Cardiovascular Diabetology最新文献

{"title":"Comparative performance of insulin resistance-related indices in predicting adverse cardiovascular events among individuals with NAFLD and MASLD: a multi-center cohort study.","authors":"Yanqiu Huang, Yadan Xu, Chenghao Zhang, Wen Gu, Yue Li, Haojia Zhang, Tian Wang, Tangyi Su, Yangchen Lhamu, Yichen Chen, Liang Zhou, Lipeng Hao, Yang Yang, Hui Wang","doi":"10.1186/s12933-026-03208-x","DOIUrl":"10.1186/s12933-026-03208-x","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) and non-alcoholic fatty liver disease (NAFLD) are closely linked to insulin resistance and elevated cardiovascular risk, triglyceride-glucose (TyG)-related indices, the atherogenic index of plasma (AIP), and the cardiometabolic index (CMI) have emerged as practical surrogate markers for cardiometabolic risk assessment in these populations. However, it remains unclear whether the associations of these indices with adverse cardiovascular events remain consistent when transitioning from the NAFLD to the newly defined MASLD framework, and a comprehensive comparison of these indices across both diagnostic criteria is lacking.</p><p><strong>Methods: </strong>This study included 4693/3266, 74,173/67,864, and 7823/10,576 individuals with MASLD/NAFLD from the National Health and Nutrition Examination Survey (NHANES), UK Biobank (UKB), and China Pudong cohort, respectively. Multivariate Cox proportional hazards models, restricted cubic spline analyses, and time-dependent receiver operating characteristic curves were employed to assess associations. Linear regression models evaluated relationships between TyG-related indices and cortical/subcortical structural volumes. Mediation analyses examined the role of oxidative stress, phenotypic aging, and inflammatory markers.</p><p><strong>Results: </strong>Most IR-related indices demonstrated nonlinear, predominantly J-shaped associations with cardiovascular disease (CVD) and related mortality, especially within the UKB. TyG-WC optimally predicted 3-year CVD mortality in MASLD/NAFLD across UKB and NHANES, as well as ischemic stroke (IS) in UKB-MASLD. TyG-WHTR was the strongest predictor for CVD mortality in the Pudong cohort and myocardial infarction (MI) in UKB-MASLD. Notably, elevated TyG-WHTR was consistently associated with heightened risks across all endpoints: CVD mortality (NAFLD: UKB: HR 1.60, 95%CI 1.38-1.84, NHANES: 1.90, 1.34-2.70, Pudong: 1.24, 1.10-1.40; MASLD: UKB: 1.59, 1.38-1.82, NHANES: 1.86, 1.36-2.54, Pudong: 1.70, 1.43-2.03), MI (NAFLD: 1.20, 1.09-1.33; MASLD: 1.22, 1.11-1.34), and IS (NAFLD: 1.41, 1.24-1.61; MASLD: 1.39, 1.23-1.57). Structural neuroimaging analyses revealed significant negative correlations between TyG-WC/TyG-WHTR and subcortical volumes (P < 1 × 10^-4). Mediation analyses indicated that oxidative stress, phenotypic aging, and inflammatory markers collectively accounted for 1.4-27% of the observed associations.</p><p><strong>Conclusions: </strong>Insulin Resistance-Related Indices demonstrate robust clinical utility in predicting CVD and mortality in NAFLD/MASLD across three distinct cohorts, with oxidative stress, inflammatory activation, and accelerated aging serving as potential mechanistic pathways.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13335360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opportunistic screening for incident cardiometabolic disease in metabolically healthy non-obese individuals: a prospective cohort study.","authors":"Balázs Bogner, Matthias Jung, Marco Reisert, Juliane Maushagen, Susanne Rospleszcz, Thomas Kroencke, Tobias Pischon, Jeanette Schulz-Menger, Thoralf Niendorf, Henry Völzke, Christopher L Schlett, Fabian Bamberg, Jana Taron, Jakob Weiss","doi":"10.1186/s12933-026-03265-2","DOIUrl":"10.1186/s12933-026-03265-2","url":null,"abstract":"<p><strong>Background: </strong>Metabolically healthy non-obese (MHN) individuals are considered at low cardiometabolic risk, yet a subset may harbor unfavorable visceral adiposity not captured by conventional anthropometric measures, including waist circumference (WC) and BMI.</p><p><strong>Methods: </strong>We conducted a prospective cohort study of 22,040 UK Biobank participants (median follow-up 4.2 years [interquartile range 3.4-5.6]) defined as MHN (BMI < 30 kg/m², absence of diabetes or concurrent hypertension and hyperlipidemia). Visceral (VAT) and subcutaneous adipose tissue (SAT) volumes were quantified from whole-body MRI using a validated deep learning framework. Sex-specific VAT/SAT ratio cutoffs were derived from the German National Cohort based on prevalent cardiometabolic disease and applied to the UK Biobank. The primary outcome was incident major adverse cardiovascular events (MACE); the secondary outcome was incident type 2 diabetes. Categorical net reclassification improvement (NRI), quantifying the net proportion of individuals correctly reclassified between predefined risk categories, compared VAT/SAT ratio versus WC as competing classification approaches. Cox proportional hazards models assessed associations with outcomes after stepwise adjustment for age, sex, smoking, WC, and BMI. Nested models with and without VAT/SAT ratio were compared to test for added value beyond other factors.</p><p><strong>Results: </strong>The VAT/SAT ratio improved risk classification over WC for MACE (NRI 0.088, 95%CI 0.019-0.158, p = 0.013) and diabetes (NRI 0.102, 95% CI 0.024-0.181, p = 0.010). High VAT/SAT ratio independently predicted MACE (adjusted hazard ratio [aHR] 1.30, 95%CI 1.02-1.66, p = 0.037) and diabetes (aHR 1.77, 95% CI 1.34-2.33, p < 0.001) after full adjustment. Adding VAT/SAT to fully adjusted models improved discrimination for MACE (C-index 0.694 vs. 0.690, p = 0.036) and diabetes (C-index 0.723 vs. 0.715, p < 0.001).</p><p><strong>Conclusion: </strong>The VAT/SAT ratio identifies MHN individuals at elevated cardiometabolic risk beyond conventional anthropometric measures, with particularly strong associations for incident diabetes. These findings support the concept of opportunistic imaging-based risk assessment and provide the prognostic foundation for future trials investigating whether targeted intervention in VAT/SAT-reclassified individuals improves outcomes.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin resistance surrogate indices and incident cardiovascular disease across cardiovascular-kidney-metabolic stages 0-3: a prospective cohort study.","authors":"Ningning Xue, Letong Ma, Ziwen Zhou, Tiantian Bai, Xianjie Jia, Xing Wei","doi":"10.1186/s12933-026-03280-3","DOIUrl":"10.1186/s12933-026-03280-3","url":null,"abstract":"<p><strong>Background: </strong>The American Heart Association (AHA) recently proposed the concept of Cardiovascular-Kidney-Metabolic (CKM) syndrome, highlighting the strong pathophysiological links among metabolic disorders, chronic kidney disease, and cardiovascular disease (CVD). Insulin resistance (IR) is regarded as a central mechanism underlying CKM syndrome. However, studies comparing the predictive value of different IR surrogate markers for incident CVD are still limited. This study aimed to evaluate the associations between multiple IR surrogate markers and incident cardiovascular disease and to further assess their predictive performance using machine learning approaches.</p><p><strong>Methods: </strong>Using data from the China Health and Retirement Longitudinal Study (CHARLS), this prospective cohort study included 5,528 participants. Twelve IR surrogate indices were assessed, including TyG-related indices, TG/HDL-C, METS-IR, CTI, CHG, and eGDR. Incident CVD was defined as self-reported physician-diagnosed heart disease or stroke during follow-up. Cox proportional hazards models were used to estimate associations between standardized IR indices and incident CVD. Restricted cubic splines, weighted quantile sum regression, and quantile g-computation were used to examine dose-response patterns and the relative contribution of correlated IR indices. Predictive performance was evaluated using ROC analysis, calibration, Brier score, decision curve analysis, NRI, IDI, and machine-learning models.</p><p><strong>Results: </strong>During a median follow-up of 7.0 years, 741 participants developed incident CVD. In fully adjusted Cox models, several IR surrogate indices were associated with incident CVD. TyG-related composite indices incorporating adiposity-related information, particularly TyG-WC, TyG-CVAI, TyG-WHtR, and TyG-BMI, showed stronger positive associations with CVD risk, whereas eGDR showed an inverse association. Restricted cubic spline analyses showed significant overall associations for most indices, with nonlinear patterns observed for METS-IR, CTI, and eGDR. Mixture-based analyses suggested relatively larger contributions of CTI, TyG-BMI, and TyG-WC. Among individual indices, eGDR showed the highest discrimination for incident CVD, followed by TyG-CVAI and TyG-WC. Adding selected IR indices, particularly eGDR, to the covariate-based model modestly improved discrimination and reclassification.</p><p><strong>Conclusions: </strong>Among adults with CKM syndrome stages 0-3, several IR surrogate indices were prospectively associated with incident CVD, with stronger and more consistent associations observed for TyG-based indices incorporating adiposity-related measures and for eGDR. These results suggest that the combined assessment of metabolic dysfunction, adiposity, and insulin sensitivity may provide useful information for identifying individuals at higher cardiovascular risk in early-stage CKM syndrome.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13465377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 the atherogenic index of plasma and its integrative novel adiposity-based composites with all-cause and cardiovascular mortality in individuals with cardiovascular-kidney-metabolic syndrome: novel adiposity-derived AIP indices provide modest incremental prognostic information.","authors":"Sheng Wei, Jiajun Qiu, Yong Liu, Ning Xu, Zhonghua Sun, Sha Li, Changping He, Xiangping Xie, Yanlang He","doi":"10.1186/s12933-026-03277-y","DOIUrl":"10.1186/s12933-026-03277-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cardiovascular-kidney-metabolic (CKM) syndrome is recognized as a progressive pathophysiological continuum linking metabolic dysfunction, dysfunctional adiposity, chronic kidney disease, and cardiovascular injury. The atherogenic index of plasma (AIP) reflects lipid-related atherogenic burden, whereas novel adiposity indices, including body roundness index (BRI), weight-adjusted waist index (WWI), and a body shape index (ABSI), capture body-shape-related adiposity burden. However, the associations of AIP and AIP-based adiposity composite indices with mortality outcomes across the CKM spectrum remain unclear. This study aimed to evaluate the associations of AIP and integrative AIP-based composite indices, including AIP-BRI, AIP-WWI, and AIP-ABSI, with all-cause and cardiovascular mortality among individuals across CKM stages.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a retrospective cohort analysis using prospectively collected data from 22,587 US adults in the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Following the 2023 American Heart Association (AHA) Presidential Advisory, participants were classified into a hierarchical staging framework (Stages 0-4) to reflect the CKM disease continuum. Primary outcomes were all-cause and cardiovascular mortality, identified through linkage to the National Death Index. Integrative AIP-based composite indices were constructed by directly multiplying AIP by each adiposity index, including BRI, WWI, and ABSI, yielding AIP-BRI, AIP-WWI, and AIP-ABSI, respectively. These indices were evaluated as integrated exposure variables reflecting the combined burden of atherogenic dyslipidemia and adiposity-related body shape. All analyses incorporated complex survey weights to ensure national representativeness. Survey-weighted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Model 2 adjusted for demographic and socioeconomic characteristics, lifestyle factors, blood pressure, and total cholesterol. Nonlinear associations were examined using restricted cubic splines (RCS). Incremental prognostic value was assessed using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;During follow-up, non-survivors exhibited significantly higher baseline integrative composites than survivors (P &lt; 0.001). In the fully adjusted model (Model 2), which adjusted for demographic and socioeconomic characteristics, lifestyle factors, blood pressure, and total cholesterol, each standard deviation increase in the integrative composites was independently associated with a higher risk of all-cause mortality: AIP-BRI (HR, 1.09; 95% CI, 1.05-1.14), AIP-WWI (HR, 1.07; 95% CI, 1.02-1.11), and AIP-ABSI (HR, 1.07; 95% CI, 1.02-1.11). These point estimates were numerically slightly higher than that of stand-alone AIP (HR, 1.06; 95% CI, 1.01-1.10), but the difference","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13584503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning analysis of ECGs detects Cardiovascular-Kidney-Metabolic syndrome burden in people with diabetes: a report from the Silesia Diabetes-Heart Project.","authors":"Oliwia Janota-Sosińska, Qinkai Yu, Krzysztof Irlik, Hanna Kwiendacz, Aleksandra Włosowicz-Momot, Patrycja Pabis, Wiktoria Wójcik, Anna Olejarz, Julia Piaśnik, Uazman Alam, Yalin Zheng, Janusz Gumprecht, Gregory Y H Lip, Katarzyna Nabrdalik","doi":"10.1186/s12933-026-03246-5","DOIUrl":"10.1186/s12933-026-03246-5","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular-kidney-metabolic (CKM) syndrome refers to the co-occurrence of obesity, diabetes, chronic kidney disease (CKD), and cardiovascular disease. However, it is underdiagnosed due to silent clinical nature of the early stages of its components and subsequent siloed medical care. Electrocardiography (ECG) is an inexpensive and widely available diagnostic tool but its utility in automated detection of CKM syndrome has not been previously explored.</p><p><strong>Objective: </strong>To develop and evaluate deep learning models for predicting CKM syndrome using scanned limb and augmented limb leads ECGs images in people with diabetes.</p><p><strong>Methods: </strong>Clinical data of adults with type 1 or type 2 diabetes enrolled in the prospective Silesia Diabetes-Heart Project were analyzed. CKM syndrome was defined by the presence of either CKD [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² and/or urine albumin to creatinine ratio (UACR) ≥ 30 mg/g) or established CVD. High-resolution scanned ECG tracings were processed into lead-specific inputs to train ResNet-50-based convolutional neural network (CNN) models, including single- and dual-channel variants. Class imbalance was addressed using resampling strategies, and model performance was evaluated using standard classification metrics, including area under the receiver operating characteristic curve (AUROC), with confidence intervals estimated by bootstrap resampling.</p><p><strong>Results: </strong>Among 2779 participants, 492 (17.7%) met criteria for CKM syndrome. The best-performing individual model was a dual-channel ResNet-50 with soft voting ensemble, achieving an AUROC of 0.8199 (95% CI 0.7549-0.8795), F1-score of 0.7213 (95% CI 0.6404-0.7957), accuracy of 0.7385, and balanced precision and recall. Ensemble models consistently outperformed individual architectures, particularly in handling class imbalance and improving generalization.</p><p><strong>Conclusion: </strong>Deep learning applied to scanned ECG image data predicts CKM syndrome in individuals with diabetes with reasonable accuracy. This approach holds promise as a low-cost, scalable risk stratification tool and which could augment clinical decision-making in settings particularly with limited access to advanced diagnostics. Trial registration The study is registered at ClinicalTrials.gov (NCT05626413).</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between surrogate indicators of insulin resistance and all-cause mortality in patients with severe hemorrhagic stroke: a multicenter retrospective cohort study in the United States.","authors":"Dewei Zou, Bo Lin, Bo Wu, Wanli Yu, Gang Zhang, Haotian Jiang, Chuan Shao, Nan Wu","doi":"10.1186/s12933-026-03270-5","DOIUrl":"10.1186/s12933-026-03270-5","url":null,"abstract":"<p><strong>Background: </strong>Hemorrhagic stroke (HS), including non-traumatic intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), accounts for approximately 30% of all stroke cases and over 40% of stroke-related deaths. With high mortality and disability rates, HS imposes a heavy global health burden. As a core metabolic disorder, insulin resistance (IR) has been proven to be associated with all-cause mortality (ACM) in patients with ischemic stroke in previous studies. Nevertheless, its prognostic value remains unclear in critically ill HS patients admitted to the intensive care unit (ICU). Given the markedly higher mortality and morbidity of HS compared with ischemic stroke, it is essential to explore this association. This study aimed to investigate the correlations between multiple surrogate markers of insulin resistance and all-cause mortality among critically ill HS patients in the ICU setting.</p><p><strong>Methods: </strong>Data were extracted from the public eICU-CRD database. Patients with severe HS were identified based on the International Classification of Diseases (ICD)-9/10 diagnostic codes. A total of 1538 ICU-admitted patients with severe HS were enrolled and stratified according to quartiles of various IR surrogate markers. The primary endpoint was in-hospital mortality. Cox regression analysis, Kaplan-Meier survival curves, restricted cubic splines (RCS) and receiver operating characteristic (ROC) curves were adopted for statistical analyses.</p><p><strong>Results: </strong>Among the 1538 enrolled patients, males accounted for 54.6%, and the overall in-hospital all-cause mortality was 26.59%. Multivariate Cox regression analyses revealed that all IR surrogate markers were significantly correlated with all-cause mortality in severe HS patients. SPISE was negatively correlated with all-cause mortality, while other indicators showed positive correlations. Restricted cubic spline analyses demonstrated non-linear relationships between TyG, SPISE, TG_HDL, METS_IR, TyG_BMI, TyG_RC and mortality. No significant effect modification was observed in interaction analyses. ROC curve analysis indicated that TyG exhibited the highest predictive accuracy.</p><p><strong>Conclusion: </strong>In conclusion, insulin resistance surrogate markers were significantly associated with all-cause mortality in critically ill HS patients. Despite their weak-to-moderate discriminative performance, these indices may serve as auxiliary prognostic references for risk stratification. Clinical application of these indicators is expected to optimize therapeutic strategies and disease progression management. Furthermore, this study enriches current evidence regarding the association between insulin resistance surrogate markers and hemorrhagic stroke, and clarifies their roles in predicting mortality across different stroke subtypes.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating lipometabolic and adiposity indices to enhance risk stratification for metabolic dysfunction-associated steatotic liver disease in type 2 diabetes: clinical utility and interplay between triglyceride-glucose body mass index and low-density lipoprotein cholesterol.","authors":"Yanxiu Yang, Xiaoxiao Qu, Mengran Shi, Jialu Huang, Guanghong Li, Xingyu Lu, Enxin You, Jingyun Qian, Jing Xu, Minghua Jiang, Guosong Jiang, Qipeng Xie","doi":"10.1186/s12933-026-03272-3","DOIUrl":"10.1186/s12933-026-03272-3","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) significantly exacerbates the prognosis of patients with type 2 diabetes mellitus (T2DM). We aimed to compare metabolic and adiposity-related surrogates for MASLD using data-driven feature selection and to validate a parsimonious risk model across distinct populations.</p><p><strong>Methods: </strong>We included 449 T2DM patients from the WMU cohort (discovery) and 306 from the Japanese NAGALA cohort (external validation). A two-stage data-driven feature-selection framework (Boruta and LASSO) was implemented to identify a parsimonious two-variable signature (TyG-BMI and SGLT2i). Based on these results, TyG-BMI was prioritized for systematic evaluation. Association and dose-response relationships were assessed via multivariate logistic regression and restricted cubic splines. Multiplicative and additive interactions between TyG-BMI and LDL-C were further explored. Clinical utility was evaluated via AUC, NRI, IDI, and decision curve analysis.</p><p><strong>Results: </strong>The Boruta algorithm ranked TyG-BMI as the feature with the highest importance score for MASLD classification. Subsequently, LASSO regression (utilizing the 1-standard-error criterion λ1se) identified a parsimonious two-variable signature comprising TyG-BMI and SGLT2i. In the WMU cohort, TyG-BMI exhibited a potent association with MASLD (T3 vs. T1: OR = 7.36, 95% CI 3.89-13.94) and a significant linear dose-response relationship (P for overall < 0.001). Incorporation of TyG-BMI into the baseline model improved discriminative performance (AUC increased from 0.7288 to 0.7920) and was associated with improved continuous reclassification (NRI: 0.6088, P < 0.001). DCA and calibration plots confirmed high clinical net benefit and accuracy. Furthermore, a significant synergistic interaction was observed between TyG-BMI and low-density lipoprotein cholesterol (LDL-C).</p><p><strong>Conclusions: </strong>TyG-BMI, selected through data-driven feature selection, may serve as a practical candidate predictor of MASLD in patients with T2DM. The observed interaction between TyG-BMI and LDL-C suggests that their joint assessment may further refine MASLD risk stratification. The derived parsimonious model offers a high-performing, non-invasive tool for early MASLD risk stratification across Asian populations.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid Cdc42 deficiency-mediated macrophage pyroptosis exacerbates diabetic cardiomyopathy in type 1 diabetes mellitus.","authors":"Li-Xin Liu, Jing He, Feng Zhang, Xin-Qiao Li, Xin-Yu Xiao, Xiao-Ying Zhou, Qi-Kun Yang, Ming-Hui Wu, Xu-Hui Qiao, Bing-Qian Lu, Zhe-Yu Pang, Hong-Wei Sun, Zhao-Xia Chen, Ying-Jie HongShu, Hong-Bo Xin, Ke-Yu Deng","doi":"10.1186/s12933-026-03268-z","DOIUrl":"10.1186/s12933-026-03268-z","url":null,"abstract":"<p><strong>Background: </strong>Diabetic cardiomyopathy (DCM) is one of the severe complications in type 1 diabetes mellitus (T1DM) patients with impaired cardiac function and faster progression to heart failure due to systolic malfunction. It has been demonstrated that macrophage-mediated chronic inflammation is closely associated with DCM. Cell division cycle 42 (Cdc42) plays a crucial role in regulating the polarization, migration and phagocytosis of macrophages, however, the underlying mechanism of Cdc42 in DCM remains to be elucidated.</p><p><strong>Methods: </strong>Mouse DCM models with T1DM were generated using myeloid-specific Cdc42-knockout (Cdc42^Mye) and Cdc42^Flox/Flox (Cdc42^Flox) male mice at 10-12 weeks old by injection of streptozotocin (STZ, 50 mg/kg/day) for 6 continuous days and then following the observation of 16 weeks. Cardiac functions were assessed by echocardiography in vivo, and cardiac morphological and histopathological alterations were evaluated by hematoxylin and eosin (HE), Masson's trichrome, Picrosirius red, and immunohistochemistry staining, respectively. The infiltration of myeloid macrophages was examined by multiplex immunofluorescence tyramide signal amplification (TSA) assay or Rosa mTmG fluorescent myeloid tracking reporter in mice. Macrophage pyroptosis, cardiomyocyte damage and myofibroblast activation were evaluated by Western blot and immunofluorescence analysis. Additionally, single-cell RNA-seq (scRNA-seq) data analysis was performed to explore macrophage-mediated signaling in DCM using publicly available GSE datasets from STZ-induced T1DM mice.</p><p><strong>Results: </strong>Myeloid Cdc42 deletion exacerbated T1DM-induced cardiac dysfunctions and histopathological changes including cardiac fibrosis, and promoted T1DM-induced macrophage infiltration and M1 polarization of macrophages, and facilitated T1DM-induced pyroptosis by activating NLRP3 inflammasome in the hearts in mice. Notably, there were no significant differences between Cdc42^Mye and Cdc42^Flox mice under normal condition. In addition, gene set enrichment analysis (GSEA) of scRNA-seq data indicated that low Cdc42 expression in macrophages was positively associated with the NF-κB signaling pathway in DCM. Mechanistically, we demonstrated that Cdc42 deficiency or inhibition aggravated T1DM-induced cardiomyocyte injury and cardiac fibrosis by activating ERK_1/2-NF-κB-interleukin-1β signaling pathway-mediated macrophage pyroptosis.</p><p><strong>Conclusions: </strong>This study demonstrates that myeloid Cdc42 deficiency or inhibition aggravates T1DM-induced cardiomyocyte injury and cardiac fibrosis of DCM by promoting macrophage pyroptosis and inflammatory responses, which might provide a novel therapeutic target for immunomodulatory intervention in DCM of type 1 diabetes mellitus.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of cumulative exposure and longitudinal change patterns of the triglyceride glucose-Chinese visceral adiposity index with incident cardiovascular disease in middle-aged and older adults: evidence from CHARLS.","authors":"Huilin Liu, Ximin Zhang, Kangning Tang, Xiaojiao Zhang, Sijing Li, Ziru Li, Xiaoming Dong, Huili Liao, Wenjie Long, Zhenjie Zhuang, Shihao Ni, Zhongqi Yang","doi":"10.1186/s12933-026-03258-1","DOIUrl":"10.1186/s12933-026-03258-1","url":null,"abstract":"<p><strong>Background: </strong>The triglyceride glucose-Chinese visceral adiposity index (TyG-CVAI), an integrated marker of insulin resistance and visceral adiposity, has been associated with cardiovascular outcomes. However, the longitudinal cardiovascular implications of cumulative TyG-CVAI exposure and directional changes in TyG-CVAI remain insufficiently characterized. This study aimed to examine the associations of cumulative TyG-CVAI exposure and longitudinal TyG-CVAI change patterns with incident cardiovascular disease (CVD) among middle-aged and older Chinese adults.</p><p><strong>Methods: </strong>This prospective study included 4,338 participants from the China Health and Retirement Longitudinal Study (CHARLS) who were free of CVD during the exposure assessment period from 2011 to 2015 and had complete TyG-CVAI data in 2011 and 2015. Participants were categorized into four TyG-CVAI change patterns (low-low, low-high, high-low, and high-high). Cumulative TyG-CVAI was calculated using repeated measurements from 2011 to 2015 and analyzed as both a standardized continuous variable and quartiles. Incident CVD was defined as new-onset heart disease or stroke during follow-up. Kaplan-Meier analysis, multivariable Cox proportional hazards models, and restricted cubic spline (RCS) analysis were performed.</p><p><strong>Results: </strong>During a mean follow-up of 5 years, 845 incident CVD events occurred among 4,338 participants. Compared with the low-low group, the fully adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD were 1.50 (1.21-1.88) for the low-high group, 1.64 (1.20-2.25) for the high-low group, and 1.77 (1.49-2.09) for the high-high group. When cumulative TyG-CVAI was analyzed as a standardized continuous variable, each 1-SD increase was associated with a higher risk of incident CVD after full adjustment (HR 1.10, 95% CI 1.06-1.14). When categorized into quartiles, participants in the highest quartile had a higher CVD risk than those in the lowest quartile (HR 1.91, 95% CI 1.56-2.33; P for trend < 0.001). RCS analysis revealed a significant nonlinear association between cumulative TyG-CVAI and incident CVD.</p><p><strong>Conclusion: </strong>Higher cumulative TyG-CVAI burden and unfavorable longitudinal change patterns were associated with an increased risk of incident CVD among middle-aged and older Chinese adults. These findings suggest that repeated TyG-CVAI assessment may help identify individuals with sustained or worsening metabolic-visceral burden and support longitudinal cardiovascular risk stratification.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular-liver-metabolic multimorbidity: preliminary insights into the associations with the triglyceride glucose index (TyG), its obesity-derived indices and their effects on long-term survival.","authors":"Shiming He, Yanfeng Liu, Guotai Sheng, Guobo Xie, Wei Wang, Hengli Lai, Yang Zou, Chao Wang","doi":"10.1186/s12933-026-03271-4","DOIUrl":"10.1186/s12933-026-03271-4","url":null,"abstract":"<p><strong>Background: </strong>The triglyceride-glucose (TyG) and its obesity‑derived indices are important composite parameters of insulin resistance coupled with obesity, and have been associated with cardiometabolic diseases. However, their associations with cardiovascular‑liver‑metabolic multimorbidity (CLMM) remain unclear. This study aims to systematically compare TyG and its obesity-derived indices to identify the optimal surrogate marker for CLMM, and to explore the potential impact of CLMM status on mortality.</p><p><strong>Methods: </strong>Based on a multi-stage sampling design of a national cohort, weighted logistic and Cox regression models were applied to evaluate the associations of each index with CLMM and long-term mortality. Discriminatory performance was compared using the area under the receiver operating characteristic curve (AUROC), net reclassification improvement, and integrated discrimination improvement. Additionally, weighted quantile sum regression, and mediation analysis were employed to explore the underlying disease mechanisms.</p><p><strong>Results: </strong>The study included 20,235 adults. Weighted logistic regression analyses for the individual indices revealed that the TyG and its obesity‑derived indices were all positively associated with CLMM, with TyG‑WHtR, TyG‑WWI, and TyG‑CVAI showing the strongest associations. Further longitudinal weighted interaction analyses revealed that CLMM status significantly amplified the mortality risk associated with the TyG and its obesity-derived indices. For CLMM identification, all indices showed favorable diagnostic performance (AUROC > 0.76), with TyG‑WWI and TyG‑CVAI achieving the best performance (AUROC > 0.83) and exhibiting the largest net reclassification improvement and integrated discrimination improvement. Joint XGBoost-SHAP analyses further indicated that TyG-CVAI and TyG-WWI were the major contributing variables for discriminating CLMM status. Exploratory mechanistic analyses suggested glucose metabolism as a core driver underlying CLMM development, with inflammatory factors partially mediating these associations.</p><p><strong>Conclusion: </strong>The TyG and its obesity-derived indices, particularly TyG-WWI and TyG-CVAI, exhibited significant incremental value for identifying CLMM, with CLMM status also conferring elevated subsequent mortality risk. Incorporating these indices into primary prevention monitoring systems for chronic diseases could facilitate the identification of individuals at high risk for CLMM and mortality.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}