Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy最新文献

{"title":"Elevated Markers of Intestinal Barrier Dysfunction and TLR2 Ligands in Individuals with Type 1 Diabetes.","authors":"Nafeesah Noorwali, Raphaela Staltner, Aleksejs Fedulovs, Jana Schneider, Polina Zalizko, Andris Romašovs, Ina Bergheim, Jeļizaveta Sokolovska","doi":"10.2147/DMSO.S612334","DOIUrl":"10.2147/DMSO.S612334","url":null,"abstract":"<p><p>Studies suggest that alterations of intestinal barrier function and a subsequent increased translocation of bacterial endotoxins may be critical in type 1 diabetes mellitus (T1DM) and may contribute to the proinflammatory state of patients. If Gram-positive derived bacterial toxins are also altered in the setting of T1DM is not yet clarified. In the present study, using a SEAP reporter assay and ELISA, markers of intestinal permeability, concentration of Toll like receptor (TLR) 2 ligands and soluble CD14 (sCD14) were assessed in serum of individuals with T1DM (n=19, m: 10/ f: 9) and age-matched healthy controls (n=18, m: 3/ f: 15) from the LatDiane study. BMI and HbA1c were significantly higher in individuals with T1DM. Serum concentrations of intestinal fatty acid binding protein (I-FABP) were significantly higher in individuals with T1DM than in controls as were concentrations of TLR2 ligands and sCD14 protein. A multivariable linear regression analysis revealed an independent association of T1DM with higher TLR2 ligand levels. Our findings indicate that not only bacterial endotoxin but also TLR2 ligands are elevated in patients with T1DM.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"612334"},"PeriodicalIF":3.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yiqi Huoxue Yangyin Decoction Ameliorates Diabetic Nephropathy by Targeting AMPK/mTOR-Mediated Autophagy: A Network Pharmacology-Guided in vivo and in vitro Study.","authors":"ZhiWei Xu, JinXing He, Yangli Zhang, JianHong Jin, Fei Pan, Ai Mi, XueQian Peng, WenHong Liu, YanFang Yang, Hui Wang","doi":"10.2147/DMSO.S584822","DOIUrl":"10.2147/DMSO.S584822","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the protective effects and underlying mechanisms of Yiqi Huoxue Yangyin Decoction (YHY), a multi-herb formula composed of <i>Astragalus membranaceus</i>, <i>Ligusticum chuanxiong</i>, <i>Pueraria lobata</i>, <i>Rehmannia glutinosa</i>, and <i>Trichosanthes kirilowii</i>, against diabetic nephropathy (DN), focusing on its role in modulating autophagy and attenuating podocyte senescence via the AMPK/mTOR signaling pathway.</p><p><strong>Materials and methods: </strong>Using network pharmacology and UPLC-Q-TOF-MS, this study examined the active constituents and targets of YHY. The type 2 diabetes db/db mouse model (leptin receptor-deficient BKS.Cg-Lepr<db>/+ mice, random blood glucose ≥ 16.7 mmol/L) was used to construct a DN model in vivo. Mice received daily oral gavage of YHY or vehicle for 4 weeks (n=10). YHY's protective benefits were assessed by physiological measurements, serum insulin and HbA1c by ELISA, histopathological evaluation of glomerular and tubular regions, glomerular basement membrane thickness by TEM, and protein expression in renal cortex by immunohistochemistry, immunofluorescence, and Western blot. In vitro, using a high-glucose-induced MPC-5 model, CCK-8, wound healing assays, qRT-PCR, and Western blot were performed (n=3-6) to investigate the mechanisms of YHY.</p><p><strong>Results: </strong>YHY demonstrated significant protective effects against DN. The expression levels of autophagy markers (ULK1, P62, and LC3B) in renal tissue were restored following YHY intervention. Through the AMPK/mTOR pathway, YHY regulated the expression of autophagy-related genes (ULK1, Beclin-1, P62, LC3B, ATG5, ATG7) and senescence-related genes (P21, P53), and improved the survival and migratory capabilities of high-glucose-induced MPC-5 cells. Furthermore, YHY enhanced the expression of podocyte structural proteins, including Nephrin, NPHS2, and SYNPO.</p><p><strong>Conclusion: </strong>YHY treatment was associated with activation of autophagy and attenuation of podocyte senescence, potentially through modulation of the AMPK/mTOR signaling pathway, a finding that requires validation in future mechanistic studies.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"584822"},"PeriodicalIF":3.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 Thyroid Hormone Levels with Diabetic Kidney Disease Among Euthyroid Participants with Type 2 Diabetes Mellitus: A Cross-Sectional Study.","authors":"Ting Lu, Ningyu Cai, Yun Zhao, Ping Feng, Min Feng, Mengdie Chen","doi":"10.2147/DMSO.S618165","DOIUrl":"10.2147/DMSO.S618165","url":null,"abstract":"<p><strong>Purpose: </strong>Thyroid hormones are linked to prognostic outcomes for a range of diseases. The link between thyroid hormone levels and diabetic kidney disease (DKD) risk in euthyroid individuals with type 2 diabetes mellitus (T2DM) was investigated in this study.</p><p><strong>Patients and methods: </strong>Overall, 2945 T2DM cases were enrolled and grouped as with or without DKD. Thyroid hormones were analyzed both as continuous variables and by quartiles. Logistic regression models and smooth curve fitting were applied to assess associations. Stratified analyses and interaction tests were also conducted to examine effect modification.</p><p><strong>Results: </strong>Patients with DKD had significantly decreased free triiodothyronine (FT3) levels compared to those without DKD, while free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were comparable across groups. Relative to the bottom FT3 quartile (Q1), the respective adjusted odds ratios (ORs) for DKD in Q2, Q3, and Q4 were 0.63 (95% CI: 0.50-0.80, p < 0.001), 0.60 (95% CI: 0.47-0.77, p < 0.001), and 0.63 (95% CI: 0.49-0.82, p = 0.001). The relationship between FT3 and DKD followed a nonlinear, L-shaped pattern (p for nonlinearity < 0.001), with a threshold at approximately 3.09 pg/mL. Below this inflection point, an adjusted OR for DKD of 0.622 (95% CI: 0.515-0.751, p < 0.001) was evident. Subgroup analysis suggested that this association was generally consistent across most subsets of study subjects, but was not statistically significant in several strata.</p><p><strong>Conclusion: </strong>Lower FT3 levels are independently linked to greater prevalence of DKD in euthyroid individuals with T2DM. The observed L-shaped association suggests a threshold effect, with 3.09 pg/mL as the approximate inflection point.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"618165"},"PeriodicalIF":3.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13549178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 the Systemic Inflammatory Response Index and Severe Infection in Patients with Diabetic Foot [Letter].","authors":"Qingqing Shan","doi":"10.2147/DMSO.S643299","DOIUrl":"10.2147/DMSO.S643299","url":null,"abstract":"","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"643299"},"PeriodicalIF":3.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6-Gingerol Regulates the Exosomal miR-148b-3p/ACSL4/Ferroptosis Axis in an in vitro Model of Diabetic Retinopathy.","authors":"Shuang Liu, Juan Ye, Long Suo, Tao Xu, Yiyi Chen, Wei Liu","doi":"10.2147/DMSO.S595209","DOIUrl":"10.2147/DMSO.S595209","url":null,"abstract":"<p><strong>Background: </strong>Diabetic retinopathy (DR), a leading cause of blindness, is driven by redox imbalance and ferroptosis in retinal endothelial cells. While 6-Gingerol exhibits antioxidant properties, its role in modulating exosome-mediated redox signaling in DR remains unexplored. This study investigates whether 6-Gingerol protects against DR by regulating ferroptosis via the exosomal miR-148b-3p/ACSL4 axis.</p><p><strong>Methods: </strong>Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) ± 6-Gingerol. Ferroptosis was assessed via lipid ROS, intracellular iron, and key markers (GPX4, ACSL4, FTH1). Exosomal miRNAs were profiled by sequencing, with miR-148b-3p validated as a regulator of ACSL4 through luciferase assays. Functional rescue experiments confirmed pathway specificity.</p><p><strong>Results: </strong>6-Gingerol suppressed HG-induced ferroptosis, reducing lipid ROS by 2.1-fold (P<0.01) and iron accumulation by 1.8-fold (P<0.05), while upregulating GPX4 (3.2-fold, P<0.001). Exosomal miR-148b-3p was downregulated under HG but restored by 6-Gingerol (4.5-fold, P<0.001). miR-148b-3p directly targeted ACSL4, whose knockdown mimicked 6-Gingerol's effects, whereas ACSL4 overexpression or miR-148b-3p inhibition abolished protection.</p><p><strong>Conclusions: </strong>6-Gingerol mitigates DR progression by inhibiting ferroptosis through exosomal miR-148b-3p/ACSL4-dependent redox regulation. These findings unveil a novel crosstalk between exosomal miRNAs and iron metabolism, positioning 6-Gingerol as a potential redox-targeted therapy for DR. Nonetheless, as the data are exclusively obtained from an in vitro model, in vivo validation is essential prior to making any translational inferences.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"595209"},"PeriodicalIF":3.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of Elevated Lipoprotein(a) and Its Association with Cardiovascular Disease in Patients with Overweight and Obesity in Argentina.","authors":"Ezequiel Hernán Forte, Matias Fernando Arrupe, Leonardo Bufi, Sergio Gimenez, Augusto Lavalle Cobo, Maria Gabriela Matta, Juan Patricio Nogueira, Nicolas Federico Renna, Emiliano Salmeri, Laura Schreier, Pablo Corral","doi":"10.2147/DMSO.S613034","DOIUrl":"10.2147/DMSO.S613034","url":null,"abstract":"<p><strong>Background: </strong>Lipoprotein(a) [Lp(a)] is an established independent risk factor for atherosclerotic cardiovascular disease (ASCVD). Although both obesity and elevated Lp(a) are highly prevalent, their interrelationship and combined impact on ischemic heart disease (IHD) remain incompletely understood, particularly in Latin American populations.</p><p><strong>Objective: </strong>To evaluate the distribution of elevated Lp(a) across body mass index (BMI) categories, assess its association with ischemic heart disease (IHD), and determine whether this association differs across BMI categories.</p><p><strong>Methods: </strong>We conducted a multicenter observational study including 2975 adults from specialized centers in Argentina. Patients were stratified into BMI categories: Group 1: <25, Group 2 BMI: 25-29.9, Group 3: 30-34.9 kg/m², with exploratory subgroups ≥35 and ≥40 kg/m². Elevated Lp(a) was defined as >50 mg/dL or >125 nmol/L.</p><p><strong>Results: </strong>Median Lp(a) levels decreased across higher BMI categories. The prevalence of elevated Lp(a) declined across increasing BMI categories (34.6% in BMI <25 kg/m², 29.8% in BMI 25-29.9, 30.1% in BMI ≥30, 26.4% in BMI ≥35 and 24.6% in BMI ≥40). However, after adjustment for demographic and cardiometabolic factors, overweight and obesity were associated with higher odds of elevated Lp(a) compared with normal weight (BMI 25-29.9: OR 1.97, 95% CI 1.38-2.82; BMI ≥30: OR 1.85, 95% CI 1.22-2.81) suggesting that crude prevalence estimates and adjusted associations were influenced by differences in baseline risk profiles across BMI categories. Elevated Lp(a) was independently associated with IHD across all BMI categories, without significant interaction between BMI and Lp(a).</p><p><strong>Conclusions: </strong>In this cross-sectional study, elevated Lp(a) was associated with prevalent ischemic heart disease across BMI categories despite lower crude prevalence among individuals with higher BMI. Because of the observational cross-sectional design, causal inferences cannot be made. Nevertheless, these findings support consideration of Lp(a) assessment across the BMI spectrum.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"613034"},"PeriodicalIF":3.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Effects of Exercise Snacks on Glucose and Lipid Metabolic Outcomes in Individuals with Metabolic Disorders: A Systematic Review and Meta-Analysis.","authors":"Yuxin Peng, Haijun Kong, Qiang Wang, Qingyun Sun, Changxu Qu, Zhengqing Leng","doi":"10.2147/DMSO.S624200","DOIUrl":"10.2147/DMSO.S624200","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To quantify the acute effects of exercise snacks on glucose and lipid metabolism in individuals with metabolic disorders (including those with type 2 diabetes, metabolic syndrome, and overweight or obesity) compared with sedentary behavior and continuous exercise, and to examine their effects across different exercise modalities.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Following the PRISMA 2020 guidelines, four databases (PubMed, Embase, Web of Science, and Scopus) were searched up to February 4, 2026, to identify randomized crossover trials that examined the acute effects of exercise snacks on glucose and lipid metabolism in individuals with metabolic disorders. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and the quality of evidence was assessed using the GRADE approach. The \"meta\" and \"metafor\" packages in R (version 4.5.2) were used to calculate pooled effect estimates (using Hedges' g as the effect size) and to conduct publication bias tests, subgroup analyses, and regression analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The analysis included 20 randomized crossover trials (21 studies) involving 392 participants. Compared with prolonged sedentary behavior, exercise snacks significantly reduced postprandial glucose AUC (Hedges' g = -0.37, 95% CI -0.53 to -0.22, P &lt; 0.01, I&lt;sup&gt;2&lt;/sup&gt; = 6.6%, moderate certainty of evidence) and insulin AUC (Hedges' g = -0.49, 95% CI -0.68 to -0.30, P &lt; 0.01, I&lt;sup&gt;2&lt;/sup&gt; = 15.7%, moderate certainty of evidence), whereas no significant improvement was observed for triglycerides (Hedges' g = -0.014, 95% CI -0.18 to 0.15, P = 0.87, I&lt;sup&gt;2&lt;/sup&gt; = 0.0%, low certainty of evidence). Compared with a single session of continuous exercise, exercise snacks showed no statistically significant differences in postprandial glucose (Hedges' g = -0.14, 95% CI -0.73 to 0.45, P = 0.64, I&lt;sup&gt;2&lt;/sup&gt; = 57.6%, low certainty of evidence), insulin, or triglycerides. The included studies did not provide separate data for individuals with a confirmed diagnosis of MetS; therefore, the subgroup analysis was limited to overweight or obese individuals and those with T2DM. When stratified by study population, exercise snacks significantly reduced the postprandial glucose AUC in overweight or obese individuals (Hedges' g = -0.36, 95% CI: -0.52 to -0.20, P &lt; 0.001), whereas the effect estimate in the T2DM group did not reach statistical significance (Hedges' g = -0.45, 95% CI: -1.47 to 0.56, P = 0.385), and the difference between the two subgroups was not significant (P between subgroups = 0.86). Insulin AUC was significantly reduced in both the overweight or obese group (Hedges' g = -0.42, 95% CI: -0.61 to -0.24, P &lt; 0.001) and the T2DM group (Hedges' g = -1.15, 95% CI: -1.76 to -0.54, P &lt; 0.001), and the difference between subgroups was significant (P = 0.03 between subgroups); however, the estimate for the T2DM subgroup was based on only one study. Regression analysis indicated that older partic","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"624200"},"PeriodicalIF":3.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13547458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 the Triglyceride-Glucose Index and Clinical Outcomes Modified by Diabetes Duration in Patients with Acute Coronary Syndrome and Type 2 Diabetes Mellitus.","authors":"Yixuan Duan, Miaohan Qiu, Weifeng Liu, Di Cao, Yang Li, Haiwei Liu, Kai Xu, Xiaozeng Wang, Jing Li, Yi Li, Yaling Han","doi":"10.2147/DMSO.S613317","DOIUrl":"10.2147/DMSO.S613317","url":null,"abstract":"<p><strong>Background: </strong>An elevated triglyceride-glucose (TyG) index is strongly linked to an increased risk of cardiovascular events in patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (T2DM). However, the potential impact of increasing diabetes duration on the association between the TyG index and cardiovascular risk remains unclear.</p><p><strong>Methods: </strong>Consecutive patients admitted for ACS with T2DM received PCI between March 2016 and March 2020 were enrolled in the analysis. A total of 7093 patients were categorized into tertiles according to the TyG index and T2DM duration. The primary outcome was ischemic events, composed of cardiac death, myocardial infarction, and/or stroke at 5 years. The main secondary outcomes were 5-year cardiac death and all-cause death. Interaction terms and non-linear associations of the TyG index with the clinical outcomes were examined across diabetes durations.</p><p><strong>Results: </strong>Over 5 years, 753 (10.6%) experienced ischemic events, 375 (5.3%) cardiac death, and 636 (9.0%) all-cause death. Higher TyG index and longer diabetes duration independently associated with all outcomes. Compared with the lowest TyG tertile, the highest tertile had adjusted hazard ratios (HRs) of 1.55 (95% CI: 1.29-1.88) for ischemic events and 1.23 (1.10-1.38) for all-cause death. The association between TyG index and ischemic events was strongest in the shortest duration group (HR: 1.43), with significant interaction for ischemic and cardiac death (both p < 0.05).</p><p><strong>Conclusions: </strong>A higher TyG index was independently associated with an increased risk of ischemic events and mortality among patients with ACS and T2DM. This association appeared to be attenuated with longer diabetes duration, suggesting that the prognostic relevance of the TyG index may vary according to the chronicity of diabetes.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"613317"},"PeriodicalIF":3.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Studies on the Effectiveness and Safety of Anti-Obesity Medications: A Scoping Review.","authors":"Irma Melyani Puspitasari, Dimas Setyadi Putra, Alifa Nisa Deliyana, Nurqisthi Iqlima Adiputri, Lily Indriani Octovia, Sekar Ayu Paramita, Rano Kurnia Sinuraya","doi":"10.2147/DMSO.S626279","DOIUrl":"10.2147/DMSO.S626279","url":null,"abstract":"<p><p>Obesity remains a major global public health challenge associated with increased morbidity, mortality, and reduced quality of life, necessitating effective treatment strategies beyond lifestyle modifications. The present scoping review aimed to synthesize recent evidence on the effectiveness and safety of anti-obesity medications (AOMs). A structured literature search was conducted in PubMed and Scopus in May 2025 to identify original studies published within the previous five years involving individuals with overweight or obesity receiving pharmacological interventions. A total of 42 articles representing 41 unique studies, predominantly randomized controlled trials (RCTs), were included in the evidence synthesis. The review encompassed glucagon-like peptide-1 receptor agonists (GLP-1 RA), including semaglutide, liraglutide, exenatide, and orforglipron; multi-receptor incretin agonists, including tirzepatide, retatrutide, and survodutide; amylin-based combination therapy (cagrilintide plus semaglutide); established non-incretin AOMs (orlistat, phentermine, phentermine/topiramate, and naltrexone/bupropion); microbiome-targeted therapies; and nutraceutical-based interventions. Among these, GLP-1 RA consistently demonstrated substantial weight-loss efficacy, with semaglutide achieving approximately 10-16% weight loss, while tirzepatide produced approximately 15-21% weight reduction over treatment durations of 20-70 weeks. Emerging multi-receptor incretin agonists also demonstrated promising efficacy, whereas established non-incretin AOMs, microbiome-targeted therapies, and nutraceutical-based interventions generally produced modest or more heterogeneous outcomes. Gastrointestinal adverse events (AEs) were the most frequently reported across incretin-based therapies. Overall, incretin-based therapies currently provide the greatest weight-loss benefit, although evidence for several emerging pharmacotherapies, microbiome-targeted therapies, and nutraceutical-based interventions remains limited. Further well-designed comparative trials, mechanistic studies, and long-term real-world investigations are needed to better establish the durability, safety, and clinical applicability of emerging AOMs.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"626279"},"PeriodicalIF":3.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiscale Brain Structural Network Reorganization in Diabetic Retinopathy Using Regional Radiomics Similarity Networks.","authors":"Die Hu, Rui-Yang Hu, Yu-Yue Cheng, Fang-Liang Yu, Xin Huang","doi":"10.2147/DMSO.S618259","DOIUrl":"10.2147/DMSO.S618259","url":null,"abstract":"<p><strong>Background: </strong>Diabetic retinopathy (DR), a common microvascular complication of diabetes, is increasingly viewed as a systemic disorder involving the retina-brain axis. Although neuroimaging studies have reported brain abnormalities in DR, large-scale network reorganization and its biological substrates remain unclear.</p><p><strong>Methods: </strong>This cross-sectional study included 47 patients with type 2 diabetes mellitus and non-proliferative diabetic retinopathy (T2DM-NPDR) and 45 matched healthy controls. Structural MRI data were used to construct individualized regional radiomics similarity networks (R2SNs). Group differences in network architecture were examined using multiscale network analysis and gradient mapping. Epicenter mapping identified candidate regions related to network abnormalities. Imaging-transcriptomic analysis based on the Allen Human Brain Atlas, cell-type enrichment analysis, and spatial associations with normative neurotransmitter receptor and transporter maps were performed. Machine learning classifiers and an interpretable graph neural network assessed the discriminative value of R2SN-derived features.</p><p><strong>Results: </strong>Patients with T2DM-NPDR showed widespread cortical and subcortical alterations in R2SN organization. Gradient analysis revealed a systematic shift in macroscale hierarchy, indicating disrupted cortical hierarchical organization. Epicenter mapping highlighted frontal regions, especially the inferior frontal gyrus, middle frontal gyrus, and orbitofrontal cortex, with additional involvement of the insula and parahippocampal gyrus, suggesting abnormalities beyond primary visual pathways and implicating higher-order integrative systems. Imaging-transcriptomic analysis showed that the spatial pattern of R2SN alterations was associated with gene expression profiles enriched in neuronal and glial cell populations. R2SN abnormalities also showed significant spatial correspondence with normative neurotransmitter receptor and transporter maps. Predictive models demonstrated that R2SN-derived features could distinguish patients with T2DM-NPDR from healthy controls.</p><p><strong>Conclusions: </strong>T2DM-NPDR is associated with multiscale structural brain network alterations beyond the visual system. Integrating radiomics-based network modeling, gradient analysis, molecular mapping, and graph-based prediction provides a framework for characterizing brain network disruption and potential biological associations in T2DM-NPDR.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"618259"},"PeriodicalIF":3.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}