Diabetes care最新文献

{"title":"Identification and Follow-up of At-Risk Children Mitigate Disease Severity and Improve Treatment Outcomes in Type 1 Diabetes.","authors":"Oona Kähkönen, Salla Kuusela, Jutta E Laiho, Anna Eurén, Laura Kallio, Heini Huhtala, Linnea Aitokari, Mindi Sundell, Ida Hämäläinen, Laura Kivelä, Sauli Palmu, Kalle Kurppa","doi":"10.2337/dc26-0136","DOIUrl":"10.2337/dc26-0136","url":null,"abstract":"<p><strong>Objective: </strong>Interest in screening for type 1 diabetes (T1D) is increasing, but studies assessing outcomes during the treatment period among individuals identified through population-based genetic screening and prospective follow-up remain limited.</p><p><strong>Research design and methods: </strong>Characteristics at T1D diagnosis and 1-year treatment outcomes were compared between 126 at-risk children followed in the Type 1 Diabetes Prediction and Prevention (DIPP) study and 440 children diagnosed outside the screening program.</p><p><strong>Results: </strong>DIPP participants had significantly less frequent (P < 0.05) ketoacidosis (5.6% vs. 23.6%), dehydration, electrolyte imbalances, and need for intensive care, and shorter inpatient stays, than non-DIPP children. They showed lower median HbA1c levels (46 vs. 99 mmol/mol [6.4 vs. 11.2%]) and insulin requirements (0.11 vs. 0.74 units/kg/day) both at diagnosis and 1 year later (55 vs. 61 mmol/mol [7.2 vs. 7.7%]; 0.57 vs. 0.70 units/kg/day).</p><p><strong>Conclusions: </strong>DIPP participants had a milder clinical presentation at T1D diagnosis, with lower HbA1c levels and lower insulin requirements during the first year.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1474-1479"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term Effect of C-Peptide Level on Clinical Outcomes in the Scottish Type 1 Bioresource Cohort.","authors":"Joseph C Mellor, Luke A K Blackbourn, Stuart J McGurnaghan, Paul M McKeigue, Julia Zaccai, Oliver Guenther, Antonia Ridolfi, Aymeric Mahieu, Mireille Bonnemaire, Helen M Colhoun","doi":"10.2337/dc25-1738","DOIUrl":"10.2337/dc25-1738","url":null,"abstract":"<p><strong>Objective: </strong>To characterize associations of C-peptide measurements with type 1 diabetes (T1D) complications across long-term clinical follow-up in a large representative population cohort (Scottish Diabetes Research Network Type 1 Bioresource [SDRNT1BIO]).</p><p><strong>Research design and methods: </strong>SDRNT1BIO includes people with a clinical diagnosis of T1D who are aged 16 years or older at enrollment. Their median diabetes duration is 21 (interquartile range 11-31) years. C-peptide was measured in an untimed blood sample using the Roche immunoassay with a lower limit of detection of 3 pmol/L. Incident events and continuous outcomes were captured through electronic health record linkage across follow-up. Associations were studied using Poisson generalized linear models and linear mixed models adjusted for sex, age, time-updated T1D duration, year of entry, and age/T1D duration interaction.</p><p><strong>Results: </strong>Participants (n = 5,630) were followed for a median of 10.8 years. Inverse associations were found between baseline C-peptide level and diabetic ketoacidosis (DKA) (P < 0.0001; no. of events = 1,015), severe hospitalized hypoglycemia (SHH) (P = 0.0055; n = 539), and incident retinopathy (P < 0.0001; n = 1,172). These associations persisted when adjusted for time-updated glycosylated hemoglobin. No associations were found between baseline C-peptide levels and cardiovascular disease (P = 0.9; n = 714) or death (P = 0.8; n = 566). In a subset of participants (n = 407) with serial C-peptide measures, follow-up C-peptide level was inversely associated with risk for DKA (P < 0.001; n = 92) and there was a borderline association with SHH (P = 0.015; n = 28).</p><p><strong>Conclusions: </strong>These data demonstrate the importance of C-peptide level and its maintenance for glycemic control and avoidance of acute and chronic complications of T1D.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1348-1356"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant.","authors":"Jingyi Qian, Darko Stefanovski, Phillip A K Andersen, Nina Vujovic, Lauren Kelly, Joshua Lepson, Hoa Nguyen, Sean Byrne, Wei Wang, Thomas Mandrup-Poulsen, Gail Adler, Marta Garaulet, Richa Saxena, Frank A J L Scheer","doi":"10.2337/dc26-0164","DOIUrl":"10.2337/dc26-0164","url":null,"abstract":"<p><strong>Objective: </strong>Melatonin use quintupled in recent decades. The common melatonin receptor 1B gene (MTNR1B) variant increases risk of type 2 diabetes, raising concerns about melatonin's adverse metabolic effects and highlighting the need for a genotype-based personalized approach. We aimed to comprehensively characterize the actions of melatonin on glucose homeostasis, including first- and second-phase β-cell responsivity to glucose, β-cell negative feedback by exogeneous insulin, insulin sensitivity, and whether such effects are stronger in MTNR1B G-allele risk carriers compared with noncarriers.</p><p><strong>Research design and methods: </strong>Twenty-one healthy participants of European ancestry were studied in a randomized, double-blind, placebo-controlled, crossover trial, including 10 MTNR1B risk carriers and 11 noncarriers. Each participant underwent a highly controlled 5-day laboratory protocol, during which they received 5 mg oral melatonin or placebo in randomized order on two nonconsecutive days. Glycemic dynamics were assessed using insulin-modified intravenous glucose tolerance tests with minimal-model analysis.</p><p><strong>Results: </strong>Melatonin worsened glucose tolerance and reduced early C-peptide responses in risk allele carriers (vs. placebo: 11.7% [95% CI 1.0-22.3] and -19.2% [-33.9 to -1.2], respectively; Padj < 0.05) but not in noncarriers. In carriers, impairments stemmed from a 40% (-52.4 to -24.3; Padj = 0.0003) suppression of glucose-stimulated first-phase β-cell responsivity, along with a slower insulin-induced decline in second-phase insulin secretion rate (64.3% [23.1-119.2]; Padj = 0.001). In carriers, melatonin also prevented exogenous insulin-induced hypoglycemia compared with placebo (zero vs. seven events, P = 0.001), but not in noncarriers.</p><p><strong>Conclusions: </strong>These findings identify blunted β-cell responsivity to glucose and dysregulated insulin negative feedback as key mechanisms linking melatonin signaling to diabetes risk.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1498-1506"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148321266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Integrated Personalized Multimodal Intervention Improves Adherence to Wearing Custom-Made Footwear in People With Diabetes at High Foot Ulcer Risk: A Multicenter Randomized Controlled Trial (DIASSIST).","authors":"Lisa E Vossen, Jaap J Van Netten, Chantal M Hulshof, Natasja Jelsma, Anne Slootman, Maarten J M Merkx, Sicco A Bus","doi":"10.2337/dc25-3113","DOIUrl":"10.2337/dc25-3113","url":null,"abstract":"<p><strong>Objective: </strong>Diabetes-related foot ulcers impose a large burden on patients and society. To prevent foot ulcers, adherence to wearing custom-made footwear is essential. However, adherence is often low in people at high ulcer risk, while evidence for interventions that improve adherence is scarce. We assessed the effectiveness of an integrated personalized multimodal intervention on footwear adherence in people with diabetes at high risk of ulceration.</p><p><strong>Research design and methods: </strong>In a multicenter randomized controlled trial, 126 participants with diabetes, peripheral neuropathy, ulcer history, and custom-made footwear were randomized to usual care or enhanced treatment. Usual care was guideline-based; that is, custom-made footwear, nonstructured education, and podiatric foot care and screening. Enhanced treatment consisted of usual care plus pressure-optimized custom-made footwear, provision of indoor-specific custom-made footwear, structured education, and motivational interviewing that included personalized feedback. The primary outcome was footwear adherence (i.e., percentage of steps taken wearing prescribed footwear) objectively measured at 6 and 12 months of follow-up. A secondary outcome was shoe-wearing time in hours per day, assessed 2 weeks before and after study visits.</p><p><strong>Results: </strong>Footwear adherence was significantly higher for enhanced treatment compared with usual care: 75% (SD 10) vs. 56% (SD 22) at 6 months (i.e., relative increase 34%, P < 0.001) and 58% (SD 18) vs. 49% (SD 20) at 12 months (P = 0.013). Shoe-wearing time significantly increased after the randomization visit in which structured education was provided (7.8-8.3 h/day, P = 0.049) and after the provision of indoor-specific footwear (7.7-9.4 h/day, P < 0.001).</p><p><strong>Conclusions: </strong>Footwear adherence can be significantly increased through an integrated personalized multimodal intervention.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1384-1394"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148177382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrapartum and Early Postpartum Use of Automated Insulin Delivery in Type 1 Diabetes: A Prespecified Analysis of the CIRCUIT Randomized Controlled Trial.","authors":"Lois E Donovan, Patricia Lemieux, Jennifer M Yamamoto, Amy D Dunlop, Helen R Murphy, Selina L Liu, Kathleen H Chaput, David Simmons, Rhonda C Bell, Jamie L Benham, Glynis P Ross, Kara A Nerenberg, Jane E Booth, Khorshid Mohammad, Bruce A Perkins, Susan Crawford, George Tomlinson, Denice S Feig","doi":"10.2337/dc26-0470","DOIUrl":"10.2337/dc26-0470","url":null,"abstract":"<p><strong>Objective: </strong>Following the demonstrated improvement in pregnancy glycemia with Control-IQ closed loop in the Closed-Loop Insulin Delivery by Glucose Responsive Computer Algorithms in Type 1 Diabetes Pregnancies (CIRCUIT) trial, we compared intrapartum and early postpartum glycemic effectiveness and safety with standard care in type 1 diabetes.</p><p><strong>Research design and methods: </strong>The primary outcome of this prespecified analysis was percentage of time in pregnancy-specific glucose range (63-140 mg/dL) during the 24 h prior to childbirth, measured by continuous glucose monitoring. A key secondary outcome was percentage of time at <70 mg/dL in the first postpartum week, with additional secondary outcomes including continuous glucose monitoring metrics through 6 weeks postpartum. Analyses were adjusted for baseline measure, insulin delivery mode, and site.</p><p><strong>Results: </strong>In the intrapartum period (24 h before delivery), 39 of 44 (89%) participants continued closed loop. Intravenous insulin was used intrapartum by one (2%) closed-loop participant and 20 (45%) standard-care participants (P < 0.001). Intrapartum closed-loop users spent more time in pregnancy-specific glucose range (79.6% vs. 64.8%) than the standard-care group (mean adjusted difference 13.2 percentage points; 95% CI 5.2, 21.2). In the first postpartum week, the closed-loop group spent less time <70 mg/dL (1.7% vs. 3.2%; mean adjusted difference -1.8 percentage points; 95% CI -0.9 to -2.7) compared with the standard-care group. No maternal severe hypoglycemia occurred in the closed-loop group, while one episode occurred in the standard-care group postpartum. No diabetic ketoacidosis occurred in either group.</p><p><strong>Conclusions: </strong>Use of this closed-loop system resulted in superior intrapartum and early postpartum glycemia compared with standard care without safety concerns. Together with previous results, this supports use of this closed-loop system throughout pregnancy, labor, and the early postpartum period.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1339-1347"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148045028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on Hespanhol et al. Automated Insulin Delivery Systems in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.","authors":"Sergio Di Molfetta, Ludovico Di Gioia, Irene Caruso, Luigi Laviola, Francesco Giorgino","doi":"10.2337/dc26-1007","DOIUrl":"10.2337/dc26-1007","url":null,"abstract":"","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":"49 8","pages":"e147-e148"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Signatures of 3-Year Progression From Impaired Fasting Glucose to Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study.","authors":"Mary R Rooney, Justin B Echouffo Tcheugui, Jingsha Chen, Keenan A Walker, Christie M Ballantyne, Eric Boerwinkle, Tanika N Kelly, Chiadi E Ndumele, James S Pankow, Morgan E Grams, Wendy S Post, Peter J Ganz, Alexis C Wood, Jerome I Rotter, Elizabeth Selvin, Josef Coresh","doi":"10.2337/dc26-0498","DOIUrl":"10.2337/dc26-0498","url":null,"abstract":"<p><strong>Objective: </strong>To identify proteomic signatures underlying 3-year progression from impaired fasting glucose (IFG) to diabetes.</p><p><strong>Research design and methods: </strong>We examined IFG progression in the Atherosclerosis Risk in Communities (ARIC) study from visit 2 (1990-1992) to visit 3 (1993-1995). We tested associations of 4,955 plasma proteins (SomaScan version 4.0) with ∼3-year progression from IFG (FG 100-125 mg/dL without diabetes) to diabetes (diagnosis, medication, or FG ≥126 mg/dL) using logistic regression models adjusted for demographics, cardiometabolic risk factors, and baseline glucose with Bonferroni correction (P < 10-5). We explored biological pathways enriched among the top proteins and calculated improvements in prediction (ΔAUC and net reclassification using 3-year risk thresholds of 6% and 15% in 80% training and 20% internal validation subsamples). We validated results in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.</p><p><strong>Results: </strong>There were 3,786 ARIC participants with IFG (mean [SD] age 57 [6] years, 52% female, 28% Black individuals). The 3-year cumulative incidence of diabetes was 6%. Six proteins were associated with ∼3-year progression to diabetes, namely lower receptor-type tyrosine-protein phosphatase S (PTPRS), anthrax toxin receptor 2 (ANTXR2), adiponectin (ADIPOQ), ciliary neurotrophic factor receptor subunit α (CNTFR), transmembrane protein 132C (TMEM132C), and higher ADAMTS-like protein 2 (ADAMTSL2). Altered carbohydrate metabolism and glycolysis were key pathways. Adding the six proteins to covariates improved discrimination (optimism-corrected AUC 0.81, ΔAUC 0.03, P = 0.005) and net reclassification (training 12.2%, internal validation 12.0%) with predicted diabetes risk quintiles spanning <1% to ∼20%. Two of the six proteins were validated in MESA (P < 0.008).</p><p><strong>Conclusions: </strong>We identified proteins associated with 3-year IFG progression, with improvements in diabetes risk stratification.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1490-1497"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148320791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolocumab in Patients With High-Risk Diabetes: Results From the VESALIUS-CV Trial.","authors":"Lawrence A Leiter, Robert P Giugliano, Nicholas A Marston, Gaetano De Ferrari, Jose C Nicolau, Ajay K Bhatia, Marcoli Cyrille, Jeong-Gun Park, Julia F Kuder, Sabina A Murphy, Lyrica Liu, Emileigh Walsh, Huei Wang, Andrej Džupina, Jorge Ferreira, Ioanna Gouni-Berthold, Henrik K Jensen, Johanna Kuusisto, Daniel Pella, Naveed Sattar, Konstantinos P Tsioufis, Dragos Vinereanu, Gabriel Paiva da Silva Lima, Marc S Sabatine, Erin A Bohula","doi":"10.2337/dc26-0847","DOIUrl":"10.2337/dc26-0847","url":null,"abstract":"<p><strong>Objective: </strong>This prespecified analysis of Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke (VESALIUS-CV) evaluated the efficacy of the PCSK9 inhibitor evolocumab for preventing first cardiovascular events in patients with high-risk diabetes.</p><p><strong>Research design and methods: </strong>VESALIUS-CV randomized patients with high-risk diabetes (microvascular disease, insulin use, or duration ≥10 years) or qualifying atherosclerosis, but no prior myocardial infarction (MI) or stroke, and LDL cholesterol (LDL-C) ≥90 mg/dL to evolocumab 140 mg or matching placebo every 2 weeks. The dual primary end points were a composite of coronary heart disease death, MI or ischemic stroke (three-point major adverse cardiovascular event [3P-MACE]) and 3P-MACE plus ischemia-driven arterial revascularization (four-point [4P]-MACE).</p><p><strong>Results: </strong>Of the 6,002 patients with high-risk diabetes, 67% were on a high-intensity statin and 24% were on a sodium-glucose cotransporter 2 inhibitor (SGLT2i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA) at baseline. The median LDL-C at 48 weeks was 47 mg/dL and 109 mg/dL in the evolocumab and placebo arms, respectively (P < 0.0001). After a median follow-up of 4.6 years, evolocumab decreased the relative rates of 3P-MACE and 4P-MACE by 29% (hazard ratio [HR] 0.71; 95% CI 0.59, 0.86; P = 0.0004) and 21% (HR 0.79; 95% CI 0.69, 0.91; P = 0.0013), respectively. These findings were consistent regardless of the presence or absence of qualifying atherosclerosis, baseline LDL-C, statin intensity, and SGLT2i or GLP-1RA use (Pint > 0.05 for each). The porportion of patients with all-cause death was 8.8% vs. 11.0% in the evolocumab versus placebo arms (HR 0.79; 95% CI 0.67, 0.93).</p><p><strong>Conclusions: </strong>Evolocumab reduced the rate of cardiovascular events in patients with high-risk diabetes, regardless of the presence or absence of qualifying atherosclerosis and background use of other cardioprotective agents.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1366-1373"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying the Right Diagnosis of Diabetes in Death: Unlocking A Key to Understanding Type 1 Diabetes Pathogenesis.","authors":"Laura M Jacobsen, Martha Campbell-Thompson, Clive Wasserfall, Mark A Atkinson, Desmond A Schatz","doi":"10.2337/dci26-0020","DOIUrl":"https://doi.org/10.2337/dci26-0020","url":null,"abstract":"<p><p>Accurate classification of diabetes into type 1, type 2, or monogenic forms remains a major challenge. This difficulty arises from overlapping clinical features and substantial heterogeneity within these conditions, particularly in adults, due to nonconforming presentations such as obesity coexisting with autoimmunity. Consequently, misclassification is common and can contribute to suboptimal therapeutic decisions, delayed achievement of glycemic targets, and increased risk of long-term complications. Growing evidence supports a spectrum-based view of diabetes pathophysiology rather than rigid categorical definitions, highlighting the need for improved biomarkers and a deeper mechanistic understanding of disease processes. To address this knowledge gap, over the past two decades we have conducted studies of human pancreata obtained through the Network for Pancreatic Organ donors with Diabetes (nPOD) and related programs, enabling in situ investigation of disease pathogenesis. Insights derived from such tissues and their biological relevance are based on limited clinical data at the time of terminal hospitalization. Challenges with postmortem diabetes classification have led to the creation of classification pathways that include not only clinical variables but also histopathology and genetics. For example, including the presence of insulin-negative islets and insulitic lesions on histopathology and clinical features such as C-peptide loss and increased type 1 diabetes genetic risk score, over clinical history alone, supports a more holistic diagnosis of type 1 diabetes, which may include atypical forms of diabetes. Continued integration of organ donor-based research with comprehensive clinical data is essential to refine classification systems, improve diagnostic accuracy, and advance personalized approaches to diabetes care.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148564196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accounting for Age-Related Increases in HbA1c More Accurately Quantifies Risk of Type 1 Diabetes Progression in Islet Autoantibody-Positive Adults.","authors":"Erin L Templeman, Nick Thomas, Susan Martin, Diane K Wherett, Maria J Redondo, Jennifer Sherr, Alessandra Petrelli, Laura M Jacobsen, Falastin Salami, Jacqueline Lonier, Carmella Evans-Molina, Jay Sosenko, Inês Barroso, Richard A Oram, Emily K Sims, Lauric A Ferrat","doi":"10.2337/dc26-0446","DOIUrl":"10.2337/dc26-0446","url":null,"abstract":"<p><strong>Objective: </strong>HbA1c thresholds used to define dysglycemia in autoantibody-positive individuals at risk for type 1 diabetes do not account for age-related increases in HbA1c and may overestimate progression risk in adults. We evaluated whether age-adjusted HbA1c or a higher HbA1c threshold improves risk stratification across age-groups.</p><p><strong>Research design and methods: </strong>We analyzed 5,024 autoantibody-positive relatives (3,720 children and 1,304 adults) participating in the TrialNet Pathway to Prevention study. Age-related HbA1c effects were modeled using 6,273 adults from the population-based Exeter 10000 cohort. Progression risk was compared using the standard dysglycemia threshold (HbA1c ≥5.7% [39 mmol/mol]), age-adjusted HbA1c, and an alternative threshold of HbA1c ≥6.0% (42 mmol/mol).</p><p><strong>Results: </strong>Using HbA1c ≥5.7% (39 mmol/mol), children had higher 1-year progression risk than adults among single autoantibody-positive participants (38% [95% CI 28, 47] vs. 13% [7.2, 19]) and multiple autoantibody-positive participants (55% [49, 60] vs. 38% [27, 47]) (both P < 0.001). Age adjustment reduced these differences; progression risk was similar among single autoantibody-positive participants (38% [28, 47] vs. 27% [13, 39]; P = 0.32), with attenuated differences among multiple autoantibody-positive participants. An HbA1c threshold ≥6.0% (42 mmol/mol) yielded comparable progression risk between adults and children across autoantibody subgroups. In post hoc analyses, adults aged <30 years had progression risk similar to children (P = 0.1).</p><p><strong>Conclusions: </strong>Age-related variation in HbA1c influences dysglycemia classification in adults at risk for type 1 diabetes. Age-adjusted HbA1c or a higher HbA1c threshold (≥6.0% [42 mmol/mol]) in adults aged ≥30 years identifies individuals with progression risk comparable to children and may improve age-specific risk stratification in prevention settings.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1262-1269"},"PeriodicalIF":16.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13294784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}