenon (rise in glucose in|early morning hours) as well as|pump therapy.|||||Shorter duration RAA may lead to basal|deficit during day; may need|twice-daily N.|Greater risk of nocturnal hypoglycemia|with N.|Requires relatively consistent|mealtimes and carbohydrate|intake.||

|Advantages||Can adjust basal rates for varying|insulin sensitivity by time of|day, for exercise, and for sick|days.|Flexibility in meal timing and|content.|Pump can deliver insulin in|increments of fractions of units.|Potential for integration with CGM|for AID systems.|TIR % highest and TBR % lowest|with: hybrid closed-loop > low-|glucose suspend > CGM-|augmented open-loop > BGM-|augmented open-loop.|||Can use pens for all components.|Flexibility in meal timing and|content.|Insulin analogs cause less|hypoglycemia than human|insulins.|||||||May be feasible if unable to|carbohydrate count.|All meals have RAA coverage.|N is less expensive than LAAs.||||||

|Plans Timing and distribution|Plans that more closely mimic normal insulin secretion|Insulin pump therapy (also including Basal delivery of URAA or RAA;|AID systems: hybrid closed-generally 30-50% of TDD.|loop, low-glucose suspend, Mealtime and correction: URAA or|CGM-augmented open-loop, RAA by bolus based on ICR|BGM-augmented open-loop) and/or ISF and target glucose,|with premeal insulin $15 min|before eating.|||||||||||MDI: LAA 1 flexible doses of URAA LAA once daily (insulin detemir or|or RAA at meals insulin glargine may require|twice-daily dosing); generally|30-50% of TDD.|Mealtime and correction: URAA or|RAA based on ICR and/or ISF|and target glucose.|||||MDI plans with less flexibility|Four injections daily with fixed Pre-breakfast: RAA $20% of TDD.|doses of N and RAA Pre-lunch: RAA $10% of TDD.|Pre-dinner: RAA $10% of TDD.|Bedtime: N $50% of TDD.||||||

|Medication|Glucose-||CV effects|Kidney effects| |---|---|---|---|---|

|(route of|lowering|Hypoglycemia||MASH|

|Progression of CKD Neutral Benefit: canagliflozin, dapagliflozin, empagliflozin Benefit for renal end points in CVOTs, driven by albuminuria outcomes: dulaglutide, liraglutide, semaglutide (SQ) Demonstrated benefit for progression of CKD for semaglutide (SQ) Under investigation Neutral Increased risk Neutral Neutral Benefit: canagliflozin, dapagliflozin, empagliflozin, ertugliflozin Neutral Under investigation Neutral (potential risk: saxagliptin) Neutral Neutral Neutral Neutral CKD, chronic kidney disease; CV, cardiovascular; DKA, diabetic ketoacidosis; DPP-4, dipeptidyl peptidase 4; eGFR, estimated glomerular filtration Dosing/use considerations* Metformin (oral) High No Neutral (potential for modest loss) Potential benefit • Contraindicated with eGFR < 30 mL/min/ 1.73 m 2 Neutral • GI side effects: mitigate with slow dose titration, extended-release formulations, and administration with food. • Potential for vitamin B12 deficiency: monitor and replete as appropriate. SGLT2 inhibitors (oral) Intermediate to high No Loss (intermediate) Benefit: canagliflozin, empagliflozin • See labels of individual agents for dosage considerations for kidney function • Glucose-lowering effect is minimal at eGFR < 45 mL/min/1.73 m 2 and lower; continue for cardiovascular and kidney benefit until dialysis or transplantation Unknown • DKA risk in individuals with insulin deficiency (rare in T2D): discontinue, evaluate, and treat promptly if suspected; be aware of predisposing risk factors and clinical presentations (including euglycemic DKA); mitigate risk with sick-day planning; discontinue before scheduled surgery (e.g., 3-4 days), during critical illness, or during prolonged fasting. • Genital mycotic infections: mitigate risk with genital hygiene and avoid use in high-risk individuals. • Necrotizing fasciitis of the perineum (Fournier gangrene): rare; prompt treatment if suspected. • Intravascular volume depletion: attention to volume status and blood pressure, particularly when ill or fasting; adjust other volume-contracting agents as applicable; monitor kidney function upon initiation. GLP-1 RAs (SQ; semaglutide also available in oral formulation) High to very high No Loss (intermediate to very high) Benefit: dulaglutide, liraglutide, semaglutide (SQ) • See labels of individual agents for dosage considerations for kidney function • No dose adjustment for dulaglutide, liraglutide, or semaglutide • Monitor kidney function when initiating or escalating doses in individuals with kidney impairment reporting severe adverse GI reactions Potential benefit • Thyroid C-cell tumors identified in rodents; human relevance not determined. • Ileus: risk level is not well established; provide guidance on discontinuation prior to surgical procedures. • Pancreatitis: acute pancreatitis has been reported, but causality has not been established. Do not initiate if at high risk for pancreatitis, and discontinue if pancreatitis is suspected. • Biliary disease: evaluate for gallbladder disease if cholelithiasis or cholecystitis is suspected; avoid use in at-risk individuals. • Diabetic retinopathy: close monitoring of retinopathy in those at high risk (older individuals and those with longer duration of T2D [≥10 years]). • Impact on drug absorption: orally administered drug absorption may be impaired during dose titration (including of oral contraceptives). • GI side effects: counsel on potential for GI side effects; provide guidance on dietary modifications to mitigate GI side effects (reduction in meal size, mindful eating practices [e.g. stop eating once full] , decreasing intake of high-fat or spicy food); consider slower dose titration for those experiencing GI challenges. Not recommended for individuals with gastroparesis. Neutral: exenatide once weekly, lixisenatide Dual GIP and GLP-1 RA (SQ) Very high No Loss (very high) Under investigation • See labels of individual agents for dosage considerations for kidney function • No dose adjustment • Monitor kidney function when initiating or escalating doses in individuals with kidney impairment reporting severe adverse GI reactions Potential benefit DPP-4 inhibitors (oral) Intermediate No Neutral Neutral • Dose adjustment required based on kidney function (sitagliptin, saxagliptin, alogliptin) • No dose adjustment required for linagliptin Unknown • Pancreatitis has been reported, but causality has not been established. Discontinue if pancreatitis is suspected. • Postmarketing concerns about joint pain (consider discontinuing if debilitating and other treatment options are feasible) and bullous pemphigoid (discontinue if suspected). Pioglitazone (oral) High No Gain Potential benefit • No dose adjustment required • Generally not recommended in kidney impairment due to potential for fluid retention Potential benefit • Increased risk of HF and fluid retention. Do not use in the setting of HF. • Risk of bone fractures. • Bladder cancer: do not use in individuals with active bladder cancer, and use caution in those with prior history of bladder cancer. Sulfonylureas (2nd generation) (oral) High Yes Gain Neutral • Glyburide: generally not recommended in CKD • Glipizide and glimepiride: initiate conservatively to avoid hypoglycemia Unknown • FDA Special Warning on increased risk of CV mortality based on studies of an older sulfonylurea (tolbutamide); glimepiride shown to be CV safe (see text). • Use with caution in individuals at risk for hypoglycemia, particularly if in combination with insulin. Insulin (human) (SQ; regular insulin also available as inhaled formulation) High to very high Yes Gain Neutral • Lower insulin doses required with a decrease in eGFR; titrate per clinical response Unknown • Injection site reactions • Higher risk of hypoglycemia with human insulin (NPH or premixed formulations) vs. analogs • Risk of hypoglycemia and duration of activity increases with the severity of impaired kidney function. • Refer to device-specific instructions for insulins compatible with different delivery systems (i.e., pumps, connected insulin pens, insulin patches). Insulin (analogs) (SQ) rate; FDA, U.S. Food and Drug Administration; GI, gastrointestinal; GIP, glucose-dependent insulinotropic polypeptide; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HF, heart failure; MACE, major adverse cardiovascular events; MASH, metabolic dysfunction-associated steatohepa-titis; SGLT2, sodium-glucose cotransporter 2; SQ, subcutaneous; T2D, type 2 diabetes. *For agent-specific dosing recommendations, please re-Pharmacologic Approaches to Glycemic Treatment 2 Initiate appropriate starting dose for agent selected (varies within class) Start 10 units per day OR 0.1-0.2 units/kg per day Titrate to maintenance dose (varies within class) If on bedtime NPH, consider converting to twice-daily NPH plan Conversion based on individual needs and current glycemic management. The following is one possible approach: • Total dose = 80% of current bedtime NPH dose • 2/3 given in the morning • 1/3 given at bedtime • Titrate based on individualized needs Considerations for adding basal insulin 3 Stepwise doses of prandial insulin (i.e., two, then three additional injections) Consider self-mixed/split insulin plan Can adjust NPH and short/rapid-acting insulins separately • Total NPH dose = 80% of current NPH dose each injection or 10% of reduced NPH dose • Titrate each component of the plan based on individualized needs Consider twice-daily premixed insulin plan • Usually unit per unit at the same total insulin dose, but may require adjustment to individual needs fer to manufacturers' prescribing information. diabetesjournals.org/care at the same total Proceed to full basal-bolus plan (i.e., basal insulin and prandial insulin with • Add 4 units of short/rapid-acting insulin to each meal) • 2/3 given before breakfast • 1/3 given before dinner • Titrate based on individualized needs|S191| |---|---|

|Initiation and titration of prandial insulin 5,6|| |---|---|

|Usually one dose with the largest meal or meal with greatest PPG excursion;||

|prandial insulin can be dosed individually or mixed with NPH as appropriate||

|• 4 units per day or 10% of basal insulin dose||

|• If A1C < 8% ( < 64 mmol/mol), consider lowering the||

|basal dose by 4 units per day or 10% of basal dose|•|

|For hypoglycemia: determine cause; if no clear reason, lower dose by 10-20%| |---|

|Increase dose by 1-2 units insulin dose or 10-15%|

|twice weekly|

|For hypoglycemia: determine cause; if no clear|

|reason, lower corresponding dose by 10-20%|

|mmol/L]), or when a diagnosis of type 1 diabetes is a possibility.|

|2. When selecting GLP-1 RAs, consider individual preference, A1C lowering, weight-lowering effect, and frequency of injection. If CVD is present, consider GLP-1 RA with proven CVD benefit; oral or injectable|

|GLP-1 RAs are appropriate.|

|||Dosage strength/|Maximum approved|Median AWP|Median NADAC| |---|---|---|---|---|---|

|Biguanides|Metformin|500 mg (ER)|2,000 mg|$89 ($5, $6,719)|$3 ($3, $79)|

|||850 mg (IR)|2,550 mg|$108 ($4, $189)|$2|

|||1,000 mg (IR)|2,000 mg|$87 ($3, $146)|$1|

|||1,000 mg (ER)|2,000 mg|$1,884 ($242, $7,214)|$26 ($21, $31)|

|||500 mg (Sol)|2,000 mg|$1,144 ($810, $1478)|$427|

|Sulfonylureas (2nd generation)|Glimepiride|4 mg|8 mg|$73 ($71, $198)|$2|

||Glipizide|10 mg (IR)|40 mg|$72 ($67, $91)|$5|

|||10 mg (XL/ER)|20 mg|$48 ($46, $48)|$8|

||Glyburide|6 mg (micronized)|12 mg|$54 ($48, $71)|$13|

|||5 mg|20 mg|$82 ($63, $432)|$7|

|Thiazolidinedione|Pioglitazone|45 mg|45 mg|$348 ($7, $349)|$3|

|a-Glucosidase inhibitors|Acarbose|100 mg|300 mg|$106 ($104, $378)|$20|

||Miglitol|100 mg|300 mg|$294 ($241, $346)|$320|

|Meglitinides|Nateglinide|120 mg|360 mg|$155|$23|

||Repaglinide|2 mg|16 mg|$878 ($799, $897)|$26|

|DPP-4 inhibitors|Alogliptin|25 mg|25 mg|$234|$145|

||Linagliptin|5 mg|5 mg|$630|$503|

||Saxagliptin|5 mg|5 mg|$524 ($523, $524)|$165|

||Sitagliptin|100 mg|100 mg|$588|$550|

|SGLT2 inhibitors|Bexagliflozin|20 mg|20 mg|$47|NA|

||Canagliflozin|300 mg|300 mg|$718|$574|

||Dapagliflozin|10 mg|10 mg|$664|$352|

||Empagliflozin|25 mg|25 mg|$733|$586|

||Ertugliflozin|15 mg|15 mg|$428|$343|

|GLP-1 RAs|Dulaglutide|4.5 mg pen|4.5 mg ‡|$1,173|$941|

||Exenatide|10 mg pen|20 mg|$1,020|$818|

||Exenatide (ER)|2 mg pen|2 mg ‡|$993|$1,101|

||Liraglutide|18 mg/3 mL pen|1.8 mg|$929|$1,077|

||Semaglutide|2 mg pen|2 mg ‡|$1,162|$933|

|||14 mg (tablet)|14 mg|$1,162|$933|

|Dual GIP and GLP-1 RA|Tirzepatide|15 mg pen|15 mg ‡|$1,283|$1,030|

|Bile acid sequestrant|Colesevelam|625 mg tabs|3.75 g|$692 ($674, $712)|$47|

|||3.75 g suspension|3.75 g|$674 ($673, $675)|$115|

|Dopamine-2 agonist|Bromocriptine|0.8 mg|4.8 mg|$1,220|$981|

|Amylin mimetic|Pramlintide|120 mg pen|120 mg §|$2,952|NA|

|AWP, average wholesale price; DPP-4, dipeptidyl peptidase 4; ER and XL, extended release; GIP, glucose-dependent insulinotropic polypeptide;|AWP, average wholesale price; DPP-4, dipeptidyl peptidase 4; ER and XL, extended release; GIP, glucose-dependent insulinotropic polypeptide;|AWP, average wholesale price; DPP-4, dipeptidyl peptidase 4; ER and XL, extended release; GIP, glucose-dependent insulinotropic polypeptide;|AWP, average wholesale price; DPP-4, dipeptidyl peptidase 4; ER and XL, extended release; GIP, glucose-dependent insulinotropic polypeptide;|AWP, average wholesale price; DPP-4, dipeptidyl peptidase 4; ER and XL, extended release; GIP, glucose-dependent insulinotropic polypeptide;|AWP, average wholesale price; DPP-4, dipeptidyl peptidase 4; ER and XL, extended release; GIP, glucose-dependent insulinotropic polypeptide;|

|GLP-1||||||

|diabetesjournals.org/care||Pharmacologic Approaches to Glycemic Treatment|Pharmacologic Approaches to Glycemic Treatment|Pharmacologic Approaches to Glycemic Treatment| |---|---|---|---|---|

||||Median AWP|Median NADAC|

|||U-100 cartridge|$107 †|$86 †|

|||U-100 prefilled pen|$112 †|$90 †|

||Aspart ("faster acting product")|U-100 vial|$347|$278|

|||U-100 cartridge|$430|$344|

|||U-100 prefilled pen|$447|$357|

||Glulisine|U-100 vial|$102|$82|

|||U-100 prefilled pen|$132|$105|

||Inhaled insulin|Inhalation cartridges|$1,503|$1,298|

||Lispro|U-100 vial|$30 †|$24 †|

|||U-100 cartridge|$123|$98|

|||U-100 prefilled pen|$127 †|$102 †|

|||U-200 prefilled pen|$424|$339|

||Lispro-aabc|U-100 vial|$330|$263|

|||U-100 prefilled pen|$424|$339|

||Lispro follow-on product|U-100 vial|$118|$94|

|||U-100 prefilled pen|$151|$121|

|||U-100 prefilled pen|$73 ($54, $178)|$58|

|||U-100 prefilled pen|$93 ($73, $113)|$74 ($58, $91)|

|regular insulin|||||

|||U-500 prefilled pen|$230|$184|

|||U-100 prefilled pen|$142 †|$114 †|

|||U-200 prefilled pen|$85 †|$114 †|

||Glargine|U-100 vial|$77|$109 †|

|||U-100 prefilled pen|$77|$109 †|

|||U-300 prefilled pen|$152 †|$122 †|

||Glargine biosimilar/follow-on|U-100 vial|$118 ($76, † $323)|$61 †|

||products||||

|||U-100 prefilled pen|$118 ($74, † $323)|$59 ($59, † $209)|

|||U-100 prefilled pen|$112 † ‡|$90 † ‡|

||Lispro 50/50|U-100 vial|$102|NA|

|||U-100 prefilled pen|$127|$102|

||Lispro 75/25|U-100 vial|$102|$82|

||NPH/regular 70/30|U-100 vial|$58 ($54, $58)|$45 ($43, $46)|

|||U-100 prefilled pen|$73 ($73, $113) ‡|$74 ($58, $90) ‡|

|RA products||pen|||

||Glargine/lixisenatide|100/33 mg prefilled|$713|$570|

|||pen|||

|AWP, average wholesale price; GLP-1 RA, glucagon-like peptide 1 receptor agonist; NA, data not available; NADAC, National Average Drug Ac-|AWP, average wholesale price; GLP-1 RA, glucagon-like peptide 1 receptor agonist; NA, data not available; NADAC, National Average Drug Ac-|AWP, average wholesale price; GLP-1 RA, glucagon-like peptide 1 receptor agonist; NA, data not available; NADAC, National Average Drug Ac-|AWP, average wholesale price; GLP-1 RA, glucagon-like peptide 1 receptor agonist; NA, data not available; NADAC, National Average Drug Ac-|AWP, average wholesale price; GLP-1 RA, glucagon-like peptide 1 receptor agonist; NA, data not available; NADAC, National Average Drug Ac-|

|quisition Cost. AWP (195) and NADAC (196) prices as of 1 July 2024. *AWP or NADAC calculated as in Table 9.3. †Unbranded product prices|quisition Cost. AWP (195) and NADAC (196) prices as of 1 July 2024. *AWP or NADAC calculated as in Table 9.3. †Unbranded product prices|quisition Cost. AWP (195) and NADAC (196) prices as of 1 July 2024. *AWP or NADAC calculated as in Table 9.3. †Unbranded product prices|quisition Cost. AWP (195) and NADAC (196) prices as of 1 July 2024. *AWP or NADAC calculated as in Table 9.3. †Unbranded product prices|quisition Cost. AWP (195) and NADAC (196) prices as of 1 July 2024. *AWP or NADAC calculated as in Table 9.3. †Unbranded product prices|

|used when available. ‡AWP and NADAC data presented do not include human insulins (approximately $25/vial or $43/box of 5 pens) or se-|used when available. ‡AWP and NADAC data presented do not include human insulins (approximately $25/vial or $43/box of 5 pens) or se-|used when available. ‡AWP and NADAC data presented do not include human insulins (approximately $25/vial or $43/box of 5 pens) or se-|used when available. ‡AWP and NADAC data presented do not include human insulins (approximately $25/vial or $43/box of 5 pens) or se-|used when available. ‡AWP and NADAC data presented do not include human insulins (approximately $25/vial or $43/box of 5 pens) or se-|

|lect analog insulins (approximately $73/vial or $86/box of 5 pens) available at Walmart; median listed alone when only one product and/or|lect analog insulins (approximately $73/vial or $86/box of 5 pens) available at Walmart; median listed alone when only one product and/or|lect analog insulins (approximately $73/vial or $86/box of 5 pens) available at Walmart; median listed alone when only one product and/or|lect analog insulins (approximately $73/vial or $86/box of 5 pens) available at Walmart; median listed alone when only one product and/or|lect analog insulins (approximately $73/vial or $86/box of 5 pens) available at Walmart; median listed alone when only one product and/or|

|price.|||||

|References 1. Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group. Mortality in type 1 diabetes in the DCCT/EDIC versus the general population. Diabetes Care 2016;39:1378-1383 2. Lachin JM, Bebu I, Nathan DM, DCCT/EDIC Research Group. The beneficial effects of earlier versus later implementation of intensive therapy in type 1 diabetes. Diabetes Care 2021;44:2225-2230 3. Lachin JM, Nathan DM, DCCT/EDIC Research Group. Understanding metabolic memory: the 6-Month RCT: HCL Versus CSII Control Study Group. Improved glycemia with hybrid closed-loop versus continuous subcutaneous insulin infusion therapy: results from a randomized controlled trial. Diabetes Technol Ther 2023;25:1-12 31. Russell SJ, Beck RW, Damiano ER, et al.; Bionic Pancreas Research Group. Multicenter, randomized trial of a bionic pancreas in type 1 diabetes. N Engl J Med 2022;387:1161-1172 32. Burnside MJ, Lewis DM, Crocket HR, et al. Open-source automated insulin delivery in type 1 diabetes. N Engl J Med 2022;387:869-881 33. Burnside MJ, Lewis DM, Crocket HR, et al. Extended use of an open-source automated insulin delivery system in children and adults with type 1 diabetes: the 24-week continuation phase following the CREATE randomized controlled trial. Diabetes Technol Ther 2023;25:250-259 34. Brown SA, Kovatchev BP, Raghinaru D, et al.; iDCL Trial Research Group. Six-month randomized, multicenter trial of closed-loop control in type 1 diabetes. N Engl J Med 2019;381:1707-1717 35. Collyns OJ, Meier RA, Betts ZL, et al. Improved glycemic outcomes with Medtronic MiniMed advanced hybrid closed-loop delivery: results from a randomized crossover trial com-paring automated insulin delivery with predictive low glucose suspend in people with type 1 diabetes. Diabetes Care 2021;44:969-975 36. Brown SA, Beck RW, Raghinaru D, et al.; iDCL Trial Research Group. Glycemic outcomes of use of CLC versus PLGS in type 1 diabetes: a randomized controlled trial. Diabetes Care 2020;43:1822-1828 37. Breton MD, Kovatchev BP. One year real-world use of the Control-IQ advanced hybrid closed-loop technology. Diabetes Technol Ther 2021;23:601-608 38. Lepore G, Rossini A, Bellante R, et al. Switching to the MiniMed 780G system achieves clinical targets for CGM in adults with type 1 diabetes regardless of previous insulin strategy and baseline glucose control. Acta Diabetol 2022;59: 1309-1315 39. Matejko B, Juza A, Kie c-Wilk B, et al. Transitioning of people with type 1 diabetes from multiple daily injections and self-monitoring of blood glucose directly to MiniMed 780G advanced hybrid closed-loop system: a two-center, randomized, controlled study. Diabetes Care 2022; 45:2628-2635 40. Isganaitis E, Raghinaru D, Ambler-Osborn L, et al.; iDCL Trial Research Group. Closed-loop insulin therapy improves glycemic control in adolescents and young adults: outcomes from the international diabetes closed-loop trial. Diabetes Technol Ther 2021;23:342-349 41. Forlenza GP, Carlson AL, Galindo RJ, et al. Real-world evidence supporting Tandem Control-IQ hybrid closed-loop success in the Medicare and Medicaid type 1 and type 2 diabetes populations. Diabetes Technol Ther 2022;24:814-823 42. Pease A, Zomer E, Liew D, et al. Cost-effectiveness analysis of a hybrid closed-loop system versus multiple daily injections and capillary glucose testing for adults with type 1 diabetes. Diabetes Technol Ther 2020;22:812-821 43. Lal RA, Maahs DM. Optimizing basal insulin dosing. J Pediatr 2019;215:7-8 44. Mitsui Y, Adv Med 2018;2018:1473160 prolonged influence of glycemia during the Diabetes Control and Complications Trial (DCCT) on future risks of complications during the study of the Epidemiology of Diabetes Interventions and Complications (EDIC). Diabetes Care 2021;44: 2216-2224 4. Holt RIG, DeVries JH, Hess-Fischl A, et al. The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2021;44:2589-2625 5. Tricco AC, Ashoor HM, Antony J, et al. Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis. BMJ 2014;349:g5459 6. Bartley PC, Bogoev M, Larsen J, Philotheou A. Long-term efficacy and safety of insulin detemir compared to neutral protamine Hagedorn insulin in patients with type 1 diabetes using a treat-to-target basal-bolus regimen with insulin aspart at meals: a 2-year, randomized, controlled trial. Diabet Med 2008;25:442-449 7. Little S, Shaw J, Home P. Hypoglycemia rates with basal insulin analogs. Diabetes Technol Ther 2011;13(Suppl 1):S53-S64 8. Aronson R, Biester T, Leohr J, et al. Ultra rapid lispro showed greater reduction in postprandial glucose versus Humalog in children, adolescents and adults with type 1 diabetes mellitus. Diabetes Obes Metab 2023;25:1964-1972 9. Heise T, Pieber TR, Danne T, Erichsen L, Haahr H. A pooled analysis of clinical pharmacology trials investigating the pharmacokinetic and pharmacodynamic characteristics of fast-acting insulin aspart in adults with type 1 diabetes. Clin Pharmacokinet 2017;56:551-559 10. Bode BW, McGill JB, Lorber DL, Gross JL, Chang PC, Bregman DB; Affinity 1 Study Group. Inhaled technosphere insulin compared with injected prandial insulin in type 1 diabetes: a randomized 24-week trial. Diabetes Care 2015; 38:2266-2273 11. Russell-Jones D, Bode BW, De Block C, et al. Fast-acting insulin aspart improves glycemic control in basal-bolus treatment for type 1 diabetes: results of a 26-week multicenter, active-controlled, treat-to-target, randomized, parallel-group trial (onset 1). Diabetes Care 2017;40:943-950 12. Klaff L, Cao D, Dellva MA, et al. Ultra rapid lispro improves postprandial glucose control compared with lispro in patients with type 1 diabetes: results from the 26-week PRONTO-T1D study. Diabetes Obes Metab 2020;22:1799-1807 13. Lane W, Bailey TS, Gerety G, et al.; SWITCH 1. Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 1 diabetes: the SWITCH 1 randomized clinical trial. JAMA 2017;318:33-44 14. Home PD, Bergenstal RM, Bolli GB, et al. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 1 diabetes: a randomized, phase 3a, open-label clinical trial (EDITION 4). Diabetes Care 2015;38:2217-2225 15. Yeh H-C, Brown TT, Maruthur N, et al. Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta-analysis. Ann Intern Med 2012;157:336-347 16. Speight J, Choudhary P, Wilmot EG, et al. Impact of glycaemic technologies on quality of 47. Cengiz E, Danne T, Ahmad T, et al. ISPAD Clinical Practice Consensus Guidelines 2022: insulin treatment in children and adolescents with diabetes. Pediatr Diabetes 2022;23:1277-1296 48. King AB. Mean basal insulin dose is 0.2 U/kg/d at near normal glycaemia for type 1 or 2 diabetes on continuous subcutaneous insulin infusion or once-nightly basal insulin. Diabetes Obes Metab 2021;23:866-869 49. Peters AL, Lafell L. The American Diabetes Association/JDRF Type 1 Diabetes Sourcebook. American Diabetes Association, 2013 50. Srinivasan S, Craig ME, Beeney L, et al. An ambulatory stabilisation program for children with newly diagnosed type 1 diabetes. Med J Aust 2004;180:277-280 51. Lemieux L, Crawford S, Pacaud D. Starting subcutaneous insulin doses in a paediatric population with newly diagnosed type 1 diabetes. Paediatr Child Health 2010;15:357-362 52. Chiang JL, Kirkman MS, Laffel LMB, Peters AL; Type 1 Diabetes Sourcebook Authors. Type 1 diabetes through the life span: a position statement of the American Diabetes Association. Diabetes Care 2014;37:2034-2054 53. S€ amann A, M€ uhlhauser I, Bender R, Hunger-Dathe W, Kloos C, M€ uller UA. Flexible intensive insulin therapy in adults with type 1 diabetes and high risk for severe hypoglycemia and diabetic ketoacidosis. Diabetes Care 2006;29:2196-2199 54. Builes-Montaño CE, Ortiz-Cano NA, Ramirez-Rinc on A, Rojas-Henao NA. Efficacy and safety of carbohydrate counting versus other forms of dietary advice in patients with type 1 diabetes mellitus: a systematic review and meta-analysis of randomised clinical trials. J Hum Nutr Diet 2022;35:1030-1042 55. Al Balwi R, Al Madani W, Al Ghamdi A. Efficacy of insulin dosing algorithms for high-fat high-protein mixed meals to control postprandial glycemic excursions in people living with type 1 diabetes: A systematic review and meta-analysis. Pediatr Diabetes 2022;23:1635-1646 56. DAFNE Study Group. Training in flexible, intensive insulin management to enable dietary freedom in people with type 1 diabetes: Dose Adjustment For Normal Eating (DAFNE) randomised controlled trial. BMJ 2002;325:746 57. Hopkins D, Lawrence I, Mansell P, et al. Improved biomedical and psychological outcomes 1 year after structured education in flexible insulin therapy for people with type 1 diabetes: the U.K. DAFNE experience. Diabetes Care 2012;35:1638-1642 58. Speight J, Amiel SA, Bradley C, et al. Long-term biomedical and psychosocial outcomes following DAFNE (Dose Adjustment For Normal Eating) structured education to promote intensive insulin therapy in adults with sub-optimally controlled type 1 diabetes. Diabetes Res Clin Pract 2010;89:22-29 Pharmacologic Approaches to Glycemic Treatment S201 59. Bruttomesso D, Boscari F, Lepore G, et al. A life and related outcomes in adults with type 1 diabetes: a narrative review. Diabet Med 2023; 40:e14944 17. Barnard KD, Skinner TC. Cross-sectional study into quality of life issues surrounding insulin pump use in type 1 diabetes. Practical Diabetes International 2008;25:194-200 18. Mulinacci G, Alonso GT, Snell-Bergeon JK, Shah VN. Glycemic outcomes with early initiation of continuous glucose monitoring system in recently diagnosed patients with type 1 diabetes. Diabetes Technol Ther 2019;21:6-10 19. Elbalshy M, Haszard J, Smith H, et al. Effect of divergent continuous glucose monitoring technologies on glycaemic control in type 1 diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials. Diabet Med 2022;39:e14854 20. Champakanath A, Akturk HK, Alonso GT, Snell-Bergeon JK, Shah VN. Continuous glucose monitoring initiation within first year of type 1 diabetes diagnosis is associated with improved glycemic outcomes: 7-year follow-up study. Diabetes Care 2022;45:750-753 21. Weinstock RS, Xing D, Maahs DM, et al.; T1D Exchange Clinic Network. Severe hypoglycemia and diabetic ketoacidosis in adults with type 1 diabetes: results from the T1D Exchange clinic registry. J Clin Endocrinol Metab 2013;98:3411-3419 22. Tamborlane WV, Beck RW, Bode BW, et al.; Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med 2008;359:1464-1476 23. Polonsky WH, Hessler D, Ruedy KJ, Beck RW; DIAMOND Study Group. The impact of continuous glucose monitoring on markers of quality of life in adults with type 1 diabetes: further findings from the DIAMOND randomized clinical trial. Diabetes Care 2017;40:736-741 24. Bergenstal RM, Klonoff DC, Garg SK, et al.; ASPIRE In-Home Study Group. Threshold-based insulin-pump interruption for reduction of hypoglycemia. N Engl J Med 2013;369:224-232 25. Forlenza GP, Li Z, Buckingham BA, et al. Predictive low-glucose suspend reduces hypogly-cemia in adults, adolescents, and children with type 1 diabetes in an at-home randomized crossover study: results of the PROLOG trial. Diabetes Care 2018;41:2155-2161 26. Phillip M, Nimri R, Bergenstal RM, et al. Consensus recommendations for the use of automated insulin delivery technologies in clinical practice. Endocr Rev 2023;44:254-280 27. Peacock S, Frizelle I, Hussain S. A systematic review of commercial hybrid closed-loop automated insulin delivery systems. Diabetes Ther 2023;14: 839-855 28. Choudhary P, Kolassa R, Keuthage W, et al.; ADAPT Study Group. Advanced hybrid closed loop therapy versus conventional treatment in adults with type 1 diabetes (ADAPT): a randomised controlled study. Lancet Diabetes Endocrinol 2022; 10:720-731 29. Arunachalum S, Velado K, Vigersky RA, Cordero TL. Glycemic outcomes during real-world hybrid closed-loop system use by individuals with type 1 diabetes in the United States. J Diabetes Sci Technol 2023;17:951-958 30. Garg SK, Grunberger G, Weinstock R, et al.; Adult and Pediatric MiniMed HCL Outcomes diabetesjournals.org/care "slide rule" to adjust insulin dose using trend arrows in adults with type 1 diabetes: test in silico and in real life. Diabetes Ther 2021;12: 1313-1324 60. Aleppo G, Laffel LM, Ahmann AJ, et al. A practical approach to using trend arrows on the Dexcom G5 CGM system for the management of adults with diabetes. J Endocr Soc 2017;1:1445-1460 61. Buckingham B, Xing D, Weinzimer S, et al.; Diabetes Research In Children Network (DirecNet) Study Group. Use of the DirecNet Applied Treatment Algorithm (DATA) for diabetes manage-ment with a real-time continuous glucose monitor (the FreeStyle Navigator). Pediatr Diabetes 2008; 9:142-147 62. Parise M, Di Molfetta S, Graziano RT, et al. A head-to-head comparison of two algorithms for adjusting mealtime insulin doses based on CGM trend arrows in adult patients with type 1 diabetes: results from an exploratory study. Int J Environ Res Public Health 2023;20:3945 63. Petrovski G, Campbell J, Pasha M, et al. Simplified meal announcement versus precise carbohydrate counting in adolescents with type 1 diabetes using the MiniMed 780G advanced hybrid closed loop system: a randomized controlled trial comparing glucose control. Diabetes Care 2023;46:544-550 64. Turrin KB, Trujillo JM. Effects of diabetes numeracy on glycemic control and diabetes self-management behaviors in patients on insulin pump therapy. Diabetes Ther 2019;10:1337-1346 65. White RO, Wolff K, Cavanaugh KL, Rothman R. Addressing health literacy and numeracy to improve diabetes education and care. Diabetes Spectr 2010;23:238-243 66. Frid AH, Kreugel G, Grassi G, et al. New insulin delivery recommendations. Mayo Clin Proc 2016;91:1231-1255 67. Bergenstal RM, Strock ES, Peremislov D, Gibney MA, Parvu V, Hirsch LJ. Safety and efficacy of insulin therapy delivered via a 4mm pen needle in obese patients with diabetes. Mayo Clin Proc 2015;90:329-338 68. Qiao Y-C, Ling W, Pan Y-H, et al. Efficacy and safety of pramlintide injection adjunct to insulin therapy in patients with type 1 diabetes mellitus: a systematic review and meta-analysis. Oncotarget 2017;8:66504-66515 69. Meng H, Zhang A, Liang Y, Hao J, Zhang X, Lu J. Effect of metformin on glycaemic control in patients with type 1 diabetes: a meta-analysis of randomized controlled trials. Diabetes Metab Res Rev 2018;34:e2983 70. Petrie JR, Chaturvedi N, Ford I, et al.; REMOVAL Study Group. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2017;5:597-609 71. in subjects with type 1 diabetes: the ADJUNCT TWO randomized trial. Diabetes Care 2016;39: 1693-1701 73. von Herrath M, Bain SC, Bode B, et al.; Anti-IL-21-Liraglutide Study Group Investigators and Contributors. Anti-interleukin-21 antibody and liraglutide for the preservation of b-cell function in adults with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol 2021;9: 212-224 74. Garg SK, Kaur G, Haider Z, Rodriquez E, Beatson C, Snell-Bergeon J. Efficacy of semaglutide in overweight and obese patients with type 1 diabetes. Diabetes Technol Ther 2024;26:184-189 75. Garg SK, Akturk HK, Kaur G, Beatson C, Snell-Bergeon J. Efficacy and safety of tirzepatide in overweight and obese adult patients with type 1 diabetes. Diabetes Technol Ther 2024;26:367-374 76. National Library of Medicine. National Center for Biotechnology Information. ClinicalTrials.gov. Type 1 Diabetes Impacts of Semaglutide on Cardiovascular Outcomes (T1-DISCO) (NCT05819138). Accessed 23 August 2024. Available from https:// clinicaltrials.gov/study/NCT05819138?tab=results 77. National Library of Medicine. National Center for Biotechnology Information. ClinicalTrials.gov. ADJUnct Semaglutide Treatment in Type 1 Diabetes (ADJUST-T1D) (NCT05537233). Accessed 23 August 2024. Available from https://clinicaltrials .gov/study/NCT05537233 78. Rao L, Ren C, Luo S, Huang C, Li X. Sodium-glucose cotransporter 2 inhibitors as an add-on therapy to insulin for type 1 diabetes mellitus: meta-analysis of randomized controlled trials. Acta Diabetol 2021;58:869-880 79. Li M, Liu Z, Yang X, et al. The effect of sodium-glucose cotransporter 2 inhibitors as an adjunct to insulin in patients with type 1 diabetes assessed by continuous glucose monitoring: a systematic review and meta-analysis. J Diabetes Complications 2023;37:108632 80. Chen M-B, Xu R-J, Zheng Q-H, Zheng X-W, Wang H. Efficacy and safety of sotagliflozin adjuvant therapy for type 1 diabetes mellitus: a systematic review and meta-analysis. Medicine (Baltimore) 2020;99:e20875 81. U.S. Food and Drug Administration. FDA Introductory Remarks: January 17, 2019: Endocrinologic and Metabolic Drugs Advisory Committee Meeting. 2019. Accessed 23 August 2024. Available from https://wayback.archive-it. org/7993/20190207212714/https://www.fda.gov/ downloads/AdvisoryCommittees/Committees MeetingMaterials/Drugs/Endocrinologicand MetabolicDrugsAdvisoryCommittee/UCM629782. pdf 82. Bhatt DL, Szarek M, Steg PG, et al.; SOLOIST-WHF Trial Investigators. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med 2021;384:117-128 83. on metabolic and clinical outcomes in the Diabetes Control and Complications Trial. Diabetes 2014; 63:739-748 86. Dean PG, Kukla A, Stegall MD, Kudva YC. Pancreas transplantation. BMJ 2017;357:j1321 87. U.S. Food & Drug Administration. Lantidra. Accessed 15 September 2024. Available from https://www.fda.gov/vaccines-blood-biologics/ lantidra 88. Geta ET, Terefa DR, Hailu WB, et al. Effectiveness of shared decision-making for glycaemic control among type 2 diabetes mellitus adult patients: a systematic review and meta-analysis. PLoS One 2024;19:e0306296 89. Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2022;45:2753-2786 90. Lingvay I, Sumithran P, Cohen RV, Le Roux CW. Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation. Lancet 2022;399:394-405 91. Wing RR, Lang W, Wadden TA, et al.; Look AHEAD Research Group. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care 2011;34:1481-1486 92. Adler AI, Coleman RL, Leal J, Whiteley WN, Clarke P, Holman RR. Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91). Lancet 2024;404:145-155 93. Kunutsor SK, Balasubramanian VG, Zaccardi F, et al. Glycaemic control and macrovascular and microvascular outcomes: a systematic review and meta-analysis of trials investigating intensive glucose-lowering strategies in people with type 2 diabetes. Diabetes Obes Metab 2024;26:2069-2081 94. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HAW. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577-1589 95. Bahardoust M, Mousavi S, Yariali M, et al. Effect of metformin (vs. placebo or sulfonylurea) on all-cause and cardiovascular mortality and incident cardiovascular events in patients with diabetes: an umbrella review of systematic reviews with meta-analysis. J Diabetes Metab Disord 2024;23:27-38 96. Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med 2016;164:740-751 97. Karagiannis T, Paschos P, Paletas K, Matthews DR, Tsapas A. Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis. BMJ 2012;344:e1369 99. Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus: systematic review and meta-analysis. Arch Intern Med 2003;163:2594-2602 100. Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 2010;2010: CD002967 101. Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care 2011;34:1431-1437 102. Out M, Kooy A, Lehert P, Schalkwijk CA, Stehouwer CDA. Long-term treatment with metformin in type 2 diabetes and methylmalonic acid: post hoc analysis of a randomized controlled 4.3year trial. J Diabetes Complications 2018;32: 171-178 103. Aroda VR, Edelstein SL, Goldberg RB, et al.; Diabetes Prevention Program Research Group. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab 2016; 101:1754-1761 104. Fr ıas JP, Davies MJ, Rosenstock J, et al.; SURPASS-2 Investigators. Tirzepatide versus sema-glutide once weekly in patients with type 2 diabetes. N Engl J Med 2021;385:503-515 105. Sorli C, Harashima S-I, Tsoukas GM, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol 2017;5:251-260 106. Tsapas A, Avgerinos I, Karagiannis T, et al. Comparative effectiveness of glucose-lowering drugs for type 2 diabetes: a systematic review and network meta-analysis. Ann Intern Med 2020;173:278-286 107. Kahn SE, Haffner SM, Heise MA, et al.; ADOPT Study Group. Glycemic durability of rosig-litazone, metformin, or glyburide monotherapy. N Engl J Med 2006;355:2427-2443 108. Nathan DM, Lachin JM, Balasubramanyam A, et al.; GRADE Study Research Group. Glycemia reduction in type 2 diabetes-glycemic outcomes. N Engl J Med 2022;387:1063-1074 109. Babu A, Mehta A, Guerrero P, et al. Safe and simple emergency department discharge therapy for patients with type 2 diabetes mellitus and severe hyperglycemia. Endocr Pract 2009; 15:696-704 110. Buse JB, Peters A, Russell-Jones D, et al. Is insulin the most effective injectable antihypergly-caemic therapy? Diabetes Obes Metab 2015;17: 145-151 111. D'Alessio D, H€ aring H-U, Charbonnel B, et al.; EAGLE Investigators. Comparison of insulin glargine and liraglutide added to oral agents in patients with poorly controlled type 2 diabetes. onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial. Diabetes Obes Metab 2015;17:268-275 114. Cai X, Gao X, Yang W, Han X, Ji L. Efficacy and safety of initial combination therapy in treatment-naïve type 2 diabetes patients: a systematic review and meta-analysis. Diabetes Ther 2018;9:1995-2014 115. Aroda VR, Gonz alez-Galvez G, Grøn R, et al. Durability of insulin degludec plus liraglutide versus insulin glargine U100 as initial injectable therapy in type 2 diabetes (DUAL VIII): a multicentre, open-label, phase 3b, randomised controlled trial. Lancet Diabetes Endocrinol 2019;7:596-605 116. Khunti K, Davies MJ. Clinical inertia-time to reappraise the terminology? Prim Care Diabetes 2017;11:105-106 117. Bennett WL, Maruthur NM, Singh S, et al. Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Ann Intern Med 2011; 154:602-613 118. Maloney A, Rosenstock J, Fonseca V. A model-based meta-analysis of 24 antihyperglycemic drugs for type 2 diabetes: comparison of treatment effects at therapeutic doses. Clin Pharmacol Ther 2019;105:1213-1223 119. Lajthia E, Bucheit JD, Nadpara PA, et al. Combination therapy with once-weekly glucagon like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes: a case series. Pharm Pract (Granada) 2019;17:1588 120. Violante R, Oliveira JHA, Yoon K-H, et al. A randomized non-inferiority study comparing the addition of exenatide twice daily to sitagliptin or switching from sitagliptin to exenatide twice daily in patients with type 2 diabetes experiencing inadequate glycaemic control on metformin and sitagliptin. Diabet Med 2012;29:e417-e424 121. Nauck MA, Kahle M, Baranov O, Deacon CF, Holst JJ. Addition of a dipeptidyl peptidase-4 in-hibitor, sitagliptin, to ongoing therapy with the glucagon-like peptide-1 receptor agonist liraglutide: a randomized controlled trial in patients with type 2 diabetes. Diabetes Obes Metab 2017;19:200-207 122. Pratley R, Amod A, Hoff ST, et al.; PIONEER 4 Investigators. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Lancet 2019;394:39-50 123. Del Prato S, Kahn SE, Pavo I, et al.; SURPASS-4 Investigators. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet 2021;398:1811-1824 124. Singh S, Wright EE, Kwan AYM, et al. Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta-studies in type 2 diabetic patients. Diabetes Obes Metab 2017;19:216-227 127. Giorgino F, Benroubi M, Sun J-H, Zimmermann AG, Pechtner V. Efficacy and safety of once-weekly dulaglutide versus insulin glargine in patients with type 2 diabetes on metformin and glimepiride (AWARD-2). Diabetes Care 2015; 38:2241-2249 128. Aroda VR, Bain SC, Cariou B, et al. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Lancet Diabetes Endocrinol 2017;5:355-366 129. Davies M, Heller S, Sreenan S, et al. Once-weekly exenatide versus once-or twice-daily insulin detemir: randomized, open-label, clinical trial of efficacy and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas. Diabetes Care 2013;36:1368-1376 130. Diamant M, Van Gaal L, Stranks S, et al. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet 2010;375:2234-2243 131. Dahl D, Onishi Y, Norwood P, et al. Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: the SURPASS-5 randomized clinical trial. JAMA 2022;327:534-545 132. McCoy RG, Lipska KJ, Van Houten HK, Shah ND. Association of cumulative multimorbidity, glycemic control, and medication use with hypoglycemia-related emergency department visits and hospitalizations among adults with diabetes. JAMA Netw Open 2020;3:e1919099 133. Nathan DM, Lachin JM, Bebu I, et al.; GRADE Study Research Group. Glycemia reduction in type 2 diabetes-microvascular and cardiovascular outcomes. N Engl J Med 2022;387:1075-1088 134. McCoy RG, Herrin J, Swarna KS, et al. Effectiveness of glucose-lowering medications on cardiovascular outcomes in patients with type 2 diabetes at moderate cardiovascular risk. Nat Cardiovasc Res 2024;3:431-440 135. Berg DD, Wiviott SD, Scirica BM, et al. Heart failure risk stratification and efficacy of sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes mellitus. Circulation 2019; 140:1569-1577 136. Kidney Disease: Improving Global Outcomes Diabetes Work Group. KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int 2022;102:S1-S127 137. Kristensen SL, Rørth R, Jhund PS, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol 2019;7:776-785 Pharmacologic Approaches to Glycemic Treatment S203 diabetes: a meta-analysis. JAMA Cardiol 2021;6: 148-158 140. Reyes-Farias CI, Reategui-Diaz M, Romani-Romani F, Prokop L. The effect of sodium-glucose cotransporter 2 inhibitors in patients with chronic kidney disease with or without type 2 diabetes mellitus on cardiovascular and renal outcomes: a systematic review and meta-analysis. PLoS One 2023;18:e0295059 141. Herrington WG, Staplin N, Wanner C, et al.; Empa-Kidney Collaborative Group. Empagliflozin in patients with chronic kidney disease. N Engl J Med 2023;388:117-127 142. Perkovic V, Jardine MJ, Neal B, et al.; CREDENCE Trial Investigators. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019;380:2295-2306 143. Dagogo-Jack S, Pratley RE, Cherney DZI, et al. Glycemic efficacy and safety of the SGLT2 inhibitor ertugliflozin in patients with type 2 diabetes and stage 3 chronic kidney disease: an analysis from the VERTIS CV randomized trial. BMJ Open Diabetes Res Care 2021;9:e002484 144. Cherney DZI, Cooper ME, Tikkanen I, et al. Pooled analysis of phase III trials indicate contrasting influences of renal function on blood pressure, body weight, and HbA1c reductions with empagliflozin. Kidney Int 2018;93:231-244 145. Wexler DJ, de Boer IH, Ghosh A, et al.; GRADE Research Group. Comparative effects of glucose-lowering medications on kidney outcomes in type 2 diabetes: the GRADE randomized clinical trial. JAMA Intern Med 2023;183:705-714 146. Belfort R, Harrison SA, Brown K, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006;355:2297-2307 147. Cusi K, Orsak B, Bril F, Xu et al. Liraglutide or insulin glargine treatments improves hepatic fat in obese patients with type 2 diabetes and nonalcoholic fatty liver disease in twenty-six weeks: a randomized placebo-controlled trial. Diabetes Res Clin Pract 2020;170:108487 148. Flint A, Andersen G, Hockings P, et al. Randomised clinical trial: semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging. Aliment Pharmacol Ther 2021;54:1150-1161 149. Bizino MB, Jazet IM, de Heer P, et al. Placebo-controlled randomised trial with liraglutide on magnetic resonance endpoints in individuals with type 2 diabetes: a pre-specified secondary study on ectopic fat accumulation. Diabetologia 2020;63:65-74 150. Newsome PN, Buchholtz K, Cusi K, et al.; NN9931-4296 Investigators. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med 2021;384:1113-1124 151. Loomba R, Hartman ML, Lawitz EJ, et al.; SYNERGY-NASH Investigators. Tirzepatide for meta-bolic dysfunction-associated steatohepatitis with 153. Armstrong MJ, Gaunt P, Aithal GP, et al.; LEAN Trial Team. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 2016;387:679-690 154. Sathyanarayana P, Jogi M, Muthupillai R, Krishnamurthy R, Samson SL, Bajaj M. Effects of combined exenatide and pioglitazone therapy on hepatic fat content in type 2 diabetes. Obesity (Silver Spring) 2011;19:2310-2315 155. Abdul-Ghani M, Migahid O, Megahed A, DeFronzo RA, Al-Ozairi E, Jayyousi A. Combination therapy with pioglitazone/exenatide improves beta-cell function and produces superior glycaemic control compared with basal/bolus insulin in poorly controlled type 2 diabetes: a 3-year follow-up of the Qatar study. Diabetes Obes Metab 2020; 22:2287-2294 156. Lavynenko O, Abdul-Ghani M, Alatrach M, et al. Combination therapy with pioglitazone/ exenatide/metformin reduces the prevalence of hepatic fibrosis and steatosis: the efficacy and durability of initial combination therapy for type 2 diabetes (EDICT). Diabetes Obes Metab 2022;24: 899-907 157. Garvey WT, Frias JP, Jastreboff AM, et al.; SURMOUNT-2 Investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2023;402:613-626 158. Davies M, Faerch L, Jeppesen OK, et al.; STEP 2 Study Group. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet 2021;397:971-984 159. Bonora E, Frias JP, Tinahones FJ, et al. Effect of dulaglutide 3.0 and 4.5 mg on weight in patients with type 2 diabetes: exploratory analyses of AWARD-11. Diabetes Obes Metab 2021;23:2242-2250 160. Davies MJ, Bergenstal R, Bode B, et al.; NN8022-1922 Study Group. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE diabetes randomized clinical trial. JAMA 2015;314:687-699 161. Ahmann AJ, Capehorn M, Charpentier G, et al. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): a 56-week, open-label, randomized clinical trial. Diabetes Care 2018;41:258-266 162. Schauer PR, Bhatt DL, Kirwan JP, et al.; STAMPEDE Investigators. Bariatric surgery versus intensive medical therapy for diabetes-5-year outcomes. N Engl J Med 2017;376:641-651 163. Blonde L, Merilainen M, Karwe V, Raskin P, TITRATE Study Group. Patient-directed titration for achieving glycaemic goals using a once-daily basal insulin analogue: an assessment of two different fasting plasma glucose targets-the TITRATE 166. Semlitsch T, Engler J, Siebenhofer A, Jeitler K, Berghold A, Horvath K. (Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev 2020;11: Cd005613 167. Mannucci E, Caiulo C, Naletto L, Madama G, Monami M. Efficacy and safety of different basal and prandial insulin analogues for the treatment of type 2 diabetes: a network meta-analysis of randomized controlled trials. Endocrine 2021;74:508-517 168. Russell-Jones D, Gall M-A, Niemeyer M, Diamant M, Del Prato S. Insulin degludec results in lower rates of nocturnal hypoglycaemia and fasting plasma glucose vs. insulin glargine: a meta-analysis of seven clinical trials. Nutr Metab Cardiovasc Dis 2015;25:898-905 169. Mehta R, Goldenberg R, Katselnik D, Kuritzky L. Practical guidance on the initiation, titration, and switching of basal insulins: a narrative review for primary care. Ann Med 2021;53: 998-1009 170. Cowart K. Overbasalization: addressing hesitancy in treatment intensification beyond basal insulin. Clin Diabetes 2020;38:304-310 171. Maiorino MI, Chiodini P, Bellastella G, Capuano A, Esposito K, Giugliano D. Insulin and glucagon-like peptide 1 receptor agonist combination therapy in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetes Care 2017;40:614-624 172. Castellana M, Cignarelli A, Brescia F, Laviola L, Giorgino F. GLP-1 receptor agonist added to insulin versus basal-plus or basal-bolus insulin therapy in type 2 diabetes: a systematic review and meta-analysis. Diabetes Metab Res Rev 2019; 35:e3082 173. Rodbard HW, Visco VE, Andersen H, Hiort LC, Shu DHW. Treatment intensification with stepwise addition of prandial insulin aspart boluses compared with full basal-bolus therapy (FullSTEP Study): a randomised, treat-to-target clinical trial. Lancet Diabetes Endocrinol 2014; 2:30-37 174. McCall AL. Insulin therapy and hypoglycemia. Endocrinol Metab Clin North Am 2012;41:57-87 175. Mannucci E, Monami M, Marchionni N. Short-acting insulin analogues vs. regular human insulin in type 2 diabetes: a meta-analysis. Diabetes Obes Metab 2009;11:53-59 176. Heller S, Bode B, Kozlovski P, Svendsen AL. Meta-analysis of insulin aspart versus regular human insulin used in a basal-bolus regimen for the treatment of diabetes mellitus. J Diabetes 2013;5:482-491 177. de la Peña A, Riddle M, Morrow LA, et al. Pharmacokinetics and pharmacodynamics of high-dose human regular U-500 insulin versus human regular U-100 insulin in healthy obese subjects. Diabetes Care 2011;34:2496-2501 178. Wysham C, Hood RC, Warren ML, Wang T, 138. diabetesjournals.org/care liver fibrosis. N Engl J Med 2024;391:299-310 152. Gastaldelli A, Cusi K, Fern andez Land o L, Bray R, Brouwers B, Rodr ıguez A. Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol 2022;10:393-406 study. Diabetes Obes Metab 2009;11:623-631 164. Porcellati F, Lucidi P, Cioli P, et al. Pharmacokinetics and pharmacodynamics of insulin glargine given in the evening as compared with in the morning in type 2 diabetes. Diabetes 165. Wang Z, Hedrington MS, Gogitidze Joy N, et al. Dose-response effects of insulin glargine in type 2 diabetes. Diabetes Care 2010;33:1555-1560 Morwick TM, Jackson JA. Effect of total daily dose on efficacy, dosing, and safety of 2 dose titration regimens of human regular U500 insulin in severely insulin-resistant patients with type 2 diabetes. Endocr Pract 2016;22:653-665 98. metformin-certain with type 2 diabetes (SURPASS-3 MRI): a substudy Care 2015;38:503-512 179.| |---|

|diabetesjournals.org/care|Cardiovascular Disease and Risk Management|S215| |---|---|---|

|1-High-intensity and moderate-intensity statin therapy|1-High-intensity and moderate-intensity statin therapy||

|High-intensity statin therapy|Moderate-intensity statin therapy||

|(lowers LDL cholesterol by $50%)|(lowers LDL cholesterol by 30-49%)||

|Atorvastatin 40-80 mg|Atorvastatin 10-20 mg||

|Rosuvastatin 20-40 mg|Rosuvastatin 5-10 mg||

||Simvastatin 20-40 mg||

||Pravastatin 40-80 mg||

||Lovastatin 40 mg||

||Fluvastatin XL 80 mg||

||Pitavastatin 1-4 mg||

|Once-daily dosing. XL, extended release.|||

|which enrolled asymptomatic people with|randomization to the SGLT1/2 inhibitor so-||| |---|---|---|---|

|reduced LVEF after MI, including 23% peo-|tagliflozin reduced the primary outcome of|||

|ple with diabetes, treatment with captopril|death from cardiovascular causes, hospital-|||

|reduced the development of heart failure|izations for heart failure, and urgent visits|||

|by 37% (279). Subsequent retrospective|for heart failure in people with type 2 dia-|||

|analyses from both trials revealed that con-|betes, CKD, and risk for cardiovascular|||

|comitant use of b-blockers was associated|disease (284). Therefore, SGLT inhibitor|||

|with decreased risk of progression to|treatment is recommended in asymptom-|||

|symptomatic heart failure (280,281). The|atic people with type 2 diabetes at risk or|||

|Carvedilol Post-Infarct Survival Control in|with established cardiovascular disease to|||

|Left Ventricular Dysfunction (CAPRICORN)|prevent incident heart failure and hospi-|||

|study randomized people with a history|talization from heart failure.|||

|of MI and reduced LVEF to treatment||||

|with carvedilol (282). Approximately half|Finerenone. Finerenone is a nonsteroidal|||

|of the study participants were asymptom-|MRA and has recently been studied in|||

|atic, and 23% of study participants had a|people with diabetes and CKD, including|||

|history of diabetes. Treatment with carve-|the Finerenone in Reducing Kidney Fail-|||

|dilol reduced mortality by 23%, and there|ure and Disease Progression in Diabetic|||

|was a 14% risk reduction for heart failure|Kidney Disease (FIDELIO-DKD) and the|||

|hospitalization. Finally, in the Reversal of|Efficacy and Safety of Finerenone in|||

|Ventricular Remodeling With Toprol-XL (REVERT) trial, in which 45% of the people enrolled had diabetes, metoprolol improved adverse cardiac remodeling in asymptom-|Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease (FIGARO-DKD) studies.|||

|atic individuals with an LVEF < 40% and||||

|mild left ventricular dilatation (283).||||

|SGLT Inhibitors. SGLT2 inhibitors consti-||||

|tute a key treatment approach to reduce||||

|cardiovascular disease and heart failure||||

|outcomes in people with diabetes. Peo-||||

|ple with type 2 diabetes and increased||||

|cardiovascular risk or established cardio-||||

|vascular disease should be treated with||||

|an SGLT2 inhibitor to prevent the devel-||||

|opment of incident heart failure. This in-||||

|cludes people with type 2 diabetes and||||

|asymptomatic stage B heart failure. In||||

|the EMPA-REG OUTCOME trial, only 10%||||

|of study participants had a prior history||||

|of heart failure, and treatment with em-||||

|pagliflozin reduced the relative risk for||||

|hospitalization from heart failure by 35%||||

|(255). In the CANVAS Program, hospitali-||||

|zation from heart failure was reduced by||||

|33% in people allocated to canagliflozin,||||

|and only 14% of individuals enrolled had||||

|a prior history of heart failure (256). In||||

|the DECLARE-TIMI 58 study, only 10% of study participants had a prior history of|If high risk for or established CVD|If CKD||

|heart failure, and dapagliflozin reduced||||

|cardiovascular mortality and hospitaliza-||||

|regardless of a prior history of heart failure||||

|(258). Finally, in the Effect of Sotagliflozin||||

|on Cardiovascular and Renal Events in||||

|Participants With Type 2 Diabetes and||||

|Moderate Renal Impairment Who Are||||

|at Cardiovascular Risk (SCORED) trial,||||

|S232 Cardiovascular Disease and Risk Management diabetesjournals.org/care|Diabetes Care Volume 48, Supplement 1, January 2025 Cardiovascular Disease and Risk Management S233| |---|---|

|Hypertens (Greenwich) 2003;5:202-209 64. Feldman RD, Zou GY, Vandervoort MK, Wong CJ, Nelson SAE, Feagan BG. A simplified approach to the treatment of uncomplicated hypertension: a cluster randomized, controlled trial. Hypertension 2009;53:646-653 65. Webster R, Salam A, de Silva HA, et al.; TRIUMPH Group. Fixed low-dose triple combination antihypertensive medication vs usual care for blood pressure control in patients with mild to moderate hypertension in Sri Lanka: a randomized clinical trial. JAMA 2018;320: 566-579 66. Bangalore S, Kamalakkannan G, Parkar S, Messerli FH. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med 2007;120:713-719 67. Catal a-L opez F, Mac ıas Saint-Gerons D, Gonz alez-Bermejo D, et al. Cardiovascular and renal outcomes of renin-angiotensin system blockade in adult patients with diabetes mellitus: a systematic review with network meta-analyses. PLoS Med 2016;13:e1001971 68. Palmer SC, Mavridis D, Navarese E, et al. Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis. Lancet 2015;385: 2047-2056 69. Barzilay JI, Davis BR, Bettencourt J, et al.; ALLHAT Collaborative Research Group. Cardio-vascular outcomes using doxazosin vs. chlorthal-idone for the treatment of hypertension in older adults with and without glucose disorders: a report from the ALLHAT study. J Clin Hypertens (Greenwich) 2004;6:116-125 70. Weber MA, Bakris GL, Jamerson K, et al.; ACCOMPLISH Investigators. Cardiovascular events during differing hypertension therapies in patients with diabetes. J Am Coll Cardiol 2010;56:77-85 71. Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 2000;355:253-259 72. Arnold SV, Bhatt DL, Barsness GW, et al.; American Heart Association Council on Lifestyle and Cardiometabolic Health and Council on Clinical Cardiology. Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association. Circulation 2020;141: e779-e806 73. Yusuf S, Teo K, Anderson C, et al.; Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet 2008;372:1174-1183 74. Qiao Y, Shin J-I, Chen TK, et al. Association between renin-angiotensin system blockade dis-continuation and all-cause mortality among lesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. The Care Investigators. Circulation 1998;98:2513-2519 104. Shepherd J, Barter P, Carmena R, et al. Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) study. Diabetes Care 2006;29:1220-1226 105. Sever PS, Poulter NR, Dahl€ of B, et al. Reduction in cardiovascular events with atorvastatin in 2,532 patients with type 2 diabetes: Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA). Diabetes Care 2005;28:1151-1157 106. Knopp RH, d'Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-insulin-dependent diabetes mellitus (ASPEN). Diabetes Care 2006;29:1478-1485 107. Colhoun HM, Betteridge DJ, Durrington PN, et al.; CARDS Investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004;364:685-696 108. Kearney PM, Blackwell L, Collins R, et al.; Cholesterol Treatment Trialists' (CTT) Collaborators. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008;371:117-125 109. Fulcher J, O'Connell R, Voysey M, et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet 2015;385:1397-1405 110. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardio-vascular disease. Cochrane Database Syst Rev 2013;2013:CD004816 111. Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM. Risk of incident diabetes among patients treated with statins: population based study. BMJ 2013;346:f2610 112. Mangione CM, Barry MJ, Nicholson WK, et al.; US Preventive Services Task Force. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force recommendation statement. JAMA 2022; 328:746-753 113. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/ APhA/ASPC/NLA/PCNA guideline on the man-agement of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;139:e1082-e1143 114. Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association of Clinical Endocrinologists lipid modification to reduce cardiovascular risk. Eur persons with low estimated glomerular filtration rate. JAMA Intern Med 2020;180:718-726 75. Bangalore S, Fakheri R, Toklu B, Messerli FH. Diabetes mellitus as a compelling indication for use of renin angiotensin system blockers: systematic review and meta-analysis of randomized trials. BMJ 2016;352:i438 76. Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension: is it a wise choice? Lancet 2004;364:1684-1689 77. Murphy SP, Ibrahim NE, Januzzi JL, Jr. Heart failure with reduced ejection fraction: a review. JAMA 2020;324:488-504 78. Yusuf S, Teo KK, Pogue J, et al.; ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547-1559 79. Fried LF, Emanuele N, Zhang JH, et al.; VA NEPHRON-D Investigators. Combined angiotensin inhibition for the treatment of diabetic nephro-pathy. N Engl J Med 2013;369:1892-1903 80. Makani H, Bangalore S, Desouza KA, Shah A, Messerli FH. Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials. BMJ 2013;346:f360 81. Wu C, Zhao P, Xu P, et al. Evening versus morning dosing regimen drug therapy for hypertension. Cochrane Database Syst Rev 2011; 2:Cd004184 82. Hermida RC, Ayala DE, Moj on A, Fern andez JR. Influence of time of day of blood pressure-lowering treatment on cardiovascular risk in hypertensive patients with type 2 diabetes. Diabetes Care 2011;34:1270-1276 83. Rahman M, Greene T, Phillips RA, et al. A trial of 2 strategies to reduce nocturnal blood pressure in blacks with chronic kidney disease. Hypertension 2013;61:82-88 84. Nilsson E, Gasparini A, € Arnl€ ov J, et al. Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system. Int J Cardiol 2017;245:277-284 85. Bandak G, Sang Y, Gasparini A, et al. Hyperkalemia after initiating renin-angiotensin system blockade: the Stockholm Creatinine Measurements (SCREAM) project. J Am Heart Assoc 2017;6:e005428 86. Hughes-Austin JM, Rifkin DE, Beben T, et al. The relation of serum potassium concentration with cardiovascular events and mortality in community-living individuals. Clin J Am Soc Nephrol 2017;12:245-252 87. James MT, Grams ME, Woodward M, et al.; CKD Prognosis Consortium. A meta-analysis of the association of estimated GFR, albuminuria, diabetes mellitus, and hypertension with acute kidney injury. Am J Kidney Dis 2015;66:602-612 88. Williams B, MacDonald TM, Morant S, et al.; British Hypertension Society's PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet 2015;386:2059-2068 89. Sato A, Hayashi K, Naruse M, Saruta T. Effectiveness of aldosterone blockade in patients with diabetic nephropathy. Hypertension 2003; 41:64-68 90. Mehdi UF, Adams-Huet B, Raskin P, Vega GL, Toto RD. Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximal Heart J 2020;41:111-188 117. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/ APhA/ASPC/NLA/PCNA guideline on the man-agement of blood cholesterol: executive summary: a report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;73: 3168-3209 118. Khan SU, Yedlapati SH, Lone AN, et al. PCSK9 inhibitors and ezetimibe with or without statin therapy for cardiovascular risk reduction: a systematic review and network meta-analysis. BMJ 2022;377:e069116 119. Cannon CP, Blazing MA, Giugliano RP, et al.; IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015;372:2387-2397 120. de Ferranti SD, de Boer IH, Fonseca V, et al. Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Diabetes Care 2014;37:2843-2863 121. Sabatine MS, Giugliano RP, Keech AC, et al.; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017; 376:1713-1722 122. Giugliano RP, Cannon CP, Blazing MA, et al.; IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) Investigators. Benefit of adding ezetimibe to statin therapy on cardiovascular outcomes and safety in patients with versus without diabetes mellitus: results from IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation 2018;137:1571-1582 123. Schwartz GG, Steg PG, Szarek M, et al.; ODYSSEY OUTCOMES Committees and Investi-gators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 2018;379:2097-2107 124. Ray KK, Colhoun HM, Szarek M, et al.; ODYSSEY OUTCOMES Committees and Investi-gators. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial. Lancet Diabetes Endocrinol 2019;7:618-628 125. Sabatine MS, Leiter LA, Wiviott SD, et al. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol 2017; 5:941-950 126. Moriarty PM, Jacobson TA, Bruckert E, et al. Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial. J Clin Lipidol 2014;8: 554-561 127. Type 9) inhibitor evolocumab added to statin angiotensin-converting enzyme inhibition in diabetic nephropathy. J Am Soc Nephrol 2009;20:2641-2650 91. Bakris GL, Agarwal R, Chan JC, et al.; Mineralocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy (ARTS-DN) Study Group. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA 2015;314:884-894 92. Virani SS, Newby LK, Arnold SV, et al.; Peer Review Committee Members. 2023 AHA/ ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation 2023;148:e9-e119 93. Estruch R, Ros E, Salas-Salvad o J, et al.; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med 2018;378:e34 94. Jia X, Al Rifai M, Ramsey DJ, et al. Association between lipid testing and statin adherence in the Veterans Affairs health system. Am J Med 2019; 132:e693-e700 95. Rana JS, Virani SS, Moffet HH, et al. Association of low-density lipoprotein testing after an atherosclerotic cardiovascular event with subsequent statin adherence and intensification. Am J Med 2022;135:603-606 96. Tran C, Vo V, Taylor P, Koehn DA, Virani SS, Dixon DL. Adherence to lipid monitoring and its impact on treat intensification of LDL-C lowering therapies at an urban academic medical center. J Clin Lipidol 2022;16:491-497 97. Chasman DI, Posada D, Subrahmanyan L, Cook NR, Stanton VP, Ridker PM. Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA 2004;291:2821-2827 98. Meek C, Wierzbicki AS, Jewkes C, et al. Daily and intermittent rosuvastatin 5 mg therapy in statin intolerant patients: an observational study. Curr Med Res Opin 2012;28:371-378 99. Mihaylova B, Emberson J, Blackwell L, et al.; Cholesterol Treatment Trialists' (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 ran-domised trials. Lancet 2012;380:581-590 100. Baigent C, Keech A, Kearney PM, et al.; Cholesterol Treatment Trialists' (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treat-ment: prospective meta-analysis of data from 90,056 part icipants in 14 randomised trials of statins. Lancet 2005;366:1267-1278 101. Py or€ al€ a K, Pedersen TR, Kjekshus J, Faergeman O, Olsson AG, Thorgeirsson G. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. A subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care 1997;20:614-620 102. Collins R, Armitage J, Parish S, Sleigh P, Peto R, Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003;361:2005-2016 103. Goldberg RB, Mellies MJ, Sacks FM, et al. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cho-in high-risk patients with stable atherosclerosis. Stroke 2020;51:1546-1554 129. Ray KK, Wright RS, Kallend D, et al.; ORION-10 and ORION-11 Investigators. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N Engl J Med 2020;382:1507-1519 130. University of Oxford. A randomized trial assessing the effects of inclisiran on clinical outcomes among people with cardiovascular disease (ORION-4). In: ClinicalTrials.gov. Bethesda, MD, National Library of Medicine. NLM Identifier: NCT03705234. Accessed 27 August 2024. Avail-able from https://clinicaltrials.gov/ct2/show/ NCT03705234 131. National Library of Medicine. National Center for Biotechnology Information. Study of Inclisiran to Prevent Cardiovascular (CV) Events in Participants With Established Cardiovascular Disease (VICTORION-2P) (NCT05030428). Accessed 14 August 2024. Available from https://clinicaltrials .gov/study/NCT05030428 132. National Library of Medicine. National Center for Biotechnology Information. A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients (NCT05739383). Accessed 27 August 2024. Available from https:// clinicaltrials.gov/study/NCT05739383 133. Cheeley MK, Saseen JJ, Agarwala A, et al. NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient. J Clin Lipidol 2022;16:361-375 134. Moriarty PM, Thompson PD, Cannon CP, et al.; ODYSSEY ALTERNATIVE Investigators. Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin re-challenge arm: the ODYSSEY ALTERNATIVE randomized trial. J Clin Lipidol 2015;9:758-769 135. Sullivan D, Olsson AG, Scott R, et al. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA 2012;308:2497-2506 136. Stroes E, Colquhoun D, Sullivan D, et al.; GAUSS-2 Investigators. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evo-locumab. J Am Coll Cardiol 2014;63:2541-2548 137. Nissen SE, Stroes E, Dent-Acosta RE, et al.; GAUSS-3 Investigators. Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial. JAMA 2016;315:1580-1590 138. Ray KK, Stoekenbroek RM, Kallend D, et al. Effect of 1 or 2 doses of inclisiran on low-density lipoprotein cholesterol levels: one-year follow-up of the ORION-1 randomized clinical trial. JAMA Cardiol 2019;4:1067-1075 139. Ray KK, Troquay RPT, Visseren FLJ, et al. Diabetol 2023;22:324 141. Nissen SE, Lincoff AM, Brennan D, et al.; CLEAR Outcomes Investigators. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med 2023;388:1353-1364 142. Ray KK, Nicholls SJ, Li N, et al.; CLEAR OUTCOMES Committees and Investigators. Efficacy and safety of bempedoic acid among patients with and without diabetes: prespecified analysis of the CLEAR Outcomes randomised trial. Lancet Diabetes Endocrinol 2024;12:19-28 143. Nissen SE, Menon V, Nicholls SJ, et al. Bempedoic acid for primary prevention of cardio-vascular events in statin-intolerant patients. JAMA 2023;330:131-140 144. Agarwala A, Dixon DL, Gianos E, et al. Dyslipidemia management in women of repro-ductive potential: an expert clinical consensus from the national lipid association. J Clin Lipidol. 30 May 2024 [Epub ahead of print]. 145. Roeters van Lennep JE, Tokg€ ozo glu LS, Badimon L, et al. Women, lipids, and atherosclerotic cardiovascular disease: a call to action from the European Atherosclerosis Society. Eur Heart J 2023;44:4157-4173 146. Nanna MG, Wang TY, Xiang Q, et al. Sex differences in the use of statins in community practice. Circ Cardiovasc Qual Outcomes 2019;12: e005562 147. Botha TC, Pilcher GJ, Wolmarans K, Blom DJ, Raal FJ. Statins and other lipid-lowering therapy and pregnancy outcomes in homozygous familial hypercholesterolaemia: a retrospective review of 39 pregnancies. Atherosclerosis 2018; 277:502-507 148. Toleikyte I, Retterstøl K, Leren TP, Iversen PO. Pregnancy outcomes in familial hyper-cholesterolemia: a registry-based study. Cir-culation 2011;124:1606-1614 149. M esz aros B, Veres DS, Nagyist ok L, et al. Pravastatin in preeclampsia: a meta-analysis and systematic review. Front Med (Lausanne) 2022; 9:1076372 150. Virani SS, Morris PB, Agarwala A, et al. 2021 ACC expert consensus decision pathway on the management of ASCVD risk reduction in patients with persistent hypertriglyceridemia: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2021; 78:960-993 151. Pedersen SB, Langsted A, Nordestgaard BG. Nonfasting mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis. JAMA Intern Med 2016;176:1834-1842 152. Nelson AJ, Navar AM, Mulder H, et al. Association between triglycerides and residual cardiovascular risk in patients with type 2 diabetes mellitus and established cardiovascular disease (from the Bypass Angioplasty Revas-cularization Investigation 2 Diabetes [BARI 2D] trial). Am J Cardiol 2020;132:36-43 153. Bhatt DL, Steg PG, Miller M, et al.; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380:11-22 Craig I, Alexander DD, Davidson MH. Triglyceride-lowering therapies reduce cardiovascular disease event risk in subjects with hypertriglyceridemia. J 172. Richardson K, Schoen M, French B, et al. Statins and cognitive function: a systematic review. Ann Intern Med 2013;159:688-697 173. Adhikari A, Tripathy S, Chuzi S, Peterson 312. Musso G, Sircana A, Saba F, Cassader M, Gambino R. Assessing the risk of ketoacidosis due to sodium-glucose cotransporter (SGLT)-2 in-hibitors in patients with type 1 diabetes: a meta-glucose cotransporter 2 inhibitor, on glycemic end points assessed by continuous glucose monitoring and patient-reported outcomes among people with type 1 diabetes. Diabetes Care 2017;40: in heart failure patients with preserved ejection fraction: results from the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial. Circ Heart Fail 2011;4:324-11.10 Refer to a nephrologist for uncertainty about the etiology of kidney disease, difficult management 154. 156. Maki KC, Guyton JR, Orringer CE, Hamilton-Clin Lipidol 2016;10:905-914 157. Das Pradhan A, Glynn RJ, Fruchart J-C, et al.; PROMINENT Investigators. Triglyceride lowering with pemafibrate to reduce cardiovascular risk. N Engl J Med 2022;387:1923-1934 158. Jones PH, Davidson MH. Reporting rate of rhabdomyolysis with fenofibrate 1 statin versus gemfibrozil 1 any statin. Am J Cardiol 2005;95: 120-122 159. Ginsberg HN, Elam MB, Lovato LC, et al.; ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010;362:1563-1574 160. Boden WE, Probstfield JL, Anderson T, et al.; AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011;365:2255-2267 161. Landray MJ, Haynes R, Hopewell JC, et al.; HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med 2014;371:203-212 162. Rajpathak SN, Kumbhani DJ, Crandall J, Barzilai N, Alderman M, Ridker PM. Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care 2009;32:1924-1929 163. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010;375:735-742 164. Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. J, Stone NJ. Association between statin use and cognitive function: a systematic review of randomized clinical trials and observational studies. J Clin Lipidol 2021;15:22-32 e12 174. Perk J, De Backer G, Gohlke H, et al.; European Association for Cardiovascular Prevention & Rehabilitation (EACPR); ESC Committee for Practice Guidelines (CPG). European guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J 2012;33:1635-1701 175. Belch J, MacCuish A, Campbell I, et al.; Royal College of Physicians Edinburgh. The Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and anti-oxidants in patients with diabetes and asymp-tomatic peripheral arterial disease. BMJ 2008; 337:a1840 176. Zhang C, Sun A, Zhang P, et al. Aspirin for primary prevention of cardiovascular events in patients with diabetes: a meta-analysis. Diabetes Res Clin Pract 2010;87:211-218 177. De Berardis G, Sacco M, Strippoli GFM, et al. Aspirin for primary prevention of cardio-vascular events in people with diabetes: meta-analysis of randomised controlled trials. BMJ 2009;339:b4531 178. Baigent C, Blackwell L, Collins R, et al.; analysis and meta-regression. PLoS Med 2020; 17:e1003461 313. Holt RIG, DeVries JH, Hess-Fischl A, et al. The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2021;44:2589-2625 314. Rosenstock J, Marquard J, Laffel LM, et al. Empagliflozin as adjunctive to insulin therapy in type 1 diabetes: the EASE trials. Diabetes Care 2018;41:2560-2569 315. Mathieu C, Dandona P, Gillard P, et al.; DEPICT-2 Investigators. Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes (the DEPICT-2 Study): 24-week results from a randomized controlled trial. Diabetes Care 2018;41:1938-1946 316. Garg SK, Henry RR, Banks P, et al. Effects of sotagliflozin added to insulin in patients with type 1 diabetes. N Engl J Med 2017;377:2337-2348 317. Rodbard HW, Peters AL, Slee A, Cao A, Traina SB, Alba M. The effect of canagliflozin, a sodium 171-180 318. Palanca A, van Nes F, Pardo F, Ampudia Blasco FJ, Mathieu C. Real-world evidence of 331 322. Mikhalkova D, Holman SR, Jiang H, et al. Bariatric surgery-induced cardiac and lipidomic American Diabetes Association issues, and rapidly progressing kidney disease. B 11. Chronic Kidney Disease and Professional Practice Committee* efficacy and safety of SGLT2 inhibitors as adjunctive therapy in adults with type 1 diabetes: changes in obesity-related heart failure with preserved ejection fraction. Obesity (Silver Spring) Risk Management: Standards of a European two-center experience. Diabetes Care 2022;45:650-658 319. U.S. Food and Drug Administration. 2019 2018;26:284-290 323. Kosiborod MN, Petrie MC, Borlaug BA, EPIDEMIOLOGY OF DIABETES AND Care in Diabetes-2025 CHRONIC KIDNEY DISEASE et al.; STEP-HFpEF DM Trial Committees and Meeting Materials, January 17, 2019 Meeting of Investigators. Semaglutide in patients with Diabetes Care 2025;48(Suppl. 1):S239-S251 | https://doi.org/10.2337/dc25-S011 Chronic kidney disease (CKD) is diag-the Endocrinologic and Metabolic Drugs Advisory obesity-related heart failure and type 2 diabetes. nosed by the persistent elevation of uri-Committee. 2019. Accessed 27 August 2024. Available from https://web.archive.org/web/ 20190207212714/https://www.fda.gov/downloads/ N Engl J Med 2024;390:1394-1407 nary albumin excretion (albuminuria), 324. Das SR, Everett BM, Birtcher KK, et al. 2020 low estimated glomerular filtration rate Expert consensus decision pathway on novel AdvisoryCommittees/CommitteesMeetingMaterials/ Drugs/EndocrinologicandMetabolicDrugsAdvisory Committee/UCM629782.pdf 320. Echouffo-Tcheugui JB, Xu H, DeVore AD, et al. Temporal trends and factors associated with diabetes mellitus among patients hospitalized with heart failure: findings from Get With The Guidelines-Heart Failure registry. Am Heart J 2016;182:9-20 321. Haass M, Kitzman DW, Anand IS, et al. Body mass index and adverse cardiovascular outcomes therapies for cardiovascular risk reduction in patients with type 2 diabetes: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2020;76: 1117-1145 325. American Diabetes Association Primary Care Advisory Group. Cardiovascular disease and risk management: Standards of Care in Diabetes-2024 abridged for primary care professionals. Clin Diabetes 2024;42:209-211 (eGFR), or other manifestations of kid-ney damage (1). In this section, the fo-cus is on CKD attributed to diabetes in adults, which occurs in 20-40% of peo-ple with diabetes (1-4). CKD in people with diabetes typically develops after a duration of 10 years in type 1 diabetes (the most common presentation is 5-15 years after the diagnosis of type 1 dia-betes) but may be present at diagnosis of type 2 diabetes. CKD can progress to kidney failure requiring dialysis or kid-ney transplantation and is the leading cause of end-stage kidney disease (ESKD) in the U.S. (5). In addition, among people with type 1 or type 2 di-abetes, the presence of CKD markedly Lancet 2012;380:565-571 165. Mach F, Ray KK, Wiklund O, et al.; European Atherosclerosis Society Consensus Panel. Adverse effects of statin therapy: perception vs. the evidence -focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke Antithrombotic Trialists' (ATT) Collaboration. increases cardiovascular risk and health Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis For prevention and management of diabetes complications in children and adoles-care costs (6). For details on the man-cents, please refer to Section 14, "Children and Adolescents." agement of CKD in children with diabe-of individual participant data from randomised trials. Lancet 2009;373:1849-1860 179. Bowman L, Mafham M, Wallendszus K, CHRONIC KIDNEY DISEASE $300 mg/g creatinine) and/or eGFR 11.5a For people with type 2 diabetes if used, should be switched prior tes, please see Section 14, "Children < 60 mL/min/1.73 m 2 to maximally tol-and CKD, use of a sodium-glucose co-to conception to antihypertensive and Adolescents." and cataract. Eur Heart J 2018;39:2526-2539 166. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22 167. Shepherd J, Blauw GJ, Murphy MB, et al.; PROSPER study group. PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360:1623-1630 168. Trompet S, van Vliet P, de Craen AJM, et al. Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J Neurol 2010; 257:85-90 169. Yusuf S, Bosch J, Dagenais G, et al.; HOPE-3 Investigators. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med 2016;374:2021-2031 170. Giugliano RP, Mach F, Zavitz K, et al.; EBBINGHAUS Investigators. Cognitive function in a randomized trial of evolocumab. N Engl J Med 2017;377:633-643 and not for profit, and the work is not altered. More information is available at https://www .diabetesjournals.org/journals/pages/license. extracellular fluid volume deple-tion. A als of childbearing potential who are not using reliable contraception and, decreasing eGFR and/or if the eGFR is < 30 mL/min/1.73 m 2 . A 171. 804-814 et al.; ASCEND Study Collaborative Group. Effects Screening erated dose to prevent the progression transporter 2 (SGLT2) inhibitor with medications considered safer dur-of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 2018;379: 1529-1539 180. Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet 2018; 392:1036-1046 181. McNeil JJ, Wolfe R, Woods RL, et al.; ASPREE Investigator Group. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med 2018;379:1509-1518 182. Pignone M, Earnshaw S, Tice JA, Pletcher MJ. Aspirin, statins, or both drugs for the primary prevention of coronary heart disease events in of kidney disease and reduce cardiovas-demonstrated benefit is recommended ing pregnancy. B ASSESSMENT OF ALBUMINURIA Recommendations cular events. A to reduce CKD progression and car-11.7 Aim to reduce urinary albumin AND ESTIMATED GLOMERULAR 11.1a Assess kidney function (i.e., spot urine albumin-to-creatinine ratio [UACR]) and estimated glomerular filtration rate [eGFR] in people with type 1 diabetes the stage of the kidney disease (Fig. 11.1). B Treatment Recommendations 11.2 Optimize glucose management to reduce the risk or slow the progression of CKD (Fig. 9.3). A 11.3 *A complete list of members of the American Diabetes Association Professional Practice Committee can be found at https://doi.org/10.2337/dc25-SINT. Duality of interest information for each author is available at https://doi.org/10.2337/dc25-SDIS. Suggested citation: American Diabetes Association Professional Practice Committee. 11. Chronic kidney disease and risk management: Standards of Care in Diabetes-2025. Diabetes Care 2025; 48(Suppl. 1):S239-S251 © 2024 by the American Diabetes Association. work is properly cited, the use is educational in individuals who have no signs of be avoided in sexually active individu-albumin levels and/or continuously Readers may use this article as long as the or for hypokalemia when diuretics are 11.4c An ACE inhibitor or an ARB is not recommended for the primary prevention of CKD in people with diabetes who have normal blood pressure, normal UACR ( < 30 mg/g creatinine), and normal eGFR. A 11.4d Continue renin-angiotensin sys-tem blockade for mild to moderate increases in serum creatinine (#30%) this population is recommended. A sive medications in pregnancy should have continuously increasing urinary 11.6 Potentially harmful antihyperten-evaluation by a nephrologist if they tassium levels should be monitored. A 11.9 Individuals should be referred for (if eGFR is $25 mL/min/1.73 m 2 ). Po-ysis. B tive in clinical trials is recommended problem for some individuals on dial-MRA that has been shown to be effec-protein energy wasting is a major CKD and albuminuria, a nonsteroidal g/kg/day should be considered since and CKD progression in people with dialysis, protein intake of 1.0-1.2 11.5c To reduce cardiovascular events eral population. A For individuals on ter initiation or after a dose change. B nist with demonstrated benefit in body weight per day, as for the gen-used at routine visits and 7-14 days af-protein intake should be 0.8 g/kg CKD, a glucagon-like peptide 1 ago-nary albumin (e.g., spot UACR) and eGFR 1-4 times per year depending on ceptor antagonists (MRAs) are used, dependent stage G3 or higher CKD, people with type 2 diabetes and 11.1b In people with established chronic kidney disease (CKD), monitor uri-tors, ARBs, and mineralocorticoid re-11.8 For people with non-dialysis-and kidney disease progression in treatment. B potassium levels when ACE inhibi-progression. B 11.5b To reduce cardiovascular risk with duration of $5 years and in all people with type 2 diabetes regardless of 11.4b Monitor for increased serum creatinine and for increased serum diovascular events in individuals with buminuria $300 mg/g to slow CKD eGFR $20 mL/min/1.73 m 2 . A by $30% in people with CKD and al-FILTRATION RATE|11. CHRONIC KIDNEY DISEASE AND RISK MANAGEMENT|

|3-Interventions that lower albuminuria| |---|

|• Blood glucose management|

|• Blood pressure management|

|• Treatment with ACE inhibitors or ARBs|

|• Smoking cessation|

|• Weight loss|

|•|

|diabetesjournals.org/care|Chronic Kidney Disease and Risk Management|S243| |---|---|---|

|Complication|Physical and laboratory evaluation||

|Blood pressure > 130/80 mmHg|Blood pressure, weight, BMI||

|Volume overload|History, physical examination, weight||

|Electrolyte abnormalities|Serum electrolytes||

|Metabolic acidosis|Serum electrolytes||

|Anemia|Hemoglobin; iron, iron saturation, ferritin testing||

||if indicated||

|Metabolic bone disease|Serum calcium, phosphate, PTH, vitamin 25(OH)D||

|Complications of chronic kidney disease (CKD) generally become prevalent when estimated|||

|glomerular filtration rate falls below 60 mL/min/1.73 m 2 (stage G3 CKD or greater) and be-|||

|come more common and severe as CKD progresses. Evaluation of elevated blood pressure|||

|and volume overload should occur at every clinical contact possible; laboratory evaluations are|||

|generally indicated every 6-12 months for stage G3 CKD, every 3-5 months for stage G4 CKD,|||

|and every 1-3 months for stage G5 CKD, or as indicated to evaluate symptoms or changes in|||

|therapy. 25(OH)D, 25-hydroxyvitamin D; PTH, parathyroid hormone.|||

|diabetesjournals.org/care|Chronic Kidney Disease and Risk Management|S245| |---|---|---|

|at high risk for CVD or with existing CVD|||

|examined kidney effects as secondary out-|||

|comes. These trials include EMPA-REG|||

|OUTCOME [BI 10773 (Empagliflozin) Car-|||

|diovascular Outcome Event Trial in Type 2|||

|Diabetes Mellitus Patients], CANVAS|||

|(Canagliflozin Cardiovascular Assessment|||

|Study), LEADER (Liraglutide Effect and Ac-|||

|tion in Diabetes: Evaluation of Cardiovas-|||

|cular Outcome Results), and SUSTAIN-6|||

|(Trial to Evaluate Cardiovascular and|||

|Other Long-term Outcomes With Sema-|||

|glutide in Subjects With Type 2 Diabetes)|||

|(91,95,98,111). Specifically, compared with|||

|placebo, empagliflozin reduced the risk|||

|of incident or worsening nephropathy|||

|(a composite of progression to UACR|||

|> 300 mg/g creatinine, doubling of se-|||

|rum creatinine, ESKD, or death from|||

|ESKD) by 39% and the risk of doubling of|||

|serum creatinine accompanied by eGFR|||

|#45 mL/min/1.73 m 2 by 44%; canagliflo-|||

|zin reduced the risk of progression of al-|||

|buminuria by 27% and the risk of|||

|reduction in eGFR, ESKD, or death from|||

|ESKD by 40%; liraglutide reduced the risk|||

|of new or worsening nephropathy (a|||

|composite of persistent macroalbuminu-|||

|ria, doubling of serum creatinine, ESKD, or|||

|death from ESKD) by 22%; and semaglutide|||

|reduced the risk of new or worsening ne-|||

|phropathy (a composite of persistent UACR|||

|> 300 mg/g creatinine, doubling of serum|||

|creatinine, or ESKD) by 36% (each P <|||

|0.01). These analyses were limited by evalu-|||

|ation of study populations not selected pri-|||

|marily for CKD and examination of kidney|||

|effects as secondary outcomes.|||

|Three large clinical trials of SGLT2 inhibi-|||

|tors have focused on people with CKD and|||

|assessment of primary kidney outcomes.|||

|Canagliflozin and Renal Events in Diabetes|||

|with Established Nephropathy Clinical Evalu-|||

|ation (CREDENCE), a placebo-controlled trial|||

|of canagliflozin among 4,401 adults with|||

|type 2 diabetes, UACR $300-5,000 mg/g|||

|creatinine, and eGFR range 30-90 mL/min/|||

|1.73 m 2 (mean eGFR 56 mL/min/1.73 m 2|||

|diabetesjournals.org/care||Chronic Kidney Disease and Risk Management|Chronic Kidney Disease and Risk Management|Chronic Kidney Disease and Risk Management|Chronic Kidney Disease and Risk Management| |---|---|---|---|---|---|

|Complications study. Diabetes Care 2010;33: 63. National Kidney Foundation. KDOQI clinical|36. Collard D, Brouwer TF, Peters RJG, Vogt L, 78. Mauer M, Zinman B, Gardiner R, et al. Renal||50. Whelton PK, Carey RM, Aronow WS, et al. hypertension in mouse model of type 2 diabetes|50. Whelton PK, Carey RM, Aronow WS, et al. hypertension in mouse model of type 2 diabetes||

|1536-1543 practice guideline for diabetes and CKD: 2012 van den Born B-JH. Creatinine rise during blood and retinal effects of enalapril and losartan in||2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ mellitus. Am J Nephrol 2019;49:331-342|2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ mellitus. Am J Nephrol 2019;49:331-342|||

|20. He F, Xia X, Wu XF, Yu XQ, Huang FX. Diabetic update. Am J Kidney Dis 2012;60:850-886|pressure therapy and the risk of adverse clinical type 1 diabetes. N Engl J Med 2009;361:40-51||ASPC/NMA/PCNA guideline for the prevention, 94. Heerspink HJL, Perco P, Mulder S, et al.|ASPC/NMA/PCNA guideline for the prevention, 94. Heerspink HJL, Perco P, Mulder S, et al.||

|retinopathy in predicting diabetic nephropathy in 64. Tuttle KR, Bakris GL, Bilous RW, et al. Diabetic outcomes in patients with type 2 diabetes 79. Weil EJ, Fufaa G, Jones LI, et al. Effect of||detection, evaluation, and management of high Canagliflozin reduces inflammation and fibrosis|detection, evaluation, and management of high Canagliflozin reduces inflammation and fibrosis|||

|patients with type 2 diabetes and renal disease: a meta-analysis. Diabetologia 2013;56:457-466 21. Vistisen D, Andersen GS, Hulman A, Persson kidney disease: a report from an ADA Consensus Conference. Diabetes Care 2014;37:2864-2883 65. Kidney Disease: Improving Global Outcomes 12. Retinopathy, Neuropathy, and mellitus. Hypertension 2018;72:1337-1344 37. Malhotra R, Craven T, Ambrosius WT, et al.; SPRINT Research Group. Effects of intensive losartan on prevention and progression of early diabetic nephropathy in American Indians with type 2 diabetes. Diabetes 2013;67:532-3231||blood pressure in adults: executive summary: a report of the American College of Cardiology/ American Heart Association Task Force on Clinical biomarkers: a potential mechanism of action for beneficial effects of SGLT2 inhibitors in diabetic kidney disease. Diabetologia 2019;62:1154-1166 American Diabetes Association Professional Practice Committee*|blood pressure in adults: executive summary: a report of the American College of Cardiology/ American Heart Association Task Force on Clinical biomarkers: a potential mechanism of action for beneficial effects of SGLT2 inhibitors in diabetic kidney disease. Diabetologia 2019;62:1154-1166 American Diabetes Association Professional Practice Committee*|||

|F, Rossing P, Jørgensen ME. Progressive decline in estimated glomerular filtration rate in patients with diabetes after moderate loss in kidney function-even without albuminuria. Diabetes Care 2019;42:1886-1894 (KDIGO) Diabetes Work Group. KDIGO 2022 clinical practice guideline for diabetes management in blood pressure lowering on kidney tubule injury in CKD: a longitudinal subgroup analysis in SPRINT. Am J Kidney Dis 2019;73:21-30 38. Hughes-Austin JM, Rifkin DE, Beben T, et al. The relation of serum potassium concentration chronic kidney disease. Kidney Int 2022;102: S1-S127 66. Leehey DJ, Zhang JH, Emanuele NV, et al.; VA 80. Qiao Y, Shin J-I, Chen TK, et al. Association between renin-angiotensin system blockade discontinuation and all-cause mortality among persons with low estimated glomerular filtration rate. JAMA Intern Med 2020;180:718-726 Foot Care: Standards of Care in Diabetes-2025||Practice Guidelines. Hypertension 2018;71:1269-1324 51. Murray DP, Young L, Waller J, et al. Is dietary protein intake predictive of 1-year mortality in dialysis patients? Am J Med Sci 2018;356: 95. Marso SP, Daniels GH, Brown-Frandsen K, et al.; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375:311-322 96. Cooper ME, Perkovic V, McGill JB, et al.|Practice Guidelines. Hypertension 2018;71:1269-1324 51. Murray DP, Young L, Waller J, et al. Is dietary protein intake predictive of 1-year mortality in dialysis patients? Am J Med Sci 2018;356: 95. Marso SP, Daniels GH, Brown-Frandsen K, et al.; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375:311-322 96. Cooper ME, Perkovic V, McGill JB, et al.|||

|22. Levey AS, Coresh J, Balk E, et al.; National Kidney Foundation. National Kidney Foundation NEPHRON-D Study Group. BP and renal outcomes in diabetic kidney disease: the Veterans Affairs Diabetes Care 2025;48(Suppl. 1):S252-S265 | https://doi.org/10.2337/dc25-S012 with cardiovascular events and mortality in community-living individuals. Clin J Am Soc Nephrol 81. Ohkuma T, Jun M, Rodgers A, et al.; ADVANCE Collaborative Group. Acute increases 234-243 52. DCCT/EDIC Research Group. Effect of Kidney disease end points in a pooled analysis of individual patient-level data from a large clinical||||||

|practice guidelines for chronic kidney disease: Nephropathy in Diabetes Trial. Clin J Am Soc 2017;12:245-252 in serum creatinine after starting angiotensin-intensive diabetes treatment on albuminuria in trials program of the dipeptidyl peptidase 4||||||

|evaluation, classification, and stratification. Ann Nephrol 2015;10:2159-2169|39. Bandak G, Sang Y, Gasparini A, et al. converting enzyme inhibitor-based therapy and|type 1 diabetes: long-term follow-up of the inhibitor linagliptin in type 2 diabetes. Am J|type 1 diabetes: long-term follow-up of the inhibitor linagliptin in type 2 diabetes. Am J|||

|Intern Med 2003;139:137-147 67. Emdin CA, Rahimi K, Neal B, Callender T,|Hyperkalemia after initiating renin-angiotensin effects of its continuation on major clinical Diabetes Control and Complications Trial and Kidney Dis 2015;66:441-449|||||

|23. Matzke GR, Aronoff GR, Atkinson AJ, Jr, et al. Perkovic V, Patel A. Blood pressure lowering in system blockade: the Stockholm Creatinine outcomes in type 2 diabetes mellitus. Hyper-|Epidemiology of Diabetes Interventions and 97. Mann JFE, Ørsted DD, Brown-Frandsen K,|Epidemiology of Diabetes Interventions and 97. Mann JFE, Ørsted DD, Brown-Frandsen K,||||

|Drug dosing consideration in patients with acute type 2 diabetes: a systematic review and meta-|Measurements (SCREAM) project. J Am Heart tension 2019;73:84-91|Complications study. Lancet Diabetes Endocrinol et al.; LEADER Steering Committee and|Complications study. Lancet Diabetes Endocrinol et al.; LEADER Steering Committee and|||

|and chronic kidney disease-a clinical update from Kidney Disease: Improving Global Outcomes analysis. JAMA 2015;313:603-615 68. Cushman WC, Evans GW, Byington RP, et al.; Assoc 2017;6 82. Ku E, Tighiouart H, McCulloch CE, et al. 2014;2:793-800 Investigators. Liraglutide and renal outcomes in 40. Nilsson E, Gasparini A, € Arnl€ ov J, et al. 53. de Boer IH, Sun W, Cleary PA, et al.; DCCT/ Association between acute declines in eGFR type 2 diabetes. N Engl J Med 2017;377:839-848||||||

|(KDIGO). Kidney Int 2011;80:1122-1137 24. Coresh J, Turin TC, Matsushita K, et al. Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality. JAMA 2014;311:2518-2531 25. Vassalotti JA, Centor R, Turner BJ, Greer RC, Choi M, Sequist TD, National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Practical approach to detection and management of chronic kidney disease for the primary care clinician. Am J Med 2016;129:153-162.e157 26. Zhou J, Liu Y, Tang Y, et al. A comparison of RIFLE, AKIN, KDIGO, and Cys-C criteria for the definition of acute kidney injury in critically ill patients. Int Urol Nephrol 2016;48:125-132 27. Hoste EAJ, Kellum JA, Selby NM, et al. Global epidemiology and outcomes of acute kidney injury. Nat Rev Nephrol 2018;14:607-625 28. James MT, Grams ME, Woodward M, et al.; CKD Prognosis Consortium. A meta-analysis of the association of estimated GFR, albuminuria, diabetes mellitus, and hypertension with acute kidney injury. Am J Kidney Dis 2015;66:602-612 29. Perkovic V, Jardine MJ, Neal B, et al.; CREDENCE Trial Investigators. Canagliflozin and renal outcomes in type 2 diabetes and nephro-pathy. N Engl J Med 2019;380:2295-2306 30. Nadkarni GN, Ferrandino R, Chang A, et al. Acute kidney injury in patients on SGLT2 inhibitors: a propensity-matched analysis. Diabetes Care 2017; 40:1479-1485 ACCORD Study Group. Effects of intensive blood-and MICRO-HOPE substudy. Lancet 2000;355: Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system. Int J Cardiol 2017;245:277-284 41. Zelniker TA, Raz I, Mosenzon O, et al. Effect of dapagliflozin on cardiovascular outcomes according to baseline kidney function and albuminuria status in patients with type 2 diabetes: a prespecified secondary analysis of a randomized clinical trial. JAMA Cardiol 2021;6:801-810 42. Epstein M, Reaven NL, Funk SE, McGaughey KJ, Oestreicher N, Knispel J. Evaluation of the treatment gap between clinical guidelines and the utilization of renin-angiotensin-aldosterone system inhibitors. Am J Manag Care 2015;21: S212-220 43. de Boer IH, Gao X, Cleary PA, et al.; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/ EDIC) Research Group. Albuminuria changes and cardiovascular and renal outcomes in type 1 diabetes: the DCCT/EDIC study. Clin J Am Soc Nephrol 2016;11:1969-1977 44. Sumida K, Molnar MZ, Potukuchi PK, et al. Changes in albuminuria and subsequent risk of incident kidney disease. Clin J Am Soc Nephrol 2017;12:1941-1949 45. Wexler DJ, de Boer IH, Ghosh A, et al.; GRADE Research Group. Comparative effects of glucose-lowering medications on kidney outcomes in type 2 diabetes: the GRADE randomized clinical trial. JAMA Intern Med 2023;183:705-714 during renin-angiotensin system inhibition and 89. Cherney DZI, Perkins BA, Soleymanlou N, EDIC Research Group. Intensive diabetes therapy 98. Marso SP, Bain SC, Consoli A, et al.; SUSTAIN-6 and glomerular filtration rate in type 1 diabetes. N Engl J Med 2011;365:2366-2376 54. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with con-ventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837-853 55. Patel A, MacMahon S, Chalmers J, et al.; ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358: 2560-2572 56. Ismail-Beigi F, Craven T, Banerji MA, et al.; ACCORD trial group. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet 2010;376:419-430 57. Zoungas S, Chalmers J, Neal B, et al.; ADVANCE-ON Collaborative Group. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med 2014;371:1392-1406 58. Zoungas S, Arima H, Gerstein HC, et al.; Collaborators on Trials of Lowering Glucose (CONTROL) group. Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual trials. Lancet Diabetes Endocrinol 2017;5:431-https://www.fda.gov/drugs/drug-safety-and-participant data from randomised controlled pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-1585 69. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 dia-betes: UKPDS 38. BMJ 1998;317:703-713 70. de Boer IH, Bangalore S, Benetos A, et al. Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care 2017;40:1273-1284 71. Brenner BM, Cooper ME, de Zeeuw D, et al.; RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861-869 72. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD; The Collaborative Study Group.The effect of angiotensin-converting-enzyme inhibition on diabetic nephro-pathy. N Engl J Med 1993;329:1456-1462 73. Lewis EJ, Hunsicker LG, Clarke WR, et al.; Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851-860 74. Heart Outcomes Prevention Evaluation phropathy. N Engl J Med 2013;369:1892-1903 2017. Accessed 25 August 2024. Available from with diabetes mellitus: results of the HOPE study inhibition for the treatment of diabetic ne-in certain patients with reduced kidney function, vascular and microvascular outcomes in people NEPHRON-D Investigators. Combined angiotensin regarding use of the diabetes medicine metformin Study Investigators. Effects of ramipril on cardio-Investigators. Semaglutide and cardiovascular risk of adverse outcomes. J Am Soc Nephrol outcomes in patients with type 2 diabetes. N Engl 2024;35:1402-1411 J Med 2016;375:1834-1844 83. Hattori K, Sakaguchi Y, Oka T, et al. Estimated 99. Shaman AM, Bain SC, Bakris GL, et al. Effect effect of restarting renin-angiotensin system of the glucagon-like peptide-1 receptor agonists inhibitors after discontinuation on kidney out-semaglutide and liraglutide on kidney outcomes comes and mortality. J Am Soc Nephrol 2024; in patients with type 2 diabetes: pooled analysis 35:1391-1401 of SUSTAIN 6 and LEADER. Circulation 2022;145: 84. Shulman R, Cohen JB. Navigating renin-575-585 angiotensin system inhibitors in patients with 100. Perkovic V, Tuttle KR, Rossing P, et al.; declines in eGFR. J Am Soc Nephrol 2024;35: FLOW Trial Committees and Investigators. Effects 1309-1311 of semaglutide on chronic kidney disease in 85. Bangalore S, Fakheri R, Toklu B, Messerli FH. patients with type 2 diabetes. N Engl J Med Diabetes mellitus as a compelling indication for use 2024;391:109-121 of renin angiotensin system blockers: systematic 101. Karter AJ, Warton EM, Lipska KJ, et al. For prevention and management of diabetes complications in children and adoles-review and meta-analysis of randomized trials. BMJ 2016;352:i438 Development and validation of a tool to identify cents, please refer to Section 14, "Children and Adolescents." patients with type 2 diabetes at high risk of 86. Haller H, Ito S, Izzo JL, Jr, et al.; ROADMAP hypoglycemia-related emergency department or Trial Investigators. Olmesartan for the delay or drug safety communication: FDA revises warnings 88. Fried LF, Emanuele N, Zhang JH, et al.; VA 103. U.S. Food and Drug Administration. FDA Med 2008;358:1547-1559 2009;4:1121-1127 patients at high risk for vascular events. N Engl J chronic kidney disease. Clin J Am Soc Nephrol Investigators. Telmisartan, ramipril, or both in Frequency of hypoglycemia and its significance in 87. Yusuf S, Teo KK, Pogue J, et al.; ONTARGET 102. Moen MF, Zhan M, Hsu VD, et al. betes. N Engl J Med 2011;364:907-917 1461-1470 prevention of microalbuminuria in type 2 dia-hospital use. JAMA Intern Med 2017;177: DIABETIC RETINOPATHY||||||

|31. Wanner C, Inzucchi SE, Lachin JM, et al.; 253-259||46. Klahr S, Levey AS, Beck GJ, et al.; et al. Renal hemodynamic effect of sodium-||437|availability/fda-drug-safety-communication-|

|EMPA-REG OUTCOME Investigators. Empagliflozin 75. Barnett AH, Bain SC, Bouter P, et al.; Modification of Diet in Renal Disease Study glucose cotransporter 2 inhibition in patients 59. Agrawal L, Azad N, Bahn GD, et al.; VADT fda-revises-warnings-regarding-use-diabetes-||||||

|and progression of kidney disease in type 2 Diabetics Exposed to Telmisartan and Enalapril||Group. The effects of dietary protein restriction with type 1 diabetes mellitus. Circulation 2014;||Study Group. Long-term follow-up of intensive medicine-metformin-certain|Study Group. Long-term follow-up of intensive medicine-metformin-certain|

|diabetes. N Engl J Med 2016;375:323-334 Study Group. Angiotensin-receptor blockade versus||and blood-pressure control on the progression of 129:587-597||glycaemic control on renal outcomes in the 104. Lalau J-D, Kajbaf F, Bennis Y, Hurtel-Lemaire|glycaemic control on renal outcomes in the 104. Lalau J-D, Kajbaf F, Bennis Y, Hurtel-Lemaire|

|32. Neuen BL, Ohkuma T, Neal B, et al. converting-enzyme inhibition in type 2 diabetes||chronic renal disease. N Engl J Med 1994;330: 90. Heerspink HJL, Desai M, Jardine M, Balis D,||Veterans Affairs Diabetes Trial (VADT). Diabetologia A-S, Belpaire F, De Broe ME. Metformin|Veterans Affairs Diabetes Trial (VADT). Diabetologia A-S, Belpaire F, De Broe ME. Metformin|

|Cardiovascular and renal outcomes with can-and nephropathy. N Engl J Med 2004;351:|877-884 Meininger G, Perkovic V. Canagliflozin slows|2018;61:295-299 treatment in patients with type 2 diabetes and|2018;61:295-299 treatment in patients with type 2 diabetes and|||

1-Criteria for the diagnosis of diabetes in nonpregnant individuals A1C $6.5% ($48 mmol/mol). The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay.* with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose $200 mg/dL ($11.1 mmol/L). Random is any time of the day without regard to time since previous meal. DCCT, Diabetes Control and Complications Trial; FPG, fasting plasma glucose; OGTT, oral glucose tolerance test; NGSP, National Glycohemoglobin Standardization Program; WHO, World Health Organization; 2-h PG, 2-h plasma glucose. *In the absence of unequivocal hyperglycemia, diagnosis requires two abnormal results from different tests which may be obtained at the same time (e.g., A1C and FPG), or the same test at two different time points.

|agliflozin according to baseline kidney function. 1952-1961||47. Ikizler TA, Burrowes JD, Byham-Gray LD, et al. progression of renal function decline independently 60. Papademetriou V, Lovato L, Doumas M, chronic kidney disease stages 3A, 3B, or 4.||||

|Circulation 2018;138:1537-1550 76. Wu H-Y, Peng C-L, Chen P-C, et al. KDOQI clinical practice guideline for nutrition in of glycemic effects. J Am Soc Nephrol 2017;28:||et al.; ACCORD Study Group. Chronic kidney Diabetes Care 2018;41:547-553|et al.; ACCORD Study Group. Chronic kidney Diabetes Care 2018;41:547-553|||

|33. Bakris GL, Agarwal R, Anker SD, et al.; Comparative effectiveness of angiotensin-converting||CKD: 2020 update. Am J Kidney Dis 2020;76: 368-375||disease and intensive glycemic control increase 105. Chu PY, Hackstadt AJ, Chipman J, et al.|disease and intensive glycemic control increase 105. Chu PY, Hackstadt AJ, Chipman J, et al.|

|FIDELIO-DKD Investigators. Effect of finerenone enzyme inhibitors versus angiotensin II receptor||S1-S107 91. Neal B, Perkovic V, Mahaffey KW, et al.;||cardiovascular risk in patients with type 2 Hospitalization for lactic acidosis among patients|cardiovascular risk in patients with type 2 Hospitalization for lactic acidosis among patients|

|on chronic kidney disease outcomes in type 2 blockers for major renal outcomes in patients with||48. Rhee CM, Wang AY-M, Biruete A, et al. CANVAS Program Collaborative Group. Canagliflozin||diabetes. Kidney Int 2015;87:649-659 with reduced kidney function treated with|diabetes. Kidney Int 2015;87:649-659 with reduced kidney function treated with|

|diabetes. N Engl J Med 2020;383:2219-2229 diabetes: a 15-year cohort study. PLoS One 2017;|Nutritional and dietary management of chronic and cardiovascular and renal events in type 2 61. Perkovic V, Heerspink HL, Chalmers J, et al.; metformin or sulfonylureas. Diabetes Care 2020;|||||

|34. Thakar CV, Christianson A, Himmelfarb J, 12:e0177654||kidney disease under conservative and preser-diabetes. N Engl J Med 2017;377:644-657||ADVANCE Collaborative Group. Intensive glucose 43:1462-1470|ADVANCE Collaborative Group. Intensive glucose 43:1462-1470|

|Leonard AC. Acute kidney injury episodes and 77. Parving HH, Lehnert H, Br€ ochner-Mortensen||vative kidney care without dialysis. J Ren Nutr 92. Zelniker TA, Braunwald E. Cardiac and renal control improves kidney outcomes in patients with 106. McGuire DK, Shih WJ, Cosentino F, et al.||||

|chronic kidney disease risk in diabetes mellitus. J, Gomis R, Andersen S, Arner P; Irbesartan in||2023;33:S56-S66 effects of sodium-glucose co-transporter 2 inhibitors|type 2 diabetes. Kidney Int 2013;83:517-523 Association of SGLT2 inhibitors with cardio-|type 2 diabetes. Kidney Int 2013;83:517-523 Association of SGLT2 inhibitors with cardio-||

|Clin J Am Soc Nephrol 2011;6:2567-2572 Patients with Type 2 Diabetes and Micro-||49. Mills KT, Chen J, Yang W, et al.; Chronic Renal in diabetes: JACC state-of-the-art review. J Am Coll 62. Wong MG, Perkovic V, Chalmers J, et al.; vascular and kidney outcomes in patients with||||

|35. Bakris GL, Weir MR. Angiotensin-converting albuminuria Study Group. The effect of irbesartan||Insufficiency Cohort (CRIC) Study Investigators. Cardiol 2018;72:1845-1855||ADVANCE-ON Collaborative Group. Long-term type 2 diabetes: a meta-analysis. JAMA Cardiol|ADVANCE-ON Collaborative Group. Long-term type 2 diabetes: a meta-analysis. JAMA Cardiol|

|enzyme inhibitor-associated elevations in serum on the development of diabetic nephropathy in||Sodium excretion and the risk of cardiovascular 93. Woods TC, Satou R, Miyata K, et al.||benefits of intensive glucose control for pre-2021;6:148-158|benefits of intensive glucose control for pre-2021;6:148-158|

|creatinine: is this a cause for concern? Arch patients with type 2 diabetes. N Engl J Med||disease in patients with chronic kidney disease. Canagliflozin prevents intrarenal angiotensinogen||venting end-stage kidney disease: ADVANCE-ON. 107. Zelniker TA, Wiviott SD, Raz I, et al.|venting end-stage kidney disease: ADVANCE-ON. 107. Zelniker TA, Wiviott SD, Raz I, et al.|

|Intern Med 2000;160:685-693 2001;345:870-878||JAMA 2016;315:2200-2210 augmentation and mitigates kidney injury and||Diabetes Care 2016;39:694-700 Comparison of the effects of glucagon-like peptide|Diabetes Care 2016;39:694-700 Comparison of the effects of glucagon-like peptide|

|Category|Ulcer risk|Characteristics|Examination frequency*| |---|---|---|---|

|1|Low|LOPS or PAD|Every 6-12 months|

|||LOPS 1 foot deformity, or|LOPS 1 foot deformity, or|

|||PAD 1 foot deformity|PAD 1 foot deformity|

|||History of foot ulcer|History of foot ulcer|

|||Amputation (minor or major)|Amputation (minor or major)|

|||End-stage renal disease|End-stage renal disease|

|||Lipids|Statin, unless|contraindicated|or not tolerated||||Statin, unless|contraindicated|or not tolerated||||||||Consider likelihood|of benefit with|statin||||||| |---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

||Blood|pressure|< 130/80 mmHg||||||< 130/80 mmHg||||||||||< 140/90 mmHg|||||||||

|||Bedtime glucose|80-180 mg/dL|(4.4-10.0|mmol/L)||||100-180 mg/dL|(5.6-10.0|mmol/L)||||||||110-200 mg/dL|(6.1-11.1|mmol/L)|||||||

|Fasting or|preprandial|glucose|80-130 mg/dL|(4.4-7.2 mmol/L)|||||90-150 mg/dL|(5.0-8.3 mmol/L)|||||||||100-180 mg/dL|(5.6-10.0 mmol/L)||||||||

||Reasonable CGM|goals|TIR 70-180 mg/dL|(3.9-10.0 mmol)|of $70%, and|TBR < 70 mg/dL|(3.9 mmol/L) of|< 4%)|TIR 70-180 mg/dL|(3.9-10.0 mmol)|of $50% and|TBR < 70 mg/dL|(3.9 mmol/L) of|< 1%||||||||||||||

||Reasonable A1C|goal*|< 7.0-7.5%|( < 53-58|mmol/mol)||||< 8.0%|( < 64 mmol/mol)|||||||||Avoid reliance on|A1C; glucose|management|decisions should|be based on|avoiding|hypoglycemia and|symptomatic|hyperglycemia|

|||Rationale|Longer remaining life|expectancy|||||Variable life expectancy.|Individualize goals,|considering:|Severity of comorbidities|Cognitive and functional|limitations|Frailty|Risk-to-benefit ratio of|diabetes medications|Individual preference|Limited remaining life|expectancy makes|benefit minimal|||||||

|Characteristics and health|status of person with|diabetes|Healthy (few coexisting|chronic illnesses, intact|cognitive and functional|status)|||Complex/intermediate|(multiple coexisting|chronic illnesses † or two|or more ADL impairments|or mild to moderate|cognitive impairment)|||||Very complex/poor health|(LTC or end-stage chronic|illnesses ‡ or moderate to|severe cognitive|impairment or two or|more ADL impairments)||||

|Metformin| |---|

|Metformin is a treatment option for older|

|adults with type 2 diabetes if prescription|

|guidelines are followed carefully. Metfor-|

|min may be used safely in individuals with|

|an estimated glomerular filtration rate|

|(eGFR) $30 mL/min/1.73 m 2 (111), while|

|lower doses may be used in those with|

|an eGFR 30-45 mL/min/1.73 m 2 . eGFR|

|should be monitored every 3 to 6 months|

|in those at risk for decline in kidney func-|

|tion. However, it is contraindicated in|

|those with advanced renal insufficiency|

|and should be used with caution in those|

|with hypoperfusion, hypoxemia, impaired|

|hepatic function, or heart failure because|

|of the increased risk of lactic acidosis. Met-|

|formin may be temporarily discontinued|

|before procedures including imaging stud-|

|ies using iodinated contrast, during hospi-|

|talizations, and when acute illness may|

|compromise renal or liver function. Addi-|

|tionally, metformin can cause gastrointesti-|

|nal side effects and a reduction in appetite|

|that can be problematic for some older|

|adults. The daily dose should be slowly in-|

|creased to minimize gastrointestinal side|

|effects, and reduction or elimination of|

|metformin may be necessary for those|

|experiencing persistent gastrointestinal|

|diabetesjournals.org/care||||Older Adults|S275| |---|---|---|---|---|---|

|Characteristics and|||When may medication plan|When may treatment|When may treatment|

|health status of person|Reasonable||simplification be|deintensification be|deintensification be|

|cognitive and||for glycemic|therapy, regardless of|insulin, sulfonylureas,|insulin, sulfonylureas,|

|function)||management|A1C|or meglitinides,|or meglitinides,|

|||• During acute illness,|• Wide glucose|regardless of A1C|regardless of A1C|

|||individuals may be at|excursions|• Wide glucose|• Wide glucose|

|||risk for administration or|• Cognitive or functional|excursions||

|||dosing errors|decline following acute|• Polypharmacy|• Polypharmacy|

||||illness|||

|illnesses or two or||and capacity to avoid|therapy, regardless of|lin, sulfonylureas, or|lin, sulfonylureas, or|

|more ADL impairments||hypoglycemia|A1C|meglitinides regardless|meglitinides regardless|

|or mild to moderate|||• Unable to manage|of A1C||

|cognitive impairment)|||complexity of insulin|• Wide glucose|• Wide glucose|

||||plan|excursions||

||||• Significant change in|• Polypharmacy|• Polypharmacy|

||||social circumstances,|||

||||such as loss of care|||

||||partner, change in|||

||||living situation, or|||

||||financial difficulties|||

|||avoidance of infections|during hospitalization|||

|||• Recovery from acute||||

|||illness may impair||||

|||cognitive function||||

|||• More support may be||||

|||needed on transition to||||

|||home||||

|impairment or two or||• Most important|• The individual has an|meglitinides|meglitinides|

|more ADL||outcomes are|inconsistent eating|• Taking any diabetes|• Taking any diabetes|

|impairments)||maintenance of cognitive|pattern|medications without|medications without|

|||and functional status||clear benefits|clear benefits|

||and symptomatic|comfort and avoid tasks|caused by treatment|medications without|medications without|

||hyperglycemia|or interventions that|(e.g., injections or|clear benefits in|clear benefits in|

|||cause pain or discomfort|finger sticks)|improving symptoms|improving symptoms|

|||• Care partners are|• Excessive stress of care|and/or comfort|and/or comfort|

|||important in providing|partners due to|||

|||medical care and|treatment complexity|||

|||maintaining quality of life||||

|*A complete list of members of the American| |---|

|Diabetes Association Professional Practice Committee|

|can be found at https://doi.org/10.2337/dc25-SINT.|

|Duality of interest information for each author is|

|available at https://doi.org/10.2337/dc25-SDIS.|

|Suggested citation: American Diabetes Association|

|Professional Practice Committee. 14. Children and|

|adolescents: Standards of Care in Diabetes-2025.|

|Diabetes Care 2025;48(Suppl. 1):S283-S305|

|Polycystic ovary|syndrome (for|adolescent female|individuals)|14.90 and 14.91||Screening for|symptoms;|laboratory|evaluation if positive|symptoms||At diagnosis||||Every visit||||||NA||||If no contraindications,|oral contraceptive|pills; medical|nutrition therapy;|metformin||||||||| |---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

|||Obstructive|sleep apnea|14.89||Screening for|symptoms|||||At diagnosis||||Every visit||||||NA||||If positive symptoms,|refer to sleep|specialist and|polysomnogram||||||||||

||Metabolic dysfunction-|associated steatotic|liver disease|14.87 and 14.88||AST and ALT|measurement|||||At diagnosis||||Annually||||||NA||||Refer to gastroenterology|for persistently|elevated or worsening|transaminases||||||||||

||||Dyslipidemia|14.93-14.97||Lipid profile||||||Soon after diagnosis,|preferably after|glycemia has|improved|Annually||||||LDL < 100 mg/dL, HDL|> 35 mg/dL,|triglycerides|< 150 mg/dL|If abnormal, optimize|glycemia and medical|nutrition therapy; if|LDL > 130 mg/dL after|6 months, initiate|statin therapy (for|those aged > 10|years);* if triglycerides|> 400 mg/dL fasting|or > 1,000 mg/dL|nonfasting, begin|fibrate||

||||Retinopathy|14.83-14.86||Dilated|fundoscopy|||||At or soon|after diagnosis|||If normal, annually|or every 2 years|if glycemic goals|are achieved|||No retinopathy||||Optimize glycemia;|treatment per|ophthalmology|||||||||||

||||Hypertension Nephropathy Neuropathy|Corresponding 14.72-14.75 14.76-14.80 14.81 and 14.82|recommendations|Method Blood pressure Albumin-to-creatinine Foot exam with foot|monitoring ratio; random pulses, pinprick, 10-g|sample acceptable monofilament|initially sensation tests,|vibration, and ankle|reflexes|When to start At diagnosis At diagnosis At diagnosis||||Follow-up frequency Every visit If normal, annually; If normal, annually|if abnormal, repeat|with confirmation in|two of three|samples over 6|months|Goal < 90th percentile for age, < 30 mg/g No neuropathy|sex, and height; if|$13 years old,|< 130/80 mmHg|Treatment Lifestyle modification for Optimize glycemia Optimize glycemia;|elevated blood pressure and blood pressure; referral to neurology|(90th to < 95th percentile ACE inhibitor* if|for age, sex, and height albumin-to-|or, if $13 years old, creatinine ratio is|120-129/ < 80 mmHg); elevated in two of|lifestyle modification and three samples over 6|ACE inhibitor or ARB* for months|hypertension ($95th|percentile for age, sex,|and height or, if $13|years, $130/80 mmHg)|ARB, angiotensin receptor blocker; NA, not applicable; tTG, tissue transglutaminase.|

|5 for evi-| |---|

|dence grading of other risk factors).|

|14.50 If screening is normal, repeat|

|screening at a minimum of 2-year in-|

|tervals E or more frequently if BMI is|

|increasing. C|

|14.51 Fasting plasma glucose, 2-h|

|plasma glucose during a 75-g oral glu-|

|cose tolerance test, and A1C can be|

|used to test for prediabetes or diabe-|

|tes in children and adolescents. B|

|14.52 Children and adolescents with|

|overweight or obesity in whom the|

|diagnosis of type 2 diabetes is being|

|considered should have a panel of|

|#8% [#64 mmol/mol] for 6 months) in|||| |---|---|---|---|

|approximately half of the subjects (204).||||

|The Restoring Insulin Secretion (RISE)||||

|Consortium study did not demonstrate||||

|A1C 8.5% No acidosis or ketosis differences in measures of glucose or b-cell function preservation between|A1C 8.5% No acidosis with or without ketosis||Acidosis and/or DKA and/or HHS|

|metformin and insulin, but there was||||

|• Metformin • Titrate up to 2,000 mg per day as tolerated more weight gain with insulin (205).|and titrate every 23 days based on BGM • Long-acting insulin: start at 0.5 units/kg/day per day as tolerated • Titrate up to 2,000 mg • Metformin|until results of antibody testing are known then subcutaneous, as for type 1 diabetes • Intravenous insulin until acidosis resolves, • Manage DKA or HHS||

||Pancreatic autoantibodies|||

|NEGATIVE||||

|A1C goals not met||||

|• Continue metformin||||

|• Consider adding GLP1 receptor agonist or SGLT2 inhibitor||||

|approved for youth with type 2 diabetes||||

|• Consider prioritizing and maximizing noninsulin medications to||||

|minimize weight gain before escalating insulin doses||||

|• Titrate or initiate insulin therapy; if using long-acting insulin only||||

|and glycemic goal are not met with escalating doses, add prandial|and glycemic goal are not met with escalating doses, add prandial|||

|insulin; total daily insulin dose may exceed 1 unit/kg/day||||

|Overweight and obesity or underweight| |---|

|Meal planning|

|Correction of dietary nutritional deficiencies|

|Caffeine intake|

|Safe food preparation technique|

|w Lifestyle recommendations for:|

|Regular moderate exercise|

|Avoidance of hyperthermia (hot tubs)|

|Adequate sleep|

|w|

|||Blood glucose goal|| |---|---|---|---|

|Glucose measurement|Type 1 diabetes or type 2 diabetes^GDM treated with insulin|GDM not treated with insulin||

|POSTPARTUM CARE Recommendations 15.26 Insulin requirements need to be evaluated and adjusted for individuals requiring insulin after delivery because insulin resistance decreases dramati-cally immediately postpartum. C 15.27 A contraceptive plan should be discussed and implemented with all people with diabetes of childbearing potential. A 15.28 Diabetes Treatment Postpartum| |---|

|I.V. Fluids||||Insulin||Potassium| |---|---|---|---|---|---|---|

||||Mild DKA|Moderate or severe DKA|HHS|Establish adequate renal function (uri .5 mL/kg/h)|

|Determine hydration status|||||||

||||s.c. insulin|i.v. insulin|i.v. insulin|K + 3.5 mmol/L|

|.5 mmol/L (faster K + replacement will require central venous access) 4 and 5 mmol/L 0.10-20 mmol/L/h until K + Start 0.05 units/kg/h short-acting insulin as fixed-rate i.v. infusion † or nurse-driven protocol with a variable rate based on glucose values Severe hypovolemia Mild hypovolemia Cardiac compromise 0.1 units/kg rapid-acting insulin analog as s.c. bolus Consider 0.1 units/kg short-acting insulin as i.v. bolus if there is a delay in setting up the infusion 0.9% NaCl or other cr 0 L/h) K + .5-5.0 mmol/L Give Hemodynamic monitoring/pressors 0.1 units/kg/h short-0.1 units/kg rapid-acting acting insulin i.v. insulin analog every 1 h fixed-rate i.v. insulin or 0.2 units/kg every 2 h infusion or nurse-+ driven protocol with in each liter of i.v. fluid a variable rate based as needed to keep serum K + between on glucose values|.5 mmol/L (faster K + replacement will require central venous access) 4 and 5 mmol/L 0.10-20 mmol/L/h until K + Start 0.05 units/kg/h short-acting insulin as fixed-rate i.v. infusion † or nurse-driven protocol with a variable rate based on glucose values Severe hypovolemia Mild hypovolemia Cardiac compromise 0.1 units/kg rapid-acting insulin analog as s.c. bolus Consider 0.1 units/kg short-acting insulin as i.v. bolus if there is a delay in setting up the infusion 0.9% NaCl or other cr 0 L/h) K + .5-5.0 mmol/L Give Hemodynamic monitoring/pressors 0.1 units/kg/h short-0.1 units/kg rapid-acting acting insulin i.v. insulin analog every 1 h fixed-rate i.v. insulin or 0.2 units/kg every 2 h infusion or nurse-+ driven protocol with in each liter of i.v. fluid a variable rate based as needed to keep serum K + between on glucose values|.5 mmol/L (faster K + replacement will require central venous access) 4 and 5 mmol/L 0.10-20 mmol/L/h until K + Start 0.05 units/kg/h short-acting insulin as fixed-rate i.v. infusion † or nurse-driven protocol with a variable rate based on glucose values Severe hypovolemia Mild hypovolemia Cardiac compromise 0.1 units/kg rapid-acting insulin analog as s.c. bolus Consider 0.1 units/kg short-acting insulin as i.v. bolus if there is a delay in setting up the infusion 0.9% NaCl or other cr 0 L/h) K + .5-5.0 mmol/L Give Hemodynamic monitoring/pressors 0.1 units/kg/h short-0.1 units/kg rapid-acting acting insulin i.v. insulin analog every 1 h fixed-rate i.v. insulin or 0.2 units/kg every 2 h infusion or nurse-+ driven protocol with in each liter of i.v. fluid a variable rate based as needed to keep serum K + between on glucose values|.5 mmol/L (faster K + replacement will require central venous access) 4 and 5 mmol/L 0.10-20 mmol/L/h until K + Start 0.05 units/kg/h short-acting insulin as fixed-rate i.v. infusion † or nurse-driven protocol with a variable rate based on glucose values Severe hypovolemia Mild hypovolemia Cardiac compromise 0.1 units/kg rapid-acting insulin analog as s.c. bolus Consider 0.1 units/kg short-acting insulin as i.v. bolus if there is a delay in setting up the infusion 0.9% NaCl or other cr 0 L/h) K + .5-5.0 mmol/L Give Hemodynamic monitoring/pressors 0.1 units/kg/h short-0.1 units/kg rapid-acting acting insulin i.v. insulin analog every 1 h fixed-rate i.v. insulin or 0.2 units/kg every 2 h infusion or nurse-+ driven protocol with in each liter of i.v. fluid a variable rate based as needed to keep serum K + between on glucose values|.5 mmol/L (faster K + replacement will require central venous access) 4 and 5 mmol/L 0.10-20 mmol/L/h until K + Start 0.05 units/kg/h short-acting insulin as fixed-rate i.v. infusion † or nurse-driven protocol with a variable rate based on glucose values Severe hypovolemia Mild hypovolemia Cardiac compromise 0.1 units/kg rapid-acting insulin analog as s.c. bolus Consider 0.1 units/kg short-acting insulin as i.v. bolus if there is a delay in setting up the infusion 0.9% NaCl or other cr 0 L/h) K + .5-5.0 mmol/L Give Hemodynamic monitoring/pressors 0.1 units/kg/h short-0.1 units/kg rapid-acting acting insulin i.v. insulin analog every 1 h fixed-rate i.v. insulin or 0.2 units/kg every 2 h infusion or nurse-+ driven protocol with in each liter of i.v. fluid a variable rate based as needed to keep serum K + between on glucose values|.5 mmol/L (faster K + replacement will require central venous access) 4 and 5 mmol/L 0.10-20 mmol/L/h until K + Start 0.05 units/kg/h short-acting insulin as fixed-rate i.v. infusion † or nurse-driven protocol with a variable rate based on glucose values Severe hypovolemia Mild hypovolemia Cardiac compromise 0.1 units/kg rapid-acting insulin analog as s.c. bolus Consider 0.1 units/kg short-acting insulin as i.v. bolus if there is a delay in setting up the infusion 0.9% NaCl or other cr 0 L/h) K + .5-5.0 mmol/L Give Hemodynamic monitoring/pressors 0.1 units/kg/h short-0.1 units/kg rapid-acting acting insulin i.v. insulin analog every 1 h fixed-rate i.v. insulin or 0.2 units/kg every 2 h infusion or nurse-+ driven protocol with in each liter of i.v. fluid a variable rate based as needed to keep serum K + between on glucose values|.5 mmol/L (faster K + replacement will require central venous access) 4 and 5 mmol/L 0.10-20 mmol/L/h until K + Start 0.05 units/kg/h short-acting insulin as fixed-rate i.v. infusion † or nurse-driven protocol with a variable rate based on glucose values Severe hypovolemia Mild hypovolemia Cardiac compromise 0.1 units/kg rapid-acting insulin analog as s.c. bolus Consider 0.1 units/kg short-acting insulin as i.v. bolus if there is a delay in setting up the infusion 0.9% NaCl or other cr 0 L/h) K + .5-5.0 mmol/L Give Hemodynamic monitoring/pressors 0.1 units/kg/h short-0.1 units/kg rapid-acting acting insulin i.v. insulin analog every 1 h fixed-rate i.v. insulin or 0.2 units/kg every 2 h infusion or nurse-+ driven protocol with in each liter of i.v. fluid a variable rate based as needed to keep serum K + between on glucose values|

|||||||K + 5.0 mmol/L|

||||DKA|HHS||Start insulin, but do|

||||Keep glucose between 150 and 200 mg/dL until resolution*|Target glucose to between 200 and 250 mg/dL until resolution*|not give K + ; check serum K + every 2 h||

|V Calculated serum osmolality falls t .3 or bicar|kg and ur|y k|.6 mmol/L 0.5 mL/k|8.3 mmol/L 0 mmol/L .9 mmol/L .6 mmol/L||Bicarbonate should only be consider Phosphate should not be given unless there is muscle weakness, .0 respiratory compromise, 0 mmol/L|

1-Considerations for engaging interprofessional members of a comprehensive, person-centered diabetes care team to identify and meet the needs of people with diabetes across the life span

Diabetes Obes Metab 2019;21: 812-821 281. Kahl S, Gancheva S, Straßburger K, et al. Empagliflozin effectively lowers liver fat content in well-controlled type 2 diabetes: a randomized, double-blind, phase 4, placebo-controlled trial. Diabetes Care 2020;43:298-305 282. Latva-Rasku A, Honka M-J, Kullberg J, et al. The SGLT2 inhibitor dapagliflozin reduces liver fat but does not affect tissue insulin sensitivity: a randomized, double-blind, placebo-controlled study with 8-week treatment in type 2 diabetes patients. Diabetes Care 2019;42:931-937 283. Harrison SA, Bedossa P, Guy CD, et al.; MAESTRO-NASH Investigators. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med 2024;390:497-509 284. Cusi K. Selective agonists of thyroid hormone receptor beta for the treatment of NASH. N Engl J Med 2024;390:559-561 285. Noureddin M, Charlton MR, Harrison SA, et al. Expert panel recommendations: practical clinical applications for initiating and monitoring resmetirom in patients with MASH/NASH and moderate to noncirrhotic advanced fibrosis. Clin Gastroenterol Hepatol. 20 July 2024 [Epub ahead of print]. DOI: 10.1016/j.cgh.2024.07.003 286. Chen VL, Morgan TR, Rotman Y, et al. Resmetirom therapy for metabolic dysfunctionassociated steatotic liver disease: October 2024 updates to AASLD Practice Guidance. Hepatology.

2-Macronutrient-specific nutrition recommendations Recommendations Carbohydrates 5.24 Emphasize minimally processed, nutrient-dense, high-fiber sources of carbohydrate (at least 14 g fiber per 1,000 kcal). B 5.25 Advise people with diabetes and those at risk to replace sugar-sweetened beverages (including fruit juices) with water or low-calorie or no-calorie beverages as much as possible to manage glycemia and reduce risk for cardiometabolic disease B and minimize consumption of foods with added sugar that have the capacity to displace healthier, more nutrient-dense food choices. A 5.26 Regardless of diabetes classification, individuals treated with sodium-glucose cotransporter 2 inhibitors should avoid a ketogenic eating pattern, be educated on the signs of ketoacidosis and methods of risk mitigation and provided with appropriate tools for accurate ketone measurement (i.e., serum b-hydroxybutyrate), and be instructed to avoid fasting and maintain appropriate insulin therapy. E 5.27 Provide education on the glycemic impact of carbohydrate, A fat, and protein B tailored to an individual's needs, insulin plan, and preferences to optimize mealtime insulin dosing. 5.28 When using fixed insulin doses, individuals should be provided with education about consistent patterns of carbohydrate intake with respect to time and amount while considering the insulin action time, as it can result in improved glycemia and reduce the risk for hypoglycemia. B Proteins 5.29 People with diabetes and those at risk for diabetes are advised to incorporate more plant-based protein sources (e.g., nuts, seeds, and legumes) as part of an overall diverse eating pattern to reduce cardiovascular disease risk. B 5.30 Counsel people with diabetes to consider an eating plan emphasizing elements of a Mediterranean eating

behavior change interventions have the highest efficacy for behavioral and glycemic outcomes (346,348). For youth with diabetes, familybased behavioral intervention packages and interventions that address multiple areas of the person's life (i.e., multisystem interventions) demonstrate benefits for increasing management behaviors and improving glycemic outcomes (349). Importantly, adapting and tailoring behavior change strategies to the characteristics and needs of the individual and population are crucial (350,351). Health behavior change strategies can be delivered by behavioral health professionals, CDCES, other trained health care professionals (352,353), or qualified community health workers (345). Additionally, these approaches can be delivered via digital health tools (346,353,354). Finally, diabetes care professionals should be trained to use these methods effectively (e.g., motivational interviewing) (355). Psychosocial care should be provided to all people with diabetes, with the goal of optimizing health-related quality of life and health outcomes.

7-Psychosocial concerns and their association with diabetes-related outcomes in adults with type 1 diabetes different life stages, it is important to select a tool that is appropriate for each person or population. If diabetes distress is identified, it should be acknowledged and addressed (412).

8-Psychosocial concerns and their association with diabetes-related outcomes in adults with type 2 diabetes

.2). Food and Drug Administration. FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections.

diabetes.org/SOC. It also encompasses connected insulin pens and diabetes self-management support software that serve as medical devices. Diabetes technology, coupled with education, follow-up, pharmacotherapy if needed, and support, can improve the lives and health of people with diabetes; however, the complexity and rapid evolution of the diabetes technology landscape can also be a barrier to implementation for people with diabetes, their care partners, and the health care team. Diabetes devices should be offered to people with diabetes. A 7.2 Initiation of continuous glucose monitoring (CGM) should be offered to people with type 1 diabetes early in the disease, even at time of diagnosis. A 7.3 The type(s) and selection of devices should be individualized based on a person's specific needs, circumstances, preferences, and skill level. In the setting

1-Comparison of ISO 15197:2013 and FDA blood glucose meter accuracy standards

.3 for definitions of types of CGM devices. Skin reactions, either due to irritation or allergy, should be assessed and addressed to aid in successful use of devices. E 7.21 People who wear CGM devices should be educated on potential interfering substances and other factors that may affect accuracy. C

2-Common interfering substances and/or conditions that affect glucose meters (for inpatient and outpatient use)

Injecting insulin with a syringe or pen(136)(137)(138)(139)(140)(141)(142)(143)(144)(145)(146)(147)is the insulin delivery method used by most people with diabetes(142,148), although inhaled insulin is also available.Others use insulin pumps or AID devices (see INSULIN PUMPS AND AUTOMATED INSULIN DELIVERY SYSTEMS,

4-Continuous glucose monitoring device interfering substances

2-Median monthly (30-day) AWP and NADAC of maximum or maintenance dose of weight management pharmacotherapies

1-Examples of subcutaneous insulin treatment plans

2-Features of medications for lowering glucose in type 2 diabetes

Choice of basal insulin should be based on person-specific considerations, including cost.Refer to Table9.4 for insulin cost information. Consider prescription of glucagon for emergent hypoglycemia.

• Set FPG goal (see Section 6, "Glycemic Goals and Hypoglycemia") • Choose evidence-based titration algorithm, e.g., increase 2 units every 3 days to reach FPG goal without hypoglycemia

3-Median monthly (30-day) AWP and NADAC of maximum approved daily dose of noninsulin glucose-lowering agents in the U.S. RA, glucagon-like peptide 1 receptor agonist; IR, immediate release; max, maximum; min, minimum; NA, data not available; NADAC, National Average Drug Acquisition Cost; SGLT2, sodium-glucose cotransporter 2. AWP(195)and NADAC(196)prices are as of 1 July 2024. *Calculated for 30-day supply (AWP or NADAC unit price × number of doses required to provide maximum approved daily dose × 30 days); median AWP or NADAC listed alone when only one product and/or price. †Used to calculate median AWP and NADAC (min, max); generic prices used, if available commercially. ‡Administered once weekly. §AWP and NADAC calculated based on 120 mg three times daily.

4-Median cost of insulin products in the U.S. calculated as AWP and NADAC per 1,000 units of specified dosage form or product

Kuroda A, Ishizu M, et al. Basal insulin requirement in patients with type 1 diabetes depends on the age and body mass index. J Diabetes Investig 2022;13:292-298 45. Castellano E, Attanasio R, Giagulli VA, et al.; Associazione Medici Endocrinologi (AME). The basal to total insulin ratio in outpatients with diabetes on basal-bolus regimen. J Diabetes Metab Disord 2018;17:393-399 46. Matejko B, Kukułka A, Kie c-Wilk B, Sta ˛p or A, Klupa T, Malecki MT. Basal insulin dose in adults with type 1 diabetes mellitus on insulin pumps in real-life clinical practice: a single-center experience.

. In the Survival and Ventricular Enlargement (SAVE) study, Recommendations to reduce the risk of symptomatic heart failure in people with diabetes ACEi or ARB and β-blocker for hypertension, or recent history of myocardial infarction/acute coronary syndrome, or reduced LVEF ≤40%

4-Staging of type 1 diabetes

5-Criteria for screening for diabetes or prediabetes in asymptomatic adults1. Testing should be considered in adults with overweight or obesity (BMI $25 kg/m 2 or $23 kg/m 2 in individuals of Asian ancestry) who have one or more of the following risk

However, only your doctor can tell for sure if you do have type 2 diabetes or prediabetes, a condition in which blood glucose levels are higher than normal but not yet high enough to be diagnosed as diabetes. Talk to your doctor to see if additional testing is needed.

7-Most common causes of monogenic diabetes

8-Screening for and diagnosis of GDMOne-step strategy Perform a 75-g OGTT, with plasma glucose measurement when an individual is fasting and at 1 and 2 h, at 24-28 weeks of gestation in individuals not previously diagnosed with diabetes.The OGTT should be performed in the morning after an overnight fast of at least 8 h.The diagnosis of GDM is made when any of the following plasma glucose values are met or Perform a 50-g GLT (nonfasting), with plasma glucose measurement at 1 h, at 24-28 weeks of gestation in individuals not previously diagnosed with diabetes.If the plasma glucose level measured 1 h after the load is $130, 135, or 140 mg/dL (7.2, 7.5, or 7.8 mmol/L, respectively),* proceed to a 100-g OGTT.Step 2: The 100-g OGTT should be performed when the individual is fasting. The diagnosis of GDM is made when at least two † of the following four plasma glucose levels (measured fasting and at 1, 2, and 3 h during OGTT) are met or exceeded

7. Diabetes Prevention Program Research Group. HbA1c as a predictor of diabetes and as an outcome in the Diabetes Prevention Program: a randomized clinical trial. Diabetes Care 2015;38:51-58 8. Echouffo-Tcheugui JB, Selvin E. Prediabetes and what it means: the epidemiological evidence.

Estruch R, Ros E, Salas-Salvad o J, et al. Gerstein HC, Bosch J, Dagenais GR, et al.

1-Components of the comprehensive diabetes medical evaluation at initial, follow-up, and annual visits

2-Essential components for assessment, planning, and referral

3-Highly recommended immunizations for adults with diabetes (from the Advisory Committee on Immunization Practices and Centers for Disease Control and Prevention)

Figure 4.2-Diagnostic algorithm for risk stratification and the prevention of cirrhosis in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). CV, cardiovascular; ELF, enhanced liver fibrosis test; FIB-4, fibrosis-4 index; LSM, liver stiffness measurement, as measured by vibration-controlled transient elastography. *In the absence of LSM, consider ELF a diagnostic alternative. If ELF $9.8, an individual is at high risk of metabolic dysfunction-associated steatohepatitis with advanced liver fibrosis ($F3-F4) and should be referred to a liver specialist.

type 2 diabetes: a 24-week, randomized, placebo-controlled trial. Diabetes Obes Metab 2014;16:147-158 276. Armstrong MJ, Gaunt P, Aithal GP, et al.; LEAN Trial Team. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebocontrolled phase 2 study. Lancet 2016;387:679-690 277. Gastaldelli A, Cusi K, Fern andez Land o L, Bray R, Brouwers B, Rodr ıguez A. Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallelgroup, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol 2022;10:393-406 278. Loomba R, Hartman ML, Lawitz EJ, et al.; SYNERGY-NASH Investigators. Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis. N Engl J Med 2024;391: 299-310 279. Sanyal AJ, Bedossa P, Fraessdorf M, et al.; 1404-0043 Trial Investigators. A phase 2 randomized trial of survodutide in MASH and fibrosis. N Engl J Med 2024;391:311-319 280. Cusi K, Bril F, Barb D, et al. Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes. Diabetes Obes Metab 2019;21: 812-821 281. Kahl S, Gancheva S, Straßburger K, et al. 1-Nutrition therapy recommendations Recommendations Provide medical nutrition therapy 5.10 An individualized medical nutrition therapy program, as needed to achieve treatment goals and provided by a registered dietitian nutritionist, preferably one who has comprehensive knowledge and experience in diabetes care, is recommended for all people with type 1 or type 2 diabetes, prediabetes, and gestational diabetes mellitus. A 5.11 Because diabetes medical nutrition therapy can result in cost savings B and improved cardiometabolic outcomes, A medical nutrition therapy should be adequately reimbursed by insurance. E Promote energy balance 5.12 Provide weight management treatment based on nutrition, physical activity, and behavioral therapy for all people with overweight or obesity, aiming for at least 3-7% weight loss. A For diabetes prevention and management of people with prediabetes or diabetes, recommend individualized meal plans that keep nutrient quality, total calories, and metabolic goals in mind, B as data do not support a specific macronutrient pattern. 5.14 Eating patterns should emphasize key nutrition principles (inclusion of nonstarchy vegetables, whole fruits, legumes, lean proteins, whole grains, nuts and seeds, and low-fat dairy or nondairy alternatives) and minimize consumption of red meat, sugar-sweetened beverages, sweets, refined grains, processed and ultraprocessed foods in people with prediabetes and diabetes. B 5.15 Consider reducing overall carbohydrate intake for adults with diabetes to improve glycemia, as this approach may be applied to a variety of eating patterns that meet individual needs and preferences.

4-Elements for risk calculation and suggested risk score for people with diabetes who seek to fast during Ramadan Risk categories are defined as follows: score 0-3, low risk, fasting is probably safe; score 3.5-6, moderate risk, fasting is uncertain; score > 6, high risk, fasting is probably unsafe.DKA, diabetic ketoacidosis; eGFR, estimated glomerular filtration rate; HHS, hyperglycemic hyperosmolar state; MVD, macrovascular disease (cardiac, cerebral, or peripheral).*Individualswhoarepregnant or breastfeeding have the right to not fast regardless of whether they have diabetes or not.Adapted from Hassanein et al.(230).activityincludes all movement that increases energy use, and it is an important part of the diabetes management plan.Exercise is a more specific form of physical activity that is structured and designed to improve physical fitness.Both physical activity and exercise are important.Exercise has been shown to improve blood glucose levels, reduce cardiovascular risk factors, contribute to weight loss, and improve well-being(255). Physical activity is important for the general population as well as people at risk for and with established diabetes. Exercise plays a specific role in glucose management and in the prevention of diabetes complications in those with type 2 diabe-

2-CGM metrics for clinical care in nonpregnant individuals with type 1 or type 2 diabetes CGM, continuous glucose monitoring; TAR, time above range; TBR, time below range; TIR, time in range.*Goalsfor these values are not standardized.†Somestudies suggest that lower coefficient of variation targets ( < 33%) provide additional protection against hypoglycemia for those receiving insulin or sulfonylureas.‡Goals are for level 1 and level 2 hyperglycemia combined.§Goalsare for level 1 and level 2 hypoglycemia combined.Adapted from Battelino et al.(31).

(89,assification of hypoglycemi180)or risk factors are those that have a consistent, independent association with a high risk for level 2 or 3 hypoglycemia.Other risk factors are those with less consistent evidence or a weaker association.These risk factors are identified through observational analyses and are intended to be used for hypoglycemia risk stratification.Individuals considered at high risk for hypoglycemia are those with $1 major risk factor or who have multiple other risk factors (determined by the health care professional incorporating clinical judgment)(89,90,95,(97)(98)(99)(100)120,180). Proximal causes of hypoglycemic events (e.g., exercise and sleep) are not included. eGFR, estimated glomerular filtration rate.

6-Median monthly (30-day) AWP and NADAC of glucagon formulations in the U.S.

7-Components of hypoglycemia prevention for individuals at risk for hypoglycemia at initial, follow-up, and annual visits

9-Risk factors for hyperglycemic crises

10-Clinical presentation in people with diabetes with DKA and HHS American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association.Diabetes Care 2009;32:187-192 57.Turnbull FM, Abraira C, Anderson RJ, et al.; Control Group.Intensive glucose control and macrovascular outcomes in type 2 diabetes.Diabetologia 2009;52:2288-2298 58.Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group.Intensive diabetes treatment and cardiovascular outcomes in type 1 diabetes: the DCCT/EDIC study 30-year follow-up.Diabetes Care 2016;39: 686-693 59.Nathan DM, Zinman B, Cleary PA, et al.; Diabetes Control and Complications Trial (DCCT)/ Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group.McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA.Self-report of hypoglycemia and health-related quality of life in patients with type 1 and type 2 diabetes.Endocr Pract 2013;19:792-799 83.Leiter LA, Boras D, Woo VC.Dosing irregularities and self-treated hypoglycemia in type 2 diabetes: results from the Canadian cohort of an international survey of patients and healthcare professionals.Can J Diabetes 2014;38: 38-44 84.Ghandi K, Pieri B, Dornhorst A, Hussain S. A comparison of validated methods used to assess impaired awareness of hypoglycaemia in type 1 diabetes: an observational study.Diabetes Ther 2021;12:441-451 85.Khunti K, Alsifri S, Aronson R, et al.; HAT Investigator Group.Impact of hypoglycaemia on patient-reported outcomes from a global, 24-country study of 27,585 people with type 1 and insulin-treated type 2 diabetes.Diabetes Res Clin Pract 2017;130:121-129 86.Choudhary P, Amiel SA.Hypoglycaemia in type 1 diabetes: technological treatments, their limitations and the place of psychology.Diabetologia 2018;61:761-769 87.Hopkins D, Lawrence I, Mansell P, et al.Improved biomedical and psychological outcomes 1 year after structured education in flexible insulin therapy for people with type 1 diabetes: the U.K. DAFNE experience.Diabetes Care 2012;35:1638-1642 88.Karter AJ, Moffet HH, Liu JY, Lipska KJ.Surveillance of hypoglycemia-limitations of emergency department and hospital utilization data.JAMA Intern Med 2018;178:987-988 89. Lee AK, Lee CJ, Huang ES, Sharrett AR, Coresh J, Selvin E. Risk factors for severe hypoglycemia in black and white adults with diabetes: the Atherosclerosis Risk in Communities (ARIC) study.Diabetes Care 2017;40:1661-1667 90.Pilla SJ, Kraschnewski JL, Lehman EB, et al.McCoy RG, Lipska KJ, Van Houten HK, Shah ND.Association of cumulative multimorbidity, glycemic control, and medication use with hypoglycemia-related emergency department visits and hospitalizations among adults with diabetes.JAMA Netw Open 2020;3:e1919099 97.Yun J-S, Ko S-H, Ko S-H, et al.Presence of macroalbuminuria predicts severe hypoglycemia in patients with type 2 diabetes: a 10-year followup study.Diabetes Care 2013;36:1283-1289 98. Galindo RJ, Ali MK, Funni SA, et al.Hypoglycemic and hyperglycemic crises among U.S. adults with diabetes and end-stage kidney disease: population-based study, 2013-2017.Diabetes Care 2022;45:100-107 99.Kurani SS, Heien HC, Sangaralingham LR, et al.The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes. : a systematic review and meta-analysis.Can J Cardiol 2020;36:764-774 63.Bakris GL, Weir MR; Study of Hypertension and the Efficacy of Lotrel in Diabetes (SHIELD) Investigators.Achieving goal blood pressure in patients with type 2 diabetes: conventional versus fixed-dose combination approaches.J ClinThe American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care.Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted.For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology.Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.Optimize blood pressure management (aim for < 130/80 mmHg [Fig.10.2]) and reduce blood pressure variability to reduce the risk or slow the progression of CKD and reduce cardiovascular risk. A 11.4a In nonpregnant people with diabetes and hypertension, either an ACE inhibitor or an angiotensin receptor blocker (ARB) is recommended for those with moderately increased albuminuria (UACR 30-299 mg/g creatinine) B and is strongly recommended for those with severely increased albuminuria (UACR Figure 11.1-Risk of CKD progression, cardiovascular disease risk, and mortality; frequency of visits; and referral to nephrology according to GFR and albuminuria. The numbers in the boxes are a guide to the frequency of screening or monitoring (number of times per year). Green reflects no evidence of CKD by estimated GFR or albuminuria, with screening indicated once per year. For monitoring of prevalent CKD, suggested monitoring varies from once per year (yellow) to four times or more per year (i.e., every 1-3 months [deep red]) according to risks of CKD progression and CKD complications (e.g., cardiovascular disease, anemia, and hyperparathyroidism). These are general parameters based only on expert opinion and underlying comorbid conditions, and disease state must be taken into account, as should the likelihood of impacting a change in management for any individual. CKD, chronic kidney disease; GFR, glomerular filtration rate. Adapted from de Boer et al. (1).

.2). Early vaccination against hepatitis B virus is indicated in individuals likely to progress to ESKD (see Section 4, "Comprehensive Medical Evaluation and Assessment of

1-Reasons to consider nondiabetic kidney diseases in a person with chronic kidney disease and diabetes • Type 1 diabetes duration < 5 years • Active urine sediment (e.g., containing red blood cells or cellular casts) • Chronically well-managed blood glucose • Rapidly declining eGFR • Rapidly increasing or very high UACR or urine protein/creatinine level • No retinopathy in a person with type 1 diabetes Information adapted from Liang et al.

Changes in eating patterns (decreased salt intake and/or protein intake) • Treatment with SGLT2 inhibitors, MRAs, or GLP-1 RAs ARB, angiotensin receptor blocker; GLP-1 RA, glucagon-like peptide 1 receptor agonist; MRA, mineralocorticoid receptor antagonist.

2-Screening for selected complications of chronic kidney disease

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. Implement strategies to help people with diabetes reach glycemic goals to reduce the risk or slow the progression of diabetic retinopathy. A 12.2 Implement strategies to help people with diabetes reach blood pressure and lipid goals to reduce the risk or slow the progression of diabetic retinopathy. A Diabetic retinopathy is a highly specific neurovascular complication of both type 1 and type 2 diabetes, with prevalence strongly related to both the duration of diabetes and the level of glycemic management (1). Diabetic retinopathy is the most frequent cause of new cases of blindness among adults aged 20-74 years in developed countries. Glaucoma, cataracts, and other eye disorders occur earlier and more frequently in people with diabetes.

1-International Working Group on Diabetic Foot risk stratification system and corresponding foot screening frequency Adapted with permission from Schaper et al. (99). LOPS, loss of protective sensation; PAD, peripheral artery disease. *Examination frequency suggestions are based on expert opinion and person-centered requirements.

1-Framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adults with diabetes This table represents a consensus framework for considering treatment goals for glycemia, blood pressure, and dyslipidemia in older adults with diabetes.The characteristic categories are general concepts.Not every individual will clearly fall into a particular category.Consideration of individual and care partner preferences, care partner engagement, abilities, and resources is an important aspect of treatment individualization.Additionally, an individual's health status and preferences may change over time.ADL, activities of daily living; CGM, continuous glucose monitoring; LTC, long-term care; TBR, time below range; TIR, time in range.*AlowerA1Cgoalmaybe set for an individual if achievable without recurrent or severe hypoglycemia or undue treatment burden.†Coexistingchronicillnessesareconditionsserious enough to require medications or lifestyle management and may include arthritis, cancer, heart failure, depression, emphysema, falls, hypertension, incontinence, stage 3or worse chronic kidney disease, myocardial infarction, and stroke."Multiple"meansatleastthree, but many individuals may have five or more(77).‡Thepresence of a single end-stage chronic illness, such as stage 3-4 heart failure or oxygen-dependent lung disease, chronic kidney disease requiring dialysis, or uncontrolled metastatic cancer, may cause significant symptoms or impairment of functional status and significantly reduce life expectancy.Adapted from Kirkman et al.(3).

2 provides examples of and rationale for situations where deintensification and/or insulin plan simplification may be appropriate in older adults.

.1. Figure was adapted with permission from Munshi et al. (109).

2-Considerations for treatment plan simplification and deintensification/deprescribing in older adults with diabetes

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www .diabetesjournals.org/journals/pages/license. 1A-Recommendations for screening and treatment of complications and related conditions in pediatric type 1 diabetes NA, not applicable; tTG, tissue transglutaminase. *Due to the potential teratogenic effects, individuals of childbearing age should receive reproductive counseling, and medication should be avoided in individuals of childbearing age who are not using reliable contraception.

1B-Recommendations for screening and treatment of complications and related conditions in pediatric type 2 diabetes Due to the potential teratogenic effects, individuals of childbearing age should receive reproductive counseling, and medication should be avoided in individuals of childbearing age who are not using reliable contraception.

1-Checklist for preconception care for people with prediabetes, diabetes, or a history of gestational diabetes mellitus Preconception education should include: w Comprehensive nutrition assessment and recommendations for: Comprehensive diabetes self-management education w Counseling on diabetes in pregnancy per current standards, including natural history of insulin resistance in pregnancy and postpartum; preconception glycemic goals; avoidance of DKA and severe hyperglycemia; avoidance of severe hypoglycemia; progression of retinopathy in individuals with preexisting diabetes; PCOS (if applicable); fertility in people with diabetes; genetics of diabetes; risks to pregnancy including miscarriage, stillbirth, congenital malformations, macrosomia, preterm labor and delivery, hypertensive disorders in pregnancy w Supplementation Folic acid supplement (400-800 mg/day routine) Appropriate use of over-the-counter medications and supplements Health assessment and plan should include: w General evaluation of overall aluation of obstetric or gynecologic history, including a history of cesarean section, congenital malformations or fetal loss, current methods of contraception, hypertensive disorders of pregnancy, postpartum hemorrhage, preterm delivery, previous macrosomia, Rh incompatibility, and thrombotic events (DVT/PE) w Review of current medications and appropriateness during pregnancy Screening should include: w Diabetes complications and comorbidities in individuals with preexisting diabetes, including comprehensive foot exam; comprehensive ophthalmologic exam; ECG in individuals starting at age 35 years who have cardiac signs or symptoms or risk factors and, if abnormal, further evaluation; lipid panel; serum creatinine; TSH; and urine albumin-to-creatinine ratio w Anemia w Genetic carrier status (based on history): Nutrition and medication plan to achieve glycemic goals prior to conception, including appropriate implementation of blood glucose monitoring, continuous glucose monitoring (if indicated and appropriate DKA, diabetic ketoacidosis; DVT/PE, deep vein thrombosis/pulmonary embolism; ECG, electrocardiogram; MASLD, metabolic dysfunction-associated steatotic liver disease; PCOS, polycystic ovary syndrome; TSH, thyroid-stimulating hormone.

2-Blood glucose goals in pregnancies associated with diabetesGestational diabetes mellitus (GDM) blood glucose goals shown are recommended by the Fifth International Workshop-Conference on Gestational Diabetes Mellitus(42).^Lower glucose limits do not apply to individuals with type 2 diabetes treated with nutrition alone.Aim for less stringent goals if these cannot be achieved without significant hypoglycemia, based on clinical experience and individualization of care.*Optimal goal includes either a 1-h postprandial glucose level or 2-h postprandial glucose level within column of type of diabetes.eating pattern including fruits, vegetables, legumes, whole grains, nuts, seeds, fish, and other lean protein, which will provide a balance of macronutrients and healthy n-3 fatty acids. C 15.15 Lifestyle behavior change is an essential component of management of GDM and may suffice as treatment for many individuals. Insulin should be added if needed to achieve glycemic goals. A 15.16 Telehealth visits used in combination with in-person visits for pregnant people with GDM can improve outcomes compared with standard inperson care alone. A 15.17 Insulin should be used to manage type 1 diabetes in pregnancy A and is the preferred agent for the management of GDM A and type 2 diabetes in pregnancy. B 15.18 Either multiple daily injections or insulin pump technology can be used in pregnancy complicated by type 1 diabetes. C 15.19 Automated insulin delivery (AID) systems with pregnancy-specific glucose targets are recommended for pregnant individuals with type 1 diabetes. A 15.20 AID systems without pregnancyspecific glucose targets or a pregnancyspecific algorithm may be considered for select pregnant individuals with type 1 diabetes when used with assistive techniques and working with experienced health care teams. B 15.21 Metformin and glyburide, individually or in combination, should not be used as first-line agents for management of diabetes in pregnancy, as both cross the placenta to the fetus A and may not be sufficient to achieve glycemic goals. B Other oral and noninsulin injectable glucose-lowering medications lack long-term safety data and are not recommended. E 15.22 Metformin, when used to treat polycystic ovary syndrome and induce ovulation, should be discontinued by the end of the first trimester. A

Breastfeeding efforts are recommended for all individuals with diabetes. A Breastfeeding is recommended for individuals with a history of GDM for multiple benefits, A including a reduced risk for type 2 diabetes later in life. B 15.29 Postpartum care should include psychosocial assessment and support for self-care. E 15.30 Screen individuals with a recent history of GDM at 4-12 weeks postpartum, using the 75-g oral glucose tolerance test and clinically appropriate nonpregnancy diagnostic criteria. B 15.31 Individuals with a history of GDM should have lifelong screening for the development of type 2 diabetes or prediabetes every 1-3 years. B 15.32 Individuals with overweight or obesity and a history of GDM found to have prediabetes should receive intensive lifestyle interventions and/or metformin to prevent diabetes. A

3. The blood glucose goal in the perioperative period should be 100-180 mg/ dL (5.6-10.0mmol/L)(126)within 4 h of the surgery. CGM should not be used alone for glucose monitoring during surgery (129). 4. Metformin should be held on the day of surgery. 5. SGLT2 inhibitors should be discontinued 3-4 days before surgery. 6. Other oral glucose-lowering agents should be held the morning of surgery or procedure. 7. Insulin dose reductions include NPH insulin to one-half of the dose or long-acting basal insulin analogs to 75-80% of the dose or adjustment of insulin pump (if not in automated mode) basal rates based on the type of diabetes and clinical judgment (see Section 7, "Diabetes Technology"). 8. Monitor blood glucose at least every 2-4 h while the individual takes nothing by mouth and administer shortor rapid-acting insulin as needed. 9. Stricter peioperative glycemic goals are not advised, as perioperative glycemic goals stricter than 80-180 mg/dL (4.4-10.0 mmol/L) may not improve outcomes and are associated with increased hypoglycemia

9% NaCl or other cr ystalloid at a clinically appropriate rate aiming to replace 50% of the estimated fluid deficit in the first 8-12 h When glucose re xtrose to the 0.9% NaCI/crystalloid In eugly xtrose needs to be started alongside 0.9% NaCl/crystalloid at the start of the insulin treatment Check electrolytes, renal function, venous pH, osmolality, and glucose every 2-4 h until stable. After resolution of DKA or HHS and when patient is able to eat and drink, initiate s.c. multidose insulin plan. To transfer from i.v. to maintenance s.c. insulin, continue i.v. insulin infusion f ter s.c. insulin. When glucose re educe short-acting insulin dose to 0.05 units/kg/h i.v. (or 0.05 units/kg/h or 0.1 units/kg ever or nurse-driven protocol with a variable rate based on glucose values Definitions of resolution (use clinical judgment and do not delay discharge or level of care if these are not met):

American Diabetes Association Professional Practice Committee can be found at https://doi.org/10.2337/dc25-SINT. Duality of interest information for each author is available at https://doi.org/10.2337/dc25-SDIS. . Available from https:// www.cms.gov/priorities/innovation/innovationmodels/ahcm . Available from https://www.cms. gov/priorities/innovation/data-and-reports/2023/ ahc-second-eval-rpt 32. Wang S, Weyer G, Duru OK, Gabbay RA, Huang ES. Can alternative payment models and value-based insurance design alter the course of diabetes in the United StatesAvailable from https://www.cms.gov/ priorities/innovation/innovation-models/part-dsavings-model 67. Baig K, Dusetzina SB. Premiums and out-ofpocket spending for long-acting insulins under the Medicare Part Available from https://diabetes.org/tools-resources/affordableinsulin/state-insulin-copay-caps 69. Suran M. All 3 major insulin manufacturers are cutting their prices-here's what the news means for patients Available from https://www.ahrq.gov/ professionals/prevention-chronic-care/improve/ community/index.html diabetesjournals.org/care Diagnosis and Classification of Diabetes S49 *A complete list of members of the American Diabetes Association Professional Practice Committee can be found at https://doi.org/10.2337/dc25-SINT. Duality of interest information for each author is available at https://doi.org/10.2337/dc25-SDIS.

A1C use as, S28-S30 fasting plasma glucose (FPG) test, S27-S28, S29, S30, S32, S33, S34, S35, S38, S40, S42, S43, S44, S192 oral glucose tolerance test (OGTT), S27, S28, S29, S34, S35, S39, S40, S41, S42-S44, S51, S53, S308, S315-S316 plasma glucose test, 2-h, S27-S28, S29, S32, S33, S34, S35, S38, S41, S43, S44, S50, S55, S293, S309, S310, S316 diet, see Medical nutrition therapy. Dietary Reference Intakes, S311 dietitian, registered nutritionist, S17, S65, S90, S175, S176, S286, S290, S295, S296, S307, S308, S330 DIAMOND trial, S269 digital health technology, S88, S106, S107, S158 dipeptidyl peptidase 4 (DPP4) inhibitors, S100, S188, S189, S191, S193, S194, S195, S198, S200, S226, S227, S273 disability, S70-S71 disordered eating behavior, S8, S63, S93, S96, S106, S107, S111, S286, S287, S288, S298 domperidone, S258 Dose Adjusted for Normal Eating (DAFNE), S121 DRCR Retina Network, S254 driving, and diabetes, S138, S147, S149, S289, S336 droxidopa, S258 dual-energy X-ray absorptiometry (DXA), S67 dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, S7, S10, S13, S76, S77, S78, S113, S171, S187, S188, S189, S191, S193, S194, S195, S197, S200, S328 dulaglutide, S191, S194, S226, S228, S252 duloxetine, S257 dyslipidemia, S12, S13, S27, S28, S47, S56, S66, S87, S96, S97, S148, S179, S180, S191, S192, S193, S202, S231, S234, S236, S248, S259-S260, S266-S267, S270, S272 e-cigarettes, S104-S105 EAGLES trial, S105 eating disorders, S96-S97, S111, S140, S288 eating patterns, S7, S8, S51, S52, S60, S75, S89, S90-S93, S94, S95, S96, S108, S111, S170, S243, S286, S317 education, see also diabetes self-management education and support (DSMES). patient, S8, S9, S15, S16, S22, S31, S34, S60, S62, S65, S260, S295, S299, S313, S322, S323, S328 preconception, S307-S308 staff, S21, S54, S61 education specialists, S17, S54, S65, S330 electrical stimulation, gastric, S258 EMPA-REG OUTCOME trial, S227, S228, S246 empagliflozin, S68, S191, S194, S225, S226, S227, S228, S246, S294, S296 EMPEROR-Preserved trial, S228, S247 EMPEROR-Reduced trial, S228, S247 employment, diabetes and, S135, S3336 enalapril, S226, S258 end-of-life care, S270, S278 enteral/parenteral feedings, S322, S324, S326-S327 erectile dysfunction, S7, S71-S72, S255, S256, S258 ertugliflozin, S68, S191, S225-S226, S325 erythromycin, S258 erythropoietin therapy, A1C and, S29, S30, S270 ESSENSE trial, S76 estimated average glucose (eAG), S129 ETDRS study, S254-S255 ethnicity, S2, S19, S20, S31, S35, S71, S129, S170 European Association for the Study of Obesity (EASO), S67 evidence-grading system, S3 evolocumab, S217, S218 EXAMINE trial, S227 exenatide, S191, S194, S226, S228, S257 exercise. see physical activity. exocrine pancreas diseases, S30, S78 eye exam, S11, S12, S62, S65, S253, S292, S297, S298, S253, S309 ezetimibe, statins and, S215, S216, S217, S218, S220 family history, S7, S30, S31, S32, S34, S35, S36, S40, S62, S69, S110, S173, S221, S293, S296 farmworkers, migrant and seasonal, S21 fasting, S8, S8, S51 nonreligious, S97-S98 religious, S97, S98, S99 fasting plasma glucose (FPG) test, S27-S28, S29, S30, S32, S33, S34, S35, S38, S40, S42, S43, S44, S192 fat bias, S9, S168 fats, dietary, S8, S89, S91, S92, S94, S176, S219, S291, S297, S311 FDA standards, for glucose meters, S148 fear, of hypoglycemia, S8, S9, S63, S72, S106, S107, S110, S111, S135, S137, S182, S266, S267, S268, S288 Female Sexual Function Index (FSFI), S72 female sexual dysfunction, S7, S72-S73, S256 fenofibrate, S219, S220, S255 fibrate, S219, S285, S297 plus statin therapy, S219, S220 fibrosis-4 index (FIB-4), S7, S64, S73, S74 FIDELIO-DKD trial, S227, S247, S248 FIGARO-DKD trial, S227, S229, S247, S248 finerenone, S225, S227, S229-S230, S194, S296 gastric aspiration therapy, S175 gastric bypass, Roux-en-Y gastric, S175, S194 gastric electrical stimulation, S258 gastrointestinal neuropathies, S256 gastroparesis, S191, S256, S258, S274 gemfibrozil, S220 genetic testing, S31, S40, S41, S73 genitourinary disturbances, S256 gestational diabetes mellitus (GDM), S7, S12, S35, S42-S44, S52, S53, S54, S55, S152, S306, S307, S308, 310, S311, S312, S313, S314, glargine, S100, S182, S183, S189, S193, S194, S195, S196, S199, S274, S324 glibenclamide, S99 gliclazide, S99, S100 glimepiride, S99, S100, S189, S191, S193, S194, S225, S169, S172, S196, S202 glipizide, S191, S273 glomerular filtration rate, estimated, S68, S94, S100, S136, S187, S189, S190, S191, S213, S223, S229, S239, S240, S241, S242, S243, S245, S273, S274, S292, S297, S315 glucagon, S40, S70, S135, S138, S139, S171, S196-S197, S228, S330 glucagon-like peptide 1 receptor agonists (GLP-1 RA), S7, S32, S68, S75, S76, S77, S96, S100, S133, S170, S172, S173, S174, S186, S187, S191, S192, S193, see blood glucose monitoring. glucose-6-phosphate dehydrogenase deficiency, A1C and, S29, S30, S129 glucose-dependent insulinotropic polypeptide (GIP).

see dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP). glucose-lowering therapy, S7, S9, S10, S12, S18, S39, S40, S61, S64, S65, S68, S69, S71, S75, S76, S77, S92, S113, S134, S141, S153, S167, S170-S174, S187, S188-S189, S190, S193, S198 and cardiovascular outcomes, S225-S226 and heart failure outcome, S227-S230 direct kidney effects of, S244-S245 in hospitalized people, S324-S325 in older adults, S273-S277 with cancer treatment, S198-S199 with cardiovascular disease or risk factors, S193 with child-bearing potential, S197 with chronic kidney disease, 193-S194, S245-S247 with medication unavailability, S197 with metabolic comorbidities, S195 glulisine, S199, S274 glutamic acid decarboxylase, S30, S32, S33 glyburide, S12, S99, S100, S189, S191, S198, S273, S311, S313 glycemic goals, S9, S12, S13, S128-S145 ambulatory glucose profile, S132 assessment of glycemic status, S128-S130 based on individual health and function, S133 continuous glucose monitoring, S131, S132

for nonpregnant adults, S134 in diabetic kidney disease, S243-S244 in hospitalized patients, S322-S323 in pregnancy, S309-S310 hyperglycemic crises, S139-S141 hypoglycemia prevention and treatment, S135-S138 intercurrent illness, S138-S139 in older adults, S269-S272 in pediatric type 1 diabetes, S289-S290 in pediatric type 2 diabetes, S294-S296 setting and modifying, S134-S145 glycemic treatment, S10, S181-S206

for adults with type 1 diabetes, S181-S186 for adults with type 2 diabetes, S186-S197 other recommendations for all patients, S196-S197 special circumstances and populations, S197-S200 Grading of Recommendations Assessment, Development, and Evaluation (GRADE), S61, S66-S67 GRADE trial, S189, S193, S194, S243 growth factors, S261, S262 guanfacine, S258 gut microbiome, S7, S36, S93 health literacy, S21-S22, S92, S136, S185, S194, S270, S287, S298 health numeracy, S21-S22, S92, S185, S194 health promotion, S6, S14-S26 hearing impairment, S78, S267 heart failure, S10, S11, S19, S60, S61, S65, S76, S89, S101, S134, S135, S168, S171, S186, S187, S190, S191, S208, S209, S210, S211, S221, S222-S224, S225, S246-S248, S270, S271, S273, S325 glucose-lowering medications and, S227-S230 prevention and treatment of, S226-S227 hemodialysis, A1C and, S29, S30, S71 hemoglobinopathies, A1C and, S43, S51, S62, S293 hepatitis B, S62, S66 hepatitis B vaccines, S62, S66, S242 hepatitis C infection, S71 hepatitis, autoimmune, S33, omelessness, S63 homeostatic modeling assessment (HOMA), S39, S55 hospital care, S12-S13, S321-S334 admissions, S321-S322 care delivery standards, S322-S322 continuous glucose monitoring, S323-S324 critical care setting, S324 diabetes care specialists in, S322 diabetic ketoacidosis, S328, S329 enteral/parenteral feedings, S326-S327 glucocorticoid therapy, S327 glucose abnormality definitions, S322 glucose-lowering treatment in, S324-S325 glucose monitoring, S323-S324 glycemic goals in, S322-S323 hyperosmolar hyperglycemic state, S328, S329 hypoglycemia, S325-S326 insulin therapy, S324-S325 medical nutrition therapy in, S326 medication reconciliation, S329 noninsulin therapies, S325 perioperative care, S327-S328 preventing admissions and readmissions, S330 self-management in, S326 standards for special situations, S326 structured discharge communication, S329-S330 transition to ambulatory setting, S328-S329 type 1 diabetes, S324-S325 HOT trial, S210 housing insecurity, S19, S25 HPS2-THRIVE trial, S220 human im see automated insulin delivery systems. hyperbaric oxygen therapy, S261 hyperglycemia, S7, S12, S20, S27, S28, S29, S30, S31, S32, S33, S36, S38, S40, S41, S52, S55, S70, S72, S75, S93, S95, S98, S102, S113, S129, S130, S131, S133, S139-S140, S148, S151, S152, S155, S168, S175, S181, S189, S192, S194-S195, S197-S199, S208, S209, S227, S241, S252, S253, S277 in children, S286, S287, S288, S289, S294, S298 in gestational diabetes mellitus, S42-S44, S309, S316 in hospitalized patients, S321-S325, S327, S328, S329, S330 in MASH and MASLD, S75-S77, S188, S194 in pregnancy, S306, S307, S308-S310, S316 in older adults, S269, S270, S271, S272, S273, S275, S277, S278 Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, S43, S44, S309 hyperglycemic crises, S9, S139-S141 hyperglycemic hyperosmolar state, S9, S12, S27, S69, S100, S138, S139, S294, S295, S324, S328, S329 hypertension, S10, S11, S12, S15, S16, S35, S36, S52, S54, S65, S71, S72, S73, S89, S90, S100, S102, S113, S134, S168, S172, S207, S225, S226, S240, S41, S243, S244, S245, S248, S253, S257, S266, S269, S270, S271, S272, S273, S278, S284, S286, S291, S295, S296-S297, S306, S308, S314 blood pressure management and, S209-S214 hypertriglyceridemia, S29, S94, S182, S189, S219 hypoglycemia, S8, S9, S10, S12, S13, S19, S20, S41, S60, S61, S63, S64, S65, S68, S69, S70, S72, S90, S91, S93, S95, S97, S98-S100, S101, S102, S103-S104, S106-S107, S110, S112, S147-S149, S150-S153, S154-S157, S158, S172, S175-S176, S182-S185, S186, S188-S189, S191, S193-S195, S196, S225, S244, S245, S256 classification, S136 definitions and event rates, S135-S136 glycemic goals and, S128-S145 in children, S286-S290, S294, S298 diabetesjournals. org/care Index S347 in hospitalized patients, S322-S326, S327-S328, S330 in older adults, S266, S268-S270, S271, S272-S275, S276, S277, S278 in pregnancy, S306, S308, S309-S310, S311, S313, S315 prevention, S138-S139 risk assessment, S136-S137 treatment, S137-S138 hypogonadism, S7, S71, S77, S258 hypokalemia, S10, S212, S214, S240, S242 icosapent ethyl, S219 idiopathic type 1 diabetes, S34 illness, intercurrent, glycemic targets in, S138, S139, S149 immune checkpoint inhibitors, S7, S23, S32, S33, S26 immune-mediated diabetes, S32-S34 immunizations, S12, S61-S63, S66, S283 impaired fasting glucose (IFG), S28, S33, S35, S51, S55 impaired glucose tolerance (IGT), S28, S33, S35, S36, S39, S44, S51, S53, S55 inclisiran, S215, S217, S218 incretin-based therapies, S8, S53, S78, S98, S111, S197, S200 Indian Diabetes Prevention Program (IDPP-1), S54 infections, S7, S33, S34, S36, S39, S40, S62, S66, S71, S72, S104, S140, S155, S158, S183, S185, S191, S200, S241, S257, S261, S275, S276, S315, S327, S328 influenza vaccines, S62, S66 inhaled insulin, S10, S153, S154, S181, S184, S185, S192, S196 injection techniques, S153-S154, S186, S191, S290 inpatient care. see hospital care. Ipswich touch test, S11, S258 islet transplantation, S186 insulin analogs, S155, S181-184, S195, S276, S289, S324, S327, S328 insulin delivery, S153-S158 automated systems, S155-S158 injection techniques, S153-S154, S186, S191, S290 IV, transitioning to SC, S13, S325, S328 pens and syringes, S153-S154 pumps, S154-S155 insulin physiology, S309 insulin pump therapy, S15, S17, S148, S154-S155, S183, S200, S289, S295 insulin resistance, S30, S31, S32, S35, S36, S38, S39, S40, S54, S55, S70, S73, S75, S101, S113, S195, S198, S199, S294, S298, S308, S309, S311, S312, S313, S315, S324, insulin secretagogues, S90, S98, S103, S104, S137, S171, S273 insulin therapy, S9, S17, S39, S40, S41, S75, S91, S129, S136, S140, S149, S157, S181-S186, S189, S193, S194-S196 access to, S141, S155 alternative routes, S196 basal, S10, S99, S100, S136, S140, S149, S151, S153, S154, S156, S158, S181, S182, S183, S185, S192, S193, S194-S195, S196, S269, S274, S275, S276, S277, S278, S287, S289, S290, S309, S312, S324, S325, S326, S327, S52, S55, S75, S77, S90, S94, S95, S96, S101, S102, S134, S167-S180, S187, S214, S272, S293, S294, S295, S307, S308, S314 oxygen, glucose monitors and, S149 oxygen therapy, S150 hyperbaric, S261, S262 topical, S259, S261, S262 P2Y12 receptor antagonists, S220, S221-S222 palliative care, S270, S276, S277-S278 pancreas transplantation, S186, S187 pancreatectomy, S39, S78, S157 pancreatic diabetes, S39-S40 pancreatitis, S35, S39, S69, S78, S172, S191, S200, S219, S297 paramedics, S22, S59, S197 patch, bolus insulin, S10, S196 patient-centered medical home model, S16 pens, insulin, S146, S147, S150, S152, S153-S154, S183, S185, S191, S196, S199, S268, S276, S289, S324, parenteral feeding, S322, S324, S326-S327 periodontal disease, S35, S38, S69 perioperative care, S327-S328 peripheral arterial disease, S11, S259-S260 peripheral neuropathy, S70, S71, S95, S102, S104, S155, S256, S259 pernicious anemia, S33, S63 person-centered care goals, S6, S14, S15, S17, S37, S54, S55, S59-S61, S86, S87, S96, S106, S110, S130, see also specific medications, medication classes.212, S214, S225, S226, S258 for type 1 diabetes prevention or delay, S55-S56 for type 2 diabetes prevention, S51-S52, S53 frequency and type of, S101-S102 glycemic management and, S102, S130, S137, S147, S148 (PCSK9) inhibitors, S215, S216-S218, S220, S315 protease inhibitors, S38 protein intake, S93-S94, S99, S138, S171, S181, S240, S243, S272 psychosocial care, S8, S19, S86, S106-S114 anxiety disorders, S110 assessment and treatment, S107 cognitive capacity/impairment, S112-S113 depression, S110-S111 diabetes distress, S107-S110 disordered eating behavior, S111 in pediatric type 1 diabetes, S287-S289 in pediatric type 2 diabetes, S298 referral to mental health specialist, S107-S108, S110, S268, S288, S299 screening, S106-S107 serious mental illness, S111-S112 sleep health, S113_S114 pumps, insulin, S13, S15, S17, S63, S88, S93, S99, S104, S146, S148, S151, S152, S154-S158, S182, S183, S185, S196, S200, S228, S269, S276 automated systems, S155 in pregnancy, S311-S313 in youth, S155, S289-S290, S295 in hospitalized patients, S158-S159, S323, S325, S326, S328 open-source automated dosing with, S157

for adults with type 1 diabetes, S181-S186 for adults with type 2 diabetes, S186-S196 for cardiovascular and renal disease, S212-S214, S225 for neuropathy, S257-S258 for obesity, S170-S174 for pediatric type 2 diabetes, S294-S296 for retinopathy, S255-S256 for smoking cessation, S105 in older adults, S272-S275 in pregnancy, S312-S314 interfering substances for glucose meter readings, S150 medication costs and affordability, S196-S197, S198-S199 to delay or prevent type 2 diabetes, S7, S53-S54 to delay type 1 progression, S53 to glycemic treatment, S10, S181-S206 phentermine, S53, S171, S172-S173, S174 phentermine/topiramate ER, S171, S172, S174, S296 phosphodiesterase type 5 inhibitors, S71, S258 photocoagulation surgery, S254, S255 physical activity, S7, S8, S12, S15, S16, S28, S36, S62, S65, S67, S70, S75, S90, S96, S100-S104, S158, S212, S214, S225, S226, S258 for type 1 diabetes prevention or delay, S55-S56 for type 2 diabetes prevention, S51-S52, S53 frequency and type of, S101-S102 glycemic management and, S102, S130, S137, S147, S148 (PCSK9) inhibitors, S215, S216-S218, S220, S315 protease inhibitors, S38 protein intake, S93-S94, S99, S138, S171, S181, S240, S243, S272 psychosocial care, S8, S19, S86, S106-S114 anxiety disorders, S110 assessment and treatment, S107 cognitive capacity/impairment, S112-S113 depression, S110-S111 diabetes distress, S107-S110 disordered eating behavior, S111 in pediatric type 1 diabetes, S287-S289 in pediatric type 2 diabetes, S298 referral to mental health specialist, S107-S108, S110, S268, S288, S299 screening, S106-S107 serious mental illness, S111-S112 sleep health, S113_S114 pumps, insulin, S13, S15, S17, S63, S88, S93, S99, S104, S146, S148, S151, S152, S154-S158, S182, S183, S185, S196, S200, S228, S269, S276 automated systems, S155 in pregnancy, S311-S313 in youth, S155, S289-S290, S295 in hospitalized patients, S158-S159, S323, S325, S326, S328 open-source automated dosing with, S157

sensor augmented, S155-S157 quality improvement, S6, S14, S15, S19, S321, S326

RAAS inhibitors, S184 race, S19, S20, S30, S35, S71, S129, S170, S242 Ramadan, fasting during, S8, S98, S99 rapid-acting insulin analog, S154, S157, S182, S184, S192, S195, S199, S274, S310, S324, S326, S327 real-time CGM devices, S9, S138, S149, S150, S152, S176, S276, S289, S290, S294, S309, S310 REDUCE-IT trial, S94, S219 referrals, S7, S11 for behavioral health professionals, S107-S108, S110, S268, S288, S299 for cognitive assessment, S270 for community screening, S39 for comprehensive eye exam, S53, S292, S297, S309 for dental care, A70 for disability, S70 for DSME, S88, S89, S267 for initial care management, S65 for local community resources, S19 for medical nutrition therapy, S89 for tobacco cessation, S54 from dentist to primary care, S38 to a liver specialist, S74 to a specialized center, S32, S34, S73, S308 to foot care specialist, S261 to gastroenterologist, S297 to nephrologist, S40, S241, S242, S248, S297 to neurologist, S256, S284, S285 to ophthalmologist, S11, S104, S253, S254 to sleep speciali diabetics fasting during Ramadan, S99 risk management cardiovascular disease, S10-S11, S207-S238 S350 Index Diabetes Care Volume 48, Supplement 1, January 2025 chronic kidney disease, S11, S239-S251 risk, screening for type 1 diabetes, S32-S34, S284 prediabetes and type 2, S27-S30, S34, S35-S38, S293 rivaroxaban, S220, S222 rosiglitazone, S189 Roux-en-Y gastric bypass, S175, S194 sarcopenic obesity, S8, S102 SAVOR-TIMI trial, S227, S228 S191, S198, S227, S325 schizophrenia, S108, S109, S112 schools, diabetes care in, S13, S17, S63, S135, S138, S147, S196, S286, S287-S28, S293, S335-S336 SCORED trial, S227 screening, S6, S7, S8, S9, S10, S11, S12, S15 after organ transplantation, S40 by age, S38 community, S38 for cardiovascular risk factors, S35, S54, S209, S222-S225, S291-S292, S297 for celiac disease, S64, S290-S291 for chronic kidney disease, S239-S241, S242-S243 for cystic fibrosis -related diabetes, S39-S40 for disordered eating behavior, S112 for food insecurity, S20, S99 for fracture risk, S65, S67 for see blood glucose monitoring (BGM) semaglutide, S53, S76, S77, S170, S171, S173, S174, S186, S189, S191, S193, S194, S198, S226, S228, S230, S245, S247, S252, S274 sensor-augmented pumps, S110, S155, S185, S269, S289, S312, S313 sensory impairment, S78 setmelanotide, S171 sexual dysfunction female, S7, S72, S256 male, S71-S72, S256 sickle cell disease, S30, S129, S308 simvastatin, S215, S220 sitagliptin, S189, S191, S193, S194, S198, S227 sitting, prolonged, S8, S100, S103 skilled nursing facilities, S276, S277, S329 sleep apnea. see Obstructive sleep apnea. sleep health, S7, S113-S114 smart pens.1, S12, S13, S14-S15, S16, S79, S92, S166 sodium channel blockers, S257, S258 sodium intake, S94, S212 sodium-glucose cotransporter 2 (SGLT2) inhibitors, S10, S11, S68, S76, S77, S93, S98, S100, S113, S133, S134, S135, S139, S140, S186, S187, S191, S193-S194, S195, S198, S200, S208, S222-S223, S226-S230, S240, S242, S243, S244-S248, S267, S268, S274, S276, S295, S325, S327 SOLOIST-WHF trial, S228 sotagliflozin, S186, S227, S228 SPRINT trial, S210-S211, S226 staging of diabetic kidney disease, S65, S241-S242 of liver disease risk, S10 of type 1 diabetes, S33 statin therapy, S11, S12, S35, S38, S54-S55, S76, S77, S78, S133, S214-S220, S284, S285, S292, S314 stem cell therapies, for wounds, S261, S262 STEP-HFpEF trial, S230 strength training, S51, S99, S291 substance use, S63, S136, S140, S150, S176 pediatric, S298-S299 sulfonylureas, S10, S20, S41, S64, S67, S68, S70, S77, S98, S99, S113, S130, S131, S134, S135, S136, S139, S171, S188, S189, S191, S194, S195, S196, S198, S200, S272, S273, S275, S276, S313 supplements, dietary, S8, S67, S90, S94-S95, S153, S169, S170, S176, S308 surgery, in patients with diabetes, S327 surgical treatment, for type 1 diabetes, S186 surveillance behavioral risk factor surveillance system, S110 BGM system, S148 for foot problems, S259, S260 for hypoglycemia, S326 for prediabetes, S74 of chronic kidney disease, S242-S243 survodutide, S77 SUSTAIN-6 trial, S246 sweeteners, nonnutritive, S8, S90, S95-S96 sympathomimetic amine anorectics, S172, S174 in combination with antiepileptic, S172, S174 syringes, insulin, S153-S154S196, S197, S276, S330 tapentadol, S257, S258 technology, diabetes, S9, S17, S88, S146-S166 assessment of patient's use of, S62, S88 blood glucose monitoring, S147-S149 continuous glucose monitoring devices, S149-S153 digital health, S158-S159 during fasting, S98 general device principles, S146-S147 insulin delivery, S153-S158 technology-assisted prevention programs, S51, S53 TECOS trial, S227 TEDDY study, S34, S55 telehealth, S15, S16, S18, S21, S53, S87-S89, S311 temperature of glucose monitor, S149 of room, for optimum sleep, S113 perception of, S255, S256, S258, S259 teplizumab, S7, S56, S186 testing interval, S38 testosterone in diabetes prevention, S53 low, in men, S7, S71 tetanus, diphtheria, pertussis (TDAP) vaccine, S66 thiazide-like diuretics, S212, S213, S214, S244 thiazolidinediones, S53, S64, S65, S67, S171, S194, S196, S227, S267 thyroid disease, S284, S308 autoimmune, S7, S41, S63, S290 in pediatric type 1 diabetes, S290 ticagrelor, S222 time-restricted eating, S97 tirzepatide, S53, S68, S77, S78, S170-S171, S173, S186, S189, S194, S197, S198, S274, S46, S62, S68, S148, S149, S152, S165, S168, S169, S172, S252 tobacco use/cessation, S8, S54, S61, S72, S104-S105, S213, S226, S243, S298-S299 training blood glucose awareness, S138, S139 diabetes self-management, S88, S89 for family and other caregivers, S112, S146 for school personnel, S287, S335 health professionals/staff, S88, S106, S176, S276, S277, S322, S323-S324 high-intensity interval, S215, S216, S217, S218, S219 in detention facilities, S336 on device use, S146, S147, S158 resistance, S52, S75, S99, S102, S171, S272 self-care, S21, S109 strength, S51, S99, S291 tramadol, S257, S258 transfusion, A1C and, S29, S129, S270 transition from hospital to ambulatory setting, S275, S328-S330 from IV to SC insulin, S13, S325, S328 from obstetric care to primary care, S17 from pediatric to adult care, S299 transplantation, S62, S200 islet, S137, S186, S187 liver, S73 organ, post-transplant diabetes mellitus after, S28, S40, S200 pancreas, S186, S187 renal, S186, S187, S200, S241, S246 tricyclic antidepressants, S171, S257-S258 TWILIGHT trial, S222 two-hour plasma glucose (2-h PG) test, S27-S28, S32, S33, S34, S35, S41, S43, S44, S50, S53, S55, S309-S310, S316 diabetesjournals. see connected insulin pens smoking cessation, S8, S54, S61, S72, S104-S105, S213, S226, S243, S298-S299 Simplified Nutritional Appetite Questionnaire (SNAQ), S99, S174 social capital, S19, S22 social context, S19-S22 social determinants of health (SDOH), S15, S18, S19, S20, S22, S88, S106, S191, S12, S13, S14-S15, S16, S79, S92, S166 sodium channel blockers, S257, S258 sodium intake, S94, S212 sodium-glucose cotransporter 2 (SGLT2) inhibitors, S10, S11, S68, S76, S77, S93, S98, S100, S113, S133, S134, S135, S139, S140, S186, S187, S191, S193-S194, S195, S198, S200, S208, S222-S223, S226-S230, S240, S242, S243, S244-S248, S267, S268, S274, S276, S295, S325, S327 SOLOIST-WHF trial, S228 sotagliflozin, S186, S227, S228 SPRINT trial, S210-S211, S226 staging of diabetic kidney disease, S65, S241-S242 of liver disease risk, S10 of type 1 diabetes, S33 statin therapy, S11, S12, S35, S38, S54-S55, S76, S77, S78, S133, S214-S220, S284, S285, S292, S314 stem cell therapies, for wounds, S261, S262 STEP-HFpEF trial, S23 , S308 surgery, in patients with diabetes, S327 surgical treatment, for type 1 diabetes, S186 surveillance behavioral risk factor surveillance system, S110 BGM system, S148 for foot problems, S259, S260 for hypoglycemia, S326 for prediabetes, S74 of chronic kidney disease, S242-S243 survodutide, S77 SUSTAIN-6 trial, S246 sweeteners, nonnutritive, S8, S90, S95-S96 sympathomimetic amine anorectics, S172, S174 in combination with antiepileptic, S172, S174 syringes, insulin, S153-S154S196, S197, S276, S330 tapentadol, S257, S258 technology, diabetes, S9, S17, S88, S146-S166 assessment of patient's use of, S62, S88 blood glucose monitoring, S147-S149 continuous glucose monitoring devices, S149-S153 digital health, S158-S159 during fasting, S98 general device principles, S146-S147 insulin delivery, S153-S158 technology-assisted prevention programs, S51, S53 TECOS trial, S227 TEDDY study, S34, S55 telehealth, S15, S16, S18, S21, S53, S87-S89, S311 temperature of glucose monitor, S149 of room, for optimum sleep, S113 S7, S41, S63, S290 in pediatric type 1 diabetes, S290 ticagrelor, S222 time-restricted eating, S97 tirzepatide, S53, S68, S77, S78, S170-S171, S173, S186, S189, S194, S197, S198, S274, S46, S62, S68, S148, S149, S152, S165, S168, S169, S172, S252 tobacco use/cessation, S8, S54, S61, S72, S104-S105, S213, S226, S243, S298-S299 training blood glucose awareness, S138, S139 diabetes self-management, S88, S89 for family and other caregivers, S112, S146 for school personnel, S287, S335 health professionals/staff, S88, S106, S176, S276, S277, S322, S323-S324 high-intensity interval, S215, S216, S217, S218, S219 in detention facilities, S336 on device use, S146, S147, S158 resistance, S52, S75, S99, S102, S171, S272 self-care, S21, S109 strength, S51, S99, S291 tramadol, S257, S258 transfusion, A1C and, S29, S129, S270 transition from hospital to ambulatory setting, S275, S328-S330 from IV to SC insulin, S13, S325, S328 from obstetric care to primary care, S17 from pediatric to adult care, S299 transplantation, S62, org/care Index

References

引用 / 出处

2025 ADA 糖尿病医学诊疗标准. 2025.