Diabetes Care最新文献

{"title":"Gestational Diabetes Mellitus Subtypes and Maternal Cardiometabolic Outcomes 10–14 Years After Delivery","authors":"Christine Field, William A. Grobman, Jiqiang Wu, Alan Kuang, Mark B. Landon, Denise Scholtens, William Lowe, Nilay S. Shah, Jami Josefson, Sadiya Khan, Kartik K. Venkatesh","doi":"10.2337/dc26-1180","DOIUrl":"https://doi.org/10.2337/dc26-1180","url":null,"abstract":"OBJECTIVE The association of gestational diabetes mellitus (GDM) subtypes with maternal cardiometabolic health is not known. We examined whether GDM subtypes were differentially associated with cardiometabolic health 10–14 years after delivery. RESEARCH DESIGN AND METHODS We used data from the prospective Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study. The exposure was GDM subtype (insulin deficient, insulin resistant, mixed defect, unclassified). The outcomes were prediabetes or diabetes and, secondarily, hypertension, dyslipidemia, metabolic syndrome, and predicted cardiovascular disease. RESULTS Of 4,693 women, 3.0% had insulin-deficient, 9.0% insulin-resistant, 1.6% mixed-defect, and 0.7% unclassified GDM. Compared with no GDM, all GDM subtypes except unclassified were associated with higher risk of prediabetes or diabetes (adjusted risk ratios 2.14–2.88), metabolic syndrome, and predicted cardiovascular disease. Only insulin-resistant GDM was associated with dyslipidemia. CONCLUSIONS All GDM subtypes were associated with an increased risk of prediabetes or diabetes, metabolic syndrome, and high predicted cardiovascular disease 10–14 years after delivery.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"129 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148717323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Islet Autoantibody Patterns Vary by Race and Ethnicity and Area Deprivation Index for Individuals at Risk for Type 1 Diabetes","authors":"Ananta Addala, Susanne Cabrera, David Cuthbertson, Ingrid Libman, Mustafa Tosur, Alejandro F. Siller, Linda A. DiMeglio, Kevan C. Herold, Maria J. Redondo, Heba M. Ismail","doi":"10.2337/dc26-0387","DOIUrl":"https://doi.org/10.2337/dc26-0387","url":null,"abstract":"OBJECTIVE Islet autoantibody positivity (AB+) has not been evaluated across different race, ethnicity, and socioeconomic deprivation categories in individuals at risk for type 1 diabetes. We examined data from TrialNet of persons screened for ABs and evaluated patterns by race and ethnicity and socioeconomic deprivation. RESEARCH DESIGN AND METHODS This analysis included 139,963 relatives of people with type 1 diabetes screened by TrialNet between 9 January 2012 and 31 December 2022. Race and ethnicity were categorized as non-Hispanic White, Hispanic, non-Hispanic Black, and non-Hispanic other. Home addresses were used to assign deprivation, ranging from least deprived (1) to most deprived (100), analyzed in quintiles. Descriptive and multivariate analyses assessed associations among race and ethnicity, deprivation, and AB+, adjusting for age and protocol period. RESULTS Single AB+ (SAB+) and multiple AB+ (MAB+) varied by age, race and ethnicity, and deprivation. Younger individuals had increased odds of MAB+ and decreased odds of SAB+. Non-Hispanic Black participants had significantly higher odds of AB+ (adjusted odds ratio 1.44 [95% CI 1.29, 1.62]), SAB+ (1.59 [1.38, 1.85]), and MAB+ (1.26 [1.06, 1.51]), while Hispanic individuals had higher odds of SAB+ (1.26 [1.15, 1.39]) and lower odds of MAB+ (0.81 [0.72, 0.91]) compared with non-Hispanic White individuals. Lowest deprivation was associated with higher odds of MAB+ (1.21 [1.06, 1.37]) but not SAB+. CONCLUSIONS AB+ patterns vary by race, ethnicity, and deprivation. Screening and prevention strategies should be designed to identify individuals at risk based on these factors to enable equitable risk stratification and access to diabetes preventive therapies.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"38 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 2 Diabetes and Longitudinal Changes in Cortical and Trabecular Bone Density, Microarchitecture, and Strength: The Framingham Study","authors":"Alyssa B. Dufour, Mary L. Bouxsein, Musong Gao, Douglas P. Kiel, Gary F. Mitchell, Steven K. Boyd, Chandler Da Cruz, Laiji Yang, Ching-Ti Liu, Elizabeth J. Samelson","doi":"10.2337/dc26-0846","DOIUrl":"https://doi.org/10.2337/dc26-0846","url":null,"abstract":"OBJECTIVE To gain insight into higher fracture risk in individuals with type 2 diabetes, we determined the association of type 2 diabetes glycemic status and severity with longitudinal changes in peripheral bone density and microarchitecture. RESEARCH DESIGN AND METHODS We conducted a longitudinal study of 769 participants from the Framingham Study who underwent high-resolution, peripheral, quantitative computed tomography (HR-pQCT) at the tibia and radius, in 2012–2016 and 2021–2023 (mean 8-year follow-up). Linear regression models estimated mean 8-year percent changes in bone measures, across indicators of diabetes severity, adjusting for age, sex, weight, and height. RESULTS The mean age was 67 ± 7 years, and 59% of participants were women. More than half (57%) were normoglycemic (fasting plasma glucose [FPG] <100 mg/dL, not on any treatment), 31% had prediabetes (100 ≤ FPG ≤125 mg/dL), and 12% had type 2 diabetes (FPG >125 mg/dL or on treatment). Adjusted mean percent changes in HR-pQCT bone measures were similar across diabetes severity, including glycemic status, use of diabetes medications, duration of diabetes, and HbA1c. For example, cortical volumetric bone mineral density at the radius changed by −1.50% (95% CI −2.43, −0.56) in type 2 diabetes and −1.96% (−2.53, −1.39), in prediabetes, compared with −2.42% (−2.86, −1.97) in normoglycemia (reference group; all P > 0.05). CONCLUSIONS The magnitude of peripheral bone loss over 8 years did not differ between individuals with type 2 diabetes and those with normoglycemia, suggesting that bone deterioration alone does not explain the higher fracture risk in older adults with type 2 diabetes. Future studies should address other contributors to skeletal fragility.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"93 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148675390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Utero Exposure to Preexisting or Gestational Diabetes Mellitus Increases Incidence of Diabetes in the Children of First Nations and Non–First Nations Mothers: A Retrospective Cohort Study","authors":"Baiju R. Shah, Tomi Odugbemi, Zhiyin Li, Cal Stewart, Michael E. Green, Carmen R. Jones, Jennifer D. Walker, Brandy Wicklow","doi":"10.2337/dc26-0710","DOIUrl":"https://doi.org/10.2337/dc26-0710","url":null,"abstract":"OBJECTIVE We conducted this First Nations–engaged and –co-led project to determine the incidence of diabetes in the children of mothers with preexisting diabetes, gestational diabetes mellitus, and no diabetes, and to evaluate whether periconception glycemic control was associated with the risk of diabetes in the children. RESEARCH DESIGN AND METHODS We conducted a longitudinal population-based study using health care administrative data that included all children of mothers aged 12–49 years born between April 1994 and March 2016. The exposure of interest was maternal diabetes status, and we examined both First Nations and non–First Nations mothers. Children were followed for incident diabetes. Among women with preexisting diabetes, periconception HbA1c was evaluated as a predictor. RESULTS There were 2,851,583 children followed to a median age of 16 years (interquartile range 11–22). Among children of non–First Nations mothers, the adjusted hazard ratios for incident diabetes were 5.18 (95% CI 4.82–5.57) with maternal preexisting diabetes and 1.75 (1.65–1.84) with gestational diabetes mellitus. Among children of First Nations mothers, hazard ratios were 7.68 (5.91–9.98) and 2.59 (2.07–3.24), respectively. The hazard ratio for incident diabetes in children of mothers with preexisting diabetes was 0.89 (0.80–0.995, P = 0.04) for each 1% (11 mmol/mol) decrease in periconception HbA1c. CONCLUSIONS Exposure to either preexisting diabetes or gestational diabetes mellitus in utero was associated with an increased incidence of diabetes in children and young adults, with a stronger association among First Nations people. Better periconception glycemic control was associated with decreased diabetes incidence in children of mothers with preexisting diabetes.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"27 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetes Care in 2050: A Human-Centered Road Map From Time in Range to Time in Happiness","authors":"Guy Fagherazzi, Emmanuel Cosson, Chantal Mathieu, Renza Scibilia, Kyle Jacques Rose, Kamil Armacky, Korey Hood, Bart Torbeyns, Elise Bismuth, Stéphane Besancon, Pratik Choudhary, Roberto Mallone, Pierre-Yves Benhamou, Dianna J. Magliano, Carine de Beaufort, Jean-Pierre Riveline, Michael Joubert","doi":"10.2337/dci26-0059","DOIUrl":"https://doi.org/10.2337/dci26-0059","url":null,"abstract":"By 2050, diabetes care should transform into a human-centered, technology-augmented ecosystem focused on well-being. In this work, we first present a deliberately idealistic, forward-looking scenario in which advanced treatments, artificial intelligence, and integrated care delivery significantly reduce the burden on individuals with diabetes and enable person-centered health care. In this utopian vision, success in diabetes care is measured not only by glycemic metrics such as time in range but also by time in happiness, i.e., the quality time people spend unencumbered by their condition. Second, while such idealistic progress may be unlikely by 2050 due to socioeconomic and public health constraints, we build on existing gaps to outline a road map of co-designed solutions, health system reforms, and ethical innovations to move closer to it. This work serves as a “North Star” document that articulates the key values and next steps for achieving an ideal diabetes prevention and care ecosystem.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"34 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148522431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Diabetes: Rapidly Changing Landscape and a Rising Tide of Opportunities: The 2025 Distinguished International Service in the Cause of Diabetes Award Lecture","authors":"K.M. Venkat Narayan","doi":"10.2337/dci25-0116","DOIUrl":"https://doi.org/10.2337/dci25-0116","url":null,"abstract":"Diabetes affects an estimated 828 million people worldwide; prevalence is growing rapidly in low- and middle-income countries (LMICs), with major health and development consequences. Diabetes-related complications and mortality rates have declined across several high-income countries (HICs), largely through structured chronic disease care, sustained implementation of quality improvement strategies, and active risk factor control. However, rates of diabetes complications and mortality have been rising in LMICs. Along with evidence there are tools (e.g., teams, task shifting, data systems, decision-support mechanisms, etc.) for translating the gains in HICs to LMICs. Lessons from global collaborations in vaccines and antiretroviral therapy, especially in innovative ways of leveraging infrastructure, and lowering costs of therapeutics, can be applied to diabetes prevention and control. Furthermore, the following are several transformational opportunities that, if leveraged, can propel global diabetes prevention and control: 1) increasing recognition of diabetes heterogeneity and the differences in the frequency of diabetes subtypes in LMICs; 2) growth in therapeutics and technologies (e.g., mobile health [mHealth], telemedicine, artificial intelligence), which can help overcome infrastructural constraints and stimulate innovative models of prevention care; and 3) sustained economic growth across several LMICs, which offers possibilities of investment in health and data infrastructure and in research and development. Importantly, while ∼80% of the diabetes burden is in LMICs, >95% of diabetes-related research occurs in populations residing in HICs. This burden-knowledge gap is a major source of health inequity that must be strategically addressed to effectively prevent and control diabetes globally.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"50 1","pages":"1297-1307"},"PeriodicalIF":16.2,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148522516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IgG N-Glycosylation and Incident Neuropathy and Nephropathy in People With Type 2 Diabetes: A Pooled Analysis of Prospective Cohort Studies","authors":"Cecilia Martinez Escobedo, Anna Birukov, Ralph Heijmans, Olga Kuxhaus, Fabian Eichelmann, Roderick C. Slieker, Elham Memarian, Nina Simunic-Briski, Femke Rutters, Marieke T. Blom, Marta Riera, Marta Crespo, Manfred Wuhrer, Clara Barrios, Mandy van Hoek, Leen M. 't Hart, Eric Sijbrands, Gordan Lauc, Matthias B. Schulze, Clemens Wittenbecher","doi":"10.2337/dc26-0620","DOIUrl":"https://doi.org/10.2337/dc26-0620","url":null,"abstract":"OBJECTIVE To examine whether IgG N-glycosylation patterns are prospectively associated with incident diabetic nephropathy and neuropathy. RESEARCH DESIGN AND METHODS We analyzed IgG N-glycosylation profiles in four cohorts: EPIC-Potsdam, DiaGene, GenoDiabMar, and Hoorn DCS. Among 3,263 individuals with and without type 2 diabetes at profiling, 674 incident neuropathy and 639 incident nephropathy cases occurred after diabetes diagnosis. Associations of IgG N-glycan peaks (IgG-GPs) and traits with incident outcomes were examined using Cox models and meta-analyzed across cohorts. RESULTS Agalactosylated, asialylated, and bisected IgG-GPs were associated with higher nephropathy risk (IgG-GP3: hazard ratio [HR] 1.13 [95% CI 1.04–1.24]; IgG-GP4: HR 1.15 [95% CI 1.05–1.26]), while galactosylated and sialylated IgG-GPs were associated with lower risk (IgG-GP14: HR 0.86 [95% CI 0.78–0.94]; IgG-GP18: HR 0.85 [95% CI 0.77–0.94]) (all false discovery rate <0.05). Associations of IgG-GPs with incident neuropathy were rendered nonsignificant after multiple testing correction. CONCLUSIONS IgG N-glycosylation may reflect immune-related mechanisms relevant to diabetic nephropathy; but the evidence between IgG-GPs and diabetic neuropathy remains inconclusive.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"46 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What Makes the Difference? Predicting Glycemic Trajectories Following Initiation of Automated Insulin Delivery Systems in Youth With Type 1 Diabetes","authors":"Jayde Hooven-Davis, Christina M. Lalama, Sarah A. Syer, Scott D. Rothenberger, Ingrid M. Libman, Christine A. March","doi":"10.2337/dc26-0634","DOIUrl":"https://doi.org/10.2337/dc26-0634","url":null,"abstract":"OBJECTIVE To identify glycemic trajectories following automated insulin delivery (AID) initiation in youth with type 1 diabetes and associated factors. RESEARCH DESIGN AND METHODS We used group-based trajectory modeling to characterize groups for time in range (TIR) and hemoglobin A1c (HbA1c), measured at baseline and at 3, 6, 12, and 18 months of AID use, in 713 youth (ages 6–18). Multinomial logistic regression estimated associations between clinical and sociodemographic predictors and glycemic trajectories. RESULTS Four TIR and three HbA1c trajectories emerged. All trajectories showed rapid improvement from baseline to 3 months, continued but gradual improvement between 3 and 6 months, followed by waning or sustained improvements after 6 months. Only a small subset (group 4, 12.7%) achieved TIR ≥70%, although more (43.3%) reached an HbA1c <7%. In the TIR model after adjusting for age, sex, type 1 diabetes duration, and prior treatment, participants with fewer user-initiated boluses (odds ratio [OR] 2.46; 95% CI 1.78, 3.39), higher insulin doses/kg (OR 1.54; 95% CI 1.25, 1.91), and fewer appointments (OR 2.69; 95% CI 1.21, 6.00) had higher odds of membership in the lowest TIR group (group 1) than in the highest TIR group (group 4). In the HbA1c model, lower baseline insulin doses/kg and more boluses were associated with membership in the most optimal group. CONCLUSIONS Distinct glycemic trajectories exist following AID initiation, with all groups experiencing rapid early improvements in TIR and HbA1c that plateau or decline over time. Baseline bolus frequency and insulin doses/kg remain key predictors, highlighting the persistent influence of preexisting behaviors and insulin needs on long-term outcomes.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"44 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood-Based DNA Methylation Models Improve Short-term Cardiovascular Risk Stratification in Individuals With Type 2 Diabetes","authors":"Michele Longo, Antonella Desiderio, Maria Masulli, Jyotirmoy Das, Rosa Spinelli, Luca Parrillo, Mariacristina Rotondo, Federica Zatterale, Massimiliano Volpe, Gabriele Riccardi, Olga Vaccaro, Claudia Miele, Raffaele Napoli, Francesco Beguinot, Gregory A. Raciti","doi":"10.2337/dc26-0738","DOIUrl":"https://doi.org/10.2337/dc26-0738","url":null,"abstract":"OBJECTIVE Cardiovascular complications are the leading cause of death in type 2 diabetes mellitus (T2DM). We investigated whether blood-based DNA methylation (DNAm) biomarkers could improve risk stratification for major adverse cardiovascular events (MACE) in individuals with T2DM. RESEARCH DESIGN AND METHODS Epigenome-wide DNAm was profiled in peripheral blood mononuclear cells obtained at baseline from 305 T2DM participants of the Thiazolidinediones Or Sulphonylureas and Cardiovascular Accidents. Intervention Trial (TOSCA.IT) study, including 81 who experienced MACE within 5 years (T2DMACE) and 224 who did not (T2D). The population was randomly divided into training and internal test sets for model development and evaluation. Differential DNAm analyses were performed under five frameworks differing by covariate adjustment. Binomial least absolute shrinkage and selection operator (LASSO) logistic regression with stability selection was used to generate DNAm-based models to stratify individuals at higher risk of incident MACE over 5 years. RESULTS Differential DNAm analysis identified 23,839, 21,529, 21,500, 12,114, and 7,101 differentially methylated CpG sites across the five analytical frameworks. LASSO logistic regression was used to develop five DNAm-based models. Stability selection retained 22–26 CpG predictors per model. When evaluated in the internal test cohort, the five models showed high discriminative performance, with receiver operating characteristic area under the curve values ranging from 0.915 to 0.937 and area under the precision-recall curve values from 0.866 to 0.940. Several CpGs were independently associated with either increased or decreased risk of MACE, including 12 CpGs identified across all of the models. CONCLUSIONS The DNAm-based models we have generated may improve risk stratification for short-term cardiovascular events in individuals with T2DM, providing a promising approach to refine identification of those at increased risk of MACE.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"13 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148461858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BMI Normalization Is Associated With Lower Risk of Progression to Type 1 Diabetes, Primarily in Youth","authors":"Maria J. Redondo, David Cuthbertson, Raquel Gupta, Alejandro F. Siller, Sridevi Devaraj, Kendra Vehik, Heba M. Ismail, Ashok Balasubramanyam","doi":"10.2337/dc26-0833","DOIUrl":"https://doi.org/10.2337/dc26-0833","url":null,"abstract":"OBJECTIVE Elevated BMI is associated with increased risk of progression to stage 3 type 1 diabetes (T1D). We tested whether normalization of BMI is associated with lower stage 3 risk among autoantibody-positive individuals with overweight or obesity. RESEARCH DESIGN AND METHODS We studied 833 autoantibody-positive participants in the TrialNet Pathway to Prevention study with overweight or obesity at baseline. Cumulative incidence of stage 3 T1D was evaluated using Cox proportional hazards models. Reported P values were adjusted for baseline age, BMI z score, and T1D stage, unless otherwise noted. RESULTS During follow-up, BMI normalized in 26.8% of participants and was associated with a lower risk of progression to stage 3 T1D (hazard ratio 0.516, P < 0.001) over a median follow-up time of 4.1 years. This association was primarily observed in youth (n = 421, hazard ratio 0.497, P = 0.001), including boys <12 years old (n = 140, P < 0.001) and girls ≥12 years old (n = 73, P = 0.043), but not in adults (n = 412, P = 0.130). BMI normalization was also associated with a lower risk of transition from stage 1 to stage 2 and from stage 2 to stage 3, but not clearly from stage 0 to stage 1 (P = 0.010, P = 0.003, and P = 0.051, respectively, adjusted for baseline age and BMI z score). In exploratory models, adjustment for insulin sensitivity/resistance indices or oral disposition index weakened the association between BMI normalization and lower progression risk, whereas adjustment for insulin secretion, glycemia-adjusted C-peptide, or progression-risk indices generally strengthened it. CONCLUSIONS Among autoantibody-positive individuals with overweight or obesity, BMI normalization was associated with a 48.4% lower risk of clinical T1D, primarily in youth.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"48 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}