Showing papers in "Diabetes Care in 2023"

Relation of Incident Type 1 Diabetes to Recent COVID-19 Infection: Cohort Study Using e-Health Record Linkage in Scotland

Abstract: OBJECTIVE Studies using claims databases reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection >30 days earlier was associated with an increase in the incidence of type 1 diabetes. Using exact dates of diabetes diagnosis from the national register in Scotland linked to virology laboratory data, we sought to replicate this finding. RESEARCH DESIGN AND METHODS A cohort of 1,849,411 individuals aged <35 years without diabetes, including all those in Scotland who subsequently tested positive for SARS-CoV-2, was followed from 1 March 2020 to 22 November 2021. Incident type 1 diabetes was ascertained from the national registry. Using Cox regression, we tested the association of time-updated infection with incident diabetes. Trends in incidence of type 1 diabetes in the population from 2015 through 2021 were also estimated in a generalized additive model. RESULTS There were 365,080 individuals who had at least one detected SARS-CoV-2 infection during follow-up and 1,074 who developed type 1 diabetes. The rate ratio for incident type 1 diabetes associated with first positive test for SARS-CoV-2 (reference category: no previous infection) was 0.86 (95% CI 0.62, 1.21) for infection >30 days earlier and 2.62 (95% CI 1.81, 3.78) for infection in the previous 30 days. However, negative and positive SARS-CoV-2 tests were more frequent in the days surrounding diabetes presentation. In those aged 0–14 years, incidence of type 1 diabetes during 2020–2021 was 20% higher than the 7-year average. CONCLUSIONS Type 1 diabetes incidence in children increased during the pandemic. However, the cohort analysis suggests that SARS-CoV-2 infection itself was not the cause of this increase.

The National Clinical Care Commission Report to Congress: Leveraging Federal Policies and Programs for Population-Level Diabetes Prevention and Control: Recommendations From the National Clinical Care Commission

Abstract: The etiology of type 2 diabetes is rooted in a myriad of factors and exposures at individual, community, and societal levels, many of which also affect the control of type 1 and type 2 diabetes. Not only do such factors impact risk and treatment at the time of diagnosis but they also can accumulate biologically from preconception, in utero, and across the life course. These factors include inadequate nutritional quality, poor access to physical activity resources, chronic stress (e.g., adverse childhood experiences, racism, and poverty), and exposures to environmental toxins. The National Clinical Care Commission (NCCC) concluded that the diabetes epidemic cannot be treated solely as a biomedical problem but must also be treated as a societal problem that requires an all-of-government approach. The NCCC determined that it is critical to design, leverage, and coordinate federal policies and programs to foster social and environmental conditions that facilitate the prevention and treatment of diabetes. This article reviews the rationale, scientific evidence base, and content of the NCCC’s population-wide recommendations that address food systems; consumption of water over sugar-sweetened beverages; food and beverage labeling; marketing and advertising; workplace, ambient, and built environments; and research. Recommendations relate to specific federal policies, programs, agencies, and departments, including the U.S. Department of Agriculture, the Food and Drug Administration, the Federal Trade Commission, the Department of Housing and Urban Development, the Environmental Protection Agency, and others. These population-level recommendations are transformative. By recommending health-in-all-policies and an equity-based approach to governance, the NCCC Report to Congress has the potential to contribute to meaningful change across the diabetes continuum and beyond. Adopting these recommendations could significantly reduce diabetes incidence, complications, costs, and inequities. Substantial political resolve will be needed to translate recommendations into policy. Engagement by diverse members of the diabetes stakeholder community will be critical to such efforts.

Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People With Type 2 Diabetes

Abstract: OBJECTIVE To evaluate the effects of tirzepatide on body composition, appetite, and energy intake to address the potential mechanisms involved in body weight loss with tirzepatide. RESEARCH DESIGN AND METHODS In a secondary analysis of a randomized, double-blind, parallel-arm study, the effects of tirzepatide 15 mg (N = 45), semaglutide 1 mg (N = 44), and placebo (N = 28) on body weight and composition, appetite, and energy intake were assessed at baseline and week 28. RESULTS Tirzepatide treatment demonstrated significant reductions in body weight compared with placebo and semaglutide, resulting in greater fat mass reduction. Tirzepatide and semaglutide significantly reduced appetite versus placebo. Appetite scores and energy intake reductions did not differ between tirzepatide and semaglutide. CONCLUSIONS Differences in energy intake during ad libitum lunch were not sufficient to explain the different weight outcomes. Further evaluation is needed to assess mechanistic differences related to tirzepatide actions on 24-h energy intake, substrate utilization, and energy expenditure.

Erratum. 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes-2023. Diabetes Care 2023;46(Suppl. 1):S19-S40.

Abstract: In Table 2.3 of the article cited above, the hypertension risk factor was incorrectly defined as "≥140/90 mmHg or on therapy for hypertension"; this has been corrected to "≥130/80 or on therapy for hypertension." More information on updated hypertension guideline recommendations can be found in Section 10 of Standards of Care in Diabetes-2023, "Cardiovascular Disease and Risk Management" (https://doi.org/10.2337/dc23-S010). The online version of the article (https://doi.org/10.2337/dc23-S002) has been updated to correct the error.

Structural Racism as an Upstream Social Determinant of Diabetes Outcomes: A Scoping Review.

Abstract: OBJECTIVE To evaluate the evidence on the role of structural racism as an upstream factor impacting diabetes outcomes, identify current gaps, and recommend areas for future work. RESEARCH DESIGN AND METHODS A reproducible search of Medline and Ovid was used. Structural factors based on the World Health Organization social determinants of health framework (governance, macroeconomic policy, social policy, public policy, and cultural and societal values) had to be included as measured variables or contextual factors discussed as upstream influences. Outcomes included 1) hemoglobin A1c (HbA1c), 2) LDL, 3) BMI, 4) quality of life, 5) self-efficacy, 6) mortality, 7) years of life lost, and 8) self-care behaviors. RESULTS Thirteen articles were included for final synthesis. Ten studies focused on governance, two on social policies, one on public policies, and one on cultural and societal values. Results highlight significant associations between structural racism and poorer clinical outcomes (HbA1c and blood pressure), worse self-care behaviors (diet and physical activity), lower standards of care, higher mortality, and more years of life lost for adults with diabetes. CONCLUSIONS There is a paucity of work investigating the relationship between structural racism and diabetes outcomes. Five areas for future work include 1) more rigorous research on the relationship between structural racism, downstream social determinants, and health outcomes in diabetes, 2) policy assessments specific to diabetes outcomes, 3) research designed to examine pathways and mechanisms of influence, 4) intervention development to mitigate the impact of structural racism, and 5) tracking and monitoring of change over time.

Once-Weekly Basal Insulin Fc Demonstrated Similar Glycemic Control to Once-Daily Insulin Degludec in Insulin-Naive Patients With Type 2 Diabetes: A Phase 2 Randomized Control Trial

Abstract: OBJECTIVE Basal insulin Fc (BIF) (insulin efsitora alfa; LY3209590), a fusion protein combining a novel single-chain insulin variant with a human IgG Fc domain, is designed for once-weekly basal insulin administration. This phase 2 study assessed the safety and efficacy of BIF versus degludec in insulin-naive patients with type 2 diabetes (T2D) previously treated with oral antihyperglycemic medications. RESEARCH DESIGN AND METHODS During this randomized, parallel, open-label study, 278 insulin-naive patients with T2D were randomly assigned (1:1) to receive BIF once weekly or degludec once daily over the 26-week treatment period. Both groups were titrated to fasting glucose of 80–100 mg/dL (4.4 to <5.6 mmol/L). The primary end point was HbA1c change from baseline to week 26 (noninferiority margin 0.4%). Secondary end points included fasting blood glucose (FBG), six-point glucose profiles, and rate of hypoglycemia. RESULTS After 26 weeks of treatment, BIF demonstrated a noninferior HbA1c change from baseline versus degludec, with a treatment difference of 0.06% (90% CI −0.11, 0.24; P = 0.56). Both BIF and degludec treatment led to significant reductions in FBG from baseline. At week 26, the between-treatment difference for BIF versus degludec was 4.7 mg/dL (90% CI 0.1, 9.3; P = 0.09). The rate of level 2 hypoglycemia was low and not significantly different between treatment groups (BIF 0.22 events/patient/year, degludec 0.15 events/patient/year; P = 0.64); there was no severe hypoglycemia. The occurrence of treatment-emergent adverse events was also similar between BIF and degludec. CONCLUSIONS Once-weekly BIF achieved excellent glycemic control similar to degludec, with no concerning hypoglycemia or other safety findings.

Combination of Multiple Low-Risk Lifestyle Behaviors and Incident Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies

Abstract: OBJECTIVE Combined low-risk lifestyle behaviors (LRLBs) have been associated with a reduction in type 2 diabetes risk. This relationship has not been systematically quantified. RESEARCH DESIGN AND METHODS A systematic review and meta-analysis was conducted to assess the association of combined LRLBs with type 2 diabetes. Databases were searched up to September 2022. Prospective cohort studies reporting the association between a minimum of three combined LRLBs (including healthy diet) with incident type 2 diabetes were included. Independent reviewers extracted data and assessed study quality. Risk estimates of extreme comparisons were pooled using a random-effects model. Global dose-response meta-analysis (DRM) for maximum adherence was estimated using a one-stage linear mixed model. The certainty of the evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluations). RESULTS Thirty cohort comparisons (n = 1,693,753) involving 75,669 incident type 2 diabetes cases were included. LRLBs, with author-defined ranges, were healthy body weight, healthy diet, regular exercise, smoking abstinence or cessation, and light alcohol consumption. LRLBs were associated with 80% lower risk of type 2 diabetes (relative risk [RR] 0.20; 95% CI 0.17–0.23), comparing the highest with lowest adherence. Global DRM for maximum adherence to all five LRLBs reached 85% protection (RR 0.15; 95% CI 0.12–0.18). The overall certainty of the evidence was graded as high. CONCLUSIONS There is a very good indication that a combination of LRLBs that includes maintaining a healthy bodyweight, healthy diet, regular exercise, smoking abstinence or cessation, and light alcohol consumption is associated with a lower risk of incident type 2 diabetes.

Incidence, Severity, and Presentation of Type 2 Diabetes in Youth During the First and Second Year of the COVID-19 Pandemic.

Abstract: OBJECTIVE To describe the evolving impact of the coronavirus disease 2019 pandemic on the incidence and presentation of new-onset pediatric type 2 diabetes. RESEARCH DESIGN AND METHODS Retrospective medical record review of youth with new-onset type 2 diabetes comparing the prepandemic period (1 January 2017-29 February 2020) with the first (1 March 2020-31 December 2020) and second pandemic year (1 January 2021-31 December 2021). RESULTS The annualized incidence of type 2 diabetes increased nearly threefold during the pandemic versus prior, with a 61% increase in the 2nd versus 1st year. BMI increased during the pandemic versus prior (129% of 95th percentile vs. 141%, P = 0.02). In the 1st year, patients were younger (12.9 years vs. 14.8, P < 0.001), with higher incidence of diabetic ketoacidosis and/or hyperglycemic hyperosmolar syndrome (20% vs. 3.5%, P = 0.02) versus prior. CONCLUSIONS Providers should be aware of the escalating incidence of youth-onset type 2 diabetes to avoid delays in diagnosis and inform educational programs to combat the continued impact of the pandemic on health outcomes.

Youth-Onset Type 2 Diabetes: The Epidemiology of an Awakening Epidemic.

Abstract: In this narrative review, we describe the epidemiology (prevalence, incidence, temporal trends, and projections) of type 2 diabetes among children and adolescents (<20 years), focusing on data from the U.S. and reporting global estimates where available. Secondarily, we discuss the clinical course of youth-onset type 2 diabetes, from prediabetes to complications and comorbidities, drawing comparisons with youth type 1 diabetes to highlight the aggressive course of this condition, which, only recently, has become recognized as a pediatric disease by health care providers. Finally, we end with an overview of emerging topics in type 2 diabetes research that have potential to inform strategies for effective preventive action at the community and individual levels.

The National Clinical Care Commission Report to Congress: Background, Methods, and Foundational Recommendations

Abstract: Since the first Federal Commission on Diabetes issued its report in 1975, the diabetes epidemic in the U.S. has accelerated, and efforts to translate advances in diabetes treatment into routine clinical practice have stalled. In 2021, the National Clinical Care Commission (NCCC) delivered a report to Congress that provided recommendations to leverage federal policies and programs to more effectively prevent and treat diabetes and its complications. In the five articles in this series, we present the NCCC’s evidence-based recommendations to 1) reduce diabetes-related risks, prevent type 2 diabetes, and avert diabetes complications through changes in federal policies and programs affecting the general population; 2) prevent type 2 diabetes in at-risk individuals through targeted lifestyle and medication interventions; and 3) improve the treatment of diabetes and its complications to improve the health outcomes of people with diabetes. In this first article, we review the successes and limitations of previous federal efforts to combat diabetes. We then describe the establishment of and charge to the NCCC. We discuss the development of a hybrid conceptual model that guided the NCCC’s novel all-of-government approach to address diabetes as both a societal and medical problem. We then review the procedures used by the NCCC to gather information from federal agencies, stakeholders, key informants, and the public and to conduct literature reviews. Finally, we review the NCCC’s three foundational recommendations: 1) improve the coordination of non–health-related and health-related federal agencies to address the social and environmental conditions that are accelerating the diabetes epidemic; 2) ensure that all Americans at risk for and with diabetes have health insurance and access to health care; and 3) ensure that all federal policies and programs promote health equity in diabetes.

Comparative Incidence of Diabetes Following Hospital Admission for COVID-19 and Pneumonia: A Cohort Study.

Abstract: OBJECTIVE The incidence of diabetes may be elevated following coronavirus disease 2019 (COVID-19), but it is unclear whether this is specific to severe acute respiratory syndrome coronavirus 2 infection, associated with shared risk factors for severe COVID-19 and diabetes, and/or a generic risk following illness. RESEARCH DESIGN AND METHODS People admitted to the hospital for COVID-19 and/or pneumonia between 1 April 2020 and 31 August 2020 in England were linked with the National Diabetes Audit to identify incident diabetes after discharge up to 31 March 2021. Comparator cohorts admitted with pneumonia over the same dates in 2017, 2018, and 2019 were followed until 31 March 2018, 31 March 2019, and 31 March 2020, respectively. Poisson regression models were used to calculate adjusted diabetes incidence rates. RESULTS Using the cohort of people discharged from the hospital following a diagnosis of COVID-19 without pneumonia in 2020 as the standard population (incidence rate 16.4 [95% CI 12.8-20.7] per 1,000 person-years), adjusting for age, sex, ethnicity, and deprivation, gave incidence rates of 19.0 (95% CI 13.8-25.6) and 16.6 (95% CI 13.3-20.4) per 1,000 person-years for those admitted for COVID-19 with pneumonia and pneumonia without COVID-19, respectively, in 2020. These rates are not significantly different from those found after hospital admission for pneumonia in 2019, 2018, and 2017, at 13.7 (95% CI 10.8-17.3), 13.8 (95% CI 10.9-17.4), and 14.2 (95% CI 10.9-18.3) per 1,000 person-years, respectively. CONCLUSIONS Our data do not support a clear impact of COVID-19 on the incidence of diabetes compared with risks in several comparator groups, including contemporaneously assessed risks in people hospitalized with pneumonia.

Erratum. 10. Cardiovascular disease and risk management: Standards of Care in Diabetes-2023. Diabetes Care 2023;46(Suppl. 1):S158-S190.

Abstract: Fig. 10.2 of the article cited above provides recommendations for the treatment of confirmed hypertension in people with diabetes. Due to a composition error, the initial blood pressure range for the left side of the algorithm was given as ≥140/90 and <160/100 mmHg; the correct initial blood pressure range is ≥130/80 and <160/100 mmHg. The online version of the article (https://doi.org/10.2337/dc23-S010) has been updated to correct the error.

High Prevalence of NASH and Advanced Fibrosis in Type 2 Diabetes: A Prospective Study of 330 Outpatients Undergoing Liver Biopsies for Elevated ALT, Using a Low Threshold.

Abstract: OBJECTIVE Most people with type 2 diabetes (T2DM) and nonalcoholic steatohepatitis (NASH) or advanced fibrosis (AF) remain undiagnosed, resulting in missed opportunities for early intervention. This multicenter, prospective study assessed the yield of using routinely available data to identify these patients. RESEARCH DESIGN AND METHODS A total of 713 outpatients with T2DM, screened in four diabetology clinics for nonalcoholic fatty liver disease according to American Diabetes Association criteria, were referred to hepatologists for further work-up (Fibrosis-4 and vibration-controlled transient elastography [VCTE]). A liver biopsy was proposed when ALT levels were persistently >20 IU/L in female patients or >30 IU/L in male patients, in the absence of other liver disease. RESULTS Liver biopsies were performed in 360 patients and considered adequate for reading after central review for 330 specimens (median patient age, 59 years; male patients, 63%; median BMI and HbA1C values, 32 and 7.5%, respectively). Prevalence of NASH, AF, and cirrhosis were 58%, 38%, and 10%, respectively. Liver lesions were independently associated with the components of metabolic syndrome but not with the micro- and macrovascular complications of T2DM. Models based on routinely available data with or without VCTE had good accuracy to predict AF (respectively: area under the receiver operating characteristic curve [AUROC], 0.84 and 0.77; and correctly classified 59% and 45%) and NASH (respectively: AUROC, 0.82 and 0.81; 44% and 42%). CONCLUSIONS Despite the use of a low ALT threshold, prevalence of NASH (58%) or AF (38%) was high. Routinely available data had a high yield in identifying patients with T2DM with AF and/or NASH requiring further liver assessment.

Evaluation of a Produce Prescription Program for Patients With Diabetes: A Longitudinal Analysis of Glycemic Control

Abstract: OBJECTIVE Produce prescriptions have shown promise in improving diabetes care, although most studies have used small samples or lacked controls. Our objective was to evaluate the impacts of a produce prescription program on glycemic control for patients with diabetes. RESEARCH DESIGN AND METHODS Participants included a nonrandom enrollment of 252 patients with diabetes who received a produce prescription and 534 similar control participants from two clinics in Hartford, Connecticut. The start of the COVID-19 pandemic in March 2020 coincided with program implementation. Produce prescription enrollees received vouchers ($60 per month) for 6 months to purchase produce at grocery retail. Controls received usual care. The primary outcome was change in glycated hemoglobin (HbA1c) between treatment and control at 6 months. Secondary outcomes included 6-month changes in systolic (SBP) and diastolic blood pressure (DBP), BMI, hospitalizations, and emergency department admissions. Longitudinal generalized estimating equation models, weighted with propensity score overlap weights, assessed changes in outcomes over time. RESULTS At 6 months, there was no significant difference in change in HbA1c between treatment and control groups, with a difference of 0.13 percentage points (95% CI −0.05, 0.32). No significant difference was observed for change in SBP (3.85 mmHg; −0.12, 7.82), DBP (−0.82 mmHg; −2.42, 0.79), or BMI (−0.22 kg/m2; −1.83, 1.38). Incidence rate ratios for hospitalizations and emergency department visits were 0.54 (0.14, 1.95) and 0.53 (0.06, 4.72), respectively. CONCLUSIONS A 6-month produce prescription program for patients with diabetes, implemented during the onset of the COVID-19 pandemic, was not associated with improved glycemic control.

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

Abstract: OBJECTIVE We aimed to compare glucose control in adolescents with type 1 diabetes (T1D) using the MiniMed 780G system who used simplified meal announcement with those who used precise carbohydrate counting. RESEARCH DESIGN AND METHODS This randomized controlled trial included 34 participants (age 12–18 years) with T1D who were on multiple daily injections or insulin pump and were scheduled to start using the MiniMed 780G system at Sidra Medicine in Qatar. After a 7-day run-in period, participants were randomly assigned to the fix group (simplified meal announcement by preset of three personalized fixed carbohydrate amounts) or the flex group (precise carbohydrate counting) and followed for 12 weeks. Between-group difference in time in range (TIR) was the primary end point. Secondary end points included HbA1c and other glycometrics. RESULTS During the 12-week study phase, TIR was 73.5 ± 6.7% in the fix and 80.3 ± 7.4% in the flex group, with a between-group difference of 6.8% in favor of flex (P = 0.043). Time >250 mg/dL was better in the flex group (P = 0.012), whereas HbA1c (P = 0.168), time below range (P = 0.283), and time between 180 and 250 mg/dL (P = 0.114) did not differ. CONCLUSIONS Adolescents using the MiniMed 780G system with a preset of three personalized fixed carbohydrate amounts can reach international targets of glycemic control. Therefore, it may be a valuable alternative to precise carbohydrate counting in users who are challenged by precise carbohydrate counting. Because carbohydrate counting further improves outcomes, these skills remain important for MiniMed 780G users.

CGM Metrics Identify Dysglycemic States in Participants From the TrialNet Pathway to Prevention Study.

Abstract: OBJECTIVE Continuous glucose monitoring (CGM) parameters may identify individuals at risk for progression to overt type 1 diabetes. We aimed to determine whether CGM metrics provide additional insights into progression to clinical stage 3 type 1 diabetes. RESEARCH DESIGN AND METHODS One hundred five relatives of individuals in type 1 diabetes probands (median age 16.8 years; 89% non-Hispanic White; 43.8% female) from the TrialNet Pathway to Prevention study underwent 7-day CGM assessments and oral glucose tolerance tests (OGTTs) at 6-month intervals. The baseline data are reported here. Three groups were evaluated: individuals with 1) stage 2 type 1 diabetes (n = 42) with ≥2 diabetes-related autoantibodies and abnormal OGTT; 2) stage 1 type 1 diabetes (n = 53) with ≥2 diabetes-related autoantibodies and normal OGTT; and 3) negative test for all diabetes-related autoantibodies and normal OGTT (n = 10). RESULTS Multiple CGM metrics were associated with progression to stage 3 type 1 diabetes. Specifically, spending ≥5% time with glucose levels ≥140 mg/dL (P = 0.01), ≥8% time with glucose levels ≥140 mg/dL (P = 0.02), ≥5% time with glucose levels ≥160 mg/dL (P = 0.0001), and ≥8% time with glucose levels ≥160 mg/dL (P = 0.02) were all associated with progression to stage 3 disease. Stage 2 participants and those who progressed to stage 3 also exhibited higher mean daytime glucose values; spent more time with glucose values over 120, 140, and 160 mg/dL; and had greater variability. CONCLUSIONS CGM could aid in the identification of individuals, including those with a normal OGTT, who are likely to rapidly progress to stage 3 type 1 diabetes.

Glucagon Prescribing and Costs Among U.S. Adults With Diabetes, 2011-2021.

Abstract: OBJECTIVE To characterize contemporary trends in glucagon fill rates and expenditures in a nationwide cohort of adults with diabetes overall and by key demographic and clinical characteristics. RESEARCH DESIGN AND METHODS In this retrospective cohort study, we examined 1) glucagon fill rates per 1,000 person-years and 2) patient out-of-pocket and health plan costs per filled glucagon dose among adults with diabetes included in OptumLabs Data Warehouse between 1 January 2011 and 31 March 2021. RESULTS The study population comprised 2,814,464 adults with diabetes with a mean age of 62.8 (SD 13.2) years. The overall glucagon fill rate decreased from 2.91 to 2.28 per 1,000 person-years (-22%) over the study period. In groups at high risk for severe hypoglycemia, glucagon fill rates increased from 22.46 to 36.76 per 1,000 person-years (64%) among patients with type 1 diabetes, 11.64 to 16.63 per 1,000 person-years (43%) among those treated with short-acting insulin, and 16.08 to 20.12 per 1,000 person-years (25%) among those with a history of severe hypoglycemia. White patients, women, individuals with high income, and commercially insured patients had higher glucagon fill rates compared with minority patients, males, individuals with low income, and Medicare Advantage patients, respectively. Total cost per dosing unit increased from $157.97 to $275.32 (74%) among commercial insurance beneficiaries and from $150.37 to $293.57 (95%) among Medicare Advantage beneficiaries. CONCLUSIONS Glucagon fill rates are concerningly low and declined between 2011 and 2021 but increased in appropriate subgroups with type 1 diabetes, using short-acting insulin, or with a history of severe hypoglycemia. Fill rates were disproportionately low among minority patients and individuals with low income.

Abatacept for Delay of Type 1 Diabetes Progression in Stage 1 Relatives at Risk: A Randomized, Double-Masked, Controlled Trial

Abstract: OBJECTIVE Previous studies showed that inhibiting lymphocyte costimulation reduces declining β-cell function in individuals newly diagnosed with type 1 diabetes. We tested whether abatacept would delay or prevent progression of type 1 diabetes from normal glucose tolerance (NGT) to abnormal glucose tolerance (AGT) or to diabetes and the effects of treatment on immune and metabolic responses. RESEARCH DESIGN AND METHODS We conducted a phase 2, randomized, placebo-controlled, double-masked trial of abatacept in antibody-positive participants with NGT who received monthly abatacept/placebo infusions for 12 months. The end point was AGT or diabetes, assessed by oral glucose tolerance tests. RESULTS A total of 101 participants received abatacept and 111 placebo. Of these, 81 (35 abatacept and 46 placebo) met the end point of AGT or type 1 diabetes diagnosis (hazard ratio 0.702; 95% CI 0.452, 1.09; P = 0.11) The C-peptide responses to oral glucose tolerance tests were higher in the abatacept arm (P < 0.03). Abatacept reduced the frequency of inducible T-cell costimulatory (ICOS)+ PD1+ T-follicular helper (Tfh) cells during treatment (P < 0.0001), increased naive CD4+ T cells, and also reduced the frequency of CD4+ regulatory T cells (Tregs) from the baseline (P = 0.0067). Twelve months after treatment, the frequency of ICOS+ Tfh, naive CD4+ T cells, and Tregs returned to baseline. CONCLUSIONS Although abatacept treatment for 1 year did not significantly delay progression to glucose intolerance in at-risk individuals, it impacted immune cell subsets and preserved insulin secretion, suggesting that costimulation blockade may modify progression of type 1 diabetes.

The National Clinical Care Commission Report to Congress: Leveraging Federal Policies and Programs to Prevent Diabetes in People With Prediabetes

Abstract: Individuals with an elevated fasting glucose level, elevated glucose level after glucose challenge, or elevated hemoglobin A1c level below the diagnostic threshold for diabetes (collectively termed prediabetes) are at increased risk for type 2 diabetes. More than one-third of U.S. adults have prediabetes but fewer than one in five are aware of the diagnosis. Rigorous scientific research has demonstrated the efficacy of both intensive lifestyle interventions and metformin in delaying or preventing progression from prediabetes to type 2 diabetes. The National Clinical Care Commission (NCCC) was a federal advisory committee charged with evaluating and making recommendations to improve federal programs related to the prevention of diabetes and its complications. In this article, we describe the recommendations of an NCCC subcommittee that focused primarily on prevention of type 2 diabetes in people with prediabetes. These recommendations aim to improve current federal diabetes prevention activities by 1) increasing awareness of and diagnosis of prediabetes on a population basis; 2) increasing the availability of, referral to, and insurance coverage for the National Diabetes Prevention Program and the Medicare Diabetes Prevention Program; 3) facilitating Food and Drug Administration review and approval of metformin for diabetes prevention; and 4) supporting research to enhance the effectiveness of diabetes prevention. Cognizant of the burden of type 1 diabetes, the recommendations also highlight the importance of research to advance our understanding of the etiology of and opportunities for prevention of type 1 diabetes.

The National Clinical Care Commission Report to Congress: Leveraging Federal Policies and Programs to Improve Diabetes Treatment and Reduce Complications

Abstract: The Treatment and Complications subcommittee of the National Clinical Care Commission focused on factors likely to improve the delivery of high-quality care to all people with diabetes. The gap between available resources and the needs of people living with diabetes adversely impacts both treatment and outcomes. The Commission’s recommendations are designed to bridge this gap. At the patient level, the Commission recommends reducing barriers and streamlining administrative processes to improve access to diabetes self-management training, diabetes devices, virtual care, and insulin. At the practice level, we recommend enhancing programs that support team-based care and developing capacity to support technology-enabled mentoring interventions. At the health system level, we recommend that the Department of Health and Human Services routinely assess the needs of the health care workforce and ensure funding of training programs directed to meet those needs. At the health policy level, we recommend establishing a process to identify and ensure pre-deductible insurance coverage for high-value diabetes treatments and services and developing a quality measure that reduces risk of hypoglycemia and enhances patient safety. We also identified several areas that need additional research, such as studying the barriers to uptake of diabetes self-management education and support, exploring methods to implement team-based care, and evaluating the importance of digital connectivity as a social determinant of health. The Commission strongly encourages Congress, the Department of Health and Human Services, and other federal departments and agencies to take swift action to implement these recommendations to improve health outcomes and quality of life among people living with diabetes.

Optimization of Albuminuria-Lowering Treatment in Diabetes by Crossover Rotation to Four Different Drug Classes: A Randomized Crossover Trial

Abstract: OBJECTIVE Renin–angiotensin system (RAS) inhibitors decrease the urinary albumin to creatinine ratio (UACR) but are ineffective in up to 40% of patients. We hypothesized that rotation through different drug classes overcomes RAS inhibitor resistance and tested this in a randomized crossover trial. RESEARCH DESIGN AND METHODS We assigned 26 adults with type 1 diabetes and 37 with type 2 diabetes and UACR between 30 and 500 mg/g and estimated glomerular filtration rate >45 mL/min/1.73 m2 to 4-week treatment periods with telmisartan 80 mg, empagliflozin 10 mg, linagliptin 5 mg, and baricitinib 2 mg in random order, separated by 4-week washout periods. Each participant was then re-exposed for 4 weeks to the drug that induced that individual’s largest UACR reduction. Primary outcome was the difference in UACR response to the best-performing drug during the confirmation period versus UACR response to the other three drugs. RESULTS There was substantial variation in the best-performing drug. Telmisartan was best performing for 33 participants (52%), empagliflozin and linagliptin in 11 (17%), and baricitinib in 8 participants (13%). The individuals’ best-performing drug changed UACR from baseline during the first and confirmatory exposures by a mean of −39.6% (95% CI −44.8, −33.8; P < 0.001) and −22.4% (95% CI −29.7, −12.5; P < 0.001), respectively. The Pearson correlation for first versus confirmatory exposure was 0.39 (P = 0.017). The mean change in UACR with the other three drugs was +1.6% (95% CI −4.3%, 8.0%; P = 0.593 versus baseline; difference versus individuals’ best-performing drug at confirmation, 30.9% [95% CI 18.0, 45.3]; P < 0.001). CONCLUSIONS We demonstrated a large and reproducible variation in participants’ responses to different UACR-lowering drug classes. These data support systematic rotation through different drug classes to overcome therapy resistance to RAS inhibition.

Global Prevalence of Prediabetes.

Abstract: OBJECTIVE To estimate the global, regional, and national prevalence of prediabetes, defined by impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). RESEARCH DESIGN AND METHODS We reviewed 7,014 publications for high-quality estimates of IGT (2-h glucose, 7.8-11.0 mmol/L [140-199 mg/dL]) and IFG (fasting glucose, 6.1-6.9 mmol/L [110-125 mg/dL]) prevalence for each country. We used logistic regression to generate prevalence estimates for IGT and IFG among adults aged 20-79 years in 2021 and projections for 2045. For countries without in-country data, we extrapolated estimates from countries with available data with similar geography, income, ethnicity, and language. Estimates were standardized to the age distribution for each country from the United Nations. RESULTS Approximately two-thirds of countries did not have high-quality IGT or IFG data. There were 50 high-quality studies for IGT from 43 countries and 43 high-quality studies for IFG from 40 countries. Eleven countries had data for both IGT and IFG. The global prevalence of IGT in 2021 was 9.1% (464 million) and is projected to increase to 10.0% (638 million) in 2045. The global prevalence of IFG in 2021 was 5.8% (298 million) and is projected to increase to 6.5% (414 million) in 2045. The 2021 prevalence of IGT and IFG was highest in high-income countries. In 2045, the largest relative growth in cases of IGT and IFG would be in low-income countries. CONCLUSIONS The global burden of prediabetes is substantial and growing. Enhancing prediabetes surveillance is necessary to effectively implement diabetes prevention policies and interventions.

The National Clinical Care Commission Report to Congress: Recommendations to Better Leverage Federal Policies and Programs to Prevent and Control Diabetes

Abstract: The National Clinical Care Commission (NCCC) was established by Congress to make recommendations to leverage federal policies and programs to more effectively prevent and treat diabetes and its complications. The NCCC developed a guiding framework that incorporated elements of the Socioecological and Chronic Care Models. It surveyed federal agencies and conducted follow-up meetings with representatives from 10 health-related and 11 non–health-related federal agencies. It held 12 public meetings, solicited public comments, met with numerous interested parties and key informants, and performed comprehensive literature reviews. The final report, transmitted to Congress in January 2022, contained 39 specific recommendations, including 3 foundational recommendations that addressed the necessity of an all-of-government approach to diabetes, health equity, and access to health care. At the general population level, the NCCC recommended that the federal government adopt a health-in-all-policies approach so that the activities of non–health-related federal agencies that address agriculture, food, housing, transportation, commerce, and the environment be coordinated with those of health-related federal agencies to affirmatively address the social and environmental conditions that contribute to diabetes and its complications. For individuals at risk for type 2 diabetes, including those with prediabetes, the NCCC recommended that federal policies and programs be strengthened to increase awareness of prediabetes and the availability of, referral to, and insurance coverage for intensive lifestyle interventions for diabetes prevention and that data be assembled to seek approval of metformin for diabetes prevention. For people with diabetes and its complications, the NCCC recommended that barriers to proven effective treatments for diabetes and its complications be removed, the size and competence of the workforce to treat diabetes and its complications be increased, and new payment models be implemented to support access to lifesaving medications and proven effective treatments for diabetes and its complications. The NCCC also outlined an ambitious research agenda. The NCCC strongly encourages the public to support these recommendations and Congress to take swift action.

Examining the Acute Glycemic Effects of Different Types of Structured Exercise Sessions in Type 1 Diabetes in a Real-World Setting: The Type 1 Diabetes and Exercise Initiative (T1DEXI)

Abstract: OBJECTIVE Maintenance of glycemic control during and after exercise remains a major challenge for individuals with type 1 diabetes. Glycemic responses to exercise may differ by exercise type (aerobic, interval, or resistance), and the effect of activity type on glycemic control after exercise remains unclear. RESEARCH DESIGN AND METHODS The Type 1 Diabetes Exercise Initiative (T1DEXI) was a real-world study of at-home exercise. Adult participants were randomly assigned to complete six structured aerobic, interval, or resistance exercise sessions over 4 weeks. Participants self-reported study and nonstudy exercise, food intake, and insulin dosing (multiple daily injection [MDI] users) using a custom smart phone application and provided pump (pump users), heart rate, and continuous glucose monitoring data. RESULTS A total of 497 adults with type 1 diabetes (mean age ± SD 37 ± 14 years; mean HbA1c ± SD 6.6 ± 0.8% [49 ± 8.7 mmol/mol]) assigned to structured aerobic (n = 162), interval (n = 165), or resistance (n = 170) exercise were analyzed. The mean (± SD) change in glucose during assigned exercise was −18 ± 39, −14 ± 32, and −9 ± 36 mg/dL for aerobic, interval, and resistance, respectively (P < 0.001), with similar results for closed-loop, standard pump, and MDI users. Time in range 70–180 mg/dL (3.9–10.0 mmol/L) was higher during the 24 h after study exercise when compared with days without exercise (mean ± SD 76 ± 20% vs. 70 ± 23%; P < 0.001). CONCLUSIONS Adults with type 1 diabetes experienced the largest drop in glucose level with aerobic exercise, followed by interval and resistance exercise, regardless of insulin delivery modality. Even in adults with well-controlled type 1 diabetes, days with structured exercise sessions contributed to clinically meaningful improvement in glucose time in range but may have slightly increased time below range.

Novel Once-Weekly Basal Insulin Fc Achieved Similar Glycemic Control With a Safety Profile Comparable to Insulin Degludec in Patients With Type 1 Diabetes

Abstract: OBJECTIVE Basal Insulin Fc (BIF; insulin efsitora alfa; LY3209590), a fusion protein combining a novel single-chain insulin variant with a human IgG Fc domain, is designed for once-weekly basal insulin administration. This phase 2 study assessed safety and efficacy of BIF versus degludec in 265 patients with type 1 diabetes (T1D) using multiple daily injections. RESEARCH DESIGN AND METHODS During this randomized, parallel, open-label study, patients with T1D were randomized (1:1) to receive BIF once weekly or degludec once daily over the 26-week treatment period. Both groups were titrated to a fasting glucose level of 80–100 mg/dL. The primary end point was HbA1c change from baseline to week 26 (noninferiority margin, 0.4%). Secondary end points included percent time in range (TIR) (70–180 mg/dL), continuous glucose monitoring (CGM) fasting glucose (FG) level, and rate of hypoglycemia. RESULTS After 26 weeks, patients receiving BIF had noninferior HbA1c change from baseline versus those receiving degludec, with a statistically significant treatment difference of 0.17% (90% CI 0.01, 0.32; P = 0.07) favoring the comparator. Percent TIR was similar for patients in the BIF (56.1%) and degludec (58.9%; P = 0.112) groups at week 26. FG values were significantly higher for patients receiving BIF (158.8 mg/dL) versus degludec (143.2 mg/dL; P = 0.003). Rates of CGM-derived hypoglycemia were not statistically significantly different for BIF and degludec over 24 h for level 1 (P = 0.960) or level 2 (P = 0.517) hypoglycemia during the treatment period. Occurrence of serious adverse events was similar between the BIF and degludec groups. CONCLUSIONS Once-weekly BIF demonstrated noninferior glycemic control to once-daily degludec (treatment difference: 0.17% favoring degludec) and no difference in hypoglycemia or other safety findings in patients with T1D.

Addendum. 2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes-2023. Diabetes Care 2023;46(Suppl. 1):S19-S40.

Abstract: Section 2, "Classification and Diagnosis of Diabetes," of the Standards of Care in Diabetes-2023 has been updated to refine the diagnostic criteria for type 1 diabetes based on recent U.S. Food and Drug Administration approval of a new drug to delay the incidence of type 1 diabetes. The online version of the article (https://doi.org/10.2337/dc23-S002) reflects the changes described below. Jason L. Gaglia, of Joslin Diabetes Center and Harvard Medical School, Boston, MA, has been added as an author due to his expertise in immunology and type 1 diabetes. The author list and disclosures table (p. S281) have been updated accordingly. In the section "Type 1 Diabetes," Recommendations 2.5 and 2.6 have been revised to reflect current U.S. Food and Drug Administration guidance on the therapies to delay the occurrence of type 1 diabetes. Recommendation 2.5 (p. S22) has been revised to read as follows:"2.5 Screening for presymptomatic type 1 diabetes may be done by detection of autoantibodies to insulin, glutamic acid decarboxylase (GAD), islet antigen 2, or zinc transporter 8. B" Recommendation 2.6 (p. S23) has been revised to read as follows:"2.6 Multiple confirmed islet autoantibodies is a risk factor for clinical diabetes. Testing for dysglycemia may be used to further forecast near-term risk. 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" The last paragraph of the section has been revised to read as follows:"Several screening programs are available in Europe (e.g., Fr1da, gppad.org) and the U.S. (e.g., trialnet.org, askhealth.org, cascadekids.org). Family history of autoimmune diabetes and personal or family history of allergic diseases or other autoimmune diseases increases risk of autoimmune diabetes compared with the general population. Individuals who test autoantibody positive should be either provided with or referred for counseling about the risk of developing diabetes, diabetes symptoms, DKA prevention, and consideration of additional testing as applicable to help determine if they meet criteria for intervention aimed at delaying progression."

Phenotypes Associated With Zones Defined by Area Under the Curve Glucose and C-peptide in a Population With Islet Autoantibodies

Abstract: OBJECTIVE Metabolic zones were developed to characterize heterogeneity of individuals with islet autoantibodies. RESEARCH DESIGN AND METHODS Baseline 2-h oral glucose tolerance test data from 6,620 TrialNet Pathway to Prevention Study (TNPTP) autoantibody-positive participants (relatives of individuals with type 1 diabetes) were used to form 25 zones from five area under the curve glucose (AUCGLU) rows and five area under the curve C-peptide (AUCPEP) columns. Zone phenotypes were developed from demographic, metabolic, autoantibody, HLA, and risk data. RESULTS As AUCGLU increased, changes of glucose and C-peptide response curves (from mean glucose and mean C-peptide values at 30, 60, 90, and 120 min) were similar within the five AUCPEP columns. Among the zones, 5-year risk for type 1 diabetes was highly correlated with islet antigen 2 antibody prevalence (r = 0.96, P &lt; 0.001). Disease risk decreased markedly in the highest AUCGLU row as AUCPEP increased (0.88–0.41; P &lt; 0.001 from lowest AUCPEP column to highest AUCPEP column). AUCGLU correlated appreciably less with Index60 (an indicator of insulin secretion) in the highest AUCPEP column (r = 0.33) than in other columns (r ≥ 0.78). AUCGLU was positively related to “fasting glucose × fasting insulin” and to “fasting glucose × fasting C-peptide” (indicators of insulin resistance) before and after adjustments for Index60 (P &lt; 0.001). CONCLUSIONS Phenotypes of 25 zones formed from AUCGLU and AUCPEP were used to gain insights into type 1 diabetes heterogeneity. Zones were used to examine GCRC changes with increasing AUCGLU, associations between risk and autoantibody prevalence, the dependence of glucose as a predictor of risk according to C-peptide, and glucose heterogeneity from contributions of insulin secretion and insulin resistance.

A National Physician Survey of Deintensifying Diabetes Medications for Older Adults With Type 2 Diabetes.

Abstract: OBJECTIVE To determine physicians' approach to deintensifying (reducing/stopping) or switching hypoglycemia-causing medications for older adults with type 2 diabetes. RESEARCH DESIGN AND METHODS In this national survey, U.S. physicians in general medicine, geriatrics, or endocrinology reported changes they would make to hypoglycemia-causing medications for older adults in three scenarios: good health, HbA1c of 6.3%; complex health, HbA1c of 7.3%; and poor health, HbA1c of 7.7%. RESULTS There were 445 eligible respondents (response rate 37.5%). In patient scenarios, 48%, 4%, and 20% of physicians deintensified hypoglycemia-causing medications for patients with good, complex, and poor health, respectively. Overall, 17% of physicians switched medications without significant differences by patient health. One-half of physicians selected HbA1c targets below guideline recommendations for older adults with complex or poor health. CONCLUSIONS Most U.S. physicians would not deintensify or switch hypoglycemia-causing medications within guideline-recommended HbA1c targets. Physician preference for lower HbA1c targets than guidelines needs to be addressed to optimize deintensification decisions.

Insulin Deficiency From Insulin Gene Mutation Leads to Smaller Pancreas

Abstract: OBJECTIVE To determine the mechanism of reduced pancreas size in type 1 diabetes and the significance of islet-derived insulin in pancreatic growth. RESEARCH DESIGN AND METHODS Using a validated and standardized MRI protocol, we measured pancreas volume and shape in a family with an autosomal-dominant insulin gene mutation that results in insulin deficiency similar in severity to that of type 1 diabetes but without autoimmunity. DNA sequencing confirmed the mutation in all four affected individuals and none of the four control family members. Insulin secretory capacity was determined by measuring postprandial urinary C-peptide. RESULTS Family members with this form of monogenic diabetes had a markedly smaller pancreas and a severely impaired postprandial C-peptide level than family members without diabetes. CONCLUSIONS These results suggest that severe insulin deficiency, rather than islet-directed autoimmunity, leads to reduced pancreas size in type 1 diabetes and that insulin is a major trophic factor for the exocrine pancreas.