Cardiovascular Diabetology最新文献

{"title":"Associations of the atherogenic index of plasma and its modified indices with the incidence and progression of cardiovascular-liver-metabolic multimorbidity: a prospective cohort study from UK Biobank.","authors":"Qida He, Mengtong Sun, Jiazhen Yao, Yu Wang, Yueping Shen","doi":"10.1186/s12933-026-03225-w","DOIUrl":"10.1186/s12933-026-03225-w","url":null,"abstract":"<p><strong>Background: </strong>The atherogenic index of plasma (AIP) and its modified indices integrate atherogenic dyslipidaemia with overall or central adiposity and have been associated with cardiovascular-liver-metabolic (CLM) diseases. However, their associations with cardiovascular-liver-metabolic multimorbidity (CLMM) remain unclear. This study examined the relationships of AIP and its modified indices with the incidence and progression of CLMM and further explored whether selected biomarkers explained part of these associations.</p><p><strong>Methods: </strong>A total of 370,258 participants without baseline CLM diseases were included in this prospective cohort analysis. AIP and its seven modified indices were evaluated: AIP, AIP-BMI, AIP-WC, AIP-WHtR, AIP-ABSI, AIP-WWI, AIP-BRI, and AIP-VAI. Multivariable Cox models were applied to evaluate associations between these indices and both the incidence and progression of CLMM. Exploratory mediation analyses were further conducted to estimate the contributions of inflammatory, hepatic, and renal biomarkers. Predictive ability was evaluated using C-index, net reclassification improvement, and integrated discrimination improvement.</p><p><strong>Results: </strong>During the median 16.0-year follow-up, 8646 participants developed CLMM, and each of the eight indices was associated with a higher risk of incident CLMM, with fully adjusted hazard ratios per standard deviation (SD) increase ranging from 1.18 for AIP-VAI to 1.68 for AIP and AIP-BMI. Consistent associations were also observed for CLMM progression, particularly for AIP-BMI, AIP-WC, and AIP-WHtR. Per 1-SD increase in each index, the risks of transition from a healthy state to the first CLM disease increased by 38%, 36%, and 37%, the risks of progression from the first disease to CLMM increased by 28%, 26%, and 27%, and the risks of progression from CLMM to triple diseases increased by 20%, 17%, and 18%, respectively. Exploratory mediation analyses indicated that biomarkers of systemic inflammation and impaired liver and kidney function jointly accounted for 28.28 to 45.45% of the observed associations. All indices improved predictive performance, with AIP-BRI and AIP-BMI showing the highest overall performance, followed by AIP-WC and AIP-WHtR.</p><p><strong>Conclusions: </strong>Higher AIP and its modified indices were independently associated with increased risks of both incident CLMM and its progression. These indices may help improve CLMM risk stratification and early identification of individuals at elevated risk.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136354","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":"Large-scale multi-omics enhance risk prediction for type 2 diabetes.","authors":"Ruijie Xie, Christian Herder, Ben Schöttker","doi":"10.1186/s12933-026-03223-y","DOIUrl":"10.1186/s12933-026-03223-y","url":null,"abstract":"<p><strong>Background: </strong>Polygenic risk scores (PRS), metabolomics, and proteomics have each shown promise in improving type 2 diabetes risk prediction, but their combined utility beyond established clinical models remains unclear. We aimed to evaluate whether integrating multi-omics biomarkers enhances 10-year type 2 diabetes risk prediction beyond single-omics extensions and the clinical Cambridge Diabetes Risk Score (CDRS), which includes HbA_1c measurements.</p><p><strong>Methods: </strong>We analysed data from 42,840 UK Biobank participants without diagnosed diabetes at baseline. The study population was split into a derivation set (Phase 1 metabolomics release, N = 23,108) to fit models and an independent validation set (Phase 2 release, N = 19,732) to evaluate performance. Data for a PRS for type 2 diabetes, 11 metabolites, and 15 proteins were added to the CDRS to develop multi-omics prediction models. Model performance was evaluated using Harrell's C-index and the net reclassification index (NRI).</p><p><strong>Results: </strong>During 10 years of follow-up, 1090 participants developed incident type 2 diabetes. Among individual omics layers, proteomics contributed the greatest improvement in predictive performance, increasing the C-index from 0.862 (clinical CDRS) to 0.884 (ΔC-index; + 0.022; P < 0.001), with a continuous NRI of 42.0%. The full multi-omics model further significantly increased the C-index compared to a model combining the clinical CDRS with proteomics data (C-index, 0.891; ΔC-index; + 0.007; P < 0.001).</p><p><strong>Conclusion: </strong>Integrating proteomics, metabolomics, and a diabetes-PRS into a clinical model substantially improves type 2 diabetes risk prediction beyond single-omics extensions. Several of the selected proteins and metabolites are on cardiovascular disease pathways, highlighting the link between diabetes and cardiovascular risk. However, the C-index difference between the proteomics extended and full multi-omics extended models is small, and the clinical models extended with proteomics data would be easier to translate into routine care because it needs only the measurement of 15 proteins. External validation and cost-effectiveness analyses are needed to support clinical adoption.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13217982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052909","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":"Incidence, risk factors and sequelae of long/post-COVID in people with diabetes compared to people without diabetes in Germany (longcovid-diab): a study protocol.","authors":"Tatjana Kvitkina, Maria Narres, Silke Andrich, Stefan Wilm, Andrea Icks, Heiner Claessen","doi":"10.1186/s12933-026-03222-z","DOIUrl":"10.1186/s12933-026-03222-z","url":null,"abstract":"<p><strong>Background: </strong>Several studies have shown that people with diabetes are at higher risk of experiencing a severe course of COVID-19 infection. However, it remains unclear whether diabetes per se is a risk factor for the development of Long/Post-COVID. In addition, there is a lack of nationwide, population-based studies on the epidemiology of Long/Post-COVID in people with diabetes. The aim of this project is to analyze: (1) incidence and time trends of Long/Post-COVID in people with and without diabetes between 2021 and 2023 in Germany as well as potential risk factors; (2) mortality, any hospitalization and hospitalization due to acute myocardial infarction, stroke, amputation and diabetic foot syndrome (DFS) after a Long/Post-COVID diagnosis, including an analysis of potential risk factors.</p><p><strong>Methods: </strong>This study is planned as a non-interventional longitudinal observational study based on statutory health insurance (SHI) data in Germany. The data holder is the Health Data Lab (HDL: data pool of billing data for all persons with statutory health insurance). The incidence rates of Long/Post-COVID will be estimated separately in the populations with and without diabetes and compared as corresponding relative risk. Moreover, we will analyse age- and sex-standardized mortality and hospitalization rates within 12, 24, and 36 months after a Long/Post-COVID diagnosis in the years 2021 to 2024. Potential uncertainties in diagnosing Long/Post-COVID (e.g., underreporting) will be addressed in sensitivity analyses.</p><p><strong>Discussion: </strong>The expected results will have high potential for use in epidemiological research on Long/Post-COVID, including the identification of potential risk factors in people with diabetes. The findings will serve to provide optimized healthcare for Long/Post-COVID patients with diabetes. Trial registration The study has been registered in the German Clinical Trials Register with identifier DRKS00036279. Registration Date 15.05.2025.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13218030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052840","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":"Changes in cardiac myosin acetylation disrupt the super-relaxed state in genotype-negative hypertrophic cardiomyopathy with type 2 diabetes.","authors":"Edgar E Nollet, Chahida Chaami, Helena Bogdanovic Keleman, Elise Gerlach Melhedegaard, Christopher T A Lewis, Robert A E Seaborne, Julia E Visch, Stephan A C Schoonvelde, Miao Feng, Qian Wang, Anthony L Hessel, Michel N Kuehn, Bauke V Schomakers, Michel van Weeghel, Michelle Michels, Diederik W D Kuster, Jolanda van der Velden, Julien Ochala","doi":"10.1186/s12933-026-03211-2","DOIUrl":"10.1186/s12933-026-03211-2","url":null,"abstract":"<p><strong>Background: </strong>Patients with hypertrophic cardiomyopathy (HCM) and type 2 diabetes (T2D) have a more severe cardiac phenotype and worse clinical course than non‑diabetic patients. To identify how T2D aggravates the disease and whether the most abundant cardiac protein, myosin, is involved, we combined functional, structural and mass spectrometry analyses of human samples.</p><p><strong>Methods: </strong>Left ventricular septal myectomy samples from genotype‑negative (G-) HCM patients without T2D (G- , N = 19) and with T2D (G-T2D, N = 15) were analyzed mainly using fluorescent ATP chase experiments, small‑angle X‑ray diffraction and targeted myosin heavy chain proteomics.</p><p><strong>Results: </strong>Mant‑ATP chase measurements showed a lower fraction of myosin heads in the energy‑conserving super‑relaxed (SRX) state in G-T2D compared to non-diabetic myocardium. In parallel, X‑ray diffraction showed trends toward structural alterations in myosin organization in G-T2D tissue, consistent with altered OFF/ON state equilibrium. Targeted mass spectrometry identified hyperacetylation of several myosin lysine residues in G-T2D, including K847 within the S2 region. All‑atom molecular dynamics simulations indicated that K847 acetylation disrupts stabilizing electrostatic interactions in the interacting‑heads motif, which is associated with the OFF state.</p><p><strong>Conclusions: </strong>Disruption of myosin super‑relaxation emerges as a central cellular defect in G-T2D HCM myocardium and can be mechanistically linked to site‑specific myosin hyperacetylation at K847, providing a potential therapeutic target for genotype‑negative HCM with T2D.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exerkine dysregulation links visceral adiposity to skeletal muscle impairment in end-stage heart failure with reduced ejection fraction: proteomic evidence for a cardio-adipose-muscle axis.","authors":"Marta Załęska-Kocięcka, Maciej Mazuruk, Karolina Szcześniak, Piotr Łaba, Marta Kacperska, Łukasz Nogajski, Maksymilian Nowakowski, Maciej Mączewski, Hanna Czerwińska, Miłosz Rosa, Piotr Olbryś, Aleksandra Mączyńska, Jarosław Kuriata, Piotr Kołsut, Zuzanna Wojdyńska, Ilona Michałowska, Aleksandra Paterek, Przemysław Błyszczuk, Przemysław Leszek, Michał Mączewski","doi":"10.1186/s12933-026-03190-4","DOIUrl":"10.1186/s12933-026-03190-4","url":null,"abstract":"<p><strong>Background: </strong>Heart failure with reduced ejection fraction (HFrEF) is associated with profound alterations in body composition, skeletal muscle dysfunction, and impaired exercise capacity. Exerkines representing exercise-responsive signaling molecules released by skeletal muscle, adipose tissue, and other organs may mediate systemic metabolic communication between tissues. However, their role in advanced HFrEF and their relationship with adiposity and skeletal muscle characteristics remain poorly understood.</p><p><strong>Methods: </strong>We studied 73 patients with end-stage HFrEF and 16 healthy controls. Body composition was assessed using computed tomography, including visceral (VAT), subcutaneous (SAT), and epicardial adipose tissue (EAT), as well as skeletal muscle quantity (psoas muscle index, PMI) and quality (psoas muscle density, PMD). Functional performance was evaluated using handgrip strength (HGT) and the 6-min walk test (6MWT). Circulating exerkines were quantified using the Olink technology. Associations between proteins and clinical variables were assessed using age- and creatinine-adjusted linear models with false discovery rate correction.</p><p><strong>Results: </strong>Among patients with HFrEF, 36% were obese and 38% exhibited central obesity independent of BMI. Muscle strength and muscle quality were strongly associated with functional capacity. VAT correlated with muscle mass but not with muscle quality or performance. Compared with controls, HFrEF patients demonstrated elevated inflammatory and metabolic stress-related exerkines including CXCL8, CCL2, IL-6, TNF, IL-15, GDF15, FGF21, ANGPTL4, CTSB, DCN, and resistin. In contrast, proteins associated with muscle integrity and regenerative signaling (myostatin, BDNF, IL-7, SPARC) were significantly reduced. In HFrEF patients leptin strongly correlated with adiposity measures. Metabolic stress mediators (GDF15, IL-15, FGF21, CTSB) were inversely associated with muscle quality and functional performance, whereas myostatin positively correlated with muscle quality, strength, and exercise capacity. BDNF was inversely associated with frailty.</p><p><strong>Conclusions: </strong>Advanced HFrEF is characterized by a dysregulated exerkine network linking adiposity, skeletal muscle quality, and functional performance. Four biologically coherent axes were identified: a leptin-driven adiposity axis, a metabolic stress-muscle quality axis, a myostatin-related muscle function axis, and a neurotrophic frailty axis. These findings support the presence of a systemic cardio-adipose-muscle signaling network in end-stage HFrEF and identify candidate molecular mediators of sarcopenia and functional decline.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of the combined C-reactive protein-triglyceride glucose index and frailty index in different dimensions with incident stroke among individuals with stages 0-3 cardiovascular-kidney-metabolic syndrome.","authors":"Honglin Zheng, Yao Zhang, Li Li, Mingye Zhu, Wei Kong, Jialin Wang, Ruxi Liu, Fang Wang","doi":"10.1186/s12933-026-03199-9","DOIUrl":"10.1186/s12933-026-03199-9","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have revealed the relationships of separated C-reactive protein-triglyceride glucose (CTI) levels and the frailty index (FI) with stroke. However, the impact of combined CTI and FI (CTI-FI) on stroke incidence is unclear, especially among those with cardiovascular kidney metabolic (CKM) syndrome stages 0-3.</p><p><strong>Objective: </strong>This research aimed to validate the associations between different CTI-FI dimensions (baseline CTI-FI, cumulative CTI-FI (cuCTI-FI), and dynamic trajectories of CTI-FI (traCTI-FI)) and stroke risk among individuals with CKM syndrome stages 0-3.</p><p><strong>Methods: </strong>The enrolled participants and the utilized data were derived from five waves of the China Health and Retirement Longitudinal Study. K-means clustering was used to categorize participants into an appropriate number of clusters. Cox regression analysis, restricted cubic spline (RCS) curves, and Kaplan-Meier (K-M) survival curves were used to evaluate the relationships between different CTI-FI dimensions and stroke risk. Receiver operating characteristic (ROC) curves and the DeLong test were constructed to assess the performance of various dimensions of CTI-FI in predicting stroke.</p><p><strong>Results: </strong>In this study, the mean age of the 5293 participants was 57.94 years, and 53.45% were female. During the nearly 9-year follow-up period, 540 (10.20%) stroke events occurred. A 61% and 41% increase in stroke risk was associated with each 1-unit increase in the baseline CTI-FI and cuCTI-FI, respectively. The RCS modeling further revealed significant positive nonlinear associations between baseline CTI-FI (P_overall < 0.001, P_nonlinear = 0.049) and cuCTI (P_overall < 0.001, P_nonlinear = 0.047) and stroke incidence. Compared with the lowest different dimensions CTI-FI level groups, the highest level groups had a greater stroke risk. The fully adjusted HRs (95% CIs) were as follows: baseline CTI-FI (Q4 vs. Q1), 2.36 (1.76, 3.15); cuCTI-FI (Q3 vs. Q1), 4.75 (2.73, 8.27); and traCTI-FI (Cluster 3 vs. Cluster 1), 6.24 (3.72, 10.46). In terms of predicting stroke risk, baseline CTI-FI, cuCTI-FI, and traCTI-FI performed better than CTI and FI, and cuCTI-FI and traCTI-FI performed significantly better than baseline CTI-FI (P < 0.001 and = 0.022, respectively).</p><p><strong>Conclusion: </strong>Persistently high CTI-FI is associated with increased stroke risk. CTI-FI, especially cuCTI-FI and traCTI-FI, are potent predictors of stroke. Long-term surveillance of CTI-FI alterations and maintenance of its low levels is clinically important for early stroke detection and prevention in patients with stages 0-3 CKM syndrome.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027332","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":"Effects of semaglutide on mortality, cardiovascular, and kidney outcomes across the cardio-kidney-metabolic continuum: a systematic review and meta-analysis.","authors":"Federica Marzano, Stefania Paolillo, Paola Gargiulo, Ciro Cotticelli, Mariafrancesca Di Santo, Ermanno Nardi, Giuseppe Maria Abbellito, Laura Liccardi, Fabrizio Perrone Filardi, Dario Bruzzese, Pasquale Perrone Filardi","doi":"10.1186/s12933-026-03215-y","DOIUrl":"10.1186/s12933-026-03215-y","url":null,"abstract":"<p><strong>Background: </strong>Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated cardiometabolic benefits in randomized controlled trials (RCTs). However, its overall effects on mortality, cardiovascular (CV) and kidney outcomes have not been comprehensively synthesized. This meta-analysis aimed to assess the prognostic impact of semaglutide across the cardio-kidney-metabolic continuum.</p><p><strong>Methods: </strong>A systematic literature search was conducted to identify all eligible RCTs comparing the prognostic effects of semaglutide with placebo across diverse patient populations. Primary outcomes were all-cause and CV mortality. Secondary outcomes included major CV and kidney events, while major adverse limb events (MALE) were analyzed as an exploratory endpoint. A random-effects model was used to pool hazard ratios (HRs) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>Eight trials encompassing 39,204 patients were included. In patients treated with semaglutide a significant reduction of all-cause (HR, 0.84; 95% CI, 0.77-0.92; p = 0.0001) and CV mortality (HR, 0.83; 95% CI, 0.72-0.95; p = 0.0078), major adverse CV events (MACE, HR, 0.82; 95% CI, 0.77-0.87; p < 0.0001), nonfatal myocardial infarction (MI, HR, 0.75; 95% CI, 0.68-0.84; p < 0.0001), worsening heart failure (HF, HR, 0.84; 95% CI, 0.73-0.98; p = 0.0245), and kidney outcomes (HR, 0.83; 95% CI, 0.73-0.95; p = 0.0080) was observed compared to placebo. No significant effects were observed for nonfatal stroke.</p><p><strong>Conclusions: </strong>Treatment with semaglutide, compared to placebo, is associated with significant lower incidence of all-cause and CV mortality, as well major CV and kidney events across the continuum of cardio-kidney-metabolic syndrome.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013584","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":"Shared pathophysiological mechanisms between diabetes and calcific aortic valve disease: an immunometabolic perspective.","authors":"Zhang Yue, Qiuchen SiTu, Jin-Hui Bian, Hong-Xiang Lu","doi":"10.1186/s12933-026-03219-8","DOIUrl":"10.1186/s12933-026-03219-8","url":null,"abstract":"<p><p>This review synthesizes the immunometabolic mechanisms linking diabetes mellitus to accelerated calcific aortic valve disease (CAVD) and evaluates their therapeutic implications. Despite the absence of disease-modifying pharmacotherapy for CAVD, diabetes consistently increases incident aortic stenosis risk (HR 1.3-1.7), calcification burden, and disease severity, independent of traditional cardiovascular risk factors. Epidemiological, imaging, and histological evidence demonstrate that dysglycemia promotes earlier onset, denser valvular calcium deposits, and worse post-intervention outcomes. We delineate seven interconnected and partially overlapping pathways through which diabetes remodels the aortic valve: hyperglycemia-driven valvular interstitial cell (VIC) phenotypic switching and insulin resistance; advanced glycation end-product-RAGE signaling; oxidative stress and mitochondrial dysfunction; macrophage NLRP3-IL-1β inflammasome activation; endothelial barrier compromise; BMP-Runx2-Wnt-Notch osteogenic reprogramming; and CKD-mineralocorticoid receptor cross-talk. These processes convert metabolic stress into sustained valvular inflammation, matrix remodeling, and ectopic ossification. Mechanistic and observational data provide a rationale for evaluating metformin, SGLT2 inhibitors, IL-1β/NLRP3 inhibitors, and Lp(a)-lowering strategies as candidate approaches to modulate calcification progression. Integrated metabolic-inflammatory-imaging biomarkers offer potential for risk stratification and trial enrichment. This immunometabolic framework identifies actionable nodes and underscores the urgent need for dedicated, valve-focused randomized trials in diabetic CAVD to translate mechanistic insights into clinical benefit.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13390458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013653","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":"Joint association of atherogenic index of plasma (AIP) and body roundness index (BRI) with cardiometabolic multimorbidity in adults in Guangzhou, China.","authors":"Haonan Li, Chunzi Zeng, Zhifeng Li, Yuting Qin, Yujie Peng, Jiahe Feng, Jie Huang, Shiyun Luo, Jun Yuan, Jing Gu, Yan Li","doi":"10.1186/s12933-026-03202-3","DOIUrl":"10.1186/s12933-026-03202-3","url":null,"abstract":"<p><strong>Background: </strong>Cardiometabolic multimorbidity (CMM) is one of the most prevalent patterns of multimorbidity worldwide and presents a growing challenge to public health. Metabolic dysregulation and visceral adipose play central roles in the development of CMM. The atherogenic index of plasma (AIP) has been proposed as a comprehensive indicator of lipid metabolic abnormalities, whereas the body roundness index (BRI) is a novel anthropometric measure reflecting central obesity and visceral adipose tissue (VAT). However, evidence regarding the associations of AIP and BRI with CMM remains limited, particularly in southern Chinese populations and young adults. This study examined the separate and joint associations of AIP and BRI with CMM, aiming to provide preliminary scientific evidence to identify individuals more likely to have prevalent CMM.</p><p><strong>Methods: </strong>This cross-sectional study included 2505 adults from the 2024 Guangzhou Residents' Nutrition Survey. Multivariable logistic regression models and segmented logistic regression analyses were employed to examine the association patterns of AIP and BRI with CMM, as well as to assess potential threshold effects. For joint analysis, participants were categorized into four groups by AIP and BRI levels to evaluate the joint association and interaction between these indices and CMM.</p><p><strong>Results: </strong>Among the 2505 participants, 213 (8.50%) were diagnosed with CMM. Compared with the lowest tertile, the highest tertile of AIP (OR = 4.025, 95% CI 2.591-6.455) and BRI (OR = 10.461, 95% CI 5.523-22.496) were associated with a higher likelihood of CMM. AIP was linearly associated with CMM. In contrast, BRI demonstrated a nonlinear association with CMM, with an inflection point at 4.52, below which the odds of CMM increased more rapidly. Joint analyses revealed that participants in the \"high AIP+high BRI\" group had the strongest association with CMM (OR = 5.081, 95% CI 3.354-7.828). Subgroup analysis revealed that the association between the \"high AIP+high BRI\" group and CMM was stronger in participants < 60 years.</p><p><strong>Conclusion: </strong>Individuals with elevated levels of AIP and BRI are more likely to have CMM. AIP is linearly associated with CMM, whereas a threshold effect is observed for BRI. The joint assessment of AIP and BRI demonstrates a stronger association with CMM compared to either indicator alone. These findings suggest that the joint assessment of AIP and BRI may be a useful tool for identifying individuals at a higher likelihood of prevalent CMM, particularly in young and middle-aged adults.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962228","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":"Predicting cardiovascular death in overweight/obese people with prediabetes using machine learning-a proof-of-concept study.","authors":"Amalie K Andersen, Kristine Færch, Dorte Vistisen, Bernt J von Scholten, Nils B Jørgensen, Simon L Cichosz, Morten H Jensen","doi":"10.1186/s12933-026-03210-3","DOIUrl":"10.1186/s12933-026-03210-3","url":null,"abstract":"<p><strong>Background: </strong>Individuals with prediabetes face an increased risk of cardiovascular (CV) complications, which can ultimately lead to premature mortality. However, existing risk stratification tools are not targeted for people with prediabetes. We aimed to develop a simple explainable model to predict if a person will develop a fatal CV outcome or not among people with prediabetes.</p><p><strong>Methods: </strong>Participants ≥ 45 years with prediabetes (HbA1c 39-47 mmol/mol (5.7-6.4%)) and established CV disease and overweight/obesity were included. A binary logistic regression model was trained to predict CV death using stratified threefold cross-validation. The model's risk estimates were calibrated, and the predictive capability was evaluated using receiver operating characteristic (ROC) area under the curve (AUC), precision and recall.</p><p><strong>Results: </strong>In total 5636 participants with 182 (3.2%) CV deaths (mean time-to-event of 2.0 years) and a mean trial duration of 3.3 years were included. Seven easily collected demographic and clinical variables were selected for the model. Discrimination (ROC AUC) was acceptable at 0.730 (95% CI 0.659-0.801). Applying our prediabetes cohort on existing benchmark models developed for major adverse cardiovascular events (MACE) in a general and type 2 diabetes population without prior CVD, demonstrated lower performance for CV death (ROC AUC: 0.630 (SCORE2) and 0.643 (SCORE2-Diabetes)) compared to our model. Lower performance was also observed for predicting MACE in our cohort (ROC AUC: 0.596 and 0.603) using the established models compared to the original populations (ROC AUC: 0.739 and 0.66-0.73). No comparative models for people with prediabetes and prior CVD exists. Thus, even with the limitations in different populations and outcome targets, this indicates that prediabetes-specific prediction models could potentially improve early prevention in this high-risk population.</p><p><strong>Conclusion: </strong>We have developed a prediabetes-specific proof-of-concept model that predicts whether a person is at high risk of cardiovascular death. External validation of the model is crucial before adoption to a real-world setting to clarify whether the model generalizes beyond the studied population.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13348561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962158","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}