Diabetology & Metabolic Syndrome最新文献

{"title":"Editorial Expression of Concern: Neuroprotective effect of resveratrol in diabetic cerebral ischemic-reperfused rats through regulation of inflammatory and apoptotic events.","authors":"Hoda E Mohamed, Sahar E El-Swefy, Rehab A Hasan, Ahmed A Hasan","doi":"10.1186/s13098-026-02318-6","DOIUrl":"10.1186/s13098-026-02318-6","url":null,"abstract":"","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074033","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":"Burden of atherosclerotic cardiovascular disease attributable to high body mass index, high fasting plasma glucose or high low density lipoprotein cholesterol in young and middle-aged adults from 1990 to 2050.","authors":"Hua Zhang, Jun Li, Kaixin Qin, Yuan Zhao, Qi Yan, Wenhao Wu, Jin Li","doi":"10.1186/s13098-026-02236-7","DOIUrl":"10.1186/s13098-026-02236-7","url":null,"abstract":"<p><strong>Aims: </strong>This study aims to analyze the global burden of atherosclerotic cardiovascular disease (ASCVD) attributable to high low-density lipoprotein cholesterol (LDL-c), high body mass index (BMI), or high fasting plasma glucose (FPG) in young and middle-aged adults (15-49 years) from 1990 to 2021, with projections extending to 2050.</p><p><strong>Methods: </strong>Leveraging data from the Global Burden of Disease (GBD) 2021 study, we concentrated on ASCVD burden attributable to three risk factors in young and middle-aged adults. We scrutinized crude death rates, number of deaths, and estimated annual percentage changes (EAPCs) across sexes, countries, regions, and socio-demographic index (SDI) categories. To forecast future trends, we employed the Bayesian age-period-cohort (BAPC) model. Locally weighted scatterplot smoothing (LOESS) regression (span = 0.5) was used to visualize associations between crude death rates and SDI levels across 21 GBD regions and 204 countries.</p><p><strong>Results: </strong>The ASCVD burden attributable to three risk factors in young and middle-aged adults followed broadly similar epidemiological patterns. In 2021, ischemic heart disease (IHD) burden attributable to three risk factors substantially exceeded ischemic stroke (IS) and lower extremity peripheral artery disease (LEPAD), and men exhibited consistently a higher burden than women. From 1990 to 2021, global trends in crude death rates for ASCVD attributable to three risk factors in young and middle-aged adults remained relatively stable. Significant regional and national variation was observed. At regional SDI levels, crude death rates for IHD showed an inverted M-shaped pattern (peaks at SDI 0.45 and 0.70), while IS and LEPAD demonstrated inverted L-shaped patterns (plateauing at SDI 0.70-0.76). Across 204 countries in 2021, crude death rates from ASCVD attributable to three risk factors increased gradually below SDI 0.60, showed a slight U-shape between 0.60-0.75, and declined sharply above 0.75. Projections indicate that ASCVD attributable to three risk factors will increase to varying degrees in young and middle-aged adults by 2050.</p><p><strong>Conclusion: </strong>The burden of ASCVD attributable to three risk factors in young and middle-aged adults calls for concerted and integrated management strategies. Urgent public health measures targeting these risk factors are needed to mitigate the projected rise in ASCVD burden.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13576271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975881","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":"Cumulative average metabolic indices and cardiovascular disease risk: additive predictive effects and partial mediating role of intrinsic capacity in early-stage CKM syndrome.","authors":"Yonghuan Wang, Zhenhua Li, Weijia Zhang, Rui Yan, Min Guo","doi":"10.1186/s13098-026-02307-9","DOIUrl":"10.1186/s13098-026-02307-9","url":null,"abstract":"<p><strong>Background: </strong>Early stages (0-3) of cardiovascular-kidney-metabolic (CKM) syndrome represent a critical window for cardiovascular disease (CVD) prevention. Triglyceride-glucose (TyG)-derived indices reflect insulin resistance and metabolic burden, but their cumulative effects and the role of intrinsic capacity (IC) remain unclear.</p><p><strong>Methods: </strong>In this prospective study from the China Health and Retirement Longitudinal Study (CHARLS), 3,832 adults with CKM stages 0-3 and without baseline CVD were included. Fourteen cumulative average metabolic indices were derived from repeated measurements. Multivariable logistic regression and restricted cubic spline models were used to evaluate associations and dose-response relationships, with false discovery rate (FDR) correction applied for multiple comparisons. Joint effects with IC, predictive performance (AUC, calibration, decision curve analysis, NRI, and IDI), and mediation effects were assessed.</p><p><strong>Results: </strong>During a median follow-up of 4.0 years, 303 incident CVD cases (7.9%) occurred. Five indices (TyG-BMI, TyG-WHtR, TyG-CI, TyG-CVAI, and METS-IR) were significantly associated with higher odds of new-onset CVD after full adjustment and FDR correction (per SD OR range: 1.27-1.36), with approximately linear dose-response relationships. Lower IC was associated with higher CVD risk. Individual indices showed modest discrimination (AUC range: 0.580-0.604), and incorporating IC provided incremental predictive information (AUC up to 0.621, both NRI and IDI P < 0.01). IC partially mediated these associations, with modest mediation proportions (≈ 4%-7%).</p><p><strong>Conclusions: </strong>Cumulative metabolic burden is independently associated with CVD risk in early-stage CKM syndrome. IC showed joint associations and modest mediating effects and provided complementary information for CVD risk assessment. Integrating metabolic and functional assessments may enhance early risk stratification.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179112","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 low skeletal muscle mass assessed by deep learning-based CT and MASLD: a prospective cohort study.","authors":"Yaping Wang, Jing Lu, Jiulou Zhang, Wen Guo, Shumei Miao, Xinyuan Ge, Wentao Yao, Hongwei Xu, Yuxiang Yan, Chengxiao Yu, Ci Song, Qun Zhang","doi":"10.1186/s13098-026-02279-w","DOIUrl":"10.1186/s13098-026-02279-w","url":null,"abstract":"<p><strong>Background: </strong>To explore the role of abdominal skeletal muscle mass in metabolic dysfunction-associated steatotic liver disease (MASLD) incidence and resolution, we established two independent cohorts in a Chinese population.</p><p><strong>Methods: </strong>This study included 3139 participants without MASLD (incidence cohort) and 1130 MASLD patients (resolution cohort) at baseline, all of whom underwent abdominal computed tomography (CT) during routine health examinations from 2019 to 2024. Skeletal muscle mass was quantified from the third lumbar vertebra (L3) CT images using automated deep learning and analyzed in tertiles. MASLD was diagnosed by ultrasonographic hepatic steatosis and cardiometabolic risk factors. Cox models assessed the association of muscle mass with MASLD; logistic regression was used to assess the joint effects of skeletal muscle change rate and MASLD-related genetic risk on resolution.</p><p><strong>Results: </strong>Among the incidence cohort (median follow-up: 1.8 years), 516 developed MASLD. Lower body weight-adjusted total abdominal muscle area (TAMA/weight) was associated with higher MASLD incidence, regardless of sex. Compared with the highest tertile of TAMA/weight, the lowest tertile had hazard ratio (HR) of 2.39 (95% confidence interval [CI], 1.75 to 3.26) in men, and 2.11 (95% CI, 1.45 to 3.07) in women, respectively. Higher annual TAMA/weight promoted MASLD resolution, with the odds ratio (OR) of 1.81 (95% CI, 1.28-2.56) in men and 1.75 (95% CI, 1.04-2.96) in women. Increased muscle mass tended to be more associated with MASLD resolution in low genetic risk individuals.</p><p><strong>Conclusions: </strong>Lower muscle mass correlates with higher MASLD risk. Increasing skeletal muscle mass may help prevent and manage the disease.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148825215","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":"Impact of GLP-1 and GLP-1/GIP receptor agonists before, during, and after pregnancy: a narrative review.","authors":"Lenita Zajdenverg, Vitor Masson Santos, Ana Clara Martins Rodrigues, Laura Kensy Previdelli, Carlos Antonio Negrato","doi":"10.1186/s13098-026-02235-8","DOIUrl":"10.1186/s13098-026-02235-8","url":null,"abstract":"<p><p>Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptor agonists (GLP-1RA and GIP-RA) are a class of medications that mimic the endogenous effects of GLP-1 and have gained increasing attention due to their substantial clinical potential. Originally developed for glycemic control in individuals with type 2 diabetes mellitus (T2DM), these agents have also been widely used for obesity management and weight control. A narrative literature review was conducted to summarize the main findings available regarding the use of GLP-1RAs across three distinct phases of women's reproductive trajectory: the preconception period, pregnancy, and the postpartum. Owing to their metabolic and hormonal optimization effects, GLP-1RAs have additionally emerged as a therapeutic ally in the management of infertility associated with hormonal imbalance secondary to metabolic syndrome. However, the safety of these medications during pregnancy remains insufficiently established, largely due to the limited number of published studies to date. Similarly, their use during the postpartum period is controversial, given the same lack of robust evidence. Overall, current data are insufficient to support routine use of GLP-1RAs and GLP-1RA/GIP-RAs during pregnancy and postpartum.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13584491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988510","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":"Correction: Polygenic risk and air pollution trends in relation to type 2 diabetes: evidence from the Taiwan Biobank.","authors":"Osama Aziz, Bing-Fang Hwang, Ai-Ru Hsieh, Chau-Ren Jung","doi":"10.1186/s13098-026-02263-4","DOIUrl":"10.1186/s13098-026-02263-4","url":null,"abstract":"","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668678","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":"Unpacking adiposity: a narrative critical appraisal of diverse obesity definitions.","authors":"Marcio C Mancini, Bruno Halpern, Maria Edna de Melo, Caroline K Kramer","doi":"10.1186/s13098-026-02261-6","DOIUrl":"10.1186/s13098-026-02261-6","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a complex, multifaceted chronic disease that poses a major global health challenge. Traditionally, population-level screening and follow-up have relied heavily on body mass index (BMI). Although BMI provides a simple, standardized measure for epidemiological studies, it does not account for individual variations in muscle mass, fat distribution, or metabolic health. Consequently, relying solely on weight-to-height ratios-even when supplemented with waist circumference, waist-to-hip ratio, or waist-to-height ratio-limits precise individual diagnosis and comprehensive health risk assessment. Comprehensive risk stratification incorporating clinical factors beyond body weight is therefore needed to capture the heterogeneity of obesity and enable a more individualized, patient-centered approach to management.</p><p><strong>Main body: </strong>This critical narrative review evaluates the main definitions and classification systems used for obesity, including the traditional World Health Organization classification, the Edmonton Obesity Staging System (EOSS), the Lancet Commission framework, the European Association for the Study of Obesity framework, and classifications based on weight history. BMI remains valuable for population-level assessment and may also be useful at the individual level when combined with additional anthropometric measurements and sex-, age-, and ethnicity-specific cutoff values. The EOSS complements anthropometric assessment by incorporating metabolic, physical, psychological, and functional consequences, thereby supporting treatment intensity according to disease severity. The Lancet Commission definitions of preclinical and clinical obesity broaden diagnosis beyond BMI but have raised concerns regarding the absence of standardized screening tools, potential diagnostic inconsistency, and possible delays in treatment for people classified as having preclinical obesity. Such limitations may be particularly relevant for children and adolescents, in whom delayed intervention may increase long-term health risks. Weight-history classifications provide an additional perspective by incorporating maximum weight attained in life, supporting realistic treatment goals, reinforcing the chronic nature of obesity, reducing stigma, and encouraging long-term treatment adherence.</p><p><strong>Conclusion: </strong>No single classification adequately captures the biological and clinical heterogeneity of obesity. BMI should not be abandoned, but interpreted alongside anthropometric, metabolic, functional, psychological, and weight-history information. Integrating complementary classification systems may improve diagnostic accuracy, risk stratification, treatment prioritization, and patient-centered obesity care.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954845","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":"Therapeutic potential of GLP-1 receptor agonists and SGLT2 inhibitors in diabetic neuropathy: a critical appraisal.","authors":"Dan Ziegler, Peter Kempler, Cornelia Bala, Boris Mankovsky, Oliver Schnell, Vincenza Spallone, Alin Stirban, Solomon Tesfaye","doi":"10.1186/s13098-026-02241-w","DOIUrl":"10.1186/s13098-026-02241-w","url":null,"abstract":"<p><p>The management of type 2 diabetes (T2D) has recently witnessed a paradigm shift extending beyond blood glucose regulation towards cardiovascular and renal health targeted by cardiovascular outcome trials (CVOTs) of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Preclinical studies suggest a potential role for GLP-1RAs and SGLT2i in the treatment of diabetic neuropathy and neuropathic pain. However, to date largely only small-size phase II shorter-term randomized controlled trials (RCTs) of heterogeneous designs and quality have been performed, without clear evidence of favorable effect of both GLP-1RAs and SGLT2i on clinical and neurophysiological neuropathic outcomes. Moreover, responses to GLP1-RA and SGLT2i treatments in real‑world clinical practice appear heterogeneous, with relatively high rates of non-responders and discontinuation. Several possible risks associated with GLP-1RAs and SGLT2i treatment in real-world practice have been identified requiring increased attention by physicians, their professional societies, and patients alike. Unfortunately, the opportunity has been missed to use simple tools for the detection and monitoring of diabetic sensorimotor polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) in the multiple published large-scale pivotal CVOTs. Diabetic neuropathy is linked to considerable patient burden and mortality, and there remains an unmet need for the disease modifying effects of novel pharmacotherapies derived from the pathogenetic concepts of diabetic neuropathy. In the future, when designing and conducting RCTs more emphasis should be placed on considering neuropathy as a serious and potentially life-threatening complication.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629801","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 of sarcopenic obesity with advanced cardiovascular-kidney-metabolic syndrome and incident cardiovascular disease: a longitudinal and cross-sectional study.","authors":"Roushan Zhang, Dianping Yu, Xin Liu, Hui Xue, Jiajun Xie, Li Wang","doi":"10.1186/s13098-026-02247-4","DOIUrl":"10.1186/s13098-026-02247-4","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to examine the associations of sarcopenic obesity, obesity only, and sarcopenia only with advanced cardiovascular-kidney-metabolic (CKM) syndrome and incident cardiovascular disease (CVD), and to assess whether sarcopenia and obesity were jointly associated with long-term cardiovascular risk.</p><p><strong>Research design and methods: </strong>We adopted a dual-cohort design combining longitudinal discovery and cross-sectional validation. The discovery cohort included 7,759 participants from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2018). Body composition phenotypes were classified into four groups: Normal, Obesity Only, Sarcopenia Only, and Sarcopenic Obesity (SO). Sarcopenia was defined by AWGS 2019 criteria. CKM syndrome was staged (0-4) according to the 2023 American Heart Association (AHA) Presidential Advisory. Cox proportional hazards models were used to estimate the association between body composition phenotypes and incident CVD during follow-up. In participants with complete CKM staging data at both 2011 and 2015, a descriptive 4-year observed CKM transition probability matrix was constructed to describe stage movement from 2011 to 2015. External consistency was examined using data from 3,936 participants in NHANES 2011-2018, where muscle mass was measured by dual-energy X-ray absorptiometry (DXA).</p><p><strong>Results: </strong>In the CHARLS longitudinal cohort, sarcopenic obesity showed the highest cumulative incidence of CVD events (29.3%). After full adjustment, sarcopenic obesity was associated with a more than two-fold higher risk of incident CVD compared with the Normal group (HR 2.07, 95% CI 1.76-2.45), followed by Obesity Only (HR 1.51, 95% CI 1.31-1.74) and Sarcopenia Only (HR 1.23, 95% CI 1.03-1.45). A positive additive interaction between sarcopenia and obesity was observed (RERI = 0.34, P = 0.027). This association remained consistent in the restricted analysis among participants free of advanced CKM at baseline. In the descriptive four-year transition analysis, early CKM stages frequently moved toward higher-risk stages, whereas advanced stages were more persistent. In NHANES, sarcopenic obesity was associated with the highest likelihood of prevalent advanced CKM syndrome (OR 2.04, 95% CI 1.53-2.70).</p><p><strong>Conclusion: </strong>Sarcopenic obesity was consistently associated with a greater burden of advanced CKM and a higher risk of incident CVD in the CHARLS longitudinal cohort, with similar cross-sectional associations observed in the NHANES validation cohort. Although causal relationships cannot be established, these findings suggest that sarcopenic obesity may serve as a clinically useful phenotypic marker for identifying individuals at increased cardiometabolic risk.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705642","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":"GlycA-gene interactions in cardiovascular-kidney-metabolic syndrome: evidence from genetic association.","authors":"Mingyang Yuan, Suwen Cao, Xing Wan, Yuting Yang, Siyu Fan, Jiang Xie, Han Wang","doi":"10.1186/s13098-026-02252-7","DOIUrl":"https://doi.org/10.1186/s13098-026-02252-7","url":null,"abstract":"<p><strong>Objective: </strong>Cardiovascular-Kidney-metabolic (CKM) syndrome is a concept introduced by the American Heart Association, describing systemic diseases resulting from the pathophysiological interaction among obesity, stroke, type 2 diabetes, chronic kidney disease, and cardiovascular disease. Glycoprotein acetyls (GlycA) is a novel biomarker for systemic inflammation and cardiovascular risk. This study aims to uncover the shared genetic architecture between GlycA and CKM, identify common risk loci and key tissues, and clarify the mechanisms linking these conditions.</p><p><strong>Methods: </strong>Using summary data from large-scale GWAS studies, we evaluated both global and local genetic correlations between GlycA and various components of CKM. A cross-trait pleiotropic analysis was conducted to identify shared pleiotropic loci and related genes. FUSION was used to find susceptibility genes linked to GlycA and CKM. A comprehensive set of functional annotations and tissue-specific analyses was performed to uncover potential connections between these traits. Furthermore, a multi-trait colocalization method was utilized to explore the underlying mechanisms of the association between GlycA and CKM.</p><p><strong>Results: </strong>Our study revealed a close genetic correlation between GlycA and CKM. We identified 260 potential SNPs that were corrected using the Bonferroni method, of which 30 passed the colocalization test (PP.H4 > 0.70). Notably, locus 9q34.2 appeared in both GlycA-T2D and GlycA-HF trait pairs. By integrating post-GWAS methods, we identified 53 potentially drug targets (CMIP, DNAJC5G, FCGRT, etc.). FUSION analysis identified 23 shared susceptibility genes for GlycA and CKM (ZPR1, IL6R, PABPC4, etc.). Analysis of tissue enrichment at the SNP level revealed pleiotropic mechanisms associated with whole blood and liver. Gene-level analysis highlighted important roles of metabolic signaling pathways. Furthermore, multi-trait colocalization analysis suggested that rs1260326 and rs2925979 may play significant roles in the mechanistic link between GlycA and CKM.</p><p><strong>Conclusion: </strong>Our study confirmed a significant genetic association and shared genetic structure between GlycA and CKM, revealing potential mechanisms that may be involved.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227512","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}