Diabetology & Metabolic Syndrome最新文献

{"title":"Comparison of CTI and its modified indices in predicting cardiovascular disease risk across different glycemic statuses: a nationwide prospective cohort study.","authors":"Xinjiang Dong, Beibei Wang, Jiefu Yang, Tong Zou","doi":"10.1186/s13098-026-02169-1","DOIUrl":"10.1186/s13098-026-02169-1","url":null,"abstract":"<p><strong>Background: </strong>The C-reactive protein-triglyceride glucose index (CTI) has emerged as a promising composite biomarker for cardiovascular disease (CVD) risk. However, whether incorporating obesity-related metrics such as waist circumference (WC), body mass index (BMI), or waist-to-height ratio (WHtR) into CTI to form modified indices such as CTI-WC, CTI-BMI, and CTI-WHtR improves predictive performance remains uncertain. The performance of these modified indices requires validation in large-scale prospective cohorts stratified by glycemic status.</p><p><strong>Methods: </strong>This study used data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2020, involving 7,579 participants aged ≥ 45 years. Multivariate Cox regression and restricted cubic splines (RCSs) analyses were used to assess the associations of the CTI and its modified indices with CVD risk. To compare the predictive performance, time-dependent Harrell's C-indices, integrated discrimination improvement and net reclassification index were utilized. Weighted quantile sum (WQS) regression was used to evaluate component contributions.</p><p><strong>Results: </strong>During a mean follow-up of 8.28 years, 1,871 (24.69%) participants experienced their first CVD event. The CTI and its modified indices were effective in predicting CVD incidence in the general population. RCS analysis revealed positive linear dose-response relationships between these indices and CVD risk in the general population, which persisted in both normal glucose regulation (NGR) and prediabetes mellitus (Pre-DM) patients. WQS regression analysis revealed that, in the general population, TG contributed the most to CVD risk in the CTI, while WC, BMI, and WHtR had greater weights in their modified indices. In the general population, all modified CTI indices demonstrated superior predictive ability than did the original CTI (C-index: CTI-WC 0.619, CTI-WHtR 0.616, CTI-BMI 0.614, and CTI 0.612). In the population with NGR, Pre-DM, and DM, the predictive capability of CTI-WC is superior to that of the original CTI, with its C-index being greater across all these populations.</p><p><strong>Conclusions: </strong>The CTI and its modified indices are effective in predicting CVD risk in the general population. The modified CTI indices, especially the CTI-WC, show superior predictive ability across different glycemic statuses. These findings suggest that incorporating obesity-related metrics into the CTI may enhance its utility for CVD risk prediction.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419552","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":"Integrating untargeted metabolomics and machine learning to reveal an aberration of sphingolipid metabolism in cardiometabolic HFpEF.","authors":"Xinxin Mao, Lu Zhao, Pengfei Liu, Yajiao Wang, Shuqing Shi, Qingqiao Song","doi":"10.1186/s13098-026-02237-6","DOIUrl":"10.1186/s13098-026-02237-6","url":null,"abstract":"<p><strong>Background: </strong>Cardiometabolic heart failure with preserved ejection fraction (HFpEF) is a high-risk phenotype primarily driven by metabolic syndrome, with a significantly increased incidence and risk of adverse outcomes. A fundamental reason for this is the lack of early clinical diagnosis. As a tool capable of accurately capturing pathophysiological states, metabolomics provides a critical entry point for addressing this issue; however, studies focusing on the metabolic characteristics of this population remain limited.</p><p><strong>Methods: </strong>This study integrated a clinical cohort and untargeted metabolomics to compare serum metabolic profiles between patients with cardiometabolic HFpEF and those with metabolic syndrome (MetS). Baseline characteristics were balanced using propensity score matching (PSM). Differential metabolites were identified by untargeted metabolomics, followed by KEGG pathway enrichment analysis. Machine-learning approaches were further applied to screen candidate metabolites with potential diagnostic efficacy, and weighted gene co-expression network analysis (WGCNA) together with SHapley Additive exPlanations (SHAP) were used to evaluate phenotype association and feature contribution. In an independent clinical cohort, total sphingomyelin (SM) levels were assessed by ELISA as an external evaluation strategy based on clinical applicability.</p><p><strong>Results: </strong>Differential metabolites between the two groups were mainly enriched in sphingolipid metabolism and glycerophospholipid metabolism pathways. Through multi-method screening, C24:1 Sphingomyelin was identified as a candidate metabolite with potential diagnostic efficacy. The co-expression module containing C24:1 Sphingomyelin was significantly correlated with NT-proBNP, a key biomarker of heart failure, and SHAP analysis indicated that C24:1 Sphingomyelin contributed substantially to the classification model. In the external cohort, total SM levels were associated with disease status, suggesting the potential clinical association of sphingolipid-related signals.</p><p><strong>Conclusion: </strong>This study preliminarily characterized the metabolic features distinguishing cardiometabolic HFpEF from MetS alone, suggesting that sphingolipid dysregulation is associated with the development and progression of this phenotype. Among the identified metabolites, C24:1 Sphingomyelin was identified as a candidate metabolite with potential diagnostic performance, and SM showed potential clinical applicability. These findings provide new clues for biomarker discovery and preliminary clinical translational exploration in cardiometabolic HFpEF.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419568","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 diabetes and elevated circulating advanced oxidation protein products: a comprehensive systematic review and meta-analysis.","authors":"Muhammad Shahid Iqbal, Mohd Faiyaz Khan, Sadaf Farooqui, Muhammad Zahid Iqbal, Salah-Ud-Din Khan, Nazia Khan, Vidya Devanathadesikan Seshadri, Amr Ali Mohamed Abdelgawwad El-Sehrawy","doi":"10.1186/s13098-026-02228-7","DOIUrl":"10.1186/s13098-026-02228-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Oxidative stress is a central feature of the metabolic disturbances observed in diabetes, often leading to cellular and molecular damage. Advanced oxidation protein products (AOPPs), formed during oxidative modification of plasma proteins, have been proposed as biomarkers of systemic oxidative stress. Despite increasing interest, the relationship between these markers and diabetes remains inconclusive. This study aimed to systematically evaluate and quantify differences in circulating AOPPs levels in diabetes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A systematic review and meta-analysis was performed in accordance with PRISMA guidelines. Searches were conducted across PubMed, Scopus, Embase and Web of Science databases up to March 2025 to identify relevant observational studies involving adults aged 18 years or older. Studies were included if they reported circulating levels of AOPPs in individuals with type 1 diabetes (T1DM), type 2 diabetes (T2DM), or impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), compared to non-diabetic controls. Data extraction and quality assessment were conducted independently by two reviewers, and a random-effects model was used for meta-analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Sixteen eligible articles with twenty individual studies were identified, encompassing diverse populations and diabetes subtypes. The meta-analysis demonstrated significantly elevated circulating AOPPs in both T&lt;sub&gt;1&lt;/sub&gt;DM (WMD ≈ 17.5 µmol/L) and T&lt;sub&gt;2&lt;/sub&gt;DM (WMD ≈ 24.68 µmol/L) compared with controls, though heterogeneity was high. Subgroup analyses confirmed the consistent direction of effect, with stronger associations in younger populations, studies with higher baseline AOPPs, and certain designs or regions. Meta-regression showed that examined moderators (continent, study design, baseline AOPPs, age, sample size, gender, study quality, presence of overweight/ obesity, hypertension, smoking and abnormal serum lipids) explained little to none of the variability. Sensitivity analyses indicated that results were robust. Publication bias assessment revealed funnel plot asymmetry for type 2 diabetes, but trim-and-fill analysis did not materially alter the pooled estimates, supporting the stability of the findings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Elevated levels of AOPPs appear to be associated with diabetes, supporting the role of oxidative stress in its pathophysiology. Although pooled analyses demonstrated significantly higher circulating AOPP concentrations in patients with diabetes mellitus, substantial between-study heterogeneity and wide prediction intervals suggest that the magnitude and consistency of this association may vary across different populations and study settings. Also, the observational design of included studies limits the strength and generalizability of the pooled estimates. Therefore, causal inferences cannot be drawn, and further well-designed prospective research is wa","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13355358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419597","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":"Continuous glucose monitoring use is associated with higher physical activity in adults with type 1 diabetes: a nationwide cross-sectional study.","authors":"Jurga Šuminienė, Rimantas Stukas, Virginija Gaigalaite, Natalja Istomina","doi":"10.1186/s13098-026-02238-5","DOIUrl":"https://doi.org/10.1186/s13098-026-02238-5","url":null,"abstract":"<p><strong>Background: </strong>Physical activity is a key component of type 1 diabetes (T1D) management, yet many adults do not achieve recommended activity levels. Continuous glucose monitoring (CGM) may reduce glycemic uncertainty during exercise; however, its association with real-world physical activity remains unclear.</p><p><strong>Objective: </strong>To examine whether CGM use is independently associated with physical activity and to identify psychological factors related to perceived exercise facilitation among CGM users.</p><p><strong>Methods: </strong>In this nationwide cross-sectional study, 368 adults with self-reported T1D in Lithuania (197 CGM users and 171 non-users) completed the International Physical Activity Questionnaire-Short Form (IPAQ-SF). Multivariable linear and logistic regression models adjusted for demographic and clinical covariates were used to evaluate associations between CGM use and physical activity outcomes. Among CGM users, logistic regression was applied to identify factors associated with perceived facilitation of physical activity.</p><p><strong>Results: </strong>CGM users reported higher total physical activity (median 427.5 vs. 270 min/week, p = 0.001) and were more likely to engage in any moderate-to-vigorous physical activity (adjusted OR 4.4, 95% CI 2.2-8.0, p = 0.001) and to achieve ≥ 600 MET-min/week (adjusted OR 2.2, 95% CI 1.2-4.5, p = 0.035). Associations remained significant after adjustment for acute and chronic diabetes-related complications. Among CGM users, trust in CGM accuracy during exercise was strongly associated with perceived facilitation (adjusted OR 9.2, 95% CI 2.2-23.0, p = 0.008), whereas higher emotional diabetes-related distress was inversely associated (adjusted OR 0.65, 95% CI 0.44-0.90, p = 0.04).</p><p><strong>Conclusions: </strong>CGM use was independently associated with higher physical activity levels in adults with T1D. Psychological factors, particularly technology-related trust and emotional distress, may contribute to differences in perceived exercise facilitation among CGM users. These findings should be interpreted as associative rather than causal.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between hs-CRP-triglyceride glucose index and coronary plaque morphology: insights from optical coherence tomography.","authors":"Hongying Yao, Qianyun Guo, Qian Ma, Yujing Cheng, Xuezhi Chen, Yujie Zhou","doi":"10.1186/s13098-026-02227-8","DOIUrl":"10.1186/s13098-026-02227-8","url":null,"abstract":"<p><strong>Background: </strong>Accumulating evidence has underscored that coronary plaque morphology is the key determinant of acute cardiovascular events. The high-sensitivity C-reactive protein-triglyceride-glucose index (CTI) has been shown to correlate strongly with cardiovascular events and mortality. However, no previous study has investigated the relationship between CTI and detailed plaque morphological features evaluated using in vivo optical coherence tomography (OCT).</p><p><strong>Methods: </strong>In this retrospective cross-sectional study, 444 patients with coronary artery disease (CAD) who underwent OCT prior to percutaneous coronary intervention (PCI) were analyzed. The association between CTI and plaque morphology was examined employing multivariable logistic regression models. Stratified analyses according to clinical presentation (stable angina pectoris [SAP] vs. acute coronary syndrome [ACS]) and tests for interaction were further performed. Receiver operating characteristic (ROC) curve analysis was used to assess the discriminative ability of CTI for identifying vulnerable plaques.</p><p><strong>Results: </strong>The study revealed that participants divided into CTI quartiles exhibited a steadily rising prevalence of macrophage accumulation and healed plaque. Compared with the low CTI groups (Q1 and Q2), the incidences of cholesterol crystals and multiple healed plaques (≥ 2) were significantly higher in the high CTI groups (Q3 and Q4) (cholesterol crystals: 35.1% and 24.3% vs. 18.9% and 13.5%; multiple healed plaques: 18.9% vs. 12.6%). After accounting for the effects of different covariates, analyzing CTI as a continuous variable revealed a significant link to healed plaque (OR = 1.62, 95%CI:1.21-2.16, P = 0.001), cholesterol crystals (OR = 1.64, 95%CI:1.17-2.30, P = 0.004), macrophage accumulation (OR = 1.49, 95%CI:1.13-1.98, P = 0.005), and plaque rupture (OR = 1.54, 95%CI:1.07-2.21, P = 0.019). The statistically significant association persisted when CTI was split into quartiles. Notably, stratified analyses revealed that these significant associations were only present in patients with ACS. The RCS analysis demonstrated a linear association between CTI and various lipid plaque-related parameters. The area under the ROC curve (AUC) demonstrated that CTI exhibited a stronger correlation with plaque vulnerability compared with other single factors.</p><p><strong>Conclusion: </strong>In patients with ACS, elevated CTI is linked to an increased risk of healed plaque and vulnerable plaques. There is a linear relationship between CTI and various lipid plaque-related parameters. As a single factor, CTI provides a superior discriminative capacity for vulnerable plaque.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410629","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":"Sex/race categories, social determinants, and cardiovascular events in Brazilian adults with diabetes: a longitudinal analysis from ELSA-Brasil.","authors":"Leonardo Fonseca Maia, Ane Karoline Medina Néri, Simon Ds Fraser, Rosa Malena Fagundes Xavier, Maria Teresita Del Niño Jesus Fernandez Bendicho, Jamile Costa Cerqueira, Maria da Conceição Chagas de Almeida, Antonio Augusto Ferreira Carioca, Sandhi Barreto, Antonio Alberto Lopes, Sheila Maria Alvim de Matos, Geraldo Bezerra da Silva Junior","doi":"10.1186/s13098-026-02234-9","DOIUrl":"10.1186/s13098-026-02234-9","url":null,"abstract":"<p><strong>Background: </strong>Social determinants of health influence both the development of diabetes and its complications. However, evidence on how combined sex/race categories relate to cardiovascular risk among individuals with diabetes remains limited, particularly in middle-income countries.</p><p><strong>Objectives: </strong>To investigate whether combined categories of sex and self-reported race/skin color are associated with incident cardiovascular events in Brazilian adults with diabetes.</p><p><strong>Methods: </strong>This prospective cohort study included adults with diabetes and no prior cardiovascular disease at baseline (2008-2010) from ELSA-Brasil. Participants were followed through subsequent study waves. The primary outcome was incident major cardiovascular events. The main exposure was a cross-classified sex/race variable (White men, Black men, White women, and Black women). Cox proportional hazards models were fitted using a hierarchical strategy, from minimally adjusted models to models additionally including socioeconomic and clinical variables. Variables such as HbA1c, hypertension, obesity, diabetes duration, chronic kidney disease, and albuminuria were considered potential downstream factors and were therefore interpreted cautiously.</p><p><strong>Results: </strong>During follow-up, incident cardiovascular events were observed. In minimally adjusted analyses, differences across combined sex/race groups were observed but were attenuated after adjustment for socioeconomic and clinical factors. Lower educational attainment, longer diabetes duration, higher HbA1c, hypertension, and kidney disease markers were more consistently associated with cardiovascular events than the sex/race categories themselves.</p><p><strong>Conclusions: </strong>In this ELSA-Brasil cohort of adults with diabetes, combined sex/race categories were not statistically associated with incident cardiovascular events after accounting for measured socioeconomic and clinical variables. These findings should not be interpreted as evidence that intersectional or structural inequalities are unimportant; rather, they suggest that measurable socioeconomic and cardiometabolic pathways may partly explain the observed disparities. Limited event numbers, possible overadjustment, and the absence of direct measures of racism, discrimination, and healthcare barriers should be considered when interpreting the results.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410547","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":"A putative SGLT-relevant mechanistic perspective on quercetin-3-O-glucoside and rutin in diabetic kidney disease.","authors":"Dante Saksono Harbuwono, Yulia Wardhani, Edwin Hadinata, Siti Nur Rohmah, Adha Fauzi Hendrawan, Ade Meidian Ambari, Metalia Puspitasari, Danny Pratama Kuswadi, Pringgodigdo Nugroho, Eka Ginanjar, Raymond Rubianto Tjandrawinata, Fahrul Nurkolis","doi":"10.1186/s13098-026-02233-w","DOIUrl":"10.1186/s13098-026-02233-w","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) is escalating worldwide and remains difficult to control durably, in part because progressive β-cell dysfunction undermines many therapies and because long-term management must balance efficacy, safety, and affordability. Recent decades have shown that targeting sodium-glucose cotransporters (SGLTs) especially renal SGLT2 can reduce glucose levels independently of insulin and, crucially, deliver cardio-renal benefits that extend beyond glycaemic control. Yet, despite the clinical success of synthetic \"gliflozins\", gaps remain, adverse events, incomplete inhibition of renal glucose reabsorption, and limited access in some health systems.</p><p><strong>Methods: </strong>This review focuses on two quercetin glycosides quercetin-3-O-glucoside (isoquercitrin) and quercetin-3-O-rutinoside (rutin) as potential SGLT-focused modulators. This study employed a narrative mechanistic review approach integrating published experimental evidence, physicochemical structure-activity relationship (SAR) analysis, and exploratory molecular docking to examine potential SGLT-related interactions and complementary glucose-regulatory pathways of Q3G and rutin.</p><p><strong>Results: </strong>We synthesise mechanistic evidence suggesting that Q3G and rutin may modulate SGLT-related pathways through intestinal SGLT1 interaction, regulation of renal SGLT2 expression, and complementary glucose-regulatory mechanisms. However, direct inhibition of human SGLT2 transport activity has not yet been experimentally demonstrated, and current evidence predominantly may indicate indirect pathway modulation rather than gliflozin-like transporter inhibition. Contradictory findings across assay systems are discussed in relation to structure-activity relationships shaped by glycosylation. We further examine pharmacokinetics, tissue exposure plausibility, and translational feasibility, and propose a stepwise development roadmap emphasising transporter-specific assays, quantitative target engagement, and clinically meaningful biomarkers.</p><p><strong>Conclusion: </strong>Q3G and rutin may exhibit putative SGLT-relevant activity within a broader polypharmacological framework; however, direct transporter-specific inhibition and clinically relevant renal exposure remain to be established through future functional and translational studies.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381865","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":"Dysregulation of the miR-4286 in diabetic kidney disease and its role in inflammatory response.","authors":"Jiayong Zhang, Qilin Tang, Mengmeng Pu, Lin Yan, Yijun Chen, Bin Wang","doi":"10.1186/s13098-026-02230-z","DOIUrl":"10.1186/s13098-026-02230-z","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to investigate the expression level and diagnostic value of miR-4286 in serum of DKD patients and validate its effect on podocyte inflammatory response and apoptosis in vitro.</p><p><strong>Methods: </strong>We detected the expression level of serum miR-4286 and CADM1 in DKD patients and healthy individuals. Clinical correlations of miR-4286 with estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and KDIGO risk categories were analyzed. We detected the expression change of miR-4286 in podocytes treated. ROC analysis was used to evaluate the diagnostic value of miR-4286. Dual-luciferase assay and RNA immunoprecipitation (RIP) were used to validate the targeting relationship between miR-4286 and CADM1. TNF-α and IL-1β in supernatants were detected by ELISA, CADM1 protein expression was assessed by Western blotting, and apoptosis was detected by flow cytometry.</p><p><strong>Results: </strong>In DKD patients, upregulation of serum miR-4286 and downregulation of CADM1 were observed and negatively correlated. MiR-4286 levels were negatively correlated with eGFR, positively correlated with UACR, and increased across KDIGO risk categories. In vitro, mimicking diabetic conditions revealed that miR-4286 was upregulated and CADM1 was downregulated at both mRNA and protein levels in podocytes in HG group. Functionally, suppressing miR-4286 could ameliorate the HG-induced inflammation and apoptosis. While CADM1 knockdown aggravated both two kinds of damages. Importantly, suppressing CADM1 partly rescued the apoptosis from co-silencing miR-4286.</p><p><strong>Conclusion: </strong>This study demonstrated that miR-4286 could regulate inflammatory response and podocyte function in DKD by targeting CADM1. Upregulation of miR-4286 would suppress CADM1, further enhancing the release of inflammatory factors and apoptosis.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374943","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":"Exosomal miR-20a-5p derived from renal tubular epithelial cells regulates podocyte cytoskeletal remodeling via targeting myosin X in diabetic kidney disease.","authors":"Rui Zhang, Xingyan Zhou, Ziwei Guo, Tian Zhang, Mingjun Shi, Ying Xiao, Qianwen Chi, Bing Guo, Rui Yan","doi":"10.1186/s13098-026-02229-6","DOIUrl":"10.1186/s13098-026-02229-6","url":null,"abstract":"<p><strong>Background: </strong>Renal tubular epithelial cells are increasingly recognized as active participants in the pathogenesis of diabetic kidney disease, where tubular injury often precedes glomerular dysfunction. Exosomes, as critical mediators of intercellular communication, may transmit signals between renal tubules with glomeruli. However, the specific role of exosomes derived from renal tubular epithelial cells (RTECs) in modulating podocyte function, particularly during the early stages of diabetic kidney disease, remains unclear.</p><p><strong>Methods: </strong>Exosomes derived from RTECs cultured under high glucose and palmitic acid (HG + PA) conditions were isolated and administered to wild-type mice or incubated with cultured podocytes to evaluate their biological impact. In parallel, plasma exosomes from diabetic kidney disease patients were isolated to assess their biological effects. Exosomes derived from HK-2 cells cultured under HG + Pa conditions were isolated and subjected to miRNA sequencing, followed by target screening via miRDB prediction. The functional role of miR-20a-5p was assessed in vivo using adeno-associated virus (AAV) mediated overexpression and knockdown in db/m and db/db mice, respectively. Furthermore, an in vitro co-culture system of HK-2 cells and podocytes was established to mimic tubule-to-podocyte crosstalk. The molecular interaction between myosin X and F-actin was interrogated using dual-luciferase reporter assays, co-immunoprecipitation, and molecular dynamics simulations.</p><p><strong>Results: </strong>Exosomes derived from HG + PA-treated RTECs induced podocyte foot process effacement and downregulated key cytoskeleton-associated proteins including nephrin, CD2AP, and myosin X. Exosomal miRNA sequencing identified miR-20a-5p as the most significantly upregulated miRNA under diabetic conditions. Overexpression of miR-20a-5p in db/m mice recapitulated podocyte injury, whereas knockdown in db/db mice mitigated foot process effacement. Dual-luciferase assays confirmed that miR-20a-5p directly targets the 3' untranslated region of myo10. The knockdown of myo10 disrupted its binding to F-actin and decreased the expression of cytoskeletal regulatory proteins. Molecular dynamics simulations were employed to assess the structural stability and interaction dynamics between myosin X and F-actin. In co-culture systems, miR-20a-5p modified HK-2 cells significantly altered podocyte morphology and F-actin integrity, confirming its regulatory role via exosome-mediated signaling.</p><p><strong>Conclusion: </strong>This study identifies miR-20a-5p as a key exosomal mediator released by RTECs under diabetic conditions, contributing to podocyte cytoskeletal remodeling by targeting myo10. These findings offer new insights into the pathogenic crosstalk between tubules and glomeruli, indicating exosome-mediated miRNA signaling as a potential target in early diabetic kidney disease.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367384","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":"Trajectories, cumulative burden of the dynamic triglyceride glucose-Chinese visceral adiposity index, and risk of incident cardiovascular diseases: a large prospective cohort study.","authors":"Ao Men Lu, Qian Xu, Yun Tao Wu","doi":"10.1186/s13098-026-02221-0","DOIUrl":"https://doi.org/10.1186/s13098-026-02221-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The composite indicator (TyG-CVAI), constructed by combining the triglyceride-glucose index and the Chinese visceral adiposity index, can quantify the combined pathogenic effects of insulin resistance and visceral obesity. However, an in-depth exploration of the long-term longitudinal evolution trajectories, cumulative exposure burden of TyG-CVAI, and its nonlinear association with the risk of cardiovascular disease (CVD) subtypes is still lacking. This study aims to prospectively evaluate the dynamic evolution pattern of TyG-CVAI and its predictive value for incident CVD, stroke, and heart disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Based on the Kailuan prospective cohort, this study included 32,841 participants without CVD prior to the 2012 baseline. Using data from four repeated measurements between 2006 and 2012, the longitudinal evolution trajectories of TyG-CVAI were identified through the K-means clustering algorithm, and its cumulative exposure burden (cumTyG-CVAI) was calculated. Multivariable Cox proportional hazards regression models were utilized to evaluate its association with incident CVD and its subtypes after 2012, and its dose-response relationship and predictive accuracy were assessed using restricted cubic splines (RCS) and receiver operating characteristic (ROC) curves.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;During a median follow-up of 6.9 years, a total of 3,212 incident CVD events were recorded. Longitudinal analysis identified three distinct evolutionary trajectories: low, moderate, and high. After fully adjusting for confounding factors, compared with the low trajectory group, the high trajectory group faced the highest risk of incident total CVD (HR 1.837, 95% CI 1.588-2.126), stroke (HR 1.919, 95% CI 1.672-2.203), and heart disease (HR 2.260, 95% CI 1.827-2.796). For each standard deviation (SD) increase in cumulative TyG-CVAI, the risks of the aforementioned outcomes significantly increased by 29.2%-34.1%, respectively. RCS analysis showed that TyG-CVAI was positively and linearly correlated with the risk of stroke, while exhibiting a significant nonlinear threshold effect with the risks of total CVD (cumulative inflection point: 4683.98) and heart disease (cumulative inflection point: 4828.73). ROC analysis confirmed that the cumulative TyG-CVAI (AUC: 0.624-0.655) provided incremental improvements in predictive performance compared with single baseline measurements and traditional single or composite metabolic indices (all P &lt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The dynamic elevation of TyG-CVAI and its long-term cumulative burden are independent predictors of incident CVD, stroke, and heart disease. Compared to single baseline assessments and traditional static indicators, cumulative TyG-CVAI demonstrates improved risk stratification value for cardiovascular risk, highlighting the clinical utility of integrating longitudinal metabolic monitoring into routine cardiovascular screening. Fur","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}