Diabetes, Obesity & Metabolism最新文献

{"title":"The estrous cycle moderates the food and body weight suppressive effects of glucagon-like peptide-1 receptor agonism.","authors":"Sarah V Applebey, Allison G Xiao, Benjamin C Reiner, Matthew R Hayes","doi":"10.1111/dom.70177","DOIUrl":"https://doi.org/10.1111/dom.70177","url":null,"abstract":"<p><strong>Aims: </strong>Emerging data suggest more young women than men are prescribed weight loss pharmacotherapies targeting the glucagon-like peptide-1 receptor (GLP-1R). However, preclinical literature has largely used male animals to characterize the neural mechanisms underlying the weight loss abilities of GLP-1R agonists (GLP-1RAs), highlighting a need for female-specific investigations. Recently, we described data pointing to the female estrous cycle as a possible moderator of GLP-1RA's effects in rats. Expression of brainstem Glp1r and the GLP-1 precursor gene, Gcg, increased during two estrous phases, proestrus and estrus (P/E), compared to males and compared to other phases, metestrus and diestrus (M/D). On this basis, we hypothesized that the weight-reducing effects of GLP-1RAs may be potentiated during P/E.</p><p><strong>Materials and methods: </strong>In separate experiments, we determined whether timing administration of acute liraglutide or chronic semaglutide to either P/E or M/D would moderate food intake and weight loss in female rats maintained on a high fat diet. We also used qPCR to explore estrous cycle-dependent variation in Glp1r within widely distributed nuclei relevant to energy balance control.</p><p><strong>Results: </strong>GLP-1RA administration during P/E, compared to M/D, enhanced the intake-suppressive effects of liraglutide and semaglutide. Moreover, semaglutide administered only during P/E led to greater body weight loss compared to M/D-administered semaglutide. We also observed greater Glp1r expression in P/E compared to M/D in multiple nuclei.</p><p><strong>Conclusions: </strong>GLP-1RAs administered in P/E lead to significantly greater body weight loss via reduction in food intake. Collectively, these data may have translational implications for the timing of GLP-1RA administration across the menstrual cycle.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184382","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":"Risk of depression with GLP-1 receptor agonists use in overweight or obese adults with type 2 diabetes: A new-user, active-comparator cohort study.","authors":"Yu Chang, Ming-Hong Hsieh, Po-Chung Ju, Cheng-Chen Chang","doi":"10.1111/dom.70175","DOIUrl":"https://doi.org/10.1111/dom.70175","url":null,"abstract":"<p><strong>Aims: </strong>The association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and depression remains uncertain due to contradictory evidence. We compared the risk of incident depression between GLP-1 RAs and sodium-glucose cotransporter-2 inhibitors (SGLT2is) in overweight or obese adults with type 2 diabetes.</p><p><strong>Materials and methods: </strong>We conducted a new-user, active-comparator cohort study using a deidentified electronic health record network from January 2016 to July 2024. After 1:1 propensity score matching, we compared 25 704 new GLP-1 RA users to 25 704 SGLT2i users with newly diagnosed type 2 diabetes and overweight/obesity, excluding those with prior mood disorders. The primary outcome was a composite of incident depression diagnosis or antidepressant initiation, assessed from 1 month to 1 year post-initiation using Cox models and time-varying analyses.</p><p><strong>Results: </strong>In 51 408 patients (mean age 56.8 years, 48.9% male), GLP-1 RA use was associated with higher depression incidence versus SGLT2i use (17.0% vs. 14.8%; hazard ratio 1.09, 95% CI 1.04-1.14; p < 0.001), with an absolute risk difference of 2.2%. The association was stronger in adults ≥65 years (HR 1.15) and plateaued after approximately 6 months. In secondary analysis, GLP-1 RA use was associated with a lower rate of all-cause mortality (HR 0.74, 95% CI 0.63-0.88).</p><p><strong>Conclusions: </strong>GLP-1 RA initiation was associated with a statistically significant increase in depression risk compared to SGLT2i use (9% relative increase, 2.2% absolute risk difference over 1 year), particularly during the subacute period and in older adults. This observed association must be balanced against substantial mortality benefits. Enhanced monitoring and shared decision-making are warranted.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184408","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":"Shared and divergent acute cardiovascular risk protein responses to lipid infusion in women with and without PCOS.","authors":"Ebrahim Rajab, Abu Saleh Md Moin, Manjula Nandakumar, Thozhukat Sathyapalan, Alexandra E Butler, Stephen L Atkin","doi":"10.1111/dom.70154","DOIUrl":"https://doi.org/10.1111/dom.70154","url":null,"abstract":"<p><strong>Aims: </strong>Elevated circulating lipids are linked to cardiovascular disease (CVD), especially in insulin-resistant states like polycystic ovary syndrome (PCOS), but their effects on cardiovascular risk proteins (CVRPs) remain unclear. This study used a two-step approach to examine acute cardiovascular proteomic responses to lipid-induced metabolic stress. We first identified proteins altered by lipids and insulin in healthy control (HC) women, then assessed whether these responses were similar or divergent in women with PCOS.</p><p><strong>Methods: </strong>In a randomised cross-over study, 10 healthy controls and 12 women with PCOS underwent 5-h saline (control) or intralipid infusions. After 3 h, a 2-h hyperinsulinemic-euglycemic clamp was initiated. Plasma CVRP expression was assessed at baseline, post-lipid (180 min) and post-clamp (300 min) using SOMAscan proteomics. STRING and pathway enrichment analyses were performed to explore functional associations.</p><p><strong>Results: </strong>In the HC group, lipid infusion altered the expression of 11 out of 54 CVRPs including increases in RANK, IL2RA, TACI, SLAF5 and DCN (p <0.05) and decreases in THPO, BOC, SOD2, FGF23, and AgRP (p <0.05). Most changes reversed with insulin, but BOC, SOD2, MMP12, FGF23, and DCN remained dysregulated. In PCOS, responses mirrored the HC group except for lower AgRP following lipid infusion (p <0.01), and persistent elevation of SLAF5 and DCN following insulin (p <0.05). Enrichment analysis linked altered proteins to immune activation, cell proliferation, and cytokine-receptor signalling.</p><p><strong>Conclusion: </strong>Acute lipid infusion revealed shared and phenotype-specific proteomic responses linked to early vascular stress. In PCOS, persistent dysregulation suggests reduced metabolic adaptability, with exploratory signals that may complement established biomarkers of early cardiovascular risk.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184322","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":"Comparative cardiovascular risk of sulfonylureas with low- and high-affinities for cardiac mitochondrial adenosine triphosphate-sensitive potassium channels versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: A cohort study.","authors":"Mei-Hsiu Chen, Liang-Yu Lin, Tung-Ying Hung, Tzu-Chieh Lin, Chia-Yu Li, Tzu-Han Lin, Yi-Hsuan Chen, Jun-Ting Liou, Meng-Ting Wang","doi":"10.1111/dom.70157","DOIUrl":"https://doi.org/10.1111/dom.70157","url":null,"abstract":"<p><strong>Aims: </strong>To individually evaluate the cardiovascular safety of low- and high-affinity cardiac mitochondrial ATP-sensitive potassium (mitoK_ATP) channel sulfonylureas by comparing each to dipeptidyl peptidase-4 inhibitors (DPP-4i), a generally cardiovascular-neutral comparator, given prior evidence suggesting greater cardiovascular risk with high-affinity agents and the absence of a neutral active comparator.</p><p><strong>Methods: </strong>A new user, active comparator cohort study using propensity score-based inverse probability of treatment weighting was conducted with Taiwan's nationwide claims database (2012-2022). Patients with recent pre-entry cardiovascular events were excluded. The primary outcome was 3-point major adverse cardiovascular events (MACE: ischaemic stroke, myocardial infarction, cardiovascular death); secondary outcomes included each MACE component and all-cause mortality.</p><p><strong>Results: </strong>The study cohort included 466 158, 83 031, and 473 539 new users of low-affinity mitoK_ATP-channel sulfonylureas (gliclazide, glimepiride), high-affinity sulfonylureas (glyburide, glipizide), and DPP-4i, respectively (mean age, 60.2 years; 55.6% male). Compared with DPP-4i, low-affinity sulfonylureas were not associated with increased risks of 3-point MACE (Hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.96-1.06), cardiovascular death (HR, 1.01; 95% CI, 0.93-1.08), or all-cause mortality (HR, 0.97; 95% CI, 0.93-1.01). Conversely, high-affinity sulfonylureas were associated with 1.17-1.31-fold increased risks of 3-point MACE, cardiovascular death, and all-cause mortality.</p><p><strong>Conclusions: </strong>Initiating low-affinity mitoK_ATP-channel sulfonylureas demonstrated cardiovascular safety comparable to DPP-4i, whereas high-affinity sulfonylureas were linked to increased cardiovascular risk and all-cause mortality. These findings suggest low-affinity sulfonylureas are a safer alternative to high-affinity agents and as safe as DPP-4i. They may be appropriate for individuals with diabetes when newer therapies are inaccessible or unnecessary.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184390","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":"Tirzepatide and the 10-year predicted risk of cardiovascular disease and type 2 diabetes in adults with obesity and prediabetes: A post hoc analysis from the three-year SURMOUNT-1 trial.","authors":"Emily R Hankosky, Jeremie Lebrec, Clare J Lee, Georgios K Dimitriadis, Irina Jouravskaya, Adam Stefanski, W Timothy Garvey","doi":"10.1111/dom.70143","DOIUrl":"https://doi.org/10.1111/dom.70143","url":null,"abstract":"<p><strong>Aim: </strong>We assessed the association between tirzepatide and the 10-year predicted risk of developing cardiovascular disease (CVD) and type 2 diabetes (T2D) among three-year SURMOUNT-1 trial participants.</p><p><strong>Materials and methods: </strong>This post hoc analysis applied validated risk engines that predict 10-year CVD (atherosclerotic cardiovascular disease [ASCVD], heart failure [HF], and total CVD) and T2D risk to the three-year SURMOUNT-1 clinical trial data at baseline and 176 weeks. In the trial, participants with obesity and prediabetes at baseline were randomly assigned to once weekly tirzepatide (5/10/15 mg) or placebo for 176 weeks of treatment. Changes in risk scores from baseline to week 176 were compared between tirzepatide and placebo using a mixed model of repeated measures.</p><p><strong>Results: </strong>Tirzepatide treatment was associated with greater reductions in the 10-year predicted risk of CVD and T2D compared with placebo. Mean percent change from baseline to week 176 in predicted ASCVD risk score was greater in tirzepatide-treated groups using the ACC/AHA (5 mg: -4.6%; 10 mg: -7.5%; 15 mg: -9.2%) and PREVENT risk equations (5 mg: -3.7%; 10 mg: -6.3%; 15 mg: -8.8%) versus increased risk in placebo (57.9% and 40.5%, respectively; p < 0.0001 for all). Mean absolute change in T2D risk scores from baseline to week 176 using Cardiometabolic Disease Staging (CMDS) was greater in tirzepatide-treated groups (5 mg: -17.0%; 10 mg: -19.6%; 15 mg: -19.5%) versus placebo (-4.3%, p < 0.0001).</p><p><strong>Conclusion: </strong>Tirzepatide treatment was associated with a reduction in the 10-year predicted risk of both cardiovascular outcomes and T2D in people with obesity and prediabetes.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184401","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":"An interpretable machine learning model for predicting metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes.","authors":"Zhuolin Zhou, Nan Gao, Jiaojiao Liu, Xuerong Ma, Zhijuan Ge, Cheng Ji","doi":"10.1111/dom.70168","DOIUrl":"https://doi.org/10.1111/dom.70168","url":null,"abstract":"<p><strong>Aim: </strong>Patients with type 2 diabetes mellitus (T2DM) exhibit an elevated prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and are at greater risk of liver-related adverse events. Existing non-invasive tools show limited diagnostic performance in this population. This study aims to develop a predictive model that accurately identifies the risk of MASLD among T2DM patients.</p><p><strong>Materials and methods: </strong>Clinical data were collected from T2DM patients hospitalised at Nanjing Drum Tower Hospital between January 2018 and May 2025. Eight machine learning methods were developed to predict the risk of MASLD in T2DM patients. The discriminatory ability of the models was evaluated using area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), accuracy, recall, negative predictive value, positive predictive value, and F1 score. Calibration curves and decision analysis curves were employed to evaluate the calibration and clinical utility. The models were interpreted using the Shapley additive explanations method, and unsupervised clustering was performed to identify potential high-risk subgroups.</p><p><strong>Results: </strong>A total of 3836 T2DM patients constituted the complete dataset, with a MASLD incidence rate of 55.9%. Thirteen feature variables were selected for model construction, and the XGB model achieved optimal overall performance, with an AUROC of 0.873 and an AUPRC of 0.904. Unsupervised clustering identified several high-risk subgroups with distinct metabolic characteristics.</p><p><strong>Conclusion: </strong>The model developed enables reliable and interpretable MASLD risk prediction in T2DM patients based on selected commonly available clinical data, providing a practical tool for routine identification and stratified management.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184327","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":"Plasma sphingolipids predict advanced liver fibrosis development in patients with type 2 diabetes.","authors":"Sarah Béland-Bonenfant, Damien Denimal, Jean-Paul Pais-de-Barros, Hélène Choubley, Alexia Rouland, Isabelle Simoneau, Laurence Duvillard, Ludwig-Serge Aho-Glélé, Benjamin Bouillet, Jean-Michel Petit, Bruno Vergès","doi":"10.1111/dom.70156","DOIUrl":"https://doi.org/10.1111/dom.70156","url":null,"abstract":"<p><strong>Aims: </strong>Patients with type 2 diabetes (T2D) are at an elevated risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD), with a significant likelihood of progression to advanced liver fibrosis (AF)-a stage linked to adverse outcomes. Considering the critical role of lipids in the pathophysiology of MASLD and AF, we aimed to identify lipidomic biomarkers that could predict the development of AF in individuals with T2D.</p><p><strong>Materials and methods: </strong>We included 67 T2D patients, followed for a mean duration of 10.2 ± 3.9 years. We measured baseline plasma concentrations of 148 molecular species of phospholipids, sphingolipids, and free fatty acids. We assessed the development of AF during the follow-up period using liver stiffness measurement (AF if ≥8.0 kPa). Patients who developed ultrasonographic signs of cirrhosis were classified as having AF.</p><p><strong>Results: </strong>AF developed in 14 patients (20.9%) during the follow-up period. Univariate analysis revealed that baseline plasma levels of two sphingolipids among 148 lipid species assessed, namely d18:1/18:0 sphingomyelin and d18:0/20:0 dihydroceramide, were significantly predictive of AF development. Machine-learning multivariate approaches identified baseline plasma levels of d18:0/20:0 dihydroceramide and d18:1/18:0 sphingomyelin as the most predictive variables for AF development, independently of follow-up duration, baseline body mass index, and baseline levels of transaminases, gamma-glutamyl transferase, and the fibrosis-4 index.</p><p><strong>Conclusions: </strong>Baseline levels of two plasma sphingolipid species are independent predictors of AF development in patients with T2D. These findings could help identify T2D patients at elevated risk of adverse hepatic and extrahepatic outcomes, potentially allowing for new targeted therapeutic interventions.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129697","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":"Phase I study of the oral GLP-1 receptor agonist DA-302168S: Safety, pharmacokinetics, and pharmacodynamics in healthy and overweight/obese adults.","authors":"Liang Zheng, Yuanxun Yang, Guangxin Dong, Xiaolong Qin, Wenwen Li, Yuwen Zhang, Haiyan Li, Shaofeng Zhang, Peng He, Qijun Ye, Zhou Yu, Yi Li, Juan Li, Wei Hu","doi":"10.1111/dom.70159","DOIUrl":"https://doi.org/10.1111/dom.70159","url":null,"abstract":"<p><strong>Aim: </strong>This first-in-human Phase I study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DA-302168S, a novel oral small-molecule glucagon-like peptide-1 receptor agonist (GLP-1RA).</p><p><strong>Materials and methods: </strong>The study comprised three parts: a single ascending dose (SAD) phase in healthy adults (Phase Ia; 2.5-50 mg), and two multiple ascending dose (MAD) phases-a 28-day study in healthy adults (Phase Ib) and a 28-day, weekly-titration study in overweight/obese adults (Phase Ic; 7.5-30 mg QD). All parts were randomised, double-blind, and placebo-controlled. Safety and tolerability were the primary endpoints.</p><p><strong>Results: </strong>DA-302168S was generally well tolerated, with gastrointestinal events (primarily nausea) being the most common adverse events. PK profiles were dose proportional with moderate inter-individual variability across SAD and MAD phases. Robust, dose-dependent efficacy was observed in overweight/obese subjects (Phase Ic), with mean weight loss ranging from -5.67% to -7.26%, significantly exceeding placebo (-2.90%). This was accompanied by significant metabolic improvements, including reduced glucose fluctuations, lowered HbA1c, and optimised lipid profiles.</p><p><strong>Conclusions: </strong>DA-302168S demonstrates a favourable safety and PK profile, coupled with substantial, dose-dependent weight loss and metabolic benefits. These results strongly support its continued development as a promising once-daily oral therapy for obesity and type 2 diabetes.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135909","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":"Boosting the engraftment of subcutaneously transplanted pancreatic islets by nanofat.","authors":"Selina Wrublewsky, Caroline Bickelmann, Lea Stefanie Meßmer, Cedric Wilden, Charlotte Berhorst, Leticia Prates-Roma, Bruce Morgan, Sandra Rother, Michael D Menger, Matthias W Laschke, Andrea Weinzierl, Emmanuel Ampofo","doi":"10.1111/dom.70127","DOIUrl":"https://doi.org/10.1111/dom.70127","url":null,"abstract":"<p><strong>Aims: </strong>In the therapy of type 1 diabetes mellitus, the subcutaneous space has been suggested to be a clinically preferable transplantation site for pancreatic islets due to its easy accessibility. However, its poor vascularisation capacity and, thus, challenging environment typically result in islet engraftment failure. In the present proof-of-principle study, we demonstrate that this problem can be overcome by nanofat, an emulsified fat derivative already used in clinical practice.</p><p><strong>Materials and methods: </strong>The cellular composition of nanofat was assessed by immunohistochemistry. The angiogenic activity of the soluble and cellular nanofat fraction was analyzed by an angiogenic protein array, tube formation and spheroid sprouting assays. The viability and endocrine function of islets exposed to the nanofat fractions was investigated by flow cytometry, qRT-PCR and ELISA. In vivo, islets and nanofat were co-transplanted under the kidney capsule as well as into the subcutaneous space of diabetic animals.</p><p><strong>Results: </strong>In a panel of in vitro assays, we showed that the soluble and cellular nanofat fraction improve the viability, hormone release, and angiogenic activity of islets. The beneficial effects of these two fractions were validated in vivo in the murine diabetic kidney capsule model, as indicated by an accelerated restoration of normoglycaemia. The co-transplantation of islets with nanofat resulted in successful islet engraftment within the subcutaneous space of diabetic mice.</p><p><strong>Conclusions: </strong>These findings demonstrate that nanofat markedly boosts the vascularisation and endocrine function of islet grafts. Hence, its co-transplantation with pancreatic islets represents a simple, clinically feasible approach to make the subcutaneous space available for future islet transplantation.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135949","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":"Probiotics and dietary fibre fermented milk supplementation initiated in the first trimester to prevent gestational diabetes mellitus in overweight and obese pregnant women: A randomized controlled trial.","authors":"Lirui Zhang, Jia Wang, Wei Zheng, Xianxian Yuan, Cheng Liu, Yan Xin, Wei Song, Xiaoxin Wang, Shengnan Liang, Lijun Chen, Junying Zhao, Yanpin Liu, Guanghui Li","doi":"10.1111/dom.70158","DOIUrl":"https://doi.org/10.1111/dom.70158","url":null,"abstract":"<p><strong>Aims: </strong>To evaluate the effects of intensive dietary and lifestyle (IDL) interventions and probiotic and dietary fibre fermented milk (PFM) supplementation, initiated in the first trimester, on the risk of gestational diabetes mellitus (GDM) and pregnancy outcomes in overweight and obese women.</p><p><strong>Materials and methods: </strong>In this parallel randomized controlled trial, 478 women with a prepregnancy body mass index ≥25 kg/m², enrolled at 6-12⁺⁶ weeks of gestation, were randomly assigned to IDL, PFM, or standard care (SC) groups. The primary outcome was GDM; secondary outcomes included maternal weight changes, pregnancy outcomes, and gut microbiota profiles assessed by 16S rRNA sequencing.</p><p><strong>Results: </strong>GDM incidence was 25.60% in the IDL group (32/125), 18.42% in the PFM group (21/114), and 33.33% in the SC group (39/117) (p = 0.035). PFM reduced GDM risk by 55% compared with SC (OR = 0.45, 95% CI: 0.25-0.83). At the time of the oral glucose tolerance test (OGTT), median weight gain was lower in the IDL group (4.00 kg) than in the PFM (5.20 kg) and SC (5.65 kg) groups (p = 0.009). Correlation analysis revealed that Acidovorax abundance in PFM was negatively associated with OGTT 0 h glucose, while Megasphaera in the SC group was positively correlated with 2-hour post-load glucose (p < 0.05).</p><p><strong>Conclusions: </strong>PFM supplementation initiated in the first trimester reduced GDM incidence. IDL reduced weight gain but had no significant effect on GDM. PFM may be a promising strategy for GDM prevention in these high-risk populations.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129680","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}