Diabetes, Obesity & Metabolism最新文献

{"title":"Protective effect of metformin against dementia in patients with obesity: Results from a global federated health network analysis","authors":"Yu-Liang Lin MD,&nbsp;Yi-Jui Hung MD,&nbsp;Jin-Hua Chen PhD,&nbsp;Jia-Ying Sung MD,&nbsp;Min-Huei Hsu MD,&nbsp;Hoang Khanh Dinh MD,&nbsp;Kee-Hsin Chen PhD,&nbsp;Chiehfeng Chen MD","doi":"10.1111/dom.16647","DOIUrl":"10.1111/dom.16647","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Metformin, a first-line medication for Type 2 diabetes (T2D), has been suggested to reduce dementia risk. We investigated whether metformin use was associated with lower long-term incidence of dementia and all-cause mortality in obese patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We analysed electronic health record data from the TriNetX network. Patients were categorised into four body mass index (BMI) groups (25–29.9, 30–34.9, 35–39.9 and over 40). In each group, those prescribed metformin were compared with matched controls who were not prescribed metformin, using propensity score matching. Kaplan–Meier survival analysis was used to estimate dementia incidence and all-cause mortality over a 10-year follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The matched cohorts included 132 920 (BMI 25–29.9), 142 723 (30–34.9), 94 402 (35–39.9) and 82 732 (over 40) patients per group. After 10 years of follow-up, metformin users exhibited significantly lower risks of both dementia and all-cause mortality compared to controls. Specifically, the hazard ratios for dementia across each BMI group were 0.875 (95% confidence interval [CI]: 0.848–0.904), 0.917 (0.885–0.951), 0.878 (0.834–0.924) and 0.891 (0.834–0.953), respectively. For all-cause mortality, the corresponding hazard ratios were 0.719 (0.701–0.737), 0.727 (0.708–0.746), 0.717 (0.694–0.741) and 0.743 (0.717–0.771).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this large, multi-centre cohort study, metformin use was associated with reduced risks of dementia and all-cause mortality in obese patients. The protective effect was observed across all BMI groups, with variations noted by population. These findings support the potential of metformin in lowering dementia risk in patients with obesity. Further studies are needed to explore the underlying mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 10","pages":"5899-5909"},"PeriodicalIF":5.7,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digitally enhanced ketogenic diet versus low-fat diet for cardio-renal-metabolic health in a predominantly Hispanic adult population with overweight or obesity: Pilot randomised clinical trial.","authors":"Yan Du, Jing Wang, Shiyu Li, Christiane Meireles, Afaf Saliba, Alondra Castillo, Martin Goros, Johnathan Gelfond, Byeong Yeob Choi, Lu Qi, Chengdong Li, Kumar Sharma","doi":"10.1111/dom.70000","DOIUrl":"https://doi.org/10.1111/dom.70000","url":null,"abstract":"<p><strong>Aims: </strong>Individuals respond differently to diets for weight loss and cardio-renal-metabolic health. Advances in digital health and metabolomics hold promise for personalised lifestyle interventions. The study evaluated the feasibility and the preliminary efficacy of a digitally enhanced ketogenic diet compared with a low-fat diet, and explored the potential to use metabolites to guide personalised lifestyle interventions via digital health tools.</p><p><strong>Materials and methods: </strong>The study randomised 60 adults living with overweight or obesity to a ketogenic diet (n = 30) or a low-fat diet (n = 30). Both groups received digital lifestyle interventions, including digitally delivered education sessions, mobile and wearable devices to monitor lifestyle behaviour and health indicators, and weekly individualised feedback through digital communication platforms. Clinical outcomes (e.g., weight, blood pressure (BP), HbA1c) and targeted metabolites were collected at baseline, 3 and 6 months. Intention-to-treat analysis and linear mixed models were used to assess group and time differences.</p><p><strong>Results: </strong>The study successfully enrolled the planned sample size (N = 60) within 1 year despite COVID-19-related challenges. Retention rates were 73.3% at 3 months and 71.7% at 6 months. Participants were 58.3% Hispanic. No significant differences in clinical or metabolic outcomes were observed between the groups, except that the ketogenic group had significantly higher ketone levels than the low-fat group at 3 months (b = 0.2, 95% CI = [0.05, 0.35], p = 0.015). Both groups showed significant weight and Body Mass Index reductions at 3 and 6 months. HbA1c improved only in the ketogenic group (baseline: 6.0 ± 0.9%; 3-month: 5.5 ± 0.7%, p < 0.001; 6-month: 5.7 ± 0.8%, p = 0.004), and systolic blood pressure (BP) improved in the ketogenic group at 3 months (131.2 ± 12.9 to 123.1 ± 11.2, p = 0.006). Most targeted metabolites (e.g., isoleucine, leucine) decreased significantly from baseline to 3- (~21/29 metabolites) and 6-month (~22/29 metabolites) within both groups.</p><p><strong>Conclusions: </strong>Digitally enhanced lifestyle intervention was feasible. Both diets, enhanced by digital tools, were efficacious in weight reduction. The ketogenic diet showed potential benefits for glycaemic and BP control. Metabolite changes reflect sensitive responses to lifestyle interventions. Further research is warranted to explore the integration of digital tools and metabolic data for developing personalised lifestyle interventions.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of CT-868, a novel, fully biased, dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonist, in type 2 diabetes: A double-blind, randomized placebo controlled phase 2 trial.","authors":"Manu V Chakravarthy, Michael A Elliott, Luis Acosta, Gabriele E Sonnenberg, Damian Bialonczyk, Jingtao Wu, Federico A Argüelles-Tello, Raymundo Garcia-Reza, José Gerardo González-González, Stig K Hansen, Juan P Frias","doi":"10.1111/dom.70006","DOIUrl":"https://doi.org/10.1111/dom.70006","url":null,"abstract":"<p><strong>Aims: </strong>To assess the glycaemic efficacy and safety of CT-868, a cAMP signal-biased, dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonist, in participants with type 2 diabetes (T2D).</p><p><strong>Materials and methods: </strong>This 26-week (W), phase 2, randomized, double-blind placebo-controlled trial enrolled adults with T2D, Body Mass Index ≥27 kg/m², and glycated haemoglobin (HbA1c) 7.0-10.0%. Participants were randomized (1:2:1) to once-daily CT-868 1.75 mg, 4.0 mg, or placebo. Due to COVID-19-related CT-868 supply constraints, some participants randomized to 4.0 mg received 3.25 mg maximum and were analysed as a separate dose arm. The primary endpoint was change from baseline in HbA1c at W26. Secondary endpoints included changes from baseline to W26 in fasting glucose, 7-point self-monitored blood glucose (SMBG), body weight, lipids and the occurrence of adverse events (AEs).</p><p><strong>Results: </strong>Overall, 103 participants were enrolled (CT-868 1.75 mg, n = 26; 3.25 mg, n = 18; 4.0 mg, n = 32; placebo, n = 27). Clinically meaningful and statistically significant improvements in HbA1c were observed with CT-868 at W26 (-1.61 to -2.24%-points vs. placebo; all p < 0.001). Body weight was modestly reduced with CT-868 4.0 mg at W26 (-2.9% vs. placebo, p < 0.001). CT-868 improved fasting glucose, SMBG, and most lipid parameters vs. placebo. AEs were mostly mild/moderate. No participants experienced hypoglycaemia.</p><p><strong>Conclusions: </strong>CT-868 1.75 to 4.0 mg yielded robust, clinically meaningful decreases in HbA1c, supporting potent glycaemic-lowering effects and improved key lipid parameters in participants with overweight/obesity and T2D, despite modest weight loss. CT-868 was well tolerated, supporting future investigation of higher doses to maximize weight loss.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world titration, persistence & weight loss of semaglutide and tirzepatide in an academic obesity clinic.","authors":"Jason M Samuels, Fei Ye, Rebecca Irlmeier, Heidi Silver, Gitanjali Srivastava, Matthew Spann","doi":"10.1111/dom.70004","DOIUrl":"https://doi.org/10.1111/dom.70004","url":null,"abstract":"<p><strong>Aims: </strong>Trials of the Glucagon-like Peptide-1 Receptor Agonists (GLP1RAs) found mean weight losses of 15%-21%, yet realworld dose titration and persistence remain suboptimal, limiting effectiveness. This study aims to determine real-world titration, persistence and effectiveness of GLP1RAs in patients managed within a multidisciplinary obesity clinic.</p><p><strong>Materials and methods: </strong>This is a singlecentre, retrospective cohort study of patients seen in a multidisciplinary obesity clinic at an academic medical centre from January 2022 to December 2024. Consecutive patients aged 18-75 years enrolled in a 'no cost to patient' Medical Weight Loss Bundle program who received ≥1 prescription fill of semaglutide or tirzepatide. Of 2855 enrollees, 2306 (81%) received at least one GLP1RA prescription. The primary outcome was persistence with GLP1RA therapy (continuous prescription fills without a gap ≥84 days). Secondary measures included titration adherence and percentage change in body weight.</p><p><strong>Results: </strong>Among 2306 patients (median age 46.0 years, Interquartile Ratio [IQR] 38.0-55.0; 85% female; 68% White, 28% Black, 4% Hispanic), with median persistence 10.7 months (IQR 5.4-16.3). Semaglutide was used by 1614 (70%), tirzepatide by 117 (5%), and both agents by 575 (25%). Of semaglutide users, 81% escalated to ≥1 mg and 23% to 2.4 mg; of tirzepatide users, 75% received ≥10 mg and 28% received 15 mg. Among patients persistent for ≥6 months, median weight loss was 9.4% (IQR 6.0%-13.4%); for those persistent for ≥12 months, median weight loss was 14.4% (IQR 9.5%-20.5%).</p><p><strong>Conclusions: </strong>GLP1RA persistence and dosetitration adherence were moderate but weight loss approximated that seen in clinical trials, supporting real-world effectiveness.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iodine uptake variability as a predictive biomarker for radioiodine therapy outcomes in Graves Disease: Validation through multi-time-point RAIU assessment in a 1249-patient cohort","authors":"Yifan Li MMed,&nbsp;Meiwen He PhD,&nbsp;Zilong Hu MMed,&nbsp;Hongjun Tian MMed,&nbsp;Qiming Liu MMed,&nbsp;Sijie Yu MMed,&nbsp;Renming Li PhD,&nbsp;Nina Liu PhD,&nbsp;Limeng Pan PhD,&nbsp;Wenbin Wang PhD,&nbsp;Tianrong Pan PhD","doi":"10.1111/dom.16638","DOIUrl":"10.1111/dom.16638","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate the impact of iodine uptake variability (IUV) as a predictive biomarker associated with Graves Disease (GD) on the success rate of radioiodine (RAI) therapy for GD within 36 months, and discover IUV indicators for predicting GD prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This retrospective study included patients with GD who underwent RAI therapy at the Second Affiliated Hospital of Anhui Medical University between October 2012 and October 2022. Spearman correlation and maximal information coefficient analyses were used, along with hierarchical clustering and Kaplan–Meier survival analysis. Logistic and Cox regression were performed, and receiver operating characteristic curves and random sampling were used for validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study comprised 1249 patients (333 males (26.66%) and 916 females (73.34%)). After a 3-year follow-up, there were 1014 (81.18%) and 235 (18.82%) cases in the success and failure groups, respectively. IUV was an independent factor for GD prognosis under RAI treatment. RAIU-Range/Max was recommended as a representative indicator for IUV, with a clinical threshold of 28.8%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this study, we proposed and defined IUV as a predictive biomarker for GD, and verified its impact on the prognosis of GD treated with RAI. Low IUV was associated with a poor clinical prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 10","pages":"5831-5843"},"PeriodicalIF":5.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous glucose monitoring in noninsulin-treated type 2 diabetes: A critical review of reported trials with an updated systematic review and meta-analysis of randomised controlled trials.","authors":"Ronnie Aronson, Alexander Abitbol, Harpreet S Bajaj, Alice Y Y Cheng, Stavroula Christopoulos, Stewart B Harris, Akshay B Jain, Ronald M Goldenberg","doi":"10.1111/dom.70008","DOIUrl":"https://doi.org/10.1111/dom.70008","url":null,"abstract":"<p><strong>Aims: </strong>We aimed to review the observational and randomised clinical trial evidence and provide pragmatic recommendations for using continuous glucose monitoring (CGM) in individuals living with noninsulin-treated type 2 diabetes (T2DM).</p><p><strong>Materials and methods: </strong>We first undertook a narrative review of observational studies that enrolled noninsulin-users or mixed populations of noninsulin and insulin-users with T2DM as well as randomised controlled trials (RCTs) that enrolled mixed populations with T2DM. We then performed a systematic review of the RCTs that specifically enrolled noninsulin-treated populations with T2DM and compared CGM to BGM/usual care. A meta-analysis of glycaemic outcomes was conducted with predefined subgroups based on CGM type.</p><p><strong>Results: </strong>RCTs in mixed populations and observational studies demonstrated a largely consistent benefit of CGM on glycaemic and nonglycaemic outcomes with cost effectiveness and reduced healthcare resource utilisation. The meta-analysis of RCTs in noninsulin users included 8 studies encompassing 541 participants, among whom 297 (55%) were assigned to the CGM group. CGM was associated with significantly reduced HbA1c (weighted mean difference [WMD] -0.37%; 95% CI -0.49, -0.24; p < 0.00001; I² = 0%), increased % time in range (WMD 8.84; 95% CI 4.62, 13.06; p < 0.0001; I² = 0%) and lower % time above range (WMD -8.14; 95% CI -12.66, -3.63; p = 0.0004; I² = 0%). There were no significant subgroup differences.</p><p><strong>Conclusions: </strong>CGM use in noninsulin-treated individuals living with T2DM was associated with improved glycaemic outcomes and patient experience, reduced health care resource utilisation, and acceptable cost-effectiveness. These findings provide additional evidence to support CGM use among people living with T2DM who are not using insulin therapy.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucagon-like peptide-1 receptor agonists and the risk of nonarteritic anterior ischaemic optic neuropathy: A systematic review and meta-analysis of observational studies.","authors":"Ronald M Goldenberg, Ronnie Aronson, Jill Trinacty","doi":"10.1111/dom.70013","DOIUrl":"https://doi.org/10.1111/dom.70013","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium-glucose co-transporter 2 inhibitors reduce the intravitreal anti-VEGF treatment necessity in eyes with early diabetic macular oedema: A post-hoc analysis focusing on the fellow eye of the COMET trial","authors":"Tomoaki Tatsumi PhD,&nbsp;Yoko Takatsuna PhD,&nbsp;Ryoichi Ishibashi PhD,&nbsp;Masaya Koshizaka PhD,&nbsp;Tomomi Kaiho PhD,&nbsp;Toshiyuki Oshitari PhD,&nbsp;Yuki Shiko PhD,&nbsp;Noriko Asaumi MD,&nbsp;Shuichi Yamamoto PhD,&nbsp;Koutaro Yokote PhD,&nbsp;Takayuki Baba PhD","doi":"10.1111/dom.16636","DOIUrl":"10.1111/dom.16636","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to determine the efficacy of oral administration of sodium-glucose co-transporter 2 inhibitors (SGLT2i) therapy for early diabetic macular oedema (DMO).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We conducted a post-hoc analysis of the COMET trial, a prospective, randomized, parallel, investigator-driven protocol. Sixty patients with DMO eligible for anti-vascular endothelial growth factor (VEGF) therapy were randomized to receive either the SGLT2i luseogliflozin or sulfonylurea (SU) glimepiride. Intravitreal ranibizumab (IVR) injections were administered per protocol to both eyes over 48 weeks. For this analysis, we included eyes with no or mild macular oedema at baseline and excluded those that had received treatment within a defined period prior to enrolment. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and the number of IVR injections were compared between the SGLT2i and SU groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At baseline, 20 eyes in the SU group and 22 eyes in the SGLT2i group did not require IVR. Changes in BCVA and CRT did not differ significantly between the groups. IVR was required in 9 of 20 eyes in the SU group versus 2 of 22 eyes in the SGLT2i group. The rate of the first IVR was significantly lower in the SGLT2i group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Systemic SGLT2i therapy reduced the need for intravitreal anti-VEGF treatment in eyes with early and mild DMO. These results suggest that SGLT2i may be effective in preventing the progression of early and mild DMO.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 10","pages":"5812-5821"},"PeriodicalIF":5.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of β-cell identity in human islets treated with glibenclamide","authors":"Claudia Fernández PhD,&nbsp;Montserrat Nacher PhD,&nbsp;Kevin Rivera MSc,&nbsp;Sandra Marín-Cañas PhD,&nbsp;Maria Sorribas MD,&nbsp;Gabriel Moreno-González MD,&nbsp;Elisabet Estil·les PhD,&nbsp;Patricia San José MD,&nbsp;Noèlia Téllez PhD,&nbsp;Eduard Montanya MD","doi":"10.1111/dom.16632","DOIUrl":"10.1111/dom.16632","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Loss of β-cell identity can contribute to the reduction of functional β-cell mass in type 2 diabetes. Sulfonylureas show shorter durability of antihyperglycaemic action and higher rates of secondary failure compared to other antihyperglycaemic agents, suggesting that they could accelerate the decline of β-cell functional mass in type 2 diabetes. We aimed to investigate the impact of chronic exposure to sulfonylureas on β-cell identity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Islets from human multi-organ donors were cultured for 4–7 days at 5.6 mM glucose with or without glibenclamide. β-cell function (glucose stimulated insulin secretion, GSIS), apoptosis (TUNEL) and gene (RT-qPCR) and protein expression (immunofluorescence, genetic β-cell tracing and Western Blot) were determined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Human islets exposed to glibenclamide showed increased insulin secretion at low glucose, reduced GSIS, increased apoptosis, endoplasmic reticulum (ER) stress, and loss of β-cell identity indicated by reduced gene and protein expression of key β-cell identity markers and insulin. There were no changes in the expression of disallowed or progenitor-related genes. Genetic β-cell tracing showed a similar percentage of insulin-expressing cells in control and sulfonylurea-treated islets. Addition of the chemical chaperone 4-phenylbutyrate (PBA) to the culture medium prevented glibenclamide-induced ER stress and the downregulation of key β-cell transcription factors, indicating that ER stress mediates, at least partially, the negative effects of glibenclamide on β-cell identity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Chronic exposure of human islets to glibenclamide induced the loss of β-cell identity, which was mediated by ER stress, impaired β-cell function, and increased β-cell apoptosis. These negative effects of glibenclamide may contribute to the secondary failure of sulfonylureas and accelerate the decline of functional β-cell mass in patients with type 2 diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 10","pages":"5782-5792"},"PeriodicalIF":5.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://dom-pubs.onlinelibrary.wiley.com/doi/epdf/10.1111/dom.16632","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between sodium-glucose cotransporter 2 inhibitor use and clinical outcomes in patients with type 2 diabetes after urinary tract infection.","authors":"Hsiao-Wei Wang, Ming-Hsien Tsai, Yu-Wei Fang, Kuo-Cheng Lu, Joshua Wang, Chien-Lin Lu","doi":"10.1111/dom.70003","DOIUrl":"https://doi.org/10.1111/dom.70003","url":null,"abstract":"<p><strong>Aims: </strong>To evaluate whether initiating sodium-glucose cotransporter 2 inhibitors (SGLT2i) within 3 months after a urinary tract infection (UTI) is associated with improved long-term outcomes in patients with type 2 diabetes mellitus (T2DM), compared with dipeptidyl peptidase-4 inhibitors (DPP-4i).</p><p><strong>Materials and methods: </strong>A retrospective cohort study was conducted using the TriNetX US Collaborative Network (2016-2023). Adults with T2DM who initiated SGLT2i or DPP-4i within 90 days after a UTI or pyelonephritis diagnosis were identified. Propensity score matching (1:1) was applied to balance baseline covariates. The primary outcome was mortality. Secondary outcomes included major adverse kidney events (MAKE), major adverse cardiovascular events (MACE), hospitalisation, dialysis dependence, emergency department (ED) visits, and sepsis. Outcomes were assessed over a 4-year period using Cox proportional hazards models and Kaplan-Meier analysis.</p><p><strong>Results: </strong>After matching, 2129 patients were included in each group. Compared with DPP-4i, SGLT2i use was associated with lower risks of mortality (HR 0.59, 95% CI 0.45-0.77), MAKE (HR 0.78), hospitalisation (HR 0.89), dialysis dependence (HR 0.43), sepsis (HR 0.75), and ED visits (HR 0.88). No significant difference was found for MACE (HR 0.91, 95% CI 0.79-1.04).</p><p><strong>Conclusions: </strong>In patients with T2DM recovering from UTI, the use of SGLT2 inhibitors was associated with lower risks of mortality, kidney complications, and infection-related outcomes compared with DPP-4 inhibitors. These findings support the safety and clinical benefit of continuing or initiating SGLT2i during the post-infectious phase, even after a recent urinary tract infection.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}