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

{"title":"The Central Role of Lipid Metabolism Disorders in Diabetes Mellitus: Mechanisms, Clinical Manifestations, and Emerging Therapeutic Strategies.","authors":"Qiang Yang, Xueting Liu, Tianyi Zhang, Xu Zhao, Xiaohe Xiao","doi":"10.2147/DMSO.S591764","DOIUrl":"https://doi.org/10.2147/DMSO.S591764","url":null,"abstract":"<p><p>Diabetes mellitus, as a metabolic disease, is characterized by dual metabolic disorders of glucose and lipids. Effective prevention and control of the progression of diabetes is the key to its treatment. Dyslipidemia in Diabetes is not merely a simple increase in lipid levels; it also involves the disordered coordination of multiple lipoprotein systems and molecular pathways, serving as both a driver and accelerator for diabetes. Lipid metabolism disorders directly magnify the harm of hyperglycemia, especially for the cardiovascular and cerebrovascular systems, and are one of the core pathological links of diabetes. Mechanisms involve multiple interactions such as insulin resistance and enhanced lipolysis, increased lipid synthesis and modification induced by hyperglycemia, oxidative stress and inflammatory responses, and hormonal and signaling pathway imbalances. Lipid metabolism disorders not only accelerate large vessel lesions such as atherosclerosis, but also promote microvascular damage (such as nephropathy and retinopathy) through lipotoxicity. This article systematically reviews the mechanisms, clinical features, and management strategies of dyslipidemia in diabetes, with a particular focus on lipid metabolism pathways (e.g, cholesterol synthesis) and the therapeutic potential of novel drugs targeting the gut microbiota or inflammation. The primary objective is to provide a detailed analysis of the metabolic mechanisms in diabetes, using lipid metabolism as a framework, and to offer new perspectives for the treatment and prognosis of the disease.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"591764"},"PeriodicalIF":3.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13094772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765316","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":"Ambulatory Systolic Blood Pressure and Carotid Atherosclerosis in Type 2 Diabetes: A Critical Role of Glycemic Control Stratification.","authors":"Hui Liu, Qidong Zheng, Hengjing Wu, Jing Wu","doi":"10.2147/DMSO.S588463","DOIUrl":"10.2147/DMSO.S588463","url":null,"abstract":"<p><strong>Background: </strong>Ambulatory blood pressure monitoring (ABPM) is widely used in diabetes for cardiovascular risk assessment, but its link to early atherosclerosis, such as carotid plaques, is less clear.</p><p><strong>Aim: </strong>To assess associations between ABPM parameters and carotid plaques in type 2 diabetes by HbA1c level.</p><p><strong>Methods: </strong>This was a cross-sectional observational analysis conducted among patients with type 2 diabetes mellitus from the MMC platform.We analyzed 498 patients with 24-hour ABPM and carotid ultrasound, stratified by HbA1c (<5.7%, 5.7-6.4%, >6.4%). Logistic regression examined associations, with sensitivity and subgroup analyses.Model was adjusted for potential confounders including age, sex, BMI, history of hypertension, smoking, alcohol consumption, marital status, and educational attainment.</p><p><strong>Results: </strong>Carotid plaque prevalence was 46.6%. After covariate adjustment, elevated systolic BP (SBP) was significantly associated with plaques only in HbA1c ≥6.4%: 24-hour SBP ≥130 mmHg (OR=2.14, 95% CI: 1.30-3.56), awake SBP ≥135 mmHg (OR=1.87, 95% CI: 1.14-3.11), and asleep SBP ≥120 mmHg (OR=1.78, 95% CI: 1.08-2.95). No significant associations were observed for diastolic BP or in lower HbA1c groups. Findings were consistent across sensitivity and subgroup analyses.</p><p><strong>Conclusion: </strong>In poorly controlled diabetes, elevated SBP by ABPM is independently associated with carotid plaques, supporting combined ABPM and HbA1c assessment for early vascular risk detection.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"588463"},"PeriodicalIF":3.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721982","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":"Early Pregnancy Triglyceride to HDL-C Ratio Predicts Gestational Diabetes Mellitus and Neonatal Hypoglycemia: A Retrospective Cohort Study.","authors":"Lingxiang Jiang, Hui Shao, Xiujuan Wang, Junjiang Wu, Fen Dong","doi":"10.2147/DMSO.S590161","DOIUrl":"10.2147/DMSO.S590161","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the independent association between the early pregnancy triglyceride to high density lipoprotein cholesterol (TG/HDL-C) ratio and the risks of gestational diabetes mellitus (GDM) and neonatal hypoglycemia (NH), with a focus on its dose-response relationship and mediating pathways.</p><p><strong>Methods: </strong>This retrospective cohort study included 17,056 women with singleton pregnancies who were registered and delivered at our hospital. Early pregnancy fasting lipid profiles were collected, and the TG/HDL-C ratio was calculated. Propensity score matching (PSM) was applied to balance baseline characteristics. Logistic regression, restricted cubic spline models, and mediation analysis were employed to assess associations, nonlinear relationships, and potential mediating pathways. Subgroup analyses were conducted to explore effect heterogeneity across populations with different clinical features.</p><p><strong>Results: </strong>After PSM, balanced cohorts were obtained (10,131 cases for GDM analysis and 2,123 cases for NH analysis). A significant dose-response relationship was observed between increasing TG/HDL-C ratio quartiles and GDM risk. In the fully adjusted model after matching, the adjusted odds ratios (aORs) for Q2-Q4 were 1.20, 1.44, and 1.69, respectively (all P < 0.05). A nonlinear relationship was identified, with a threshold inflection point at 2.91; below this value, the risk increased more steeply. In contrast, the TG/HDL-C ratio was associated with NH only at the highest quartile (Q4: aOR = 1.39, P < 0.05), with no clear dose-response trend. Mediation analysis revealed that 11.14% of the effect of the TG/HDL-C ratio on NH was mediated through GDM, while the mediating effect of GH was minimal (1.41%).</p><p><strong>Conclusion: </strong>An elevated TG/HDL-C ratio in early pregnancy is an independent risk factor for GDM, demonstrating a significant dose-response relationship with a nonlinear threshold. The inflection point of 2.91 may serve as a practical reference for early risk stratification. The association with NH is modest and partially mediated through GDM. Monitoring the TG/HDL-C ratio at the initial prenatal visit may facilitate early identification of high-risk individuals, enabling targeted interventions to reduce GDM incidence and potentially lower the risk of neonatal hypoglycemia through improved GDM management.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"590161"},"PeriodicalIF":3.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721996","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":"Peripapillary Retinal and Choroidal Vasculature in Patients with Diabetes of Different Durations without Clinical Diabetic Retinopathy.","authors":"Ming Yan, Wen-Jing Zhang, Cong Chen, Zhen Huang, Ya Ye, Dong-Qiang Xu, Yu-Meng Deng, Yan-Ping Song","doi":"10.2147/DMSO.S563069","DOIUrl":"https://doi.org/10.2147/DMSO.S563069","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study is to quantitatively assess peripapillary retinal and choroidal vasculature using swept-source optical coherence tomography angiography (SS-OCTA) in patients with diabetes mellitus (DM) across different disease durations but without clinical signs of diabetic retinopathy (DR).</p><p><strong>Methods: </strong>This was a single-center, cross-sectional study conducted at General Hospital of Central Theater Command from April to September 2023. A total of 211 subjects were enrolled and categorized into four groups: non-diabetic controls (88 eyes), DM duration <5 years (135 eyes), 5-10 years (87 eyes), and ≥10 years (92 eyes). SS-OCTA was used to assess peripapillary retinal nerve fiber layer (pRNFL) thickness, ganglion cell-inner plexiform layer (pGCL-IPL) thickness, superficial capillary plexus vascular density (SCP pVD), and choroidal parameters. Linear regression analysis identified factors associated with SCP pVD.</p><p><strong>Results: </strong>Compared with the control group, peripapillary SCP pVD in the diabetic group was significantly lower (33.56 ± 2.87% vs 31.39 ± 3.77%, p < 0.05). This decrease was significantly correlated with diabetes duration (B = -0.205, p < 0.001). A progressive reduction in pRNFL thickness was observed with increasing disease duration, which reached statistical significance. Differences in macular ganglion cell-inner plexiform layer (mGCL-IPL) thickness were identified across the DM groups. Peripapillary choroidal vascularity index (CVI) was significantly lower in all DM groups compared with controls. Furthermore, SCP pVD was independently associated with diabetes duration, pRNFL thickness, peripapillary choroidal thickness, and the presence of hypertension.</p><p><strong>Conclusion: </strong>SS-OCTA can detect early progressive damage to peripapillary microvasculature and choroid in DM patients without clinical DR. These parameters (including SCP pVD, pRNFL thickness, mGCL-IPL thickness, and peripapillary CVI) may serve as early biomarkers for preclinical DR, providing a scientific basis for early screening and targeted intervention to delay the progression of diabetic retinopathy.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"563069"},"PeriodicalIF":3.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13075506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688802","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":"Determinants of Liver Steatosis Progression in Chinese Children: A Prospective Cohort Study.","authors":"Yueju Wang, Cai Tang, Peiye Yang, Xiaowei Zheng, Lihong Zhu, Haoyang Zhang, Le Zhang, Qingqing Zheng","doi":"10.2147/DMSO.S594442","DOIUrl":"https://doi.org/10.2147/DMSO.S594442","url":null,"abstract":"<p><strong>Background: </strong>Liver steatosis in children can be non-invasively assessed by the controlled attenuation parameter (CAP) derived from transient elastography. This study aimed to identify determinants of longitudinal changes in liver steatosis in a Chinese pediatric population.</p><p><strong>Methods: </strong>We established a prospective cohort in Wuxi, China, to investigate risk factors of fatty liver among school-aged children. A total of 1498 children aged 6 to 13 years were enrolled in 2023 and 1195 children completed follow-up assessments in 2024. Biomarkers based on blood, urine, and body composition were measured. The progression of liver steatosis was evaluated using CAP values. Regression analyses were conducted identify determinants of both longitudinal changes in CAP and the progression of liver steatosis.</p><p><strong>Results: </strong>The average CAP of the participants in 2023 was 193.5 dB/m, and in 2024 it was 189.0 dB/m. During the one-year follow-up period, 68 children developed new liver steatosis. Regression analyses revealed 10 biomarkers significantly associated with changes in CAP, which were further categorized into two distinct clusters characterized primarily by metabolic and inflammatory processes. Additionally, the ratio of neutrophils to albumin constituted a separate subgroup. For liver steatosis progression, stepwise logistic regression identified four independent determinants: sex, BMI z-score, lymphocyte count, and trunk body fat mass, and demonstrated good discriminatory power (AUC = 0.80).</p><p><strong>Conclusion: </strong>Several inflammatory and body composition markers were significantly associated with the progression of liver steatosis in Chinese children. These findings underscore the roles of inflammation and fat distribution in the early development of fatty liver disease, which may inform screening strategies for school-aged children.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"594442"},"PeriodicalIF":3.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13075419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688809","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":"The Diabetes Staging System (DSS): A Pilot Study Assessing Feasibility, Provider Engagement and Implementation Challenges of a Novel Staging System for Type 2 Diabetes.","authors":"Moahad S Dar, Junhong Zhang, Anna Ashline, Swetha Kota, Sandra Woolson, Nadya T Majette, Hayden B Bosworth","doi":"10.2147/DMSO.S556175","DOIUrl":"https://doi.org/10.2147/DMSO.S556175","url":null,"abstract":"<p><strong>Introduction and objective: </strong>Type 2 diabetes (DM2) currently lacks a standardized staging system that can be used to predict survival and guide providers towards guideline concordant care much like TNM staging does for cancer. We conducted a pilot study to assess the feasibility, provider engagement and implementation challenges of the DSS and examined if guideline concordant care improved especially SGLT2i/GLP-1a use in Veterans DM2 patients with cardiorenal disease.</p><p><strong>Methods: </strong>A 6-month pilot study implemented DSS in VA primary care clinics between December 2023-September 2024. Study visits were at baseline and 6 months. Primary outcome: the initiation of SGLT2i/GLP-1a in Veteran DM2 patients with CVD/CKD compared to baseline. Secondary outcomes: weight, blood pressure, hemoglobin A1C, glomerular filtration rate (GFR), and medication adherence compared to baseline. Inclusion criteria: Male or female Veterans between the ages of 18-75 years with DM2 and ≥1 CV event and/or CKD and not on SGLT2i/GLP-1a. Exclusion criteria: Veterans with contraindications to SGLT2i/GLP-1 and/or a serious mental health disorder.</p><p><strong>Results: </strong>After baseline visit, all providers prescribed to 14/14 patients at least one of the medications with 12/14 prescribed SGLT2i and 2/14 prescribed GLP-1a. We found 13/14 (93%) patients to still be on at least one of the medications at 6 months. At 6 months compared to baseline, weight (216 lbs. ± 41 → 213 lbs. ± 39), blood pressure (141/76 ± 20/10 → 132/73 ± 17/10), A1C (7.7% ± 1.5% → 7.4% ± 0.8%) modestly decreased but GFR remained stable (64 mL/min ± 17 → 64 mL/min ± 19). Medication adherence was continued for all 13 patients (Medication possession ratio was ≥80%).</p><p><strong>Conclusion: </strong>DSS use was associated with increased SGLT2i/GLP-1a prescribing by VA primary care providers and medication adherence in Veterans DM2 patients with CVD/CKD. The DSS could help improve cardiorenal outcomes and guideline concordant in their DM2 patients in the future if larger studies can validate these findings.</p><p><strong>Clinical trials registration number: </strong>NCT06142006.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"556175"},"PeriodicalIF":3.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13075421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688732","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":"Gender-Specific Predictive Utility of Twelve Anthropometric Indices for Metabolic Syndrome in Chinese Lahu Adults with Dyslipidemia.","authors":"Jie Chen, Weichang Guo, Hejia Yin, Huifang Li","doi":"10.2147/DMSO.S593804","DOIUrl":"https://doi.org/10.2147/DMSO.S593804","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the gender-specific predictive performance of 12 anthropometric indices for metabolic syndrome (MetS) among Lahu ethnic adults with dyslipidemia.</p><p><strong>Methods: </strong>This cross-sectional study employed stratified cluster sampling in two Lahu communities in southwest China. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) criteria. Twelve indices were assessed: body mass index (BMI), waist circumference (WC), lipid accumulation product (LAP), visceral adiposity index (VAI), a body shape index (ABSI), body adiposity index (BAI), body roundness index (BRI), relative fat mass (RFM), uric acid-to-HDL-C ratio (UHR), triglyceride-glucose index (TyG), cardiometabolic index (CMI), and Chinese visceral adiposity index (CVAI). Receiver operating characteristic (ROC) curve analysis evaluated predictive performance, and binary logistic regression assessed associations with MetS and its components.</p><p><strong>Results: </strong>This study of 1257 Lahu adults with dyslipidemia (48.5% male) revealed a 23.4% MetS prevalence, significantly higher in females (29.2% vs 17.2%, p<0.001). The TyG index emerged as the strongest MetS predictor in both sexes (AUC: males 0.828, females 0.784), followed by CMI, VAI, LAP and CVAI with moderate predictive ability (AUC range: 0.678-0.779). Other indices showed limited predictive value, while ABSI was not significant. For MetS components, BRI showed strong associations with elevated BP in both genders (males: 1.666[1.228-2.261]; females: 1.804[1.388-2.344]) and with elevated TG (1.644[1.248-2.166]) in males. Female‑specific associations included VAI with reduced HDL‑C, and BMI/CVAI with elevated FPG.</p><p><strong>Conclusion: </strong>Among dyslipidemic Lahu adults, all indices except ABSI demonstrated predictive efficacy for MetS, with the TyG index outperforming all others. These simple, low-cost indices could be applied for early MetS screening or risk stratification in this population, particularly in rural or resource-limited settings. Notably, gender-specific differences should be considered in clinical applications.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"593804"},"PeriodicalIF":3.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13075508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688814","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":"Metabolic Syndrome Modifies Changes in Body Composition After Sleeve Gastrectomy: A Quantitative CT Study.","authors":"Rui-Jia Yan, Chao Zhang, Min-Hong Wang, Yun-Feng Zhou, Juan Wang","doi":"10.2147/DMSO.S591808","DOIUrl":"https://doi.org/10.2147/DMSO.S591808","url":null,"abstract":"<p><strong>Objective: </strong>To investigate changes in body mass index (BMI), body composition, and laboratory indicators in obese patients with different metabolic status after laparoscopic sleeve gastrectomy (LSG).</p><p><strong>Methods: </strong>This prospective study included 52 obese patients who underwent LSG. Clinical and quantitative CT-based body composition data were collected preoperatively and at the 12-month follow-up. Patients were categorized into metabolic syndrome (MS) and non-MS groups. Changes in BMI, body composition, and laboratory indicators after LSG were compared between groups, and the correlations between body composition and clinical indicators-at both baseline and postoperatively-were analyzed, stratified by MS status.</p><p><strong>Results: </strong>Among 52 obese patients undergoing LSG, 24 (46%) had MS. All patients exhibited significant postoperative improvements in body weight, laboratory parameters, and body composition. The postoperative visceral fat area showed the greatest improvement ratio [non-MS: 0.62 (0.48, 0.70); MS: 0.60 (0.49, 0.67)] among abdominal fat compartments compared to preoperative levels, while liver fat (LF) demonstrated the most marked improvement [non-MS: 0.53 (0.24, 0.60); MS: 0.55 (0.28, 0.66)] among ectopic fat deposits. However, reductions in BMI (P = 0.036) and postvertebral muscle fat content (P = 0.041) were greater in the non-MS group. At the 12-month follow-up, changes in LF positively correlated with changes in blood glucose (r = 0.414, P = 0.044) in the MS group, whereas changes in BMI correlated with changes in triglyceride (r = 0.427, P = 0.023) and low-density lipoprotein (r = 0.480, P = 0.01) in the non-MS group.</p><p><strong>Conclusion: </strong>LSG significantly improves body composition and metabolic parameters in obese patients. The correlations between body composition and laboratory indicators, both at baseline and in their postoperative changes, differed according to metabolic status. These findings suggest that a comprehensive assessment of body composition and metabolic markers in patients undergoing bariatric surgery enables targeted interventions against the key risk factors associated with distinct metabolic phenotypes.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"591808"},"PeriodicalIF":3.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13075503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688769","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":"Sleeve Gastrectomy Alters Exosomal miR-497-5p Cargo to Ameliorate Metabolic Dysfunction-Associated Steatotic Liver by Targeting GABARAPL1.","authors":"Zenghui Li, Chenxu Tian, Mengqin Wang, Zhehong Li, Liang Wang, Zheng Wang, Chengyuan Yu, Dezhong Wang, Dongbo Lian, Nengwei Zhang","doi":"10.2147/DMSO.S568182","DOIUrl":"https://doi.org/10.2147/DMSO.S568182","url":null,"abstract":"<p><strong>Background: </strong>Obesity is strongly associated with metabolic dysfunction and steatotic liver disease (MASLD). Laparoscopic sleeve gastrectomy (LSG) effectively addresses severe obesity and its metabolic complications. Recent studies suggest that exosomes and their microRNA (miRNA) content mediate systemic metabolic improvements following bariatric surgery.</p><p><strong>Objective: </strong>This study aims to characterize plasma exosomal miRNAs before and after LSG, identify functional candidates linked to MASLD remission, and validate underlying mechanisms in vitro.</p><p><strong>Methods: </strong>Plasma exosomes from control subjects, as well as pre- and post-LSG patients, were isolated via ultracentrifugation, characterized, and subjected to high-throughput miRNA sequencing. Differential expression analysis, weighted gene co-expression network analysis, and random forest modeling were used to identify key miRNAs. Predicted targets, based on multi-database consensus, were integrated with paired liver transcriptomes from GEO (GSE106737, GSE83452). miRNA-target interactions were confirmed through dual-luciferase assays. In a free fatty acid-induced HepG2 MASLD model, miRNA mimics/inhibitors were employed to evaluate lipid accumulation (Oil Red O, intracellular triacylglycerol/total cholesterol) and target expression (qRT-PCR, Western blot).</p><p><strong>Results: </strong>LSG significantly altered circulating exosomal miRNA profiles. Six key miRNAs were identified, with miR-497-5p being the most prominent. Integrative analysis revealed GABARAPL1 as a direct target of miR-497-5p, and its upregulation in post-LSG liver tissues. Luciferase assays confirmed miR-497-5p binding to the GABARAPL1 3'UTR. In HepG2 cells, inhibition of miR-497-5p reduced lipid droplet formation and intracellular triacylglycerol/total cholesterol levels, while overexpression exacerbated steatosis. Inhibition also led to increased GABARAPL1 mRNA and protein levels.</p><p><strong>Conclusion: </strong>LSG induces significant remodeling of the circulating exosomal miRNA profile. Specifically, the downregulation of exosomal miR-497-5p post-LSG appears to alleviate hepatic lipid accumulation by derepressing its target, GABARAPL1, a key regulator of lipophagy. miR-497-5p is thus a potential biomarker and therapeutic target.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"568182"},"PeriodicalIF":3.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13075427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688734","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":"Real-World Effectiveness and Safety of Tirzepatide, Semaglutide, and Liraglutide in Adults with Overweight or Obesity without Diabetes: A Comparative Study.","authors":"Serap Cetiner","doi":"10.2147/DMSO.S594898","DOIUrl":"https://doi.org/10.2147/DMSO.S594898","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a chronic metabolic disease associated with substantial cardiometabolic risk and long-term morbidity. Although randomized controlled trials have demonstrated the efficacy of incretin-based therapies, real-world comparative data in adults with overweight or obesity without diabetes remain limited. Real-world studies provide complementary evidence by capturing treatment effectiveness, tolerability, dose escalation, and adherence in routine clinical practice.</p><p><strong>Methods: </strong>This single-center, retrospective, real-world observational study was conducted at a private internal medicine clinic in Istanbul, Turkey, using electronic medical records of consecutively treated patients between September 2023 and September 2024. Adults aged 18-75 years with overweight or obesity without diabetes who received liraglutide, semaglutide, or tirzepatide for at least 36 weeks were included. Treatment allocation was based on routine clinical decision-making. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). The primary outcome was percent change in body weight from baseline to week 36. Secondary outcomes included changes in waist circumference, lipid profile, liver enzymes, pancreatic enzymes, HbA1c, insulin resistance, and adverse events. Between-group comparisons were performed using appropriate parametric or non-parametric tests and multivariable models. Baseline hepatic steatosis was assessed by ultrasonography. Lipid-lowering therapies were recorded and considered in analyses. Adverse events were systematically collected during follow-up; mild elevations in amylase and lipase were defined as ≤3 times the upper limit of normal.</p><p><strong>Results: </strong>All three treatments were associated with significant reductions in body weight and waist circumference at week 36 (p < 0.01). Weight loss was greater in the tirzepatide group compared with the liraglutide and semaglutide groups. Improvements in lipid parameters were observed across all groups, with greater triglyceride reduction in the tirzepatide group. Liver enzyme levels improved similarly between groups. Gastrointestinal adverse events were common, particularly with liraglutide, and no clinically confirmed pancreatitis was observed.</p><p><strong>Conclusion: </strong>In this real-world cohort, liraglutide, semaglutide, and tirzepatide were effective and generally well tolerated in adults with overweight or obesity without diabetes. Tirzepatide was associated with greater weight loss; however, these findings are observational and hypothesis-generating, supporting the need for prospective or randomized comparative studies.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"594898"},"PeriodicalIF":3.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622022","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}