Diabetes care最新文献

{"title":"Glucose-Derived Personalized HbA1c Correction (GDAC) Study to Improve Alignment Between CGM-Derived Metrics and HbA1c in Different Individuals and Racial Groups With Diabetes: Implications for Clinical Practice.","authors":"Ramzi A Ajjan, Pratik Choudhary, Yongjin Xu, Timothy C Dunn","doi":"10.2337/dc26-0398","DOIUrl":"10.2337/dc26-0398","url":null,"abstract":"<p><strong>Objective: </strong>Glycated hemoglobin (HbA1c) and average glucose (AG) can show discordance due to personal variations in red blood cell (RBC) physiology, creating management difficulties. Our aims were to understand the size of the problem and refine this glycemic metric by adjusting for personal differences in RBC characteristics.</p><p><strong>Research and design and methods: </strong>A 26-week prospective study was conducted in individuals with type 1 diabetes (T1D) or type 2 diabetes across four racial groups with HbA1c collected every 2 weeks and continuous glucose monitoring (CGM) used throughout. Personal glycation ratio (PGR) was derived from HbA1c and AG data (weeks 0-12), allowing calculation of personalized HbA1c (pA1C) and subsequent testing (weeks 20-26). The relationship between AG and HbA1c or pA1C was then analyzed, documenting a clinically meaningful discordance of ≥0.5%. In addition, we used real-world data sets to further validate the accuracy of pA1C at reflecting glucose exposure.</p><p><strong>Results: </strong>Of 257 participants (19% T1D) with complete CGM and HbA1c data sets, mean age (±SD) was 53 ± 14 years (45% females). The racial background was 35% Asian, 30% White, 22% Black, and 14% other/mixed. Of the total study population, 33% showed ≥0.5% HbA1c-AG discordance, with the Black population affected most (41% discordance). Use of pA1C reduced the discordance in the whole population to 14% (58% reduction), while this was reduced in the Black population to 12% (71% reduction).</p><p><strong>Conclusions: </strong>HbA1c-AG discordance is common, particularly in the Black population, with pA1C improving alignment with glucose levels, potentially helping to optimize clinical management and reduce health disparities.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1420-1427"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201764","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":"Postpartum Dietary Interventions and Cardiometabolic Profiles After Pregnancies Complicated by Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis.","authors":"Anthea Ann Ting Phee, Ru Xun Foo, Claire Guivarch, Peipei Liu, Ron Gneezy, Shwetha Shanmugan, Cuilin Zhang, Jiayi Shen, William Chi Wai Wong, Ka Wang Cheung, Karen Kar Leon Chan, Ling-Jun Li","doi":"10.2337/dc26-0057","DOIUrl":"10.2337/dc26-0057","url":null,"abstract":"<p><strong>Background: </strong>Gestational diabetes mellitus (GDM) confers substantial long-term cardiometabolic risk. The postpartum period represents a critical window for intervention, but the benefits of dietary interventions on cardiometabolic profiles in women with prior GDM remain unclear.</p><p><strong>Purpose: </strong>To evaluate whether postpartum dietary interventions improved cardiometabolic profiles in women with GDM.</p><p><strong>Data sources: </strong>Six databases were searched from 1 January 1980-31 December 2025.</p><p><strong>Study selection: </strong>Twenty-one randomized controlled trials (RCTs) met inclusion criteria.</p><p><strong>Data extraction: </strong>Data extraction and risk-of-bias assessment followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.</p><p><strong>Data synthesis: </strong>Meta-analyses pooled mean differences (MDs) with 95% CIs using a random-effects model. Intermediate cardiometabolic surrogate markers, such as BMI, waist circumference, weight, fasting and 2-h blood glucose, HOMA of insulin resistance (HOMA-IR), hemoglobin A1c (HbA1c), systolic and diastolic blood pressure, lipids, and inflammatory biomarkers were evaluated. The meta-analysis included 19 RCTs (participants were aged 18-45 years; sample size: 23 to 1,639; follow-up: 12 weeks-3 years). Compared with standard care, postnatal dietary interventions significantly reduced BMI (MD -0.46 kg/m2; 95% CI -0.71, -0.20), waist circumference (-1.47 cm; -2.39, -0.55), weight (-0.73 kg; -1.19, -0.27), HOMA-IR (-0.55; -1.04, -0.06), and HbA1c (-0.24%; -0.46, -0.02). No improvements were found for other markers.</p><p><strong>Limitations: </strong>Heterogeneity across studies, variable adherence to counseling-based interventions, and comprehensive standard postpartum care may have limited observed effects.</p><p><strong>Conclusions: </strong>Postpartum dietary interventions yield modest but statistically significant improvements in key cardiometabolic indicators among women with prior GDM without overt disease, highlighting the postpartum period as an important window to optimize intermediate cardiometabolic markers.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1507-1520"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148177348","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":"Achieving at Least 15% Weight Loss Within 2 Years of Type 2 Diabetes Diagnosis Is Associated With Lower Risks of Macrovascular and Microvascular Complications: A U.K. Cohort Study.","authors":"Eva Johnsen, Jessica Bengtsson, Tariq Halasa, Amine Lotfi, Claire P Miller, Riia K Sustarsic, Naveed Sattar","doi":"10.2337/dc26-0937","DOIUrl":"10.2337/dc26-0937","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to evaluate whether achieving a minimum of 15% weight loss early after type 2 diabetes diagnosis was associated with subsequent lower risks of developing macrovascular and microvascular complications.</p><p><strong>Research design and methods: </strong>Using U.K. primary care data from Clinical Practice Research Datalink Aurum linked to hospital and mortality data, we conducted a cohort study (2000-2024) of adults with obesity and type 2 diabetes. Individuals with ≥15% weight loss within 2 years of type 2 diabetes diagnosis were propensity score matched 1:4 to control subjects maintaining a stable weight (<2% weight change). Cumulative incidence rates were determined, and time to first macrovascular (myocardial infarction, stroke, angina, peripheral arterial disease) and microvascular (chronic kidney disease, retinopathy, neuropathy) events was analyzed using Cox proportional hazards regression.</p><p><strong>Results: </strong>The matched cohort included 14,496 individuals with ≥15% weight loss and 57,984 control subjects. Compared with control subjects, the weight loss group had significantly lower risk of first macrovascular (hazard ratio 0.86, 95% CI 0.81-0.91) and microvascular (hazard ratio 0.90, 95% CI 0.86-0.94) events. Individually, significantly lower risks were observed for myocardial infarction, angina, chronic kidney disease, and retinopathy. The weight loss group also demonstrated better glycemic and blood pressure levels, despite fewer medications.</p><p><strong>Conclusions: </strong>Achieving ≥15% weight loss early in type 2 diabetes was associated with clinically meaningful lower risks for macro- and microvascular complications and better glycemic control compared with stable weight. These real-world findings support prioritizing early, substantial weight reduction as a core therapeutic strategy to improve glycemic control and prevent end-organ damage.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1480-1489"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148207431","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":"Clinical Potential of GIP in Type 2 Diabetes and Obesity.","authors":"Michael Nauck, Fiona Gribble, Frank Reimann, David A D'Alessio, Jonathan E Campbell","doi":"10.2337/dci25-0141","DOIUrl":"10.2337/dci25-0141","url":null,"abstract":"<p><p>Incretin-based pharmacology has revolutionized the medical treatment of type 2 diabetes and obesity. The most effective drug to date is tirzepatide, a dual incretin receptor agonist that engages both the glucagon-like peptide 1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR). While the relative contributions of GIPR and GLP-1R actions to the clinical effects of tirzepatide have not been established, the potency of this agent has reignited interest in the clinical potential of GIPR agonism. Here, we discuss incretin biology as it relates to metabolic pharmacology and contextualize the mechanisms by which GIPR activity could contribute to the development of new and effective drugs. We explore current and future applications of GIPR agonists and antagonists, to underscore the potential that this signaling system could add to treatment of type 2 diabetes and obesity.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1308-1317"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679651","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":"Clinical Risk Factors Differ by Sex for Kidney Complications but Not Retinopathy in Type 1 Diabetes: The Pittsburgh Epidemiology of Diabetes Complications Cohort.","authors":"Rachel G Miller, Tina Costacou, Samar R El Khoudary, Trevor J Orchard","doi":"10.2337/dc26-0374","DOIUrl":"10.2337/dc26-0374","url":null,"abstract":"<p><strong>Objective: </strong>Data on sex-specific risk factors for type 1 diabetes microvascular complications are limited. We assessed sex-specific associations of longitudinal clinical risk factors and 30-year retinopathy and kidney end point incidence in the Pittsburgh Epidemiology of Diabetes Complications type 1 diabetes cohort.</p><p><strong>Research design and methods: </strong>The cohort (n = 325 women and 333 men; mean baseline age 27 years; diabetes duration 19 years) was followed from 1986-1988 to 2016-2018 for the following: incident proliferative diabetic retinopathy (PDR) (Early Treatment of Diabetic Retinopathy Study grade ≥60 or laser photocoagulation); severely increased albuminuria (SIA) (albumin excretion rate ≥200 µg/min); and estimated glomerular filtration rate < 60 mL/min/1.73 m2 (chronic kidney disease [CKD] G3). Associations between longitudinal risk factors and time to each event were assessed by sex in multivariable joint models in those who were complication free at baseline.</p><p><strong>Results: </strong>PDR incidence was similar by sex (57% in women vs. 59% in men; P = 0.54). SIA incidence was lower in women (18% vs. 25% in men; P = 0.10); and CKD G3 was higher in women (28% vs. 21% in men; P = 0.11). In both sexes, independent risk factors for PDR included HbA1c and blood pressure (BP) (women's systolic BP: hazard ratio [HR] 1.27 [95% CI 1.12, 1.45]; men's diastolic BP: HR 1.40 [95% CI 1.15, 1.70]). For SIA, HbA1c was associated in both sexes, but other factors differed, including triglyceride levels (HR 1.38 per log1.2; 95% CI 1.06, 1.78) and BMI (HR 0.87; 95% CI 0.76, 1.00) in women and smoking (HR 3.46; 95% CI 1.07, 11.24) in men. For CKD G3, HbA1c was a risk factor in both sexes; smoking was also associated in men.</p><p><strong>Conclusions: </strong>Although HbA1c and BP are important risk factors for retinopathy regardless of sex, sex-specific clinical targets warrant further research to optimize kidney protection in type 1 diabetes.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1395-1403"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148159724","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":"Subtypes of Type 2 Diabetes and Prediabetes: Mortality and Excess Life Lost in South Asians.","authors":"Ram Jagannathan, Dimple Kondal, Pradeep Tiwari, Mohan Deepa, Unjali P Gujral, Shivani A Patel, Sailesh Mohan, Ranjith Mohan Anjana, Lisa R Staimez, Ruby Gupta, Yara S Beyh, Ayodipupo S Oguntade, Howard H Chang, Mohammed K Ali, Arshed Quyyumi, Yan V Sun, Dorairaj Prabhakaran, Nikhil Tandon, Viswanathan Mohan, K M Venkat Narayan","doi":"10.2337/dc26-0043","DOIUrl":"10.2337/dc26-0043","url":null,"abstract":"<p><strong>Objective: </strong>Current definitions of type 2 diabetes (T2D) and prediabetes do not capture their pathophysiological heterogeneity. We investigated data-driven subtypes of T2D and prediabetes and evaluated their associations with mortality.</p><p><strong>Research design and methods: </strong>We analyzed data from 14,036 South Asian participants from the CArdiometabolic Risk Reduction cohort using unsupervised k-means clustering based on five variables: age, BMI, HbA1c, insulin resistance, and β-cell dysfunction. For each subtype of T2D or prediabetes, we estimated Cox hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality and excess years of life lost compared with normal glucose tolerance.</p><p><strong>Results: </strong>Among 2,639 participants with T2D, three subtypes emerged: severe insulin-deficient diabetes (SIDD; 23.0%), mild insulin-deficient diabetes (MIDD; 54.5%), and severe insulin-resistant diabetes (SIRD; 22.5%). Among 4,992 participants with prediabetes, two subtypes were identified: insulin-deficient prediabetes (IDPD; 66.0%) and insulin-resistant prediabetes (IRPD; 34.0%). Over a median follow-up of 10.6 years, 1,076 deaths occurred (405 due to CVD). Compared with normal glucose tolerance, SIDD had the highest all-cause mortality (HR 3.34; 95% CI 2.39-4.68), followed by MIDD (1.39; 95% CI 1.05-1.84) and SIRD (1.67; 95% CI 1.15-2.41). Among prediabetes subtypes, IDPD was associated with increased all-cause mortality (HR 1.32; 95% CI 1.03-1.68) and CVD mortality (HR 1.53; 95% CI 1.00-2.34), whereas IRPD was not. Excess years of life lost were greatest for SIDD (17.7 years), followed by MIDD (12.8 years) and SIRD (12.0 years).</p><p><strong>Conclusions: </strong>Insulin-deficient subtypes made up a high proportion of individuals with T2D and prediabetes and were associated with higher mortality hazards and excess years of life lost.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1330-1338"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857965","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":"Extended Follow-up of Type 1 Diabetes Immunotherapy Trial Participants Suggests Benign Side Effect Profile.","authors":"Laura M Jacobsen, Dave Cuthbertson, Jamie Felton, Jennifer L Sherr, Kimber M Simmons, Jennifer Hosford, Heba M Ismail, Carla J Greenbaum, Diane K Wherrett, Ashley Pinckney, Srinath Sanda, Linda A DiMeglio, Lauren E Higdon, Carmella Evans-Molina","doi":"10.2337/dc26-0632","DOIUrl":"10.2337/dc26-0632","url":null,"abstract":"<p><strong>Objective: </strong>Long-term side effect surveillance after immunotherapy clinical trial participation in individuals with or at risk of type 1 diabetes is needed.</p><p><strong>Research design and methods: </strong>Participants from 14 randomized controlled trials (47%) joined the Long-term Investigative Follow-up in Type 1 Diabetes TrialNet or Immune Tolerance Network Type 1 Diabetes Extension Study, and 98% answered at least one health-related outcomes question.</p><p><strong>Results: </strong>Participants were observed for a median of 1.78 (interquartile range 0.89-4.04) years after original trial completion and, in some, up to 18 years. There were no differences in the frequency of self-reported health outcomes, including moderate to severe hypoglycemia events, hospitalizations, serious infections (including COVID-19 infection), new allergic reactions, autoimmune disease, and cancer incidence, between those receiving active and placebo therapy (n = 209-473 responses per question; P > 0.05 for all).</p><p><strong>Conclusions: </strong>We observed no differences in self-reported health outcomes between those who received active immunotherapy versus placebo. Continued long-term follow-up of immunotherapy trial participants is essential.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1428-1433"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229731","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":"DiaBetter Together: Outcomes of a Randomized Controlled Trial Evaluating a Peer Mentor Behavioral Intervention for Young Adults With Type 1 Diabetes During the Transfer From Pediatric to Adult Care.","authors":"Marisa E Hilliard, Charles G Minard, Samantha A Carreon, Wendy L Levy, Sarah K Lyons, Randi Streisand, Tricia S Tang, Siripoom V McKay, Sridevi Devaraj, Barbara J Anderson","doi":"10.2337/dc26-0395","DOIUrl":"10.2337/dc26-0395","url":null,"abstract":"<p><strong>Objective: </strong>Transition between pediatric and adult health care is complex, with high risk for loss to follow-up and suboptimal health outcomes for young adults with type 1 diabetes. This trial evaluated the efficacy of DiaBetter Together, a 12-month strengths-based behavioral intervention delivered by trained peer mentors. The intervention aimed to help young adults navigate the transfer process to promote optimal glycemic outcomes, shorten time to adult care follow-up, and improve psychosocial outcomes.</p><p><strong>Research design and methods: </strong>Using a single-site randomized clinical trial design, we compared the 12-month intervention to usual care among n = 100 young adults aged 17-25 years with type 1 diabetes following completion of pediatric diabetes care. Outcomes were measured at baseline and 6 and 12 months. The primary outcome was HbA1c, and secondary outcomes included person-reported psychosocial outcomes, self-management behaviors, and time to adult care.</p><p><strong>Results: </strong>There were no statistically significant differences between study arms in HbA1c, self-management behaviors, or transfer to adult care. Significant differences in diabetes-specific health-related quality of life and diabetes distress between groups at 12 months favored the intervention arm. Intervention satisfaction was high.</p><p><strong>Conclusions: </strong>DiaBetter Together produced modest benefits for psychosocial outcomes during the challenging transfer period, although glycemic, behavioral, and transfer improvements remain difficult to achieve. Reduced sample size due to the coronavirus disease 2019 pandemic may have limited power to detect significant outcomes between groups and impacted outcomes. Peer mentor-based support may be useful to support young adults during transition to adult care, although additional intervention components are likely warranted to improve clinical outcomes.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1357-1365"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148038692","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":"Effect of Finerenone on Albuminuria in Type 1 Diabetes by Baseline HbA1c Level and Diabetes Duration: An Exploratory Analysis of the FINE-ONE Trial.","authors":"Jelle M Beernink, Hiddo J L Heerspink, Andreas L Birkenfeld, David Z I Cherney, Helen M Colhoun, Per-Henrik Groop, Linong Ji, Chantal Mathieu, Sylvia E Rosas, Katherine R Tuttle, Jay S Skyler, Antonio J Amor, M Luiza Caramori, Paolo Fiorina, Niels Jongs, Uberto Pagotto, Emanuela Setola, Meike Brinker, Robert Lawatscheck, Julie Russel, Patrick Schloemer, Janet B McGill, Peter Rossing","doi":"10.2337/dc26-0882","DOIUrl":"10.2337/dc26-0882","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate whether the efficacy and safety of finerenone varied by baseline hemoglobin A1c (HbA1c) level, a proxy of glycemic control, and diabetes duration in people with type 1 diabetes and chronic kidney disease (CKD).</p><p><strong>Research design and methods: </strong>Adults with type 1 diabetes, urinary albumin-to-creatinine ratio (UACR) 200 to <5,000 mg/g, and estimated glomerular filtration rate (eGFR) 25 to <90 mL/min/1.73 m2 were randomly assigned (one to one) to finerenone or placebo. UACR change from baseline over 6 months by baseline HbA1c and diabetes duration was analyzed.</p><p><strong>Results: </strong>Baseline HbA1c was available for 240 of 242 participants; mean (SD) HbA1c, diabetes duration, and eGFR were 7.6% (1.1%; 60 [12] mmol/mol), 32.0 (14.2) years, and 58.9 (19.2) mL/min/1.73 m2, respectively. At 6 months, HbA1c (95% CI) remained unchanged (finerenone +0.03% [-0.14%, 0.20%]; placebo 0.00% [-0.12%, 0.11%]; between-group difference +0.04% [-0.17%, 0.24%]; P = 0.74). Over 6 months, median UACR decreased from 574.6 to 373.5 mg/g with finerenone and from 506.4 to 475.6 mg/g with placebo, corresponding to a -25% placebo-corrected change (95% CI -35%, -13%; P = 0.0001). Treatment effects were consistent across HbA1c tertiles (<7.1%, ≥7.1% to ≤8.1%, and >8.1%), with placebo-corrected UACR changes (95% CIs) of -17% (-40%, 13%), -18% (-39%, 10%), and -37% (-55%, -13%), respectively (P interaction = 0.41). Effects were similarly consistent across diabetes duration tertiles (P interaction = 0.70). Overall safety and incidence of hyperkalemia were similar across HbA1c tertiles.</p><p><strong>Conclusions: </strong>In adults with type 1 diabetes and CKD, finerenone reduced UACR and was well tolerated irrespective of HbA1c level or diabetes duration.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1434-1441"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148207377","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":"To Cluster or Not to Cluster? A Comparison of Approaches to Targeting Type 2 Diabetes Glucose-Lowering Therapy in the TriMaster Crossover Trial.","authors":"Laura M Güdemann, Catherine Angwin, Rury R Holman, Naveed Sattar, Ewan R Pearson, Jacques Murray Leech, Kashyap A Patel, Andrew T Hattersley, John M Dennis, Beverley M Shields, Angus G Jones","doi":"10.2337/dc26-0118","DOIUrl":"10.2337/dc26-0118","url":null,"abstract":"<p><strong>Objective: </strong>Different precision treatment approaches have been proposed for type 2 diabetes, but robust comparisons are lacking. We compared the utility of proposed approaches targeting glucose-lowering therapy in the TriMaster three-way crossover trial.</p><p><strong>Research design and methods: </strong>We evaluated four previously reported precision treatment strategies for their ability to predict overall 4-month HbA1c response and within-person differential response to sitagliptin, canagliflozin, and pioglitazone in 309 adults with type 2 diabetes who received all three medications. Approaches included allocation to clusters based on routine features and HOMA, direct outcome prediction using a routine-features treatment-selection model, type 2 diabetes cluster-specific partitioned polygenic scores (PPSs), and a model based on discriminative dimensionality reduction tree (DDRTree) analysis.</p><p><strong>Results: </strong>The routine-features model and cluster approach were both strongly associated with overall and differential HbA1c responses (P < 0.0001). The routine-features model identified the most effective therapy with significant benefit across all drug comparisons, whereas clinical clusters showed benefit for only one cluster-drug comparison (severe insulin-resistant diabetes: SGLT2i vs. thiazolidinedione [TZD], P = 0.005). DDRTree was not associated with treatment response. Of eight PPSs, only two showed modest association with differential response (lipodystrophy PPS had a greater response to SGLT2 vs. TZD; and β-cell dysfunction, negative proinsulin PPS had a greater response to TZD vs. dipeptidyl peptidase 4 inhibitor). Treatment allocation based on the routine-features model resulted in greater HbA1c reduction than cluster-based allocation (0.27% [95% CI 0.18, 0.35], 2.9 mmol/mol [95% CI 2.0, 3.8] vs. 0.16% [95% CI 0.07, 0.25], 1.7 mmol/mol [95% CI 0.8, 2.7]).</p><p><strong>Conclusions: </strong>Clinical features are more strongly associated with differential glycemic response than PPS, and direct outcome prediction outperforms data-driven subgrouping for optimizing short-term HbA1c reduction.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":"1458-1466"},"PeriodicalIF":16.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148274247","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}