Diabetes Care最新文献

{"title":"Screening for Diabetes and Prediabetes in Cystic Fibrosis Using a Nonfasting 50-Gram 1-Hour Oral Glucose Challenge Test","authors":"Monique D. Maher, Timothy Vigers, Celia Kohler, Arlene A. Stecenko, Antoinette Moran, Christine L. Chan, Lawrence S. Phillips","doi":"10.2337/dc25-2806","DOIUrl":"https://doi.org/10.2337/dc25-2806","url":null,"abstract":"OBJECTIVE Cystic fibrosis (CF)-related diabetes (CFRD) affects nearly half of adults with CF, but screening rates with the recommended oral glucose tolerance test (OGTT) are low. We evaluated the utility of a nonfasting, 50-g, 1-h oral glucose challenge test (GCT) as first-line screening for CFRD and pre-CFRD. The objectives were to define a cutoff that provides high sensitivity and reasonable specificity, and to determine how GCT compares with other opportunistic tests. RESEARCH DESIGN AND METHODS Participants with CF ≥10 years old, without known diabetes, had baseline random plasma and capillary glucose (RPG and RCG), then underwent an in-clinic GCT for collection of 1-h plasma glucose (GCTpl). This was followed by hemoglobin A1C (HbA1c) and OGTT on a separate day. Receiver operating characteristic (ROC) curves were generated for identifying CFRD and pre-CFRD. RESULTS Of 185 participants, 94 had normal glucose tolerance, 81 had pre-CFRD, and 10 had CFRD. For detecting pre-CFRD or CFRD, GCTpl had an area under the ROC curve (ROC-AUC) of 0.73 (95% CI 0.65–0.80), higher than ROC-AUCs for RPG of 0.56 (0.48–0.65, P = 0.003), RCG of 0.55 (0.46 = 0.63, P = 0.002), and HbA1c of 0.62 (0.53–0.67, P = 0.02). The ROC-AUC for detecting CFRD was 0.75 (0.64–0.86) for GCTpl, 0.64 (0.42–0.87) for RPG, and 0.56 (0.39–0.73) for HbA1c. A GCTpl of 147 mg/dL provides 90% sensitivity and 58% specificity for detecting CFRD and could reduce the OGTTs needed by 56%. CONCLUSIONS GCT offers a practical, in-clinic method for CFRD screening. This spares low-risk individuals from OGTT, while maintaining high sensitivity for CFRD.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"7 4 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147577901","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":"Impact of Missing Data and Monitoring Duration on Downstream Analyses in Continuous Glucose Monitoring","authors":"Neo Kok, Walter T. Williamson, Joyce M. Lee, Irina Gaynanova","doi":"10.2337/dc25-2935","DOIUrl":"https://doi.org/10.2337/dc25-2935","url":null,"abstract":"OBJECTIVE Consensus guidelines recommend at least 14 consecutive days of continuous glucose monitoring (CGM) monitoring with 70% completeness to represent 90-day glycemic exposure. This study quantifies bias and uncertainty introduced into downstream analyses by using CGM metrics from incomplete or reduced monitoring, relative to a 90-day complete profile. RESEARCH DESIGN AND METHODS Using a type 1 diabetes cohort with 1,010 complete 90-day CGM profiles, we simulated incomplete profiles by varying monitoring duration and data completeness. Consensus CGM metrics were computed on incomplete and complete profiles to quantify measurement error, which was propagated into two downstream regression models: 1) CGM metric is an outcome for a binary treatment (clinical trial setting); 2) CGM metric is an explanatory variable (covariate) for another continuous outcome. Bias was quantified using observed-to-true effect size ratios and uncertainty by the sample size increase required to maintain precision. RESULTS In the clinical trial setting, treatment effects remain unbiased but lose precision; for time in range (TIR), 14 days required ≥16% more participants versus 90 days; 30 days required ≥6.5%. When the CGM metric is a covariate, associations with outcomes are attenuated (biased toward zero up to 14% at 14 days and 6% at 30 days for TIR) and less precise. CONCLUSIONS Representing 90 days of glycemic exposure with 14 days can lead to bias and loss of precision in downstream analyses. We recommend study protocols require at least 30 days of CGM monitoring with 70% completeness. If 30 days is not feasible, studies should plan for increased sample sizes.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"21 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147577900","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":"Safety of Semaglutide After Dialysis Initiation: An Individual-Level Pooled Analysis","authors":"Klara R. Klein, Anna Menacher, John B. Buse, Johannes F.E. Mann, Katherine R. Tuttle, Kajsa Kvist, Margit R. Andersen, Manuel Mayrdorfer, Ildiko Lingvay","doi":"10.2337/dc26-0112","DOIUrl":"https://doi.org/10.2337/dc26-0112","url":null,"abstract":"OBJECTIVE People receiving dialysis are at high risk of cardiovascular and all-cause mortality. Semaglutide reduces major adverse cardiovascular events (MACE) in people with type 2 diabetes (T2D) and those without T2D with obesity and high cardiovascular risk. Data to establish safety and efficacy in dialysis-dependent kidney failure are scarce. We aimed to assess the safety of semaglutide in people who initiate dialysis. RESEARCH DESIGN AND METHODS In this post hoc analysis of four randomized, placebo-controlled trials (Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6], Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity [SELECT], Evaluate Renal Function With Semaglutide Once Weekly [FLOW], and Semaglutide Cardiovascular Outcomes [SOUL]), we evaluated systematically collected adverse events (AEs) from participants who initiated dialysis during study follow-up. We compared the proportion and event rates of systematically collected serious AEs (SAEs), including adjudicated MACE, and AEs leading to permanent treatment discontinuation in participants originally randomized to semaglutide or placebo who remained on treatment after dialysis initiation. RESULTS Among 34,064 participants randomized across the trials, 307 initiated dialysis, of whom 165 participants randomized to semaglutide (n = 71) or placebo (n = 94) remained on treatment. After dialysis initiation, SAEs were reported in 32 of 71 (45%) and 54 of 94 (57%) participants, and the proportion of participants who permanently discontinued trial medication was 8.5% and 10.6% in the semaglutide and placebo groups, respectively. The MACE event rates were 9.7 and 16.1 events per 100 person-years, and all-cause mortality event rates were 13.8 and 18.1 events per 100 person-years, in the semaglutide and placebo groups, respectively. CONCLUSIONS Although more evidence is needed, continuation of semaglutide after dialysis initiation appears safe and warrants efficacy testing regarding reduction in MACE and death.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"19 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147524322","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":"Metabolomic Profile of Genetic Liability to Type 2 Diabetes Among 125,000 Mexican Adults: A Mendelian Randomization Study","authors":"Fiona Bragg, Jesus Alegre-Diaz, Eirini Trichia, Jason M. Torres, Paulina Baca, Adrián Garcilazo-Ávila, Carlos González-Carballo, Raul Ramirez-Reyes, Fernando Rivas, Diego Aguilar-Ramirez, Louisa Gnatiuc Friedrichs, William G. Herrington, Michael Hill, Tabitha Hubbard, Alejandra Vergara, Rachel Wade, Rory Collins, Richard Peto, Jaime Berumen, Pablo Kuri-Morales, Roberto Tapia-Conyer, Jonathan R. Emberson","doi":"10.2337/dc25-2933","DOIUrl":"https://doi.org/10.2337/dc25-2933","url":null,"abstract":"OBJECTIVE The Mexican population experiences a notably high prevalence of type 2 diabetes (T2D) and high T2D-associated disease risks. We used targeted plasma nuclear magnetic resonance metabolomics data within a Mendelian randomization framework to characterize the metabolomic profile of genetically predicted liability to T2D in this population. RESEARCH DESIGN AND METHODS Between 1998 and 2004, 50,000 men and 100,000 women aged ≥35 years were recruited from Mexico City. Mendelian randomization analyses used a genetic risk score (GRS) comprising 1,055 established T2D-associated risk variants and eight pathway-specific T2D GRSs constructed from nonoverlapping subsets of these variants to estimate associations with 143 metabolic biomarkers (including lipids, lipoproteins, fatty acids, amino acids, ketone bodies, and other low-molecular-weight biomarkers). RESULTS Among 125,587 included participants, the T2D GRS explained 6.0% of T2D liability and was not associated with major potential confounders of the relationships of T2D with the circulating metabolome. Genetically predicted liability to T2D was strongly positively associated with concentrations of VLDL particles and lipids within these, with triglycerides, branch-chain amino acids, and glycoprotein acetyls, and more modestly positively associated with intermediate-density lipoprotein and LDL, particularly small LDL, particles. Inverse associations were found with relative concentrations of several fatty acids. Pathway-specific T2D GRSs all associated with higher T2D risk but showed differential relationships with circulating metabolic biomarkers. CONCLUSIONS T2D is associated with widespread changes in the circulating metabolome among adults in Mexico, reflecting diverse biological mechanisms and highlighting the importance of effective T2D management, including control of T2D-associated dyslipidemia, in this population.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"16 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147524751","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":"Profiles of Social Determinants of Health and Change in Diabetes Status Among U.S. Hispanic/Latino Adults: HCHS/SOL, 2008–2024","authors":"Colette J. Brown, Scott C. Roesch, Carlos E. Rosas, Jessica L. McCurley, Christina Cordero, Gabriela Trifan, Fernando Testai, Beibo Zhao, Jianwen Cai, Carmen R. Isasi, Linda C. Gallo","doi":"10.2337/dc25-2797","DOIUrl":"https://doi.org/10.2337/dc25-2797","url":null,"abstract":"OBJECTIVE Social determinants of health (SDoHs) account for more than half of the variance in racial and ethnic disparities in health. However, few studies have examined how SDoHs may cluster in ways that affect health. We aimed to identify patterns of social adversity and their differential associations with both diabetes status at baseline and change in diabetes status across ∼12 years among Hispanic/Latino adults. RESEARCH DESIGN AND METHODS Participants were from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; N = 16,415; aged 18–74 years). Diabetes status (defined as normoglycemia, prediabetes, or diabetes per American Diabetes Association criteria) was measured by clinical assessment and self-reported medications at baseline (2008–2011) and two follow-up visits (2014–2017 and 2020–2024). SDoHs were assessed at baseline and as part of the HCHS/SOL Sociocultural Ancillary Study (2010–2012). RESULTS Latent class analyses of nine SDoHs (income, education, employment status, home ownership, language and social acculturation, chronic stressors, family cohesion, and social support) revealed four distinct patterns of social adversity: 1) low adversity, 2) social/educational strengths, 3) acculturated and underresourced, and 4) high adversity. Compared with the low-adversity group, the high-adversity group had the highest odds of worse diabetes status at baseline and had greater odds of worsening diabetes status over time. CONCLUSIONS SDoHs cluster in distinct ways that affect diabetes outcomes; social adversities must be addressed to mitigate diabetes burden among Hispanic/Latino adults.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"20 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506745","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":"Data-Driven Phenotypic Clusters of Gestational Diabetes Mellitus and Associations With Risk of Perinatal Complications and Postpartum Diabetes","authors":"Yeyi Zhu, Amanda L. Ngo, Lauren D. Liao, Rachel Harvill, Ben J. Marafino, Rana F. Chehab, Mara B. Greenberg, Assiamira Ferrara","doi":"10.2337/dc25-2131","DOIUrl":"https://doi.org/10.2337/dc25-2131","url":null,"abstract":"OBJECTIVE Management of gestational diabetes mellitus (GDM) largely follows a uniform approach, despite growing recognition of GDM heterogeneity. We aimed to identify data-driven GDM clusters by using machine learning techniques and clinical data and to assess their associations with perinatal complications and postpartum diabetes risk. RESEARCH DESIGN AND METHODS In a population-based cohort study, 37,544 individuals with GDM were followed up through 12 years postpartum. In the discovery (70%) and validation (30%) sets, we applied dimension reduction and clustering methods using routinely available sociodemographic, behavioral, and clinical variables. Covariate-adjusted modified Poisson and Cox regression models were used to assess associations of GDM clusters with risk of perinatal complications and postpartum diabetes. RESULTS Four data-driven GDM phenotypic clusters were identified. Cluster 1 (C1) (65.6%), C2 (14.5%), C3 (12.0%), and C4 (7.8%) comprised the discovery set, with similar distributions in the validation set (C1–C4 66.7%, 14.0%, 12.0%, 7.4%, respectively). C2–C4 compared with C1 (late-diagnosed, lower-BMI, and postload hyperglycemia GDM) were associated with higher risks of perinatal complications and new-onset postpartum diabetes, especially C4 (early-diagnosed, comorbidity-related, and high–glucose challenge test GDM) (adjusted relative risks: severe maternal morbidity 1.43 [95% CI 1.19, 1.72] and neonatal intensive unit admission 1.53 [1.41, 1.66]; adjusted hazard ratio for diabetes 4.32 [95% CI 3.94, 4.73]). Within the largest cluster C1, three subclusters were identified, with differential risks of perinatal complications but not postpartum diabetes. CONCLUSIONS Our study identified distinct data-driven GDM phenotypic clusters with differential risks of perinatal complications and postpartum diabetes. These findings may inform personalized risk assessment and management strategies tailored to GDM phenotypic clusters to possibly reduce adverse health outcomes.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"5 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470892","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":"Hypercholesterolemia and Lipid-Lowering Therapy in Children and Adolescents With Type 1 Diabetes: Do We Implement Current Guidelines?","authors":"Jantje Weiskorn, Marianne Becker, Clemens Kamrath, Johanna Hammersen, Susanne Bechtold-Dalla Pozza, Elke Müller-Roßberg, Martin Holder, Marie-Anne Burckhardt, Reinhard Walter Holl","doi":"10.2337/dc25-2459","DOIUrl":"https://doi.org/10.2337/dc25-2459","url":null,"abstract":"OBJECTIVE We investigated the prevalence of elevated LDL cholesterol in youths with type 1 diabetes (T1D), contributing factors, the frequency of lipid-lowering medication (LLM), and the achievement of target values. RESEARCH DESIGN AND METHODS A cross-sectional analysis based on data from the Diabetes-Patienten-Verlaufsdokumentation registry (Diabetes Prospective Follow-up Registry) from 2013 to 2023. Inclusion criteria were T1D, age <18 years, and at least one documented LDL measurement. LDL cut offs of >2.6, >3.4, and >4.1 mmol/L were defined. Application of national and international treatment guidelines was examined. Descriptive analyses and linear and logistic regression models were implemented using SAS 9.4. RESULTS The study included 55,028 participants. Of these, 9.7% and 2.3% had LDL >3.4 mmol/L and >4.1 mmol/L, respectively. The parameters HbA1c (β = 1,142.7; P = 0.001), female sex (β = 861.5; P < 0.001), and BMI >70th percentile (β = 520.1; P < 0.001) had the strongest effect on LDL levels. Only 7.3% of the cohort with elevated LDL levels received LLM. The majority (92.7%) with LDL >3.4 mmol/L and 87.0% with LDL >4.1 mmol/L were not treated. Estimated odds ratios (95% CI) for the use of LLM were 19.13 (15.4–23.7) for LDL >4.1 mmol/L; 3.1 (1.82–5.41) for ages 12–18 years; 2.31 (1.9–2.1) for diabetes duration of 5–10 years; 1.8 (1.5–2.1) for BMI >70th percentile; 1.3 (1.0–1.6) for HbA1c >9%; and 1.18 (1.0–1.4) for female sex. However, only 15.7% of the treated patients (n = 707) reached the LDL target of <2.6 mmol/L, and LDL levels of 55% even remained at >3.4 mmol/L. CONCLUSIONS We found a high prevalence of LDL hypercholesterolemia. The use of LLM was low, despite treatment indication, and treatment targets were mostly not achieved either due to underdosing or nonadherence to LLM. These findings confirm that dyslipidemia remains an underestimated cardiovascular risk factor in pediatric diabetology.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"21 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470891","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":"Weight Regain Reverses Caloric Restriction–Induced Benefits on the Insulin–IGF-1 Nutrient-Sensing Pathway: Post Hoc Analysis From the CALERIE-2 Randomized Controlled Trial","authors":"Moritz V. Warmbrunn, Lin Yang, Raaj Kishore Biswas, Calen P. Ryan, Andrew Harper, Daniel W. Belsky, Giovanni Fiorito, Luigi Fontana","doi":"10.2337/dc25-1911","DOIUrl":"https://doi.org/10.2337/dc25-1911","url":null,"abstract":"OBJECTIVE To investigate the long-term metabolic and hormonal consequences of sustained weight loss versus weight regain after 1 year of caloric restriction (CR), with attention to insulin resistance and type 2 diabetes risk. RESEARCH DESIGN AND METHODS In the 2-year Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy 2 (CALERIE-2) trial (n = 220), participants were randomized to 25% CR or control diet. The intervention targeted weight loss over the first 6–12 months, followed by a 12-month maintenance phase. To assess weight-regain consequences, participants were stratified by weight trajectory regardless of randomization, and group differences were balanced by propensity score weighting. Cardiometabolic and hormonal markers of available participants (n = 190), as well as a biomarker-based estimate of biological age, were compared across weight trajectory groups. RESULTS At 12 months, weight loss ranged from 5.0 to 5.8 kg between groups. Between months 12 and 24, most participants either maintained weight (n = 112) or continued to lose weight (n = 58), whereas a smaller group regained >5% of baseline weight (n = 20). This group had the largest initial caloric reductions. Weight regain reversed improvements in insulin area under the curve and the ratio of insulin-like growth factor 1 (IGF-1) to insulin-like growth factor-binding protein 1, and sustained weight loss maintained metabolic benefits and was associated with greater reductions in biological age. CONCLUSIONS Substantial weight loss followed by weight regain can attenuate or reverse CR-induced benefits on key regulators of the insulin–IGF-1 nutrient-sensing pathway and markers of biological aging. Sustained, moderate weight loss more effectively improves insulin resistance and maintains favorable hormonal profiles linked to type 2 diabetes risk and aging biology.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"11 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465233","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":"Improving the Algorithm: The Inclusion of a Socioeconomic Status Measure in Predicting Type 2 Diabetes Development in Youth With Prediabetes","authors":"Subin Jang, Yinzhao Wang, Sisi Ma, Daniel S. Hsia, Kristina Cossen, David Haynes, Megan O. Bensignor","doi":"10.2337/dc25-3060","DOIUrl":"https://doi.org/10.2337/dc25-3060","url":null,"abstract":"OBJECTIVE To evaluate whether the Area Deprivation Index (ADI) contributes to predicting type 2 diabetes development in youth with prediabetes compared with a machine learning (ML) model built with other data elements. RESEARCH DESIGN AND METHODS Patient encounters (n = 665) from an electronic medical record were used to build supervised ML models to predict type 2 diabetes development within 1 year of prediabetes diagnosis. The ADI was constructed using patients’ census block data. Two models, trained on data with and without ADI, were built. The model selection resulted in logistic regressions with 1) HbA1c only and 2) HbA1c + ADI as the best models from each data set. RESULTS A total of 181 patient encounters (27.2%) developed type 2 diabetes. The area under the receiver operating characteristic curve of the HbA1c-only model was 0.68 and of the HbA1c + ADI model, 0.73. CONCLUSIONS The addition of ADI to the model resulted in the best performance in predicting youth-onset type 2 diabetes development.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"20 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462150","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":"A U-Shaped Association Between Blood mtDNA Copy Number and Risk of Type 2 Diabetes","authors":"Xinhao Huang, Zijian Tian, Ying Pan, Jia Zhang, Benrui Wu, Shiteng Gao, Yao Cheng, Qi Hu, Jinxiang Ma, Qi Pan, Jian Shao, Kaixin Zhou","doi":"10.2337/dc25-2198","DOIUrl":"https://doi.org/10.2337/dc25-2198","url":null,"abstract":"OBJECTIVE mtDNA copy number (CN) reflects mitochondrial function, but prior studies have reported inconsistent associations with type 2 diabetes risk, ranging from inverse to positive or null findings. We hypothesized that mtDNA-CN is nonlinearly associated with incident type 2 diabetes. RESEARCH DESIGN AND METHODS We included 34,835 adults without diabetes from the Kunshan Aging Research With E-Health (KARE) cohort and 289,338 from the UK Biobank (UKB). Associations between blood mtDNA-CN and incident type 2 diabetes were evaluated using Cox proportional hazards and restricted cubic spline models stratified by age. RESULTS A U-shaped association was observed in the KARE cohort (P < 0.001), in which the hazard ratios (95% CIs) across increasing mtDNA-CN quartiles were 1.00 (reference), 0.94 (0.88–1.00), 0.85 (0.79–0.91), and 0.93 (0.87–1.00). In contrast, the UKB cohort exhibited a predominantly inverse linear trend. Age-stratified analyses revealed that this U-shaped association was particularly evident in younger participants (aged <65 years in KARE and <50 years in UKB), indicating elevated diabetes risk at both low and high mtDNA-CN levels. Additionally, mtDNA-CN declined with age in both cohorts, with an accelerated decrease beyond ∼65 years in KARE and ∼50 years in UKB. CONCLUSIONS Blood mtDNA-CN showed a U-shaped association with incident type 2 diabetes in younger individuals.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"13 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462178","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}