Cardiovascular Diabetology最新文献

{"title":"Longitudinal inflammatory-metabolic-adiposity burden and incident heart failure across cardiovascular-kidney-metabolic stages: a prospective cohort study.","authors":"Fangyi Dai, Yong Dai","doi":"10.1186/s12933-026-03310-0","DOIUrl":"10.1186/s12933-026-03310-0","url":null,"abstract":"<p><strong>Background: </strong>Heart failure remains a major health burden among older adults. Although systemic inflammation, metabolic dysregulation, and central adiposity are individually recognized as heart failure risk factors, composite biomarkers capturing their longitudinal convergence and interaction with cardiovascular-kidney-metabolic (CKM) staging remain unexplored.</p><p><strong>Objectives: </strong>To investigate the association of longitudinal CTGW composite index (C-reactive protein × triglyceride-glucose index × waist-to-height ratio) trajectories and cumulative burden with incident heart failure, and to examine effect modification by baseline CKM stage.</p><p><strong>Methods: </strong>This prospective cohort study included 1946 participants aged 50 years and older from the English Longitudinal Study of Ageing, free of heart failure at Wave 2 (2004-2005), followed through Wave 8 (2016-2017). Group-based multi-trajectory modeling jointly classified longitudinal CRP, triglycerides, glucose, and WHtR across three waves. Cumulative CTGW burden was quantified using the trapezoidal rule. Cox proportional hazards regression with sequential adjustment and restricted cubic spline analyses were employed.</p><p><strong>Results: </strong>Over a median follow-up spanning 12 years, 113 participants (5.8%) developed incident heart failure. Three distinct trajectories were identified: low-stable (n = 697, 35.8%), moderate-metabolic (n = 943, 48.5%), and high-inflammatory (n = 306, 15.7%). In fully adjusted models, the high-inflammatory trajectory conferred the greatest risk (HR = 2.69, 95% CI 1.46-4.93, P = 0.001), followed by the moderate-metabolic trajectory (HR = 1.96, 95% CI 1.17-3.29, P = 0.011). For cumulative burden, the highest quartile was significantly associated with incident heart failure (HR = 2.35, 95% CI 1.31-4.24, P = 0.004; P for trend < 0.001), with each standard deviation increase corresponding to 19% higher risk (HR = 1.19, 95% CI 1.04-1.36, P = 0.014). A nonlinear dose-response relationship was confirmed (P for nonlinearity = 0.032), with the risk threshold identified at approximately 8.2. Stratified analyses revealed significant effect modification by CKM stage (P for interaction = 0.031), with the strongest association observed in Stage 3-4 (HR = 2.37, 95% CI 1.24-4.53, P = 0.009). Subgroup analyses demonstrated consistent effect directions across age, sex, BMI, and comorbidity strata without significant interactions.</p><p><strong>Conclusions: </strong>Longitudinal CTGW trajectories and cumulative burden are independently associated with incident heart failure in a nonlinear dose-response manner, with the association amplified across advancing CKM stages, supporting the CTGW composite index as a potential integrative biomarker for heart failure risk stratification.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886672","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 triglyceride-glucose index with subclinical left ventricular dysfunction in type 2 diabetes mellitus: mediation by myocardial energetic efficiency and resting perfusion.","authors":"Li Jiang, Yuan Li, Hua-Yan Xu, Xue-Ming Li, Ke Shi, Jin Wang, Shi-Qin Yu, Yu Jiang, Han Fang, Wei-Feng Yan, Ying-Kun Guo, Zhi-Gang Yang","doi":"10.1186/s12933-026-03308-8","DOIUrl":"10.1186/s12933-026-03308-8","url":null,"abstract":"<p><strong>Background: </strong>The triglyceride-glucose(TyG) index, a surrogate marker of insulin resistance, has been linked to cardiac dysfunction; however, its underlying associated pathways in patients with type 2 diabetes mellitus(T2DM) remain unclear. This study used cardiac magnetic resonance(CMR) to explore the association of TyG index with subclinical left ventricular(LV) myocardial dysfunction and whether imaging indicators statistically mediate this relationship.</p><p><strong>Methods: </strong>In this retrospective cross-sectional study, a total of 235 T2DM patients who underwent CMR examination were included and assigned to three groups based on the tertiles of their TyG indexes as follows: low(< 8.73, n = 78), moderate(8.73-9.36, n = 79), and high TyG index(≥ 9.36, n = 78) groups. LV geometry, function, myocardial energetic efficiency index (MEEi), resting first-pass perfusion, and global peak strain in radial(GRPS), circumferential(GCPS), and longitudinal(GLPS) directions were measured. Univariate and multivariate linear regression models and exploratory mediation analysis were used to analyze the associations of TyG index on LV global strain.</p><p><strong>Results: </strong>Compared with the low and moderate TyG index groups, the high TyG index group had significantly higher LV remodeling index, lower LV global function index, lower MEEi, impaired resting myocardial perfusion, and reduced LV global peak strain (all p ≤ 0.002). Multivariate analysis showed that TyG index remained independently associated with reduced LV strain after adjusting for confounders (GRPS β = -0.261; GCPS β = 0.271; GLPS β = 0.381; all p < 0.001). And MEEi and upslope were also independently associated with reduced LV GRPS and GLPS (all p < 0.05). Further mediation analysis revealed the statistically mediated proportions of the association between the TyG index and LV global strain were 8.2-8.6% for MEEi and 4.3% to 12.5% for upslope. In model comparison analyses, the TyG index demonstrated substantially better model fit than either component alone across all strain directions (all Akaike Information Criterion difference > 150).</p><p><strong>Conclusions: </strong>In patients with T2DM, a higher TyG index is independently associated with decreased LV global strain, and this relationship is statistically mediated by reduced MEEi and impaired resting perfusion upslope. These findings generate hypotheses regarding myocardial energetics and resting perfusion as potential pathways associated with diabetic myocardial dysfunction that warrant prospective investigation.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668429","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":"Unraveling the dual role of fibroblast growth factor 5 (FGF5) in cardiorenal diseases through multi-omics causal inference.","authors":"Ting Zan, Zhiyu Wen, Hanying Jia, Xinran Dong, Ning Shen","doi":"10.1186/s12933-026-03309-7","DOIUrl":"10.1186/s12933-026-03309-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;As populations age worldwide, multimorbidity has become an increasingly prominent public health challenge. Among age-associated conditions, cardiovascular diseases (CVDs) are among the most prevalent and life-threatening, and they frequently coexist with other chronic disorders, particularly chronic kidney disease (CKD). Pleiotropic molecules may provide an important entry point for elucidating comorbidity mechanisms and identifying therapeutic opportunities. However, the clinical translational value of different pleiotropic candidates exhibits substantial heterogeneity, and their directional effects remain poorly understood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this study, we integrated four large-scale protein quantitative trait loci (pQTL) cohorts from European and East Asian populations, and applied a dual-window Bayesian colocalization strategy to systematically screen for shared genetic signals across 2719 plasma proteins and 34 age-related diseases. We further conducted causal inference and integrative functional characterization of the core candidate protein via Mendelian randomization (MR), observational cross-sectional analysis, genetic fine-mapping, cis-regulatory element analysis and single-cell transcriptomics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Following systematic cross-ancestry screening of 2719 plasma proteins, FGF5 was identified as the core candidate protein, with its circulating pQTL signals showing strong colocalization with CVDs, CKD, and cardiorenal-related phenotypes. Notably, this genetic regulatory effect of FGF5 exhibited marked renal tissue specificity, with its pQTL signals colocalizing strongly with expression quantitative trait loci (eQTL) signals exclusively in the renal cortex, glomeruli, and renal tubules (PP.H4 &gt; 0.97). MR analysis suggested that genetically predicted elevation in circulating FGF5 levels was significantly associated with an increased risk of CVD, with 42.9-66.7% of this association potentially mediated by blood pressure. In contrast, MR analyses suggested a potentially protective effect of elevated FGF5 levels on CKD, with 8.4-11.8% of the association potentially mediated by uric acid. Clinical observational analyses provided complementary support for this bidirectional association pattern, with plasma FGF5 levels showing a positive linear association with CVD risk and a nonlinear U-shaped association with CKD prevalence. Genetic fine-mapping prioritized rs2903657 and rs17004846 as the most likely candidate causal variants within the same strongly linked cis-regulatory haplotype. Phenome-wide association scan (PheWAS) further supported the pleiotropic involvement of these two variants across blood pressure, renal function, and metabolic traits. Single-cell transcriptomic analysis further showed that FGF5 was preferentially enriched in proximal tubular epithelial cells in the injury-repair state.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study systematically elucidates t","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149236949","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":"Proteomic signatures characterized by inflammatory signaling and metabolic processes have divergent associations with 30-year incidence of coronary artery disease in type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications cohort.","authors":"J Zhou, J C Mychaleckyj, F Haddad, T Costacou, T J Orchard, R G Miller","doi":"10.1186/s12933-026-03313-x","DOIUrl":"10.1186/s12933-026-03313-x","url":null,"abstract":"<p><strong>Background: </strong>While inflammation is hypothesized to be a possible driver of the excess coronary artery disease (CAD) observed in type 1 diabetes, prior biomarker studies have focused on candidate proteins, overlooking the complex systemic processes underlying atherosclerosis. We thus applied a high-throughput proteomics approach to identify proteins prospectively associated with CAD in type 1 diabetes. We further hypothesized inflammatory proteins would partially mediate the effect of glycemic exposure on CAD risk.</p><p><strong>Methods: </strong>We measured 184 circulating proteins (Olink CVD II and III panels) in earliest available serum samples from the Pittsburgh Epidemiology of Diabetes Complications cohort of childhood-onset (< 17 years) type 1 diabetes (n = 417, baseline mean age 30, mean diabetes duration 22 years). Protein modules were identified using weighted correlation network analysis. Prospective associations between modules (per eigenvalue SD) and 30-year incident hard CAD (hCAD; CAD death, nonfatal myocardial infarction, revascularization, or blockage ≥ 50%) were estimated in Cox models. Causal mediation analysis estimated mediation of the HbA1c-hCAD association by the modules.</p><p><strong>Results: </strong>Incident hCAD occurred in 151 participants (36.2%). We identified three protein modules: one comprising 56 proteins, enriched for TNF/Notch signaling, T-cell activation, and necroptosis; another comprising 33 proteins, enriched for lipid catabolism, epithelial cell apoptosis, vitamin D response; and a third comprising 33 proteins, enriched for hemostasis, wound healing, and vascular growth factors. After adjusting for traditional covariates and HbA1c, greater abundance of proteins in the first module was associated with increased hCAD incidence (HR = 1.35, 95% CI: 1.06-1.72, p = 0.014) while the second module was protective (HR = 0.82, 95% CI: 0.70-0.96, p = 0.017). The third module was not associated with hCAD (HR = 1.03, 95%CI: 0.86-1.23, p = 0.751). The first module mediated 14% of the total HbA1c effect on hCAD.</p><p><strong>Conclusions: </strong>In this prospective analysis of a type 1 diabetes cohort, a protein signature characterized by inflammatory signaling partially mediated the effect of hyperglycemia on hCAD, while a signature characterized by metabolic processes including lipid catabolism and hormone response was associated with hCAD protection independent of glycemia. These findings move beyond single-marker associations, identifying distinct protein signatures that warrant further study as intervention targets for CAD prevention in type 1 diabetes.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13689145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149236997","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":"Baseline, repeated-measure burden, and two-time-point patterns of the triglyceride-glucose index-visceral lipid ratio (TyG-VLR) and incident cardiovascular disease in cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3: a longitudinal China Health and Retirement Longitudinal Study (CHARLS) analysis.","authors":"Ao-Men Lu, Hao-Jie Han, Qian Xu, Shuang-Ke Bai","doi":"10.1186/s12933-026-03302-0","DOIUrl":"10.1186/s12933-026-03302-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 define a population without overt clinical cardiovascular disease (CVD) but with accumulating metabolic, adiposity, lipid, and kidney-related risk. We evaluated whether baseline triglyceride-glucose-visceral lipid ratio (TyG-VLR), repeated-measure TyG-VLR burden, and two-time-point TyG-VLR patterns were associated with incident CVD and CVD subtypes in CHARLS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), with follow-up through the 2020 wave. CKM stages were operationalized using CHARLS-available measures of adiposity, prediabetes, diabetes, hypertension, dyslipidemia, chronic kidney disease, metabolic syndrome, predicted CVD risk, and clinical CVD status. TyG-VLR was calculated as TyG multiplied by the visceral lipid ratio (VLR; LDL-C × Chinese visceral adiposity index). Repeated-measure TyG-VLR burden was calculated as the average of Wave 1 and Wave 3 values multiplied by the interval between assessments before the landmark follow-up period. K-means clustering of standardized Wave 1 and Wave 3 TyG-VLR identified two-time-point patterns based on the available repeated measurements. Cox proportional hazards models, dose-response analyses, marker-specific comparisons, and prespecified sensitivity analyses were performed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The baseline analytic cohort included 7,132 participants with CKM stages 0-3 and 1,688 incident CVD events; the median follow-up for CVD was 9.00 years (IQR, 7.00-9.00). The repeated-measure/two-time-point cohort included 4,111 participants and 777 incident CVD events; the median landmark follow-up was 5.00 years (IQR, 4.92-5.00). Each 1-SD increase in baseline TyG-VLR was associated with incident CVD (HR 1.15, 95% CI 1.10-1.21), heart disease (HR 1.11, 95% CI 1.05-1.18), and stroke (HR 1.21, 95% CI 1.12-1.31). Repeated-measure TyG-VLR burden was associated with CVD (HR 1.21, 95% CI 1.12-1.30), and the highest two-time-point pattern group had greater CVD risk than the lowest group (HR 1.51, 95% CI 1.22-1.85). Restricted cubic spline and Kaplan-Meier analyses showed graded CVD risk patterns, whereas marker-specific comparisons showed that TyG-VLR performed broadly similarly to VLR, CVAI, and TyG-CVAI. Incremental discrimination beyond traditional factors and adapted CKM stage was modest. Associations remained consistent in inverse probability-weighted, multiple-imputation, alternative-formulation, and competing-risk analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In middle-aged and older adults with adapted CKM syndrome stages 0-3, higher baseline TyG-VLR, repeated-measure TyG-VLR burden, and higher two-time-point TyG-VLR patterns were associated with incident CVD, particularly stroke. TyG-VLR may be interpreted as an epidemiological marker of combined metabolic, lipid, and adiposity burden, with potential value for population-level risk charact","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148696972","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 insulin resistance-related indices and the risk of recurrence after catheter ablation in patients with nonvalvular atrial fibrillation.","authors":"Zhaofen Wang, Haijuan Wang, Xiaoxue Guo, Chu Zhang, Peng Chang","doi":"10.1186/s12933-026-03306-w","DOIUrl":"10.1186/s12933-026-03306-w","url":null,"abstract":"<p><strong>Background: </strong>Insulin resistance (IR) is closely associated with the development and recurrence of atrial fibrillation (AF). Several non-insulin-based surrogate markers of insulin resistance, including the triglyceride-glucose index (TyG), triglyceride-glucose-body mass index (TyG-BMI), metabolic score for insulin resistance (METS-IR), triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C), estimated glucose disposal rate (eGDR), and C-reactive protein-triglyceride-glucose index (CTI), can be calculated from routine clinical biomarkers. However, the value of these indices in predicting recurrence after catheter ablation for AF remains unclear. In particular, CTI, a novel marker integrating inflammatory and metabolic status, has not been fully explored for its potential role in predicting post-ablation AF recurrence. This study aimed to systematically evaluate the association and predictive performance of six insulin resistance surrogate markers for AF recurrence after catheter ablation.</p><p><strong>Methods: </strong>This retrospective two-center cohort study included 590 patients with nonvalvular AF who underwent first-time catheter ablation between January 2022 and March 2025. Six IR surrogate indices were calculated, and AF recurrence within 1 year was defined as the primary endpoint. Multivariable Cox regression, Kaplan-Meier analysis, restricted cubic spline (RCS) analysis, C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to assess associations and predictive value.</p><p><strong>Results: </strong>During 1-year follow-up, 167 patients experienced recurrence (28.31%). Multivariable Cox analysis showed that lower eGDR and higher TyG, TyG-BMI, METS-IR, and CTI were associated with increased recurrence risk, with more stable associations observed for eGDR, TyG-BMI, METS-IR, and CTI. Kaplan-Meier and RCS analyses further supported stratified differences and exposure-response relationships for some indices. For predictive performance, eGDR showed the most favorable overall performance, while CTI, TyG-BMI, and METS-IR also provided incremental predictive value. TyG and TG/HDL-C showed relatively limited incremental value. After false discovery rate correction, subgroup analyses showed generally consistent results.</p><p><strong>Conclusion: </strong>Among the six IR surrogate indices, eGDR, CTI, TyG-BMI, and METS-IR were associated with AF recurrence after catheter ablation. eGDR showed the most favorable overall predictive performance. These indices may serve as adjunctive markers for post-ablation recurrence risk stratification, although prospective validation is needed.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227359","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":"Treatment with dapagliflozin and empagliflozin reduces concentrations of N4-acetylcytidine in plasma, a biomarker associated with vascular damage.","authors":"Arne Gessner, Dennis Kannenkeril, Agnes Bosch, Joanna M Harazny, Martin F Fromm, Hannah Klinkhammer, Christian Staerk, Andreas Mayr, Roland E Schmieder, Renke Maas","doi":"10.1186/s12933-026-03292-z","DOIUrl":"10.1186/s12933-026-03292-z","url":null,"abstract":"<p><strong>Background: </strong>Inhibitors of the sodium-glucose cotransporter 2 (SGLT2) provide cardiovascular and renal protection in both diabetic and non-diabetic patients at least in part independently of glycaemic control. Some underlying mechanisms for these clinically beneficial effects were suggested, but the picture is far from complete. In this study we aimed to apply untargeted metabolomics in order to identify new mechanistic leads.</p><p><strong>Methods: </strong>Plasma and 24-hour urine samples of 48 diabetic patients taken before and after 6 weeks of treatment from two prospective, randomized, double-blind, placebo-controlled, cross-over trials with dapagliflozin or empagliflozin were used. Additionally, plasma and urine samples of 24 diabetic patients from a prospective, randomized, controlled, parallel-arm, interventional, open-label, single centre study with either empagliflozin and linagliptin or metformin and insulin glargine for 12 weeks were used for confirmation. Changes of metabolite patterns in plasma and urine were determined by untargeted high-resolution mass spectrometry. Moreover, parameters of arterial stiffness and retinal vascular remodelling were correlated with treatment effects of the SGLT2 inhibitors on the modified nucleoside N4-acetylcytidine (ac4C), a potential biomarker for the activity of the enzyme N-acetyltransferase 10 (NAT10).</p><p><strong>Results: </strong>In accordance with previously reported results treatment with SGLT2 inhibitors led to a reduction of glucose (log₂fc: - 0.23, adj. p < 0.01) and uric acid (log₂fc: - 0.23, adj. p < 0.001), while 3-hydroxybutyric acid (log₂fc: 0.84, adj. p < 0.001) and 3-hydroxybutyrylcarnitine (log₂fc: 0.57, adj. p < 0.001) were increased in plasma. As a new finding, plasma concentrations of ac4C were reduced (log₂fc: - 0.32, adj. p < 0.001) by SGLT2 inhibitors but not by the non-SGLT2 inhibiting glucose lowering treatment. Reduction of urinary concentrations of ac4C corresponded to its reduction in plasma in groups treated with the SGLT2 inhibitors. Wall thickness of retinal arterioles and central systolic blood pressure were significantly correlated to ac4C in plasma.</p><p><strong>Conclusions: </strong>Treatment with dapagliflozin and empagliflozin reduced plasma concentrations of ac4C, which was correlated with parameters for vascular health. These exploratory findings may indicate inhibition of NAT10 activity as a potential contributor to the beneficial effects on cardiovascular and renal health by SGLT2 inhibitors.</p><p><strong>Trial registrations: </strong>http://www.</p><p><strong>Clinicaltrials: </strong>gov : NCT02383238, NCT02471963, NCT02752113.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583823","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 between cardiac adipose tissue volume, measures of coronary calcification, myocardial microvascular function and systemic inflammation in individuals with type 2 diabetes free of overt cardiovascular disease.","authors":"Morten Steen Jensen, Ida K B Rasmussen, Anne-Cathrine Skriver-Møller, Philip Hasbak, Martin B Blond, Adam Chebli, Victor S Wasehuus, Mats C H Lassen, Morten Lindhardt, Allan Kofoed-Enevoldsen, Urd L Kielgast, Emilie H Zobel, Lene Holmvang, Tor Biering-Sørensen, Peter Rossing, Rasmus S Ripa, Andreas Kjaer, Tine W Hansen","doi":"10.1186/s12933-026-03298-7","DOIUrl":"10.1186/s12933-026-03298-7","url":null,"abstract":"<p><strong>Background: </strong>Peri- and epicardial adipose tissue (PEAT) is a metabolically active fat depot surrounding the heart and coronary arteries that may contribute to vascular dysfunction and inflammation in type 2 diabetes (T2D). We examined associations between PEAT volume, coronary calcification (CACS), myocardial flow reserve (MFR), and systemic inflammation (hsCRP).</p><p><strong>Methods: </strong>Cross-sectional analysis of adults with T2D without overt CVD recruited 2020-2023. PEAT was quantified on non-contrast CT; CACS was calculated by the Agatston method; MFR was measured by rubidium-82 PET/CT; hsCRP assessed systemic inflammation. Associations were tested using multivariable regression adjusting for cardiovascular risk factors.</p><p><strong>Results: </strong>Among 887 participants (mean age 65 years; 70% male; mean BMI 30 kg/m²; median PEAT 199 mL [IQR 133-283]), higher PEAT (per 100 mL) was associated with lower MFR (β - 0.04; 95% CI - 0.09 to 0.00; p = 0.041) and higher hsCRP, corresponding to a 38% increase (95% CI 28% to 48%; p < 0.001) in age- and sex-adjusted models, but not with CACS > 300 (OR 1.01; 95% CI 0.89-1.15). After further adjustment for diabetes duration, BMI, LDL cholesterol, systolic blood pressure, HbA1c, kidney function, smoking, and albuminuria, only the association with hsCRP remained significant at 14% (95%; CI 4% to 25%; p = 0.005).</p><p><strong>Conclusion: </strong>In individuals with T2D without overt CVD, PEAT volume was not independently associated with CACS or MFR after multivariable adjustment. Higher PEAT volume was associated with higher hsCRP, suggesting a relationship with systemic inflammation; however, this exploratory finding should be interpreted in the context of established links between adiposity and inflammatory burden.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223354","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":"Post-translational modifications in the insoluble fraction of platelet-poor plasma distinguish pre-COVID-19 Postural Orthostatic Tachycardia Syndrome, Long COVID, and Long COVID-POTS: a preliminary study.","authors":"Renata M Booyens, Mare Vlok, Cecile Bester, Rashmin Hira, M Asad Khan, Douglas B Kell, Satish R Raj, Etheresia Pretorius","doi":"10.1186/s12933-026-03296-9","DOIUrl":"10.1186/s12933-026-03296-9","url":null,"abstract":"<p><strong>Background: </strong>Pre-COVID-19 Postural Orthostatic Tachycardia Syndrome (PC-POTS), Long COVID with initial orthostatic hypotension (LC-IOH), and Long COVID-POTS (LC-POTS) are primarily chronic post-viral conditions with debilitating symptoms, despite routine laboratory findings often being normal. We previously identified amyloidogenic fibrinaloid microclot complexes (FMCs) in the insoluble fraction of platelet-poor plasma (PPP-IF) in Long COVID, but it remains unclear whether similar abnormalities occur in PC-POTS and LC-POTS, or whether post-translational modifications (PTMs) contribute to disease mechanisms.</p><p><strong>Methods: </strong>Platelet-poor plasma from healthy controls (n = 18), PC-POTS (n = 20), LC-IOH (n = 19), and LC-POTS (n = 18) participants underwent proteomic analysis of the PPP-IF using double trypsin digestion and data-independent LC-MS/MS. Differential protein abundance, PTMs, and amyloidogenicity were compared across groups.</p><p><strong>Results: </strong>Although few proteins were significantly dysregulated, extensive disease-specific PTM alterations were identified across coagulation, immune, and metabolic pathways. LC-IOH demonstrated prominent AGE- and oxidation-related PTMs on fibrinogen subunits, particularly fibrinogen alpha chain (FIBA), resembling diabetic glycation profiles. PC-POTS showed fewer fibrinogen PTMs but marked metabolic and immune dysregulation, including oxidised apoA1 and apoB and complement-associated proteins (C3, C4A/B, IC1), IGG1, and A2MG. LC-POTS shared coagulation-related features with LC-IOH and immune-related features with PC-POTS. Many dysregulated peptides were highly amyloidogenic in silico, consistent with β-sheet-rich FMCs. PTM dysregulation was substantially greater than protein-level changes.</p><p><strong>Conclusions: </strong>This study provides the first evidence that PTMs within the PPP-IF has the potential to distinctly differentiate PC-POTS, LC-IOH, and LC-POTS. Because PC-POTS samples predated SARS-CoV-2, their PTM signatures reflect intrinsic disease biology independent of COVID-19. PTM profiling revealed pro-coagulant fibrinogen changes in LC-IOH and LC-POTS, metabolic-oxidative dysregulation in LC-IOH and PC-POTS, and immune dysregulation in PC-POTS and LC-POTS. These abnormalities were not detectable by routine assays and may contribute to microvascular dysfunction. The findings support disease-specific biomarker development and targeted therapeutic strategies across autonomic and post-viral disorders.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223396","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 carotid atherosclerosis is independently associated with cardiovascular events and mortality in type 1 diabetes.","authors":"Clara Viñals, Ignacio Conget, Camila Milad, Montse Granados, Jesús Blanco, Maria Claro, Verónica Perea, Tonet Serés-Noriega, Irene Vinagre, Marga Giménez, Antonio J Amor","doi":"10.1186/s12933-026-03300-2","DOIUrl":"10.1186/s12933-026-03300-2","url":null,"abstract":"<p><strong>Background: </strong>To evaluate whether carotid atherosclerosis predicts future cardiovascular events (CVE) and mortality in adults with type 1 diabetes (T1D) in primary prevention.</p><p><strong>Methods: </strong>Cohort study in adults with T1D participating in a cardiovascular risk assessment program that included carotid ultrasound. Eligibility criteria included age ≥ 40 years, diabetic kidney disease regardless of age or diabetes duration, or type 1 diabetes duration ≥ 10 years in the presence of at least one additional cardiovascular risk factor.The primary endpoint was the first CVE. A secondary endpoint was a composite of CVE plus all-cause mortality. Carotid plaque burden and outcomes were analyzed using Kaplan-Meier curves and Cox regression models.</p><p><strong>Results: </strong>701 individuals were followed for a mean of 5.85 years (mean age 48.5 years; T1D duration 27 years; 51.9% males). Carotid plaques were identified in 40.4%. During follow-up, 45 CVE occurred (18 coronary artery disease, 14 peripheral artery disease, 6 stroke, 3 heart failure, 4 deaths) along with 5 non-cardiovascular deaths. Event-free survival declined progressively with increasing plaque burden (log-rank p < 0.001). In unadjusted analyses, the presence of any plaque was associated with increased risk of CVE (HR 3.14, 95%C I 1.69-5.84) and of the composite endpoint (HR 3.07, 95% CI 1.71-5.51). After multivariable adjustment for demographic, metabolic, and microvascular factors, a high plaque burden (≥ 3 plaques) remained associated with CVE (HR 3.38, 95% CI 1.37-8.38) and with the composite endpoint (HR 2.64, 95% CI 1.13-6.21).</p><p><strong>Conclusions: </strong>Preclinical carotid atherosclerosis in adults with T1D was independently associated with an increased risk of cardiovascular events and mortality. These findings support the potential role of carotid ultrasound as a complementary tool for cardiovascular risk assessment in individuals with T1D.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223398","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}