Cardiovascular Diabetology最新文献

{"title":"The triglyceride-glucose index, a marker of insulin resistance, as a predictor of thrombotic risk in atrial fibrillation.","authors":"José Miguel Rivera-Caravaca, Eva Soler-Espejo, María Pilar Ramos-Bratos, Raquel López-Gálvez, Eduardo González-Lozano, Gregory Y H Lip, Francisco Marín, Vanessa Roldán","doi":"10.1186/s12933-025-02809-2","DOIUrl":"10.1186/s12933-025-02809-2","url":null,"abstract":"","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"281"},"PeriodicalIF":8.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607428","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":"Remnant-to-LDL cholesterol discordance as a predictor of thromboembolic events in anticoagulated patients with atrial fibrillation: a report from the prospective Murcia AF project III (MAFP-III) cohort study.","authors":"Eva Soler-Espejo, Yang Chen, José Miguel Rivera-Caravaca, María Pilar Ramos-Bratos, Raquel López-Gálvez, Francisco Marín, Vanessa Roldán, Gregory Y H Lip","doi":"10.1186/s12933-025-02831-4","DOIUrl":"10.1186/s12933-025-02831-4","url":null,"abstract":"<p><strong>Background: </strong>Remnant cholesterol (RC) has emerged as an independent contributor to residual cardiovascular risk, beyond low-density lipoprotein cholesterol (LDL-C). As atrial fibrillation (AF) is a common arrhythmia associated with increased thromboembolic risk even despite anticoagulation, we assessed the prognostic value of RC in AF, with a particular focus on its association with LDL-C discordance.</p><p><strong>Methods: </strong>In this prospective cohort study, AF outpatients initiating oral anticoagulation between January 2016 and November 2021 were enrolled. Baseline LDL-C and RC levels were measured, and patients were stratified into four groups based on these values. The primary outcome was a composite of thromboembolic events; secondary outcomes included major adverse cardiovascular events (MACE), cardiovascular death, and all-cause death. Associations between RC levels and clinical outcomes across LDL-C strata were assessed using multivariable Cox proportional hazards models and as a continuous variable using restricted cubic spline (RCS) analyses.</p><p><strong>Results: </strong>Among 1,694 patients (52.5% female; median age 76 years (IQR 69-82); mean follow-up: 1.86 years, SD 0.4 years), 5.7% (97) experienced incident thromboembolic events. In the low LDL-C group, RCS analysis showed a significant linear association between RC levels and thromboembolic risk (p-overall = 0.044). High RC levels were independently associated with an increased risk of thromboembolic events compared to the low RC subgroup (aHR 1.82; 95% CI, 1.03-3.23; p = 0.039), but this was nonsignificant in the high LDL-C group. For secondary outcomes, higher RC levels were not significantly associated with increased adverse event risk in either LDL-C group.</p><p><strong>Conclusion: </strong>Despite low LDL-C levels in AF patients, elevated RC levels were still independently associated with a higher thromboembolic risk, suggesting discordance between RC and LDL-C in risk stratification among patients with AF.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"275"},"PeriodicalIF":8.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607427","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":"A scoring model integrating CXCL9, GDF15, FGF21, and NfL, predicts long-term mortality in type 2 diabetes: a retrospective study.","authors":"Matilde Sbriscia, Sara Caccese, Francesca Marchegiani, Rina Recchioni, Giulia Matacchione, Chiara Giordani, Emanuele Francini, Stefano Salvioli, Maria Conte, Matteo Landolfo, Anna Rita Bonfigli, Federica Turchi, Jacopo Sabbatinelli, Fabiola Olivieri, Angelica Giuliani","doi":"10.1186/s12933-025-02830-5","DOIUrl":"10.1186/s12933-025-02830-5","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes (T2D) is a chronic metabolic disorder associated with aging, systemic inflammation, and increased long-term mortality. Identifying prognostic biomarkers may improve risk stratification and guide personalized interventions. This study aimed to evaluate the long-term prognostic value of circulating biomarkers related to inflammation, metabolic stress, and organ damage in individuals with T2D.</p><p><strong>Methods: </strong>A retrospective study was conducted on a cohort of 478 individuals with T2D, followed for a median of 16.1 years. Ten circulating biomarkers (IL-6, IL-10, CD163, CXCL9, CCL22, GDF15, IL-33, FGF21, Follistatin, and neurofilament light chain [NfL]) were quantified using an automated immunoassay platform. Kaplan-Meier survival analysis and Cox proportional hazards models were used to assess their prognostic significance for all-cause mortality. A biomarker-based scoring model was developed by integrating independent predictors of mortality. Predictive performance was evaluated in comparison with the RECODe equation, a validated risk model for diabetes complications and mortality.</p><p><strong>Results: </strong>Deceased individuals exhibited significantly higher levels of IL-6, IL-10, CXCL9, FGF21, NfL, and GDF15. Biomarker levels correlated with both microvascular and macrovascular complications, particularly neuropathy, nephropathy, retinopathy, and major adverse cardiovascular events (MACE). In multivariable Cox regression analysis, four biomarkers emerged as independent predictors of mortality: CXCL9 (HR per 1 SD increase 1.19, 95% CI 1.05-1.36, p = 0.006), GDF15 (HR 1.16, 95% CI 1.02-1.33, p = 0.032), NfL (HR 1.25, 95% CI 1.09-1.43, p = 0.001), and FGF21 (HR 1.20, 95% CI 1.04-1.37, p = 0.009). A composite biomarker score (range: 4-12) stratified individuals into distinct risk categories, with each 1-point increase in the score associated with a 55% higher mortality risk (HR 1.53, 95% CI 1.35-1.74, p < 0.001). The biomarker score remained independently predictive after adjusting for clinical covariates and significantly improved individual-level risk classification beyond the RECODe model, as demonstrated by net reclassification and discrimination improvement metrics.</p><p><strong>Conclusions: </strong>These findings suggest that inflammatory and metabolic stress-related biomarkers independently predict long-term mortality in T2D. The biomarker-based scoring model enhances risk stratification and improves the prognostic performance of existing clinical tools, such as the RECODe equation, potentially informing targeted clinical interventions.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"270"},"PeriodicalIF":8.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590533","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":"Metabotype identification via fasting and postprandial metabolomics and its association with type 2 diabetes incidence.","authors":"Keyong Deng, David A Hughes, Renée de Mutsert, Astrid van Hylckama Vlieg, Saskia le Cessie, Frits R Rosendaal, Dennis O Mook-Kanamori, Ko Willems van Dijk, Nicholas J Timpson, Ruifang Li-Gao","doi":"10.1186/s12933-025-02821-6","DOIUrl":"10.1186/s12933-025-02821-6","url":null,"abstract":"","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"269"},"PeriodicalIF":8.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590534","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":"Efficacy and safety of Tafolecimab in Chinese patients with type 2 diabetes and hypercholesterolemia: a post-hoc analysis of pooled data from three phase 3 trials.","authors":"Litong Qi, Hua Shen, Meng Chai, Beijian Chen, Yongming He, Xiaoxia Shi, Qiufang Lian, Wang Zhao, Yanling Qu, Lei Qian, Jianwei Zhang, Haoyu Li, Yujie Zhou, Yong Huo","doi":"10.1186/s12933-025-02816-3","DOIUrl":"10.1186/s12933-025-02816-3","url":null,"abstract":"<p><strong>Background: </strong>This study evaluated the efficacy and safety of tafolecimab in patients with type 2 diabetes (T2D) and hypercholesterolemia by a post-hoc analysis of pooled data from three phase 3 trials.</p><p><strong>Methods: </strong>Data from up to 12 weeks were analyzed to assess the effects of tafolecimab 450 mg every four weeks (Q4W) in patients with T2D and hypercholesterolemia. The primary endpoint was the percentage change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Secondary endpoints included the proportion of participants achieving LDL-C levels below 1.8 mmol/L at weeks 12, the proportion of patients achieving LDL-C ≥ 50% reduction and LDL-C < 1.4 mmol/L, as well as percentage changes from baseline to week 12 in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], and triglyceride (TG) levels.</p><p><strong>Results: </strong>The reduction in LDL-C from baseline was significantly greater in patients receiving tafolecimab than in those receiving placebo (estimated treatment difference: - 64.02%, 95% confidence interval: [- 68.08%, - 59.96%], P < 0.0001). The proportion of patients achieving a reduction of over 50% and an absolute LDL-C value below 1.4 mmol/L was significantly higher in the tafolecimab group than that in the placebo group (P < 0.0001). Furthermore, a significantly greater proportion of patients in the tafolecimab group achieved LDL-C levels below 1.8 mmol/L at week 12 compared to the placebo group (P < 0.0001). The tafolecimab group also showed significant reductions in TG, non-HDL-C, apo B, and Lp(a) from baseline to week 12 compared to the placebo group (all P < 0.001). The incidence of adverse events was generally similar between the two groups.</p><p><strong>Conclusion: </strong>Tafolecimab 450 mg Q4W demonstrated a superior lipid-lowering efficacy and favorable safety profile compared to placebo. This suggests it could be a promising new treatment option for Chinese patients with T2D and hypercholesterolemia.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"264"},"PeriodicalIF":8.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559291","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":"Cardiometabolic heart failure with preserved ejection fraction: from molecular signatures to personalized treatment.","authors":"Era Gorica, Martin A Geiger, Ludovica Di Venanzio, Natalia Atzemian, Jan Alphard Kleeberger, Dominique Grigorian, Alessia Mongelli, Besa Emini Veseli, Shafeeq A Mohammed, Frank Ruschitzka, Andreas J Flammer, David Niederseer, Sarah Costantino, Francesco Paneni","doi":"10.1186/s12933-025-02774-w","DOIUrl":"10.1186/s12933-025-02774-w","url":null,"abstract":"<p><p>Heart failure with preserved ejection fraction (HFpEF) represents nearly half of all heart failure cases globally. The increased prevalence of cardiometabolic disease, driven by unhealthy lifestyles, has led to a growing population of people developing the so called \"cardiometabolic HFpEF (cmHFpEF)\" phenotype. This condition represents an end stage cardiometabolic phenotype which results from the clustering of metabolic stress (obesity), hemodynamic stress (hypertension), immune activation, and systemic inflammation. This form of HFpEF is preceded by a \"metabolic cardiomyopathy\" phenotype, characterized by myocardial metabolic remodeling, rewiring of lipid metabolism, and inflammation eventually fostering left ventricular hypertrophy, diastolic dysfunction and atrial dilatation. Recent work over the last years has unveiled the molecular cues underpinning cmHFpEF pathogenesis thus contributing to the identification of novel therapeutic approaches to treat this complex syndrome. The present review provides an overview of recent advances in cmHFpEF biology and pathophysiology with particular emphasis on the following aspects: (i) metabolic alterations associated with cmHFpEF; (ii) changes of the immune landscape; (iii) microvascular dysfunction; (iv) inflammation; (v) chromatin remodeling. Additionally, we will discuss potential mechanisms-based therapeutic strategies to tackle this growing health concern.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"265"},"PeriodicalIF":8.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559289","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":"Single nuclei RNA-sequencing unveils alveolar macrophages as drivers of endothelial damage in obese HFpEF-related pulmonary hypertension.","authors":"Era Gorica, Jacopo Spezzini, Iliana Papadopoulou, Marialucia Telesca, Valeria Masciovecchio, Shafeeq A Moahmmed, Alessandro Mengozzi, Hung-Wei Cheng, Natalia Atzemian, Ludovica Di Venanzio, Alessia Mongelli, Omer Dzemali, Vincenzo Calderone, Francesco Paneni, Christian M Matter, Burkhard Ludewig, Frank Ruschitzka, Sarah Costantino","doi":"10.1186/s12933-025-02772-y","DOIUrl":"10.1186/s12933-025-02772-y","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary hypertension (PH) is a frequent complication in obese patients showing heart failure with preserved ejection fraction (HFpEF) and correlates with poor prognosis. PH associated with cardiometabolic HFpEF (PH-cHFpEF) is characterized by inflammation and metabolic dysregulation. Alterations in the immune landscape, particularly activation of alveolar macrophages (AMs), may propagate the inflammatory response and lead to endothelial damage and vascular remodeling in the lung. Whether AMs contribute to PH in cardiometabolic HFpEF remains elusive.</p><p><strong>Purpose: </strong>The present study investigates the role of alveolar macrophages in PH-cHFpEF.</p><p><strong>Methods: </strong>Mice subjected to high-fat diet and L-NAME treatment for 15 weeks were used as experimental model of PH-cHFpEF. At the end of the treatment, echocardiography and treadmill exhaustion tests were performed. Single nucleus RNA-sequencing (snRNA-seq) was employed to study the AMs transcriptional landscape and cell-cell interactions. In vitro experiments were performed to study the mechanisms underlying metabolic stress-induced macrophage dysfunction using palmitic acid (PA), co-culture experiments were used to investigate the crosstalk between macrophages and endothelial cells.</p><p><strong>Results: </strong>Compared with control mice, PH-cHFpEF animals displayed right ventricular dysfunction, vascular remodeling and increased pulmonary pressure. SnRNA-seq of mouse lungs revealed transcriptional alterations in AMs, with a significant reduction in their abundance in PH-cHFpEF mice. These changes were associated with dysregulation of transcriptional programs involved in pyroptosis, defective autophagy and inflammation in AMs from PH-cHFpEF vs. control mice, as shown by the upregulation of c-Fos, Dusp1, Pim-1 and Ccn1. STRING analysis revealed a molecular link between these partners and highlighted c-Fos/Dusp-1 as a central axis of AMs cell death and inflammation. Metabolic stress induced by PA in isolated murine macrophages recapitulated c-Fos/Dusp-1 activation as well as IL-1β, TNF-α, and Caspase-1 upregulation resulting in inflammation, impaired autophagy and enhanced pyroptosis. Moreover, c-Fos/Dusp1 activation in macrophages promoted secretion of pro-inflammatory chemokines leading to endothelial dysfunction in a paracrine manner. Dusp1 knockdown rescued autophagy and pyroptosis while mitigating macrophage-driven inflammation and endothelial damage.</p><p><strong>Conclusions: </strong>PH-cHFpEF is characterized by AMs activation, upregulation of the cFos/Dusp-1 pathway and subsequent pyroptosis and inflammation in alveolar macrophages. Our findings highlight the role of AMs as putative targets for preventing endothelial damage in experimental PH-cHFpEF.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"268"},"PeriodicalIF":8.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559249","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":"Human cardiac tissues produce lower contractile stress and exhibit slower cross-bridge cycling in type 2 diabetes.","authors":"J H Musgrave, J-C Han, M-L Ward, N Kang, A J Taberner, K Tran","doi":"10.1186/s12933-025-02820-7","DOIUrl":"10.1186/s12933-025-02820-7","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus elevates the risk of developing heart failure and increases associated mortality rates. While the clinical features of diabetic cardiomyopathy have been extensively studied, the effects of diabetes and associated changes in metabolic state on contractile cross-bridge function are less well understood. Using our suite of experimental methods designed to measure cross-bridge kinetics and metabolite sensitivity, we aim to elucidate the mechanistic pathways by which cross-bridge alterations contribute to myocardial dysfunction observed in diabetic cardiomyopathy.</p><p><strong>Methods: </strong>Atrial trabeculae from non-diabetic and type 2 diabetic patients without heart failure were permeabilised and subjected to a series of experiments to measure their cross-bridge function and sensitivity to metabolites. Muscle active stress production and muscle active complex modulus measurements were gathered across different concentrations of ATP and inorganic phosphate (Pi) for the two groups of muscles. To link these functional data to tissue structural alterations, confocal imaging was performed to quantify the trabecula myofilament content and SWATH-MS was performed to measure the composition of myosin isoforms.</p><p><strong>Results: </strong>Diabetic trabeculae generated 20% lower active stress and had 16% lower cross-bridge stiffness on average. The reduction in active stress production can be attributed to a lower density of myocytes in the diabetic muscles. The diabetic trabeculae also had a 24% reduction in characteristic frequencies, reflecting slower cross-bridge cycling kinetics. This result was consistent with the measurement of a reduced fraction of the alpha myosin isoform in this group of patients. The interaction between diabetic status and metabolites was more complex. Although we found that diabetes did not affect the force response to changes in ATP or Pi concentrations, we found that the stiffness of cross-bridges had a lower sensitivity to ATP in diabetic tissues.</p><p><strong>Conclusions: </strong>Our key results point to potential mechanisms of clinical dysfunction in diabetic heart tissue. Lower active force production in diabetic trabeculae suggests that these patients are developing contractile dysfunction. Furthermore, slower cross-bridges can contribute to diastolic dysfunction, especially at higher heart rates, by prolonging cardiac relaxation.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"266"},"PeriodicalIF":8.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559292","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":"Interpretable machine learning analysis of immunoinflammatory biomarkers for predicting CHD among NAFLD patients.","authors":"Wenyuan Dong, Hongcheng Jiang, Yu Li, Luo Lv, Yuxin Gong, Bao Li, Hongjie Wang, Hesong Zeng","doi":"10.1186/s12933-025-02818-1","DOIUrl":"10.1186/s12933-025-02818-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Coronary Heart Disease (CHD) and Non-Alcoholic Fatty Liver Disease (NAFLD) share overlapping pathogenic mechanisms including adipose tissue dysfunction, insulin resistance, and systemic inflammation mediated by adipokines. However, the specific impact of inflammation and immune responses on CHD risk in NAFLD patients remains poorly understood. This study evaluated the predictive value of ten immunoinflammatory indexes for CHD risk in NAFLD patients using an interpretable machine learning framework.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We retrospectively analyzed 407 NAFLD patients undergoing coronary angiography, and stratifying them into NAFLD + CHD (n = 250) and NAFLD (n = 157) groups. Ten immunoinflammatory indexes were derived from the blood laboratory results. Lasso regression analysis and propensity score matching (PSM) were employed to mitigate confounding effects. Subsequently, univariate and multivariate logistic regression analyses were used to identify independent risk factors for CHD occurrence among NAFLD patients. While restricted cubic splines (RCS) and Receiver operating characteristic (ROC) curve evaluated the relationship between each immunoinflammatory indexes and CHD risk. Linear correlation methods were employed to evaluate the relationship between Gensini score and immunoinflammatory indexes. Finally, three machine learning algorithms (RF, SVM and GLM) were used to identify significant risk factors. To interpret the diagnostic model built by Random Forest, the SHapley Additive exPlanations (SHAP) method was employed, and features were ranked according to their SHAP values. Based on these rankings, a diagnostic nomogram was further constructed and the accuracy of the diagnostic model was evaluated using ROC curves.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result: &lt;/strong&gt;After PSM, among the 282 included patients with NAFLD, 141 cases (50%) were complicated with CHD. Multivariate logistic regression analysis revealed that after adjusting for age, sex, hypertension, and smoking history, the NHR index was identified as the most significant risk factor for CHD in NAFLD patients (OR, 1.375; 95% CI, 1.021-1.852; P &lt; 0.001). Additionally, NLR, SII, SIRI and NMR were also identified as risk factors. PNR was a protective factor for CHD events in patients with NAFLD. RCS analysis demonstrated linear relationships between the NHR, NLR, and PNR index with CHD occurrence, whereas the SII index exhibited a non-linear J-shaped relationship with CHD risk (non-linear P = 0.025). Correlation analysis with Gensini score showed that the NHR index had the highest correlation with the severity of CHD (R = 0.256, P &lt; 0.001). ROC curves indicated that the NHR index had good predictive and diagnostic performance (AUC = 0.703,95% CI, 0.652-0.754). Finally, the diagnostic nomogram constructed based on SHAP values demonstrated good accuracy and predictive performance (AUC = 0.834,95% CI, 0.795-0.873; P &lt; 0.001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Six ","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"263"},"PeriodicalIF":8.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559248","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":"Determinants of temporal change in telomere length and its associations with chronic complications and mortality in type 2 diabetes: the Fremantle diabetes study phase II.","authors":"Chieh-Hsin Yang, Michael L H Huang, Wendy A Davis, Alicia J Jenkins, Timothy M E Davis","doi":"10.1186/s12933-025-02832-3","DOIUrl":"10.1186/s12933-025-02832-3","url":null,"abstract":"<p><strong>Background: </strong>Relative telomere length (rTL), a biomarker of biological ageing, has been implicated in type 2 diabetes and its complications. We aimed to identify the associates of rTL change over 4 years (∆rTL), and to investigate whether rTL and ∆rTL are associated with complications and mortality in adults with type 2 diabetes from the Australian observational community-based Fremantle Diabetes Study Phase II (FDS2).</p><p><strong>Methods: </strong>Participants (n = 819) from the FDS2 cohort had baseline and Year-4 (mean ± SD 4.2 ± 0.4 years) rTL measured by qPCR (intra- and inter-assay %CV: 0.56% and 2.69%, respectively). The rTL change (∆rTL; % change/year) was categorised as Shortened (< - 2.69%), Unchanged (- 2.69% to + 2.69%) or Lengthened (> + 2.69%). Multiple logistic regression identified clinical and biochemical determinants of ∆rTL Shortened versus Not Shortened (Unchanged plus Lengthened). rTL and ∆rTL (continuous and categorical) were added to Cox and competing risk regression models of conventional predictors of major complications, CVD death and all-cause mortality during a mean ± SD 11.5 ± 2.1 years of follow-up.</p><p><strong>Results: </strong>rTL was inversely correlated with age (r = - 0.186, P < 0.001). ∆rTL was shortened in 25.5% subjects, unchanged in 10.5%, and lengthened in 64.0%. Shortening was associated with older age, male sex, smoking, obesity, lipid-modifying drug use, and higher platelet count and serum bilirubin levels (P < 0.05). There were no statistically significant unadjusted or age- and sex-adjusted associations between baseline rTL, Year-4 rTL, or ∆rTL, and any incident micro- or macrovascular complications. In unadjusted Cox regression, ∆rTL lengthening was associated with a lower risk of CVD death (hazard ratio 0.98 (0.97, 0.99), P = 0.042) but this association became non-significant after adjustment for conventional risk factors.</p><p><strong>Conclusions: </strong>In adults with type 2 diabetes, rTL does not always shorten over time. rTL and ∆rTL were associated with baseline conventional cardiometabolic risk factors but not independently with major incident complications. There was a weak association between ∆rTL and CVD mortality. These findings question the utility of rTL and ∆rTL in usual type 2 diabetes care.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"267"},"PeriodicalIF":8.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559290","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}