Cardiovascular Diabetology最新文献

{"title":"Derivatives of the triglyceride-glucose index and their association with incident hypertension in prehypertensive individuals: a 4-year cohort study augmented by mendelian randomization.","authors":"Mengmeng Wang, Tianqi Teng, Nan Zhang, Jiachao Xu, Zihan Dong, Qingying Jiao, Ning Zhang, Haichu Yu","doi":"10.1186/s12933-025-02813-6","DOIUrl":"10.1186/s12933-025-02813-6","url":null,"abstract":"<p><strong>Background: </strong>The direct association between elevated levels of the triglyceride-glucose index (TyG index) and its derived metrics and the risk of new-onset hypertension in prehypertensive populations remains unclear. The study systematically evaluated the link between the TyG index and its related indicators with new-onset hypertension by integrating cohort study methods with Mendelian randomization (MR) analysis.</p><p><strong>Methods: </strong>A total of 2,815 prehypertensive participants from the 2011 CHARLS database were included, of whom 877 (31.15%) progressed to new-onset hypertension by 2015. TyG-Waist-to-Height Ratio (TyG-WHtR), TyG-Body Mass Index (TyG-BMI), TyG-Waist Circumference (TyG-WC), and the TyG index were calculated. Logistic regression, restricted cubic spline (RCS) curves, subgroup analyses, and interaction tests were performed to assess the associations. Bayesian weighted MR (BWMR) was further used to validate causal relationships.</p><p><strong>Results: </strong>Multivariable regression analysis revealed that each unit increase in the TyG index was associated with a 45% higher risk of new-onset hypertension (odds ratio [OR]: 1.45, 95% confidence intervals [CI] 1.24-1.70, P < 0.001), while TyG-WHtR showed a 42% increased risk (OR: 1.42, 95% CI 1.26-1.60, P < 0.001). Categorizing the TyG and its derived metrics by quartiles demonstrated that higher quartiles (Q3 and Q4) were significantly linked to an elevated risk of new-onset hypertension across all models (P < 0.001). RCS models indicated significant positive linear relationships between the TyG index and TyG-WC with new-onset hypertension (P for overall < 0.001, P for nonlinearity = 0.844 and 0.165, respectively), whereas TyG-WHtR and TyG-BMI exhibited significant positive nonlinear relationships (P for overall < 0.001, P for nonlinearity = 0.001 and 0.046, respectively). Subgroup analyses highlighted stronger associations among individuals aged ≥ 70 years, those who were widowed, had cardiovascular disease, or reported a life satisfaction score of 2 (P < 0.05, P for interaction < 0.05). BWMR analysis confirmed a significant causal relationship between genetically elevated TyG index levels and an increased risk of new-onset hypertension (P < 0.05).</p><p><strong>Conclusions: </strong>Our study reveals a significant link between the TyG index and its related indicators with new-onset hypertension in prehypertensive populations. Causal analysis using BWMR confirmed that genetically elevated TyG index levels increase the risk of new-onset hypertension. These results highlight the importance of monitoring TyG-related indices for early detection and intervention in high-risk individuals, aiding in the prevention of hypertension progression.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"284"},"PeriodicalIF":8.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616314","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":"Combined impact of prediabetes and fatty liver index on cardiometabolic outcomes and mortality in middle aged adults: a nationwide cohort study.","authors":"Young Sang Lyu, Minae Park, Hee Kyung Kim, Sojeong Park, Ji Yong Park, A Ram Hong, Jee Hee Yoon, Seogsong Jeong, Youngmin Yoon, Jin Hwa Kim, Sang Yong Kim, Ho-Cheol Kang, Wonsuk Choi","doi":"10.1186/s12933-025-02793-7","DOIUrl":"10.1186/s12933-025-02793-7","url":null,"abstract":"<p><strong>Background: </strong>To investigate the combined effect of prediabetes and fatty liver index on incident diabetes (DM), major adverse cardiovascular events (MACE), and mortality in middle-aged adults.</p><p><strong>Methods: </strong>A nationwide cohort study was conducted involving 1,182,751 middle-aged adults aged 40 to 65 years, all of whom had no history of diabetes or cardiovascular disease. The primary outcomes of our study included incident DM, composite MACE and all-cause mortality.</p><p><strong>Results: </strong>Among the participants, 24.6% were diagnosed with prediabetes, while 8.8% had FLI ≥ 60 at baseline. Both conditions independently increased the risk of incident DM, composite MACE, and all-cause mortality. Stratification based on the presence of prediabetes and FLI ≥ 60 showed that their combination posed the highest risk for outcomes, even after adjusting for relevant covariates. For incident DM, the odds ratios (ORs) with 95% confidence intervals (CI) were as follows: 3.75 (3.69-3.81), 2.35 (2.29-2.42), and 6.80 (6.62-6.98) for prediabetes with FLI < 60, normoglycemia with FLI ≥ 60, and prediabetes with FLI ≥ 60, respectively. For composite MACE, the ORs (95% CI) were 1.02 (1.00-1.05), 1.23 (1.17-1.28), and 1.27 (1.21-1.33) for prediabetes with FLI < 60, normoglycemia with FLI ≥ 60, and prediabetes with FLI ≥ 60, respectively. For all-cause mortality, ORs (95% CI) were 1.12 (1.08-1.15), 1.51 (1.43-1.59), and 1.69 (1.60-1.79) for prediabetes with FLI < 60, normoglycemia with FLI ≥ 60, and prediabetes with FLI ≥ 60, respectively.</p><p><strong>Conclusion: </strong>The coexistence of prediabetes and FLI ≥ 60, which is a surrogate marker of hepatic steatosis, demonstrated a combined effect, additively increasing the risk of incident DM, composite MACE, and all-cause mortality in middle-aged adults.</p><p><strong>Trial registration: </strong>Not applicable (retrospectively registered).</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"279"},"PeriodicalIF":8.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607377","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":"Prevalence and thrombotic risk of SGLT-2 inhibitor-associated erythrocytosis: a retrospective cohort study.","authors":"Ji Yun Lee, Ju-Hyun Lee, Eun-Jung Jung, Woochan Park, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Sang-A Kim, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jeong-Ok Lee, Jin Won Kim, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang","doi":"10.1186/s12933-025-02805-6","DOIUrl":"10.1186/s12933-025-02805-6","url":null,"abstract":"<p><strong>Background: </strong>Sodium-glucose cotransporter 2 (SGLT-2) inhibitors, widely used for type 2 diabetes and cardiorenal conditions, may induce erythrocytosis, potentially increasing cardiovascular risk. This study investigates its prevalence, risk factors, and thrombotic implications.</p><p><strong>Methods: </strong>In a single-center retrospective study, we analyzed 6787 patients prescribed SGLT-2 inhibitors (2014-2024). Erythrocytosis was defined as hemoglobin > 16.5 g/dL or hematocrit > 49% in men, > 16.0 g/dL or > 48% in women. We assessed prevalence, risk factors, and thrombotic events using logistic regression.</p><p><strong>Results: </strong>Erythrocytosis occurred in 1145 patients (16.9%) over a median follow-up of 530 days (IQR, 277-981), with a median hemoglobin rise of 1.0 g/dL (IQR, 0.4-1.8). Male sex (OR 3.24, 95% CI 2.47-4.26), BMI ≥ 25 kg/m² (OR 1.97, 95% CI 1.63-2.39), and current smoking (OR 2.41, 95% CI 1.96-2.96) significantly increased risk (all p < 0.001), while age ≥ 70 years, hypertension, dyslipidemia, and chronic kidney disease were associated with reduced risk. Thrombosis was rare (0.5%, 33 patients) and associated with antiplatelet use (OR 3.57, 95% CI 1.60-7.97), anticoagulant use (OR 5.93, 95% CI 2.60-13.57), and baseline erythrocytosis (OR 3.75, 95% CI 1.41-9.96). Among 33 patients with thrombosis, five exhibited erythrocytosis at the time of the event and within the prior six months; all had arterial thrombosis associated with underlying conditions (atrial fibrillation, coronary calcification, atherosclerosis), not directly attributable to SGLT-2-induced erythrocytosis.</p><p><strong>Conclusions: </strong>SGLT-2 inhibitors are associated with a 16.9% prevalence of erythrocytosis, but thrombotic risk appears primarily driven by pre-existing conditions.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"276"},"PeriodicalIF":8.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607425","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":"Preclinical atherosclerosis and prediabetes: a cross-sectional metabolic assessment in apparently healthy population.","authors":"Natalia Zieleniewska, Jacek Jamiołkowski, Marcin Kondraciuk, Michal Ciborowski, Katarzyna Ptaszyńska, Małgorzata Chlabicz, Marlena Dubatówka, Urszula Roszkowska, Irina Kowalska, Karol Kamiński","doi":"10.1186/s12933-025-02841-2","DOIUrl":"10.1186/s12933-025-02841-2","url":null,"abstract":"<p><strong>Introduction: </strong>Prediabetes and preclinical atherosclerosis are interrelated conditions contributing to cardiovascular risk, even in apparently healthy individuals. Metabolomics provides insights into the early metabolic alterations underpinning these diseases.</p><p><strong>Objectives: </strong>This study aimed to investigate the shared and distinct metabolic signatures associated with prediabetes and preclinical atherosclerosis in a population with low to moderate cardiovascular risk, using a targeted metabolomic approach.</p><p><strong>Methods: </strong>A cross-sectional analysis was performed on 447 participants (mean age 39.7 ± 9.6 years) from the Białystok PLUS cohort. Prediabetes was diagnosed based on HbA1c and OGTT criteria. Preclinical atherosclerosis was assessed by carotid ultrasound. Targeted metabolomics profiling encompassed 434 metabolites and 218 metabolite sums or ratios using HPLC-MS/MS. Statistical analyses included ANOVA, linear regression, correlation analysis, and metabolite set enrichment analysis (MSEA).</p><p><strong>Results: </strong>Prediabetes was significantly associated with preclinical atherosclerosis (30.8% vs. 19.5%, p = 0.006). Prediabetes had a broader metabolic impact than atherosclerosis, particularly affecting amino acid and lipid metabolism. Glutamic acid, lactic acid, and L-alanine were strongly associated with prediabetes. Trimethylamine N-oxide (TMAO) was uniquely linked to both prediabetes and its interaction with atherosclerosis, suggesting a context-dependent metabolic response. Glutaminase activity emerged as a robust shared metabolic feature of both conditions. Pathway analyses revealed converging disturbances in glutathione and folate metabolism, mitochondrial function, and redox regulation.</p><p><strong>Conclusions: </strong>Prediabetes is associated with more pronounced metabolic alterations than preclinical atherosclerosis. TMAO and glutaminase activity may represent key metabolic links between these conditions. These findings highlight the potential of metabolomics in identifying early biomarkers and mechanisms relevant to the prevention of cardiometabolic diseases.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"280"},"PeriodicalIF":8.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607424","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 between modified triglyceride glucose indices and stroke risk in middle-aged and older Chinese adults: a prospective cohort study.","authors":"Jiaan Sun, Xianglong Meng, Lichun Guo, Chongwen Nian, Haina Li, Wanxin Huang","doi":"10.1186/s12933-025-02827-0","DOIUrl":"10.1186/s12933-025-02827-0","url":null,"abstract":"<p><strong>Objective: </strong>Various modified triglyceride and glucose (TyG) indices have been proposed, but the literature on the impact and ability of the modified TyG index to predict stroke disease remains limited. We aimed to investigate the associations between the modified TyG indices and incident stroke diseases and to compare their predictive power in a nationally representative cohort.</p><p><strong>Methods: </strong>This was a prospective cohort study with longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS), which was based on data from four CHARLS surveys in 2011, 2013, 2015 and 2018, and included a total of 8677 participants. The Cox proportional risk model, Restricted Cubic Spline (RCS), and Receiver Operating Characteristic curve (ROC) were analyzed for the associations of TyG-BMI, TyG-WC and TyG-WHtR with stroke risk. In addition, the robustness of the findings was further validated using a series of sensitivity analyses and subgroup analyses.</p><p><strong>Results: </strong>During the follow-up period from 2011 to 2018, 807 (9.3%) of the 8677 participants experienced stroke. After multifactorial adjustment (Model III), a 10-unit increase in TyG-BMI corresponded to a 5.5% increased risk of stroke (HR = 1.055, 95% CI 1.033-1.078), a 10-unit increase in TyG-WC corresponded to a 2.0% increased risk of stroke (HR = 1.020, 95% CI 1.012-1.027), and a 1-unit increase in TyG-WHtR corresponded to a 32.4% increased risk of stroke (HR = 1.324, 95% CI 1.178-1.487). Compared with individuals in the lowest quartile (Q₁), those in higher quartiles showed progressively elevated risks. For TyG-BMI, adjusted hazard ratios increased by 39.1% (Q₂), 62.1% (Q₃), and 86.1% (Q₄); for TyG-WC, by 40.6%, 63.0%, and 88.8%; and for TyG-WHtR, by 36.5%, 65.7%, and 83.7%, respectively. The RCS showed a nonlinear dose‒response relationship between TyG-BMI and stroke and a nonlinear dose‒response relationship between TyG-WC. In addition, TyG-WHtR had a linear dose‒response relationship with stroke. The area under the curve (AUC) values were 0.5930, 0.6078 and 0.6032, respectively, and all three had comparable predictive abilities for stroke risk, with TyG-WC having slightly greater predictive ability. The results of the sensitivity analysis and subgroup analysis were consistent with the main results.</p><p><strong>Conclusions: </strong>In middle-aged and elderly populations, TyG-BMI, TyG-WC and TyG-WHtR are positively correlated with the risk of stroke. Maintaining favorable levels of these indices through weight and waist management may help reduce stroke risk.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"274"},"PeriodicalIF":8.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607375","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 between trajectory of triglyceride-glucose index and all-cause mortality in critically ill patients with atrial fibrillation: a retrospective cohort study.","authors":"Shangsong Shi, Feng Xue, Tingbo Jiang, Lin Ling","doi":"10.1186/s12933-025-02838-x","DOIUrl":"10.1186/s12933-025-02838-x","url":null,"abstract":"<p><strong>Introduction: </strong>Previous evidence showed that triglyceride-glucose (TyG) index is strongly associated with poor prognosis in atrial fibrillation (AF) in the general population. In critically ill patients, physiological stress may cause rapid fluctuation in the TyG index, making single measurements insufficient for prognosis assessment. Furthermore, the impact of TyG index trajectories on outcomes in critically ill patients with atrial fibrillation has not yet been well elucidated. Therefore, our study aimed to assess the association between TyG index trajectories in patients with AF in intensive care unit (ICU) and all-cause mortality at 30-day, 90-day, 180-day and 365-day follow-up.</p><p><strong>Methods: </strong>We used data from Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients diagnosed with AF in ICU were enrolled. We applied group-based trajectory modeling to identify distinct TyG index trajectories, selecting the optimal model based on the Bayesian information criterion (BIC), Akaike information criterion (AIC), average posterior probability (AvePP), and clinical interpretability. Kaplan-Meier survival curve was used to compare the mortality in AF patients with different TyG index trajectories. Hazard ratios (HRs) were calculated to elucidate the association between trajectories and prognosis in Cox proportional hazard models. Restricted cubic splines (RCS) were used to assess the relationship between TyG index and outcomes.</p><p><strong>Results: </strong>A total of 1,108 AF patients were enrolled. Four TyG index trajectories were identified including: (1) traj1 group (TyG index stable at low level), (2) traj2 group (TyG index slowly ascending at moderate level), (3) traj3 group (TyG index ascending then descending at moderate high level) and (4) traj4 group (TyG index fluctuate at high level). The Traj4 group demonstrated significantly higher mortality rates at all time points (30-day, 90-day, 180-day and 365-day) compared to other trajectory groups. In addition, Cox proportional hazard models indicated that patients in traj4 group had higher risk of mortality compared to those in traj1 group at 30-day (HR = 1.71, 95% confidence interval [CI], 1.14-2.56), 90-day (HR = 1.67, 95% CI, 1.17-2.39), 180-day (HR = 1.44, 95% CI, 1.03-2.06) and 365-day (HR = 1.44, 95% CI, 1.04-1.98). Meanwhile, the RCS indicated a linear association between TyG index and all-cause mortality.</p><p><strong>Conclusion: </strong>In critically ill patients with AF, TyG index trajectories were significantly associated with 30-day, 90-day, 180-day and 365-day all-cause mortality. This suggested that TyG index trajectories could serve as a robust indicator for risk stratification and prognosis assessment in ICU patients with AF.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"278"},"PeriodicalIF":8.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607376","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":"Prognostic value of lipoprotein(a) for cardiovascular events after lower limb revascularization in diabetic patients with chronic limb-threatening ischemia.","authors":"Federico Biscetti, Maria Margherita Rando, Maria Anna Nicolazzi, Flavia Angelini, Roberto Iezzi, Luis H Eraso, Paul J Dimuzio, Dario Pitocco, Massimo Massetti, Antonio Gasbarrini, Andrea Flex","doi":"10.1186/s12933-025-02833-2","DOIUrl":"10.1186/s12933-025-02833-2","url":null,"abstract":"<p><strong>Background: </strong>Chronic limb-threatening ischemia (CLTI) presents a major clinical challenge in patients with Type 2 Diabetes Mellitus (T2DM), requiring lower extremity revascularization (LER) to mitigate adverse cardiovascular and limb outcomes. Lipoprotein(a) (Lp(a)) has been implicated in cardiovascular risk, but its role in patients with T2DM and CLTI undergoing revascularization remains unclear. Thus, this study aimed to investigate the prognostic value of Lp(a) levels in diabetic CLTI patients for major adverse cardiovascular events (MACE), major adverse limb events (MALE), or both after LER.</p><p><strong>Methods: </strong>In this prospective cohort study of 158 individuals with T2DM and CLTI undergoing LER, baseline clinical data were collected, including Lp(a) levels. Patients were followed for occurrence of MACE, MALE, or both over a 12-month period.</p><p><strong>Results: </strong>During follow-up, 74 patients (46.8%) experienced events (MACE, MALE, or both). Patients with events had significantly higher median Lp(a) levels than those without (48.0 vs. 8.1 mg/dL, p < 0.01). Lp(a) was independently associated with adverse events (HR 1.07, 95% CI 1.04-1.10; p < 0.01). In multivariable analysis, elevated Lp(a) was independently associated with both MACE (HR 1.08, 95% CI 1.03-1.13; p < 0.01) and MALE (HR 1.05, 95% CI 1.02-1.07; p < 0.01). An empirical Lp(a) cutoff of 29.6 mg/dL conferred a 3.8-fold increased risk of events (p < 0.01). Kaplan-Meier survival analysis further confirmed a significantly higher cumulative incidence of events in patients with Lp(a) levels above cutoff (p < 0.01). ROC curve comparison analysis showed that the inclusion of Lp(a) significantly improved the predictive performance of the base clinical model (AUC from 0.74 to 0.98, p < 0.01 for composite outcome; from 0.81 to 0.89, p = 0.03 for MACE; and from 0.78 to 0.92, p < 0.01for MALE).</p><p><strong>Conclusions: </strong>This study demonstrated that Lp(a) is a strong independent predictor of both cardiovascular and limb events in patients with T2DM undergoing LER for CLTI. These findings support the potential role of Lp(a) as a marker of residual risk in this high-risk population and suggest its utility in risk stratification.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"271"},"PeriodicalIF":8.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607426","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":"Triglyceride-glucose-related indices and risk of cardiovascular disease and mortality in individuals with cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3: a prospective cohort study of 282,920 participants in the UK Biobank.","authors":"Kun Liu, Jinling Hu, Yueqing Huang, Dingliu He, Jing Zhang","doi":"10.1186/s12933-025-02842-1","DOIUrl":"10.1186/s12933-025-02842-1","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular-kidney-metabolic (CKM) syndrome, proposed by the American Heart Association, is strongly linked to cardiovascular disease (CVD) incidence and mortality. Triglyceride-glucose (TyG)-related indices are established predictors of CVD risk, but their associations with CVD and mortality in individuals with CKM syndrome remain understudied.</p><p><strong>Methods: </strong>This prospective study analyzed 282,920 UK Biobank participants with CKM syndrome stages 0-3, free of CVD at baseline. Four TyG-related indices were evaluated: TyG index, TyG-body mass index (BMI), TyG-waist circumference (TyG-WC), and TyG-waist-to-height ratio (TyG-WHtR). Outcomes, including overall CVD, coronary heart disease (CHD), stroke, all-cause mortality, and cardiovascular mortality, were identified via electronic medical records and death registries. Associations were analyzed via Cox proportional hazards and restricted cubic spline (RCS) models, with incremental predictive performance evaluated by the net reclassification index (NRI), integrated discrimination improvement (IDI), and area under the curve (AUC).</p><p><strong>Results: </strong>During a median follow-up of 13.6 years, 27,134 overall CVD cases, 21,658 CHD, 6,717 strokes, 19,381 all-cause deaths, and 3,466 cardiovascular deaths occurred. Compared with the lowest quartile, the fully adjusted hazard ratios (HRs) for participants in the highest TyG quartile were 1.30 (95% CI 1.25-1.35) for overall CVD. Consistent positive associations were observed for TyG-BMI (HR: 1.49, 95% CI 1.43-1.55), TyG-WC (HR: 1.58, 95% CI 1.51-1.65), and TyG-WHtR (HR: 1.58, 95% CI 1.51-1.65). For all-cause mortality, HRs (95% CIs) in the highest versus the lowest quartile were 1.11 (1.06-1.16) for TyG-BMI, 1.24 (1.18-1.31) for TyG-WC, and 1.18 (1.13-1.24) for TyG-WHtR. Similar patterns were seen for cardiovascular mortality: TyG-BMI (HR: 1.42, 95% CI 1.27-1.59); TyG-WC(HR: 1.51, 95% CI 1.33-1.72); TyG-WHtR (HR: 1.48, 95% CI 1.31-1.67). RCS analyses revealed nonlinear associations between TyG-related indices and overall CVD (all P values for nonlinearity < 0.05), except for the TyG index, which showed a linear trend. Associations with cardiovascular mortality were predominantly linear. Furthermore, TyG-WHtR, TyG-WC, and TyG-BMI exhibited significantly higher NRI, IDI, and AUC values.</p><p><strong>Conclusion: </strong>Higher TyG-related indices, especially TyG-BMI, TyG-WC, and TyG-WHtR, were significantly associated with a higher risk of incident CVD and mortality in individuals with CKM syndrome stage 0 to 3. Integrating TyG indices with obesity measures could enhance the incremental predictive performance for prognostic outcomes in CKM syndrome patients.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"277"},"PeriodicalIF":8.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607429","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":"Acid sphingomyelinase promotes diabetic cardiomyopathy via disruption of mitochondrial calcium homeostasis.","authors":"Yu Wei, Yang Ji, Jiahui Meng, Li Yu, Yongzhong Tang, Wei-Jin Fang","doi":"10.1186/s12933-025-02801-w","DOIUrl":"10.1186/s12933-025-02801-w","url":null,"abstract":"<p><strong>Background: </strong>Impaired Ca²⁺ handling is involved in diabetic cardiomyopathy (DCM) progression. The activation of acid sphingomyelinase (ASMase) stimulated cardiomyocytes apoptosis and caused DCM. Here, we aimed to investigate whether ASMase regulates mitochondrial Ca²⁺ homeostasis by acting on mitochondrial calcium uptake 1 (MICU1) and mitochondria-associated endoplasmic reticulum membranes (MAMs) formation to induce apoptosis during DCM.</p><p><strong>Methods and results: </strong>We established a type 2 diabetes model by combining high-fat diet (HFD) with streptozotocin (STZ) injection in wild-type and cardiomyocyte-specific ASMase deletion (ASMase^Myh6KO) mice. ASMase deletion restored HFD/STZ-induced cardiac dysfunction, remodeling, myocardial lipid accumulation and apoptosis. Single cell sequencing and Gene ontology (GO) enrichment analysis pointed to \"cardiac muscle contraction\" and \"positive regulation of mitochondrial calcium ion concentration\", which were confirmed by high glucose (HG, 30 mM) and palmitic acid (PA, 200 μM) induced mitochondrial Ca²⁺ overload in H9c2 cell lines at time dependence, accompanied by the upregulation of ASMase and MICU1 protein expressions. The similar effects were noted in ASMase overexpressed cardiomyocytes. Interestingly, endoplasmic reticulum (ER) Ca²⁺ level was decreased at the corresponding time, suggesting that increased mitochondrial Ca²⁺ level may be derived from ER. Notably, enhanced MAMs formation was found in HG + PA treated H9c2 cells, accompanied by blocked autophagy, similar results were obtained in ASMase overexpressing cells or HFD/STZ hearts. Loss of ASMase prevented HFD/STZ or HG + PA incubation induced cardiac hypertrophy, mitochondrialCa²⁺ overload, ROS production, autophagy blockage and MICU1 upregulation.</p><p><strong>Conclusions: </strong>HFD/STZ-induced ASMase upregulation enhances MAMs formation, promoting mitochondrial Ca²⁺ overload through MICU1 activation, leading to ROS generation, autophagy blockage and apoptosis in DCM. Therefore, targeting ASMase-MICU1 pathway emerges as a potential therapeutic approach for managing DCM.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"272"},"PeriodicalIF":8.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607374","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":"Muscle-specific miR-499-5p delivered by small extracellular vesicles impairs endothelial function and ischemic hindlimb recovery in diabetic mice.","authors":"Zhongjian Cheng, May M Truongcao, Vandana Mallaredy, Maria Cimini, Charan Thej, Darukeshwara Joladarashi, Carolina Gonzalez, Cindy Benedict, Suresh K Verma, Venkata Naga Srikanth Garikipati, Raj Kishore","doi":"10.1186/s12933-025-02825-2","DOIUrl":"10.1186/s12933-025-02825-2","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence suggests that skeletal muscle cells (SKMC) play critical roles in the defective angiogenic response in diabetic critical limb ischemia. However, the molecular mechanisms linking skeletal muscle to impaired angiogenic properties of endothelial cells (EC) remain unidentified. The current study investigates how muscle-specific miR-499-5p may impair EC function in diabetic ischemic limbs.</p><p><strong>Methods: </strong>Eight-week-old, male C57BL/6 J, db/ + and db/db mice were employed. Hind limb ischemia was established by unilateral ligation of the left femoral artery, and blood flow recovery was monitored using Laser Doppler perfusion imaging (LDPI). ECs and SKMCs were isolated from sham or ischemic hind limbs (IHL). SKMC-derived small extracellular vesicles (SKMC-sEVs) were isolated from the culture medium of SKMCs by ultra-centrifugation.</p><p><strong>Results: </strong>miR-499-5p level was markedly increased in SKMCs and unexpectedly in ECs from hindlimb of db/db mice. Ischemic injury further enhanced miR-499-5p levels in ECs from IHL of db/db mice. Angiogenic activity was reduced in ECs from IHL of db/db mice and in miR-499-5p-overexpressing ECs. Intramuscular injection of lentiviral-anti-miR-499-5p improved blood perfusion and angiogenesis in IHL of db/db mice. Mechanistically, we found that diabetic SKMC sEVs carried high levels of miR-499-5p and transferred miR-499-5p to ECs. Intramuscular injection of diabetic SKMC-sEVs repressed IHL recovery in wildtype mice. Blocking sEV biosynthesis/release by GW4869 markedly improved neovascularization and blood perfusion in IHL of db/db mice. We identified that SRY (Sex-Determining Region Y)-Box 6 (SOX6) is a direct downstream target of miR-499-5p. Silencing of SOX6 suppressed release of proangiogenic factors from ECs. Targeted reduction of miR-499-5p significantly enhanced SOX6 levels in ECs from IHL of db/db mice. Finally, overexpression of SOX6 improved the angiogenic property of ECs from IHL of db/db mice.</p><p><strong>Conclusions: </strong>SKMC-sEV-mediated transfer of myo-miR-499-5p and subsequent suppression of SOX6 plays a critical role in diabetes-impaired neovascularization in IHL of db/db mice. Targeting miR-499-5p-mediated pathogenic communication between SKMCs and ECs may be a novel therapeutic avenue for critical limb ischemia in diabetic patients.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"273"},"PeriodicalIF":8.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607423","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}