Noh Y, Yin H, Ben Ghezala I
… +3 more, Yu OHY, Suissa S, Azoulay L
Diabetes Care
· 2026 May · PMID 41701611
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OBJECTIVE: To estimate the effect of initiating glucagon-like peptide 1 receptor agonists (GLP-1 RAs) versus dipeptidyl peptidase 4 (DPP-4) inhibitors on incident nonarteritic anterior ischemic optic neuropathy (NAION) a...OBJECTIVE: To estimate the effect of initiating glucagon-like peptide 1 receptor agonists (GLP-1 RAs) versus dipeptidyl peptidase 4 (DPP-4) inhibitors on incident nonarteritic anterior ischemic optic neuropathy (NAION) among adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: This active-comparator, new-user cohort emulated a pragmatic target trial using the U.K. Clinical Practice Research Datalink. Patients aged ≥18 years with a physician diagnosis of type 2 diabetes who newly initiated a GLP-1 RA or a DPP-4 inhibitor were included. DPP-4 inhibitors were selected as the comparator because they may be used as second-line treatment, like GLP-1 RAs, and have no established association with NAION. We estimated risks, risk differences (RDs), and risk ratios (RRs) of incident NAION, adjusted using propensity-score fine-stratification weighting. RESULTS: At 1 year, there were 14 NAION events among 106,858 GLP-1 RA initiators (18.5 per 100,000) and 53 among 416,369 DPP-4 inhibitor initiators (7.2 per 100,000). GLP-1 RAs were associated with an increased risk of NAION compared with DPP-4 inhibitors (RR 2.56; 95% CI 1.44-4.86; RD 11.3 per 100,000). The risk of NAION was higher during the first 6 months of use, diminishing with longer duration of use, and was higher in patients aged <50 years, men, ever-smokers, and those with ≥1% hemoglobin A1c reduction. CONCLUSIONS: GLP-1 RAs were associated with an increased 1-year risk of NAION compared with DPP-4 inhibitors among adults with type 2 diabetes, particularly in younger patients, men, ever-smokers, and patients with a marked hemoglobin A1c reduction.
OBJECTIVE: Expenditures on glucose-lowering prescriptions may have changed because of the introduction of new medication classes and changes in insurance policies. This study analyzed national trends in per capita expend...OBJECTIVE: Expenditures on glucose-lowering prescriptions may have changed because of the introduction of new medication classes and changes in insurance policies. This study analyzed national trends in per capita expenditures on glucose-lowering medications among U.S. adults with diabetes during 2000-2022. RESEARCH DESIGN AND METHODS: Using Medical Expenditure Panel Surveys data, we analyzed annual per capita expenditures on glucose-lowering medications among people aged ≥18 years with self-reported diabetes. Expenditures were calculated overall and by subgroups defined by age, race and ethnicity, income, and insurance status. Medications were grouped as older oral agents (metformin, sulfonylureas, thiazolidinediones, α-glucosidase inhibitors, meglitinides), newer noninsulin agents (dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, amylin analogs, combination products), human insulin, and analog insulin. Joinpoint regression was used to identify trend changes. We also estimated the change in number of users and expenditure per user for each medication category. Expenditures were adjusted to 2022 U.S. dollars. RESULTS: Total per capita expenditures on glucose-lowering medications increased by 335%, from $856 in 2000 to $3,725 in 2022. Expenditures rose by $29 per year during 2000-2012, then accelerated by $224 annually. Expenditures increased substantially on newer noninsulin agents while declining on older oral agents, and human insulin expenditures declined. Analog insulin expenditures rose initially but plateaued after 2016. The upward trend in newer high-cost therapies was primarily driven by an increased number of users. CONCLUSIONS: Per capita expenditures on newer medications have risen markedly. Identifying key drivers of these expenditures may enhance affordability and access to effective diabetes treatments.
OBJECTIVE: Maternal diabetes increases offspring risk for neurodevelopmental disorders, but its association with delayed developmental milestones is unknown. We examined milestone attainment in offspring of mothers with...OBJECTIVE: Maternal diabetes increases offspring risk for neurodevelopmental disorders, but its association with delayed developmental milestones is unknown. We examined milestone attainment in offspring of mothers with gestational diabetes mellitus (GDM) and pregestational type 1 and type 2 diabetes compared with unexposed control individuals. RESEARCH DESIGN AND METHODS: We examined a nationwide retrospective cohort study of 466,462 term singleton infants born January 2018 to December 2021 using linked national maternal-child health clinic and hospital discharge data. Developmental data were obtained from nurse-administered structured assessments at routine well-child visits through 24 months of age. Adjusted hazard ratios (aHRs) and 95% CIs for failure to attain developmental milestones were estimated by diabetes type and infant sex. RESULTS: Pregestational diabetes was associated with increased risk for delayed milestone attainment in language, personal-social, and gross motor domains compared with control groups. Offspring of mothers with type 1 diabetes showed the highest risk, followed by those with type 2 diabetes. The association between type 1 diabetes and developmental delay was primarily driven by female offspring, with elevated risks in personal-social (aHR, 1.64; 95% CI, 1.14-2.36), language (aHR, 1.44; 95% CI, 1.09-1.89), and gross motor (aHR, 1.41; 95% CI, 1.05-1.89) domains. GDM was associated with modestly increased risk limited to the fine motor domain (aHR, 1.11; 95% CI, 1.06-1.16). CONCLUSIONS: Pregestational diabetes is associated with delayed milestone attainment, with risk varying by diabetes type, developmental domain, and infant sex. Further research should explore long-term trajectories to inform early intervention for children exposed to maternal diabetes.
Guo J, Li Z, Patel SA
… +3 more, Chang HH, Ali MK, Varghese JS
Diabetes Care
· 2026 Apr · PMID 41649356
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OBJECTIVE: Understanding the pathophysiology of type 2 diabetes subtypes (severe insulin-deficient diabetes, severe insulin-resistant diabetes, mild obesity-related diabetes, and mild age-related diabetes) before diagnos...OBJECTIVE: Understanding the pathophysiology of type 2 diabetes subtypes (severe insulin-deficient diabetes, severe insulin-resistant diabetes, mild obesity-related diabetes, and mild age-related diabetes) before diagnosis can enable precision prevention. We estimated the associations of seven biomarkers with type 2 diabetes subtypes prior to diagnosis. RESEARCH DESIGN AND METHODS: We analyzed 69,725 observations from 9,661 adults without diabetes (median follow-up 10 years [range 0-17 years]) from four U.S. cohorts. Time-dependent Cox models estimated cause-specific hazard ratios (HRs) of seven pathophysiological biomarkers (BMI [kg/m2], systolic blood pressure [SBP] [per 10 mmHg], HbA1c [%], LDL cholesterol [per 10 mg/dL], homeostatic indices [HOMA2 of β-cell function (HOMA2-%B) (per 10 units) and HOMA2 of insulin resistance (HOMA2-IR)], and estimated glomerular filtration rate [eGFR] [per 10 mL/min/1.73 m2]) with incidence of type 2 diabetes and subtypes, adjusting for demographic and clinical covariates. Model performance was evaluated using participants' first and random visits before last follow-up. RESULTS: Of the pooled cohort, 1,569 individuals developed type 2 diabetes. BMI (HR 1.03 [95% CI 1.02, 1.04]), SBP (HR 1.09 [95% CI 1.05, 1.13]), HbA1c (HR 2.46 [95% CI 1.73, 3.52]), HOMA2-%B (HR 0.89 [95% CI 0.87, 0.91]), HOMA2-IR (HR 1.92 [95% CI 1.78, 2.07]), and LDL cholesterol (HR 1.02 [95% CI 1.00, 1.04]), but not eGFR (HR 1.02 [95% CI 0.98, 1.07]), were independently associated with diabetes. Associations were similar across subtypes. Models based on single time points demonstrated a high C-index (0.81-0.90) but modest F1 scores (0.26-0.51) and varying sensitivity and calibration (slope 0.22-1.24). CONCLUSIONS: Pathophysiological biomarkers were prospectively associated with type 2 diabetes and subtypes, but single-time-point measurements before diagnosis could not reliably distinguish subtypes at diagnosis.
Liu L, Peng R, Chu X
… +17 more, Xia Z, Fu Q, Fernandes Silva L, Stringham HM, Hu X, Liang Y, Ji X, Li J, Yang T, Morrison J, Wen X, Fauman E, Burant CF, Scott LJ, Boehnke M, Laakso M, Yin X
Diabetes Care
· 2026 Apr · PMID 41636648
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OBJECTIVE: We aimed to identify plasma metabolites significantly associated with existing type 2 diabetes (T2D), further characterize their associations with T2D-related laboratory measures and lifestyle-related risk fac...OBJECTIVE: We aimed to identify plasma metabolites significantly associated with existing type 2 diabetes (T2D), further characterize their associations with T2D-related laboratory measures and lifestyle-related risk factors, and evaluate their potential mediating and predictive roles for incident T2D. RESEARCH DESIGN AND METHODS: We performed metabolomic profiling in 10,163 Finnish men in the Metabolic Syndrome in Men (METSIM) study at baseline. Of these participants, 1,412 had prevalent T2D and 1,234 developed incident T2D during an average follow-up period of 13.6 years. We tested for associations of 979 named metabolites with prevalent T2D. For significant metabolites, we further evaluated their associations with 24 T2D-related laboratory measures of five groups and five T2D lifestyle-related risk factors. We performed an exploratory mediation analysis to examine the mediation effects of metabolites on incident T2D for the five risk factors. We evaluated metabolite associations with incident T2D and built exploratory metabolite predictive models for incident T2D. RESULTS: We identified 193 plasma metabolites significantly associated with prevalent T2D at baseline, including 71 previously unreported. Of these 193 metabolites, 88 were associated with incident T2D. In participants with prevalent T2D, the 193 metabolites showed associations with zero to 24 (mean 10.2) T2D-related laboratory measures. Eighty-one metabolites partially mediated the associations of the five risk factors with T2D onset under standard mediation assumptions. The significant metabolites showed improved predictive ability for future T2D. CONCLUSIONS: This study identifies T2D plasma metabolic biomarkers for further investigation in women and other populations. The findings enhance our understanding of T2D biology.
OBJECTIVE: To calculate 3-year predicted risk for diabetes with a model including individualized preventive intervention effects for metformin therapy and intensive lifestyle among U.S. adults with prediabetes. RESEARCH...OBJECTIVE: To calculate 3-year predicted risk for diabetes with a model including individualized preventive intervention effects for metformin therapy and intensive lifestyle among U.S. adults with prediabetes. RESEARCH DESIGN AND METHODS: We included 2,778 participants with prediabetes from the National Health and Nutrition Examination Survey (NHANES) cycles 2015-2020. Using a validated type 2 diabetes risk prediction model, we calculated predicted risk and summarized the optimal prevention strategy (lowest predicted risk). RESULTS: Mean predicted risk in this sample was 18.4% (95% CI 17.6, 19.3) for standard lifestyle recommendations (placebo), 14.4% (95% CI 13.9, 14.8) for metformin, 8.0% (95% CI 7.6, 8.4) for intensive lifestyle, and 7.6% (95% CI 7.2, 7.9) for participants' respective optimal intervention. The optimal intervention strategy was intensive lifestyle for 91% of the analytic sample. CONCLUSIONS: We demonstrate the potential population health benefits for diabetes prevention with use of a clinical decision tool, a diabetes risk prediction model with individualized preventive intervention effects.
McCormick N, Burrack N, Yokose C
… +8 more, Lu N, Wexler DJ, Rai SK, Challener GJ, Aviña-Zubieta JA, McCoy RG, Abuhasira R, Choi HK
Diabetes Care
· 2026 Mar · PMID 41615420
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OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) lower serum urate and are associated with a lower risk of recurrent gout flares. We used target trial emulation to compare rates of allopurinol initiation an...OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) lower serum urate and are associated with a lower risk of recurrent gout flares. We used target trial emulation to compare rates of allopurinol initiation and use of anti-inflammatories (high-dose glucocorticoids, nonsteroidal anti-inflammatory drugs [NSAIDs], colchicine) and diuretics (prototypic serum urate-raising medication) among patients with gout using SGLT2is versus dipeptidyl peptidase 4 inhibitors (DPP-4is) (primary comparator), with glucagon-like peptide 1 receptor agonists (GLP-1RAs) as an alternative comparator. RESEARCH DESIGN AND METHODS: From a general population database, we identified patients with gout and comorbid type 2 diabetes and used Cox proportional hazards and Poisson regressions with inverse probability of treatment weighting to emulate randomization to SGLT2i or DPP-4i/GLP-1RA. We also replicated the analysis in an electronic health record data set with further adjustment for serum urate and BMI. RESULTS: Among 26,739 adults with gout and type 2 diabetes (mean age 66 years), 67% had polypharmacy. Allopurinol initiation was lower among SGLT2i initiators than DPP-4i, with a hazard ratio of 0.62 (95% CI 0.52-0.73). Associations were stronger among those using diuretics at baseline (P for interaction = 0.03) and persisted when comparing SGLT2i with GLP-1RA and accounting for serum urate and BMI in the secondary data set. SGLT2i was also associated with lower rates of high-dose glucocorticoid, NSAID, colchicine, and diuretic dispensing, with rate ratios of 0.78 (95% CI 0.74-0.83), 0.85 (95% CI 0.80-0.92), 0.87 (95% CI 0.83-0.92), and 0.87 (95% CI 0.85-0.89), respectively. CONCLUSIONS: For patients with gout and type 2 diabetes, SGLT2is may reduce gout-related medication use, which could, in turn, reduce exposure to the harmful cardiovascular-kidney-metabolic effects of NSAIDs and glucocorticoids in this high-risk population.
Bonnet JB, Huguet H, Avignon A
… +2 more, Duflos C, Sultan A
Diabetes Care
· 2026 May · PMID 41615296
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OBJECTIVE: This nationwide study aimed to identify factors associated with 1-year mortality following a first diabetic foot ulcer (DFU) using the French National Health Data System (SNDS). A secondary objective was to an...OBJECTIVE: This nationwide study aimed to identify factors associated with 1-year mortality following a first diabetic foot ulcer (DFU) using the French National Health Data System (SNDS). A secondary objective was to analyze mortality after major lower-limb amputation within the same time frame. RESEARCH DESIGN AND METHODS: A retrospective cohort analysis was conducted using SNDS data to identify adults with incident DFUs between January 2017 and December 2018, with 12 months of follow-up. Inclusion criteria combined hospitalization records and community care data. Cox proportional hazards models were used to estimate associations with mortality, adjusting for demographic, clinical, treatment, and care access variables. RESULTS: Among 133,791 individuals with incident DFU, 14.6% died within 1 year, and 3.5% underwent a major amputation. Of those amputated, 28.8% died within a year. Independent predictors of 1-year mortality included male sex, older age, hospital-acquired DFU, insulin, major amputation, cardiovascular disease, cancer, dementia, ESKD, and liver disease. Protective factors included lipid-lowering therapy, glucagon-like peptide 1 (GLP-1) receptor agonists, and prior consultations with diabetologists, ophthalmologists, and podiatrists. Similar patterns were observed for postamputation mortality, with GLP-1 receptor agonists showing a consistent survival benefit. CONCLUSIONS: One-year mortality after DFU remains high and is strongly linked to age and comorbidities. Community-based identification highlights the vulnerability of these patients, even outside hospital settings. Glucagon-like peptide 1 receptor agonists and structured, multidisciplinary follow-up are associated with better survival and should be prioritized. These findings underline the urgent need to reinforce preventive care and optimize care pathways for high-risk diabetic populations.
Teufel F, Orgutsova K, Genitsaridi I
… +15 more, Carrillo-Larco RM, Varghese JS, Marcus ME, Sacre JW, Sajjadi SF, Chiwanga F, Manne-Goehler J, Seiglie J, Flood D, Harding J, Salpea P, Salim A, Boyko EJ, Magliano DJ, Ali MK
Diabetes Care
· 2026 Mar · PMID 41604596
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OBJECTIVE: Undiagnosed diabetes leads to delayed treatment and increased risk of complications, exacerbating global disease burdens. In this study, we estimated the prevalence and absolute numbers of individuals with und...OBJECTIVE: Undiagnosed diabetes leads to delayed treatment and increased risk of complications, exacerbating global disease burdens. In this study, we estimated the prevalence and absolute numbers of individuals with undiagnosed diabetes globally and across regions and quantified gaps in national diabetes detection efforts. RESEARCH DESIGN AND METHODS: We systematically compiled estimates of biomarker-based diabetes prevalence and self-reported diabetes diagnosis using 2003-2024 data from all eligible population-based studies and gray literature. We calculated proportions of individuals with undiagnosed diabetes and case numbers among adults aged 20-79 years. For countries without data, we extrapolated estimates using available data within the same geographic region and country income group. Country-level estimates were benchmarked against the World Health Organization 80% diagnosis target. RESULTS: We identified 193 data sources on undiagnosed diabetes from 109 countries. Across all 215 countries/territories, 42.8% of individuals with diabetes were undiagnosed in 2024, equating to 251.7 million (95% uncertainty interval [UI] 250.4-253.0 million) adults. Proportions undiagnosed ranged from 16.2% in Colombia to 90.4% in Burkina Faso and 29.1% in North America and the Caribbean to 72.6% in Africa. A larger proportion of individuals were undiagnosed in low-income (58.7%) compared with high-income countries (28.9%). Middle-income countries accounted for 206.0 million (95% UI 202.3-209.7 million) adults with undiagnosed diabetes (81.8% of all individuals), including 127.1 million (95% UI 121.2-133.0 million [or 50.5%]) adults in China, India, and Indonesia alone. Less than 5% of all countries attained diabetes diagnosis levels ≥80%. CONCLUSIONS: Substantial global variability in undiagnosed diabetes indicates opportunities to close existing care gaps, likely requiring context-specific solutions and investments.
Bakhsh A, Saleemi A, Budhram D
… +15 more, Zhang Y, Bapat P, Abuabat MI, Verhoeff NJ, Mumford D, Orszag A, Fralick M, Weisman A, Cheema W, Waniss MR, Ouimet JP, Tomlinson G, Cherney DZI, Lovblom LE, Perkins BA
Diabetes Care
· 2026 Mar · PMID 41591367
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OBJECTIVE: Sodium-glucose cotransporter inhibitors (SGLTi) in type 1 diabetes increase diabetic ketoacidosis (DKA) risk but may offer kidney protection. This study assesses whether a reduced estimated glomerular filtrati...OBJECTIVE: Sodium-glucose cotransporter inhibitors (SGLTi) in type 1 diabetes increase diabetic ketoacidosis (DKA) risk but may offer kidney protection. This study assesses whether a reduced estimated glomerular filtration rate (eGFR) increases DKA risk even without SGLTi. RESEARCH DESIGN AND METHODS: Time-varying eGFR and hazard of first DKA event were analyzed from 35-year data in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study using Poisson and extended Cox proportional hazards models. RESULTS: Of 1,441 participants, 297 experienced 488 DKA events. Unadjusted and adjusted DKA rates in individuals with eGFR between 30 and 90 mL/min/1.73 m2 showed no statistical difference compared with those with eGFR 90-120 mL/min/1.73 m2 (incidence rate of 0.65 events per 100 person-years). CONCLUSIONS: A reduced eGFR (between 30 and 90 mL/min/1.73 m2) alone was not associated with increased DKA risk. This finding supports further research into potential kidney-protection benefits of SGLTi for selected individuals with type 1 diabetes.
Li HY, Chan TK, Co Shih K
… +4 more, Cheung BMY, Yiu KH, Tse HF, Chan YH
Diabetes Care
· 2026 Mar · PMID 41587563
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BACKGROUND: Data concerning glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on risk of ischemic optic neuropathy (ION) are conflicting. PURPOSE: We synthesize current evidence of GLP-1 RAs on risk of optic nerve or...BACKGROUND: Data concerning glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on risk of ischemic optic neuropathy (ION) are conflicting. PURPOSE: We synthesize current evidence of GLP-1 RAs on risk of optic nerve or vision-threatening events from randomized controlled trials (RCTs) in patients with type 2 diabetes or cardiometabolic diseases. DATA SOURCE: A total of 83,288 participants with type 2 diabetes/cardiometabolic diseases from 20 published RCTs were analyzed following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). STUDY SELECTION: RCTs investigating GLP-1 RAs for type 2 diabetes/cardiometabolic disease populations and reported optic nerve or vision-related adverse events were assessed. DATA EXTRACTION: Primary outcome was a composite of optic nerve and/or vision-threatening serious adverse events, including ION, ocular ischemic syndrome, papilledema, blindness, blurred vision, visual impairment, and reduced visual acuity. Odds ratios (ORs) were derived. DATA SYNTHESIS: Type 2 diabetes occurred in 76.4% of participants. Over mean follow-up duration of 2.97 years (estimated cumulative exposure of 240,334 patient-years), GLP-1 RA use was not associated with increased risk of primary end point (OR 1.20, 95% CI 0.73-1.97, I2 = 0%). Prespecified individual adverse events, including ION (OR 1.50, 95% CI 0.49-4.63), and vision loss/disturbance events (OR 1.08, 95% CI 0.60-1.94) were not significantly associated with GLP-1 RA use. LIMITATIONS: RCTs reported vision-threatening events as adverse events rather than as prespecified outcomes. CONCLUSIONS: Based on a large number of patients who contributed to a meta-analysis of RCTs involving participants with type 2 diabetes and cardiometabolic disease, GLP-1 RAs were not associated with an increased risk of optic nerve/vision-threatening events.
Gisinger T, He JH, Oyeka CP
… +9 more, Ma J, Srialluri N, Woodward M, Michos ED, Kalyani RR, Clark JM, Kautzky-Willer A, Vaidya D, Bennett WL
Diabetes Care
· 2026 Mar · PMID 41582527
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OBJECTIVE: To investigate the association of sex hormones at baseline and 1 year after a lifestyle intervention on cardiovascular (CV) risk in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: This prospective study, f...OBJECTIVE: To investigate the association of sex hormones at baseline and 1 year after a lifestyle intervention on cardiovascular (CV) risk in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: This prospective study, following the Look AHEAD: Action for Health in Diabetes (Look AHEAD) trial, of 2,260 adults with T2D, included measurements of sex hormones and sex hormone binding globulin (SHBG). Baseline levels and 1-year changes were divided into sex-specific tertiles to assess the association with CV events (n = 488 events) and weight loss interactions. RESULTS: In men, higher baseline total testosterone was associated with lower CV risk (hazard ratio [HR] = 0.74; 95% CI 0.56-0.97). In men with ≥7% weight loss, SHBG increases were inversely associated with CV risk (HR = 0.47; 95% CI 0.26-0.85). In men with <7% weight loss, increases in estradiol were associated with CV risk (second vs. first estradiol tertile: HR = 1.64 [95% CI 1.13-2.38]; third vs. first estradiol tertile: HR = 1.88 [95% CI 1.29-2.73]). No associations were detected in women. CONCLUSIONS: In men with T2D, but not women with T2D, sex hormones were associated with CV events.
Diabetes Care
· 2026 Jul · PMID 41575388
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The 10-year Action for Health in Diabetes (Look AHEAD) clinical trial compared a multidomain intensive lifestyle intervention to a diabetes support and education program with respect to major cardiovascular disease event...The 10-year Action for Health in Diabetes (Look AHEAD) clinical trial compared a multidomain intensive lifestyle intervention to a diabetes support and education program with respect to major cardiovascular disease events (primary outcome) and other diabetes- and obesity-related outcomes. Follow-up of the cohort continues to add other aging-related outcomes and conditions to identify the long-term consequences of factors related to lifestyle and medical care. In this transition to a study of aging among individuals at risk for accelerated aging due to type 2 diabetes and overweight or obesity, the investigators have retrospectively reframed the study using the perspective of geroscience. This perspective strengthens the importance of lifestyle changes as a core component for medical care for these individuals to slow biological aging.
Marzinotto I, Pittman DL, Achenbach P
… +4 more, Akolkar B, Wasserfall CH, Lampasona V, Long AE
Diabetes Care
· 2026 Apr · PMID 41575380
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OBJECTIVE: The Islet Autoantibody Standardization Program (IASP) evaluates type 1 diabetes autoantibody assays through international interlaboratory comparison studies. This report describes 2024 IASP workshop results fo...OBJECTIVE: The Islet Autoantibody Standardization Program (IASP) evaluates type 1 diabetes autoantibody assays through international interlaboratory comparison studies. This report describes 2024 IASP workshop results for multiplex assays that simultaneously measure multiple islet autoantibodies, increasingly adopted for population screening programs. RESEARCH DESIGN AND METHODS: Participating laboratories analyzed coded sera from individuals with new-onset type 1 diabetes (n = 50), blood donors with no diabetes (n = 98), and replicate samples (n = 3). Performance was assessed using sensitivity, specificity, adjusted sensitivity at 95%, 99%, and 100% specificity, area under the receiver operating characteristic curve analysis (ROC-AUC), and partial ROC-AUC at 95% specificity (pAUC95). RESULTS: Fifteen laboratories contributed results from 19 multiplex assays using five formats: antibody-dependent agglutination PCR (ADAP) (n = 6), bridge-ELISA (n = 8), electrochemiluminescence (n = 2), luciferase immunoprecipitation system (LIPS) (n = 1), and protein A luciferase/solid-phase capture LIPS (n = 2). Median ROC-AUC was 0.98 across all platforms, with a pAUC95 of 0.048 against a theoretical maximum of 0.05. Laboratory-reported sensitivity ranged from 86% to 96% with specificity 81% to 100%. Standardized adjusted sensitivity at 99% specificity thresholds eliminated most false positives without compromising sensitivity, achieving 93-97% adjusted sensitivity. Bridge-ELISA platforms demonstrated potential for universal cutoff standardization, while ADAP showed substantial interlaboratory threshold variation. CONCLUSIONS: Multiplex assays demonstrated good overall performance for detecting islet autoantibodies and discriminating case subjects from control subjects. However, interlaboratory variability and platform-specific recognition patterns necessitate further standardization efforts. While not directly tested in this workshop, the results suggest that sequential testing strategies using complementary platforms may be necessary to achieve the stringent specificity required when these assays are used in a screening context.
Beals JW, Smith GI, Farabi SS
… +5 more, Patterson BW, Lucey BP, Broussard JL, Wright KP, Klein S
Diabetes Care
· 2026 May · PMID 41564347
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OBJECTIVE: To determine whether extending sleep improves insulin sensitivity in people with overweight or obesity, insulin resistance, and habitual short sleep schedules (<7 h/night). RESEARCH DESIGN AND METHODS: Partici...OBJECTIVE: To determine whether extending sleep improves insulin sensitivity in people with overweight or obesity, insulin resistance, and habitual short sleep schedules (<7 h/night). RESEARCH DESIGN AND METHODS: Participants were randomized to habitual sleep (HS) (n = 15) or extended sleep (ES) (n = 14) for ∼6 weeks. Multiorgan (whole-body [primarily muscle], hepatic, and adipose tissue) insulin sensitivity (assessed by the hyperinsulinemic-euglycemic clamp procedure with tracer infusions) and glycemic control (assessed by 24-h serial plasma glucose and insulin concentrations during wakefulness) were determined. RESULTS: Time in bed and sleep duration increased more in the ES group (1.3 ± 0.6 and 1.1 ± 0.5 h/night) than in the HS group (0.3 ± 0.8 and 0.0 ± 0.4 h/night). Day-to-day variability in sleep and subjective measures of sleep health improved more in the ES than HS group, without differences in multiorgan insulin sensitivity or glycemic control between groups. CONCLUSIONS: Extending sleep by ∼1 h/night for ∼6 weeks in people with overweight or obesity and short sleep schedules improves sleep health but not insulin sensitivity or glycemic control.
Ziegler AG, Albeer A, Arnolds S
… +21 more, Assfalg R, Bunk M, Daniel C, Hofelich A, Jacobsen S, Kick K, Knoop J, Kohls M, Kordonouri O, Matzke C, Pfirrmann M, Ramminger C, Sarcletti K, Scholz M, Schütte-Borkovec K, Serr I, Weigelt M, Weiss A, Winkler C, Bonifacio E, Achenbach P
Diabetes Care
· 2026 May · PMID 41563349
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OBJECTIVE: Oral administration of an antigen can induce immunological tolerance. Insulin is an autoantigen in childhood type 1 diabetes (T1D). We tested the effect of treatment with high-dose oral insulin on disease prog...OBJECTIVE: Oral administration of an antigen can induce immunological tolerance. Insulin is an autoantigen in childhood type 1 diabetes (T1D). We tested the effect of treatment with high-dose oral insulin on disease progression and immune response to insulin in children with stage 1 T1D. RESEARCH DESIGN AND METHODS: We conducted a phase 2 randomized placebo-controlled double-blind trial in children with stage 1 T1D who received daily oral insulin (7.5 mg/day for 3 months and 67.5 mg/day for 9 months; n = 110) or placebo (n = 110) for 12 months. The coprimary outcomes were 1) time from baseline to dysglycemia or clinical diabetes and 2) increased immune response to insulin within 12 months of treatment (assessed in the first 90 participants). RESULTS: Of 220 participants (112 girls; median age 4.8 years; interquartile range 3.6, 6.2), 179 completed the trial. Dysglycemia or diabetes developed in 87 participants (46 receiving oral insulin and 41 receiving placebo; hazard ratio 1.07; 95% CI 0.66-1.73; P = 0.74). The 5-year progression rate was 40% (95% CI 30-51%) in each group. A modest treatment interaction was found with the INS rs689 genotype (P = 0.03). Increased immune response to insulin was observed in 11 (25%) of 44 participants in the oral insulin group and 13 (31%) of 42 in the placebo group (P = 0.63). Oral insulin was well tolerated. No significant study-related adverse events occurred. CONCLUSIONS: In children with stage 1 T1D, 1 year of high-dose oral insulin did not alter progression to dysglycemia or diabetes or immune response to insulin.
Hughes RCE, Abraham E, Chan H
… +1 more, Williman JA
Diabetes Care
· 2026 Mar · PMID 41563346
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OBJECTIVE: We compare the risk of postpartum diabetes in people with early antenatal prediabetes, HbA1c 5.9-6.4% (41-47 mmol/mol), versus those with HbA1c <5.9% (41 mmol/mol) who developed gestational diabetes mellitus (...OBJECTIVE: We compare the risk of postpartum diabetes in people with early antenatal prediabetes, HbA1c 5.9-6.4% (41-47 mmol/mol), versus those with HbA1c <5.9% (41 mmol/mol) who developed gestational diabetes mellitus (GDM) in later pregnancy. Secondly, we perform an exploratory analysis of lipid profiling to guide antenatal and postpartum management decisions for people with antenatal prediabetes. RESEARCH DESIGN AND METHODS: We analyze a prospective cohort study conducted in New Zealand. The "antenatal prediabetes" group was identified during 2017-2022 (n = 355). The comparator "GDM" group was identified in 2017 (n = 490). Postpartum laboratory data were collected from electronic health records until November 2025. Progression to diabetes was evaluated using multivariate analysis. RESULTS: Compared with GDM, adjusted hazard ratios for postpartum type 2 diabetes following antenatal prediabetes were 4.5 (2.8-7.3) to 16.7 (10.8-25.8) for HbA1c 5.9% (41 mmol/mol) to 6.2-6.4% (44-47 mmol/mol), P < 0.001. HbA1c was the strongest predictor of type 2 diabetes, followed by BMI and Pacific ethnicity. Lipid profiles in the antenatal prediabetes cohort varied according to postpartum diagnosis: glucokinase monogenic diabetes was associated with lower serum triglycerides, mean 53.1 mg/dL (0.6 mmol/L), versus type 2 diabetes, 183.4 mg/dL (2.07 mmol/L), P = 0.012, or versus no diabetes, 165.6 mg/dL (1.87 mmol/L), P = 0.013; in type 1 diabetes, mean triglycerides were 87.7 mg/dL (0.99 mmol/L). CONCLUSIONS: Early antenatal prediabetes is a strong predictor of rapid progression to type 2 diabetes. HbA1c at booking provides an important risk stratification tool identifying people with the greatest need for preventive intervention. Further research could evaluate lipid profiling to identify genetic and autoimmune diabetes subtypes within antenatal prediabetes.
Diabetes Care
· 2026 Feb · PMID 41557995
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This article explores four little-known stories about research into, and treatment for, diabetes. Progressing in order from the participant about whose story we know the most to those about whom we know the least demonst...This article explores four little-known stories about research into, and treatment for, diabetes. Progressing in order from the participant about whose story we know the most to those about whom we know the least demonstrates that clinical research and therapeutic development are collaborative enterprises and that often key innovations and discoveries happen outside the laboratory setting. The role of unlikely individuals and collectives in reforming diabetes care is revealed, to nudge researchers into new and fruitful pathways. Further, this article shows how with a historical approach we can find the right stories of discovery to help both patients and researchers gain new insights into the prevention, management, and treatment of diabetes in all its forms.