Cardiovascular Diabetology最新文献

{"title":"Composite metabolic biomarkers for cardiovascular risk assessment in CKM syndrome.","authors":"Shaun Khanna, Francis J Ha, Nitesh Nerlekar","doi":"10.1186/s12933-026-03338-2","DOIUrl":"10.1186/s12933-026-03338-2","url":null,"abstract":"","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148825205","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":"Reduced serum acetyl-L-carnitine is associated with hypertensive disorders in women with gestational diabetes mellitus: a multi-omics study.","authors":"Xiubin Jia, Qi Wu, Xiaoyong Zhang, Hequn Lin, Jiahui Gong, Hui Ye, Xueli Hu, Zhaoxia Liang, Danqing Chen, Wei Zhu, Luyu Ma","doi":"10.1186/s12933-026-03347-1","DOIUrl":"10.1186/s12933-026-03347-1","url":null,"abstract":"<p><strong>Background: </strong>Gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) are common metabolic complications during pregnancy. GDM is an independent risk factor for HDP, while HDP is a major contributor to maternal and perinatal morbidity and mortality. Reliable early tools for identifying women with GDM who are at risk of subsequently developing HDP remain limited. This study aimed to integrate metabolomic, lipidomic, and clinical data to identify reproducible candidate biomarkers associated with subsequently diagnosed HDP in women with GDM and to characterize the accompanying metabolic and lipidomic alterations.</p><p><strong>Methods: </strong>In this prospective exploratory biomarker study, a discovery cohort (n = 128) and a validation cohort (n = 55) were recruited. Serum samples collected at 24-28 weeks of gestation were analyzed using untargeted and targeted metabolomics. Lipidomics was performed to complement the metabolomic analysis and characterize lipid-related alterations. A combined predictive model was constructed using logistic regression, and its predictive performance was evaluated using receiver operating characteristic (ROC) analysis.</p><p><strong>Results: </strong>Untargeted metabolomics identified lower serum acetyl-L-carnitine (ALC) in the GDMHDP group than in the GDM group, and this difference was confirmed by targeted LC-MS/MS in the validation cohort. The combined ALC-diastolic blood pressure (DBP) model achieved an area under the curve (AUC) of 0.907 in the discovery cohort and 0.886 in the validation cohort. Adding ALC to DBP improved discrimination and reclassification in both cohorts. Multi-omics analysis showed complementary and partly distinct lipid associations with ALC and DBP. Lower ALC was associated with selected ceramide and monolysocardiolipin species, as well as with lipid patterns consistent with altered fatty-acid handling, whereas DBP showed a partly distinct pattern of lipid correlations.</p><p><strong>Conclusions: </strong>Reduced serum ALC at 24-28 weeks of gestation was reproducibly associated with GDM complicated by HDP. Combining ALC with DBP improved discrimination between GDMHDP and uncomplicated GDM, suggesting complementary metabolic and hemodynamic information. Given the modest number of GDMHDP cases and the single-center design, these findings should be interpreted as exploratory and hypothesis-generating; they support further evaluation of ALC as a candidate metabolic marker but require confirmation in larger independent cohorts.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058530","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":"Clarifying the role of TyG-VLR in CKM risk characterization: Reply to \"Composite metabolic biomarkers for cardiovascular risk assessment in CKM syndrome\".","authors":"Ao-Men Lu, Hao-Jie Han, Qian Xu, Shuang-Ke Bai","doi":"10.1186/s12933-026-03337-3","DOIUrl":"10.1186/s12933-026-03337-3","url":null,"abstract":"","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148825224","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":"Disease-modifying anti-diabetic drugs (DMADDs): bridging the SIMPLE approach to disease interception.","authors":"Nizameddin Koca, Seyit Uyar, Yasin Şahintürk, Hamit Yıldız, Stefano Del Prato, RalphA DeFronzo","doi":"10.1186/s12933-026-03346-2","DOIUrl":"10.1186/s12933-026-03346-2","url":null,"abstract":"<p><p>The traditional glucose-centric paradigm of type 2 diabetes management is being superseded by growing evidence that certain agents, sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and pioglitazone, confer cardiovascular, renal, and hepatic benefits that extend well beyond glycemic control. Building on the previously proposed \"diabetes/disease-modifying drugs (DMDs)\" concept introduced through the SIMPLE framework, we propose a more mechanistically precise term: Disease-Modifying Anti-Diabetic Drugs (DMADDs). DMADDs are defined by four criteria: glucose-independent clinical benefit, durable organ-specific protection, mechanistic evidence of anti-inflammatory or anti-fibrotic activity, and sustained legacy effects or remission potential. Using these criteria, SGLT2i, GLP-1RA, and pioglitazone emerge as prototypical agents, while metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, insulin, and sulfonylureas do not meet the full threshold. We explicitly explain why metformin and DPP-4 inhibitors are excluded as DMADDs, situate the DMADD framework within the heterogeneity of type 2 diabetes and against what non-pharmacological interventions can achieve, and state the limitations of the proposal. Recent evidence reinforces this framework: the SOUL trial established cardiovascular superiority for oral semaglutide, extending disease-modifying properties beyond injectable formulations, while Phase 3 TRIUMPH data position retatrutide as an emerging triple-agonist candidate awaiting cardiovascular outcome data. The 2026 American Diabetes Association Standards of Care now recommend SGLT2i and GLP-1RA independent of baseline glycated hemoglobin (HbA1c), an institutional shift that mirrors the disease-interception logic proposed here. We argue that adopting the DMADD framework could reorient diabetes therapeutics from glycemic normalization toward early disease interception, potentially preserving β-cell function and expanding the clinical horizon toward remission. This terminology offers a unifying scaffold for future trials, regulatory classification, and clinical guidelines, redefining therapeutic success in type 2 diabetes beyond glucose control alone.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148825320","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":"Excess risk of cardiovascular disease and mortality after amputation in type 2 diabetes: a nationwide population study from the Swedish National Diabetes Register.","authors":"Karin Bergqvist, Henrik Imberg, Sara Hallström, Jens Michelsen, Hanna Liljebäck, Stefan Franzén, Anna Norhammar, Annika Rosengren, Marcus Lind","doi":"10.1186/s12933-026-03319-5","DOIUrl":"10.1186/s12933-026-03319-5","url":null,"abstract":"<p><strong>Background: </strong>Individuals with diabetes are prone to peripheral angiopathy and neuropathy, predisposing them to diabetic foot ulcers and, ultimately, lower-extremity amputation. The long-term cardiovascular impact of amputation in persons with type 2 diabetes remains insufficiently characterised. The aim of this study was to examine the extent to which lower-extremity amputation in individuals with type 2 diabetes is associated with an increased risk of cardiovascular disease and mortality compared to those with type 2 diabetes without amputation.</p><p><strong>Methods: </strong>This was an observational, population-based retrospective cohort study with data from the Swedish National Diabetes Register linked to the National Patient Register and the Cause of Death Register. All individuals with type 2 diabetes who underwent a major or minor lower-extremity amputation between 2006 and 2019 were identified and matched to four controls with type 2 diabetes but without previous amputation on age, sex, and calendar time. Adjusted hazard ratios (aHRs) for cardiovascular events and mortality were estimated using cause-specific Cox proportional hazards regression, accounting for demographic and clinical risk factors.</p><p><strong>Results: </strong>A total of 3,485 individuals with type 2 diabetes who had undergone amputation and 13,940 matched controls without previous amputation were included. Individuals undergoing amputation had a markedly increased risk of cardiovascular disease and mortality, with aHRs (95% CI) of 2.46 (2.31-2.61) for all-cause mortality, 2.43 (2.18-2.71) for cardiovascular mortality, 2.13 (1.92-2.36) for heart failure, 1.79 (1.55-2.08) for myocardial infarction, and 1.52 (1.31-1.76) for stroke. The hazard of all-cause mortality was more than threefold higher in the first year after amputation compared with matched controls and remained about 50% higher after five years.</p><p><strong>Conclusions: </strong>Lower-extremity amputation in individuals with type 2 diabetes is associated with a substantially increased risk of cardiovascular disease and mortality, independent of pre-existing cardiovascular disease and established risk factors. This underlines the need for intensive cardiovascular risk management both before and after amputation to improve long-term outcomes.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148825335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triglyceride-glucose waist-to-height ratio in relation to prevalent and incident multimorbidity: cross-sectional and prospective evidence from four national studies.","authors":"Zhengqi Shao, HongZhi Hu, Xing Ge, Mingjie Liu, Yuting Duan, Xiangru Guo, Danqi Zhu, Zixuan Yi, Bai Wei","doi":"10.1186/s12933-026-03320-y","DOIUrl":"10.1186/s12933-026-03320-y","url":null,"abstract":"<p><strong>Background: </strong>The triglyceride-glucose waist-to-height ratio (TyG-WHtR) integrates insulin resistance and central adiposity, but its association with generalized multimorbidity across populations and its dose-response threshold remain uncertain.</p><p><strong>Methods: </strong>We analyzed adults aged ≥ 50 years from five analytic samples derived from four national studies. Cross-sectional analyses included the National Health and Nutrition Examination Survey (NHANES; n = 1842) and the Health and Retirement Study (HRS; n = 4310), whereas prospective analyses included the China Health and Retirement Longitudinal Study (CHARLS; n = 4114), the English Longitudinal Study of Ageing (ELSA; n = 1310), and HRS (n = 971). Multimorbidity was defined as the presence of at least two of eight harmonized chronic conditions. Multivariable logistic regression and Cox proportional hazards models were used to evaluate prevalent and incident multimorbidity, respectively. Restricted cubic spline and two-piecewise regression models were used to assess nonlinear associations, and receiver operating characteristic curves were used to compare TyG-WHtR with five alternative TyG-related anthropometric indices.</p><p><strong>Results: </strong>In the cross-sectional analyses, the fully adjusted ORs comparing the highest with the lowest TyG-WHtR quartile were 5.04 (95% CI 3.02-8.42) in NHANES and 3.63 (95% CI 2.70-4.90) in HRS. In the prospective analyses, the fully adjusted HRs comparing the highest with the lowest quartile were 1.87 (95% CI 1.59-2.21) in CHARLS, 1.67 (95% CI 1.30-2.15) in ELSA, and 1.57 (95% CI 1.08-2.29) in HRS. Prospective dose-response associations were nonlinear, with inflection points of 5.92, 5.80, and 6.69, respectively; risk increased predominantly below these values. TyG-WHtR had the largest area under the curve in both cross-sectional samples and in CHARLS and ELSA. Lagged analyses and alternative multimorbidity definitions yielded consistent results.</p><p><strong>Conclusions: </strong>Higher TyG-WHtR was associated with prevalent multimorbidity in both cross-sectional samples and with incident multimorbidity in quartile-based analyses across all three prospective cohorts, although the continuous association was not statistically significant in prospective HRS. The cohort-specific inflection points suggest a provisional candidate risk-alert interval of approximately 5-7. This interval requires independent external validation and should not be interpreted as a diagnostic or treatment threshold.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030015","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":"The cholesterol, high-density lipoprotein, and glucose index and its derived indices predict cardiometabolic multimorbidity development and progression in metabolic dysfunction-associated steatotic liver disease individuals: a prospective cohort study.","authors":"Kai Mu, Jing Zhang, Shuang Liang, Dongshan Zhu, Lujie Zong, Jiang Xue","doi":"10.1186/s12933-026-03343-5","DOIUrl":"10.1186/s12933-026-03343-5","url":null,"abstract":"<p><strong>Background: </strong>Dysregulation of cholesterol, high-density lipoprotein cholesterol, and glucose metabolism is thought to be an important metabolic link between metabolic dysfunction-associated steatotic liver disease (MASLD), type 2 diabetes (T2D), and cardiovascular disease. Although the cholesterol-high-density lipoprotein-glucose (CHG) index and its adiposity-derived indices have been associated with individual cardiometabolic diseases (CMDs), their associations with cardiometabolic multimorbidity (CMM), stage-specific disease progression, and risk prediction in individuals with MASLD remain unclear.</p><p><strong>Methods: </strong>This prospective cohort study included 109,434 UK Biobank participants with MASLD and without T2D, coronary heart disease (CHD), or stroke at baseline. Eight CHG-related indices were evaluated. Incident CMM was defined as the occurrence of at least two of the three CMDs. Cox models estimated associations with incident CMM. Multistate models characterized transitions from a disease-free state to individual CMD and subsequently to CMM. Incremental prediction was assessed using the C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Exploratory mediation analyses evaluated circulating biomarkers related to metabolic, inflammatory, hepatic and renal pathways.</p><p><strong>Results: </strong>During a median follow-up of 16.4 years, 4225 participants developed CMM. All CHG-related indices were associated with higher CMM risk, with the strongest associations observed for CHG-waist-to-height ratio (CHG-WHtR; hazard ratio [HR] per 1-standard deviation [SD] increment, 1.61; 95% confidence interval [CI] 1.57-1.65) and CHG-waist circumference (CHG-WC; HR, 1.59; 95% CI, 1.55-1.63). Adding each index to conventional risk models improved discrimination and risk classification. CHG-WHtR and CHG-WC showed relatively favorable predictive performance, although the absolute differences between indices were modest. In multistate analyses, associations were strongest for disease-free to T2D and CHD-to-CMM transitions. Exploratory biomarker analyses showed that baseline biomarker domains related to glycemic regulation, lipid metabolism, inflammation, and hepatic and renal function were statistically linked to these associations.</p><p><strong>Conclusions: </strong>Among individuals with MASLD, CHG-related indices, particularly CHG-WHtR and CHG-WC, were associated with incident CMM and transition-specific disease progression and improved risk prediction. These readily available indices may help refine CMM risk stratification in MASLD.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954943","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":"Correction: Associations of cumulative exposure and dynamic trajectories of the C-reactive protein-triglyceride-glucose index with incident stroke in middle-aged and older Chinese adults: a longitudinal analysis based on CHARLS.","authors":"Yibo Yang, Aihua Liu","doi":"10.1186/s12933-026-03328-4","DOIUrl":"10.1186/s12933-026-03328-4","url":null,"abstract":"","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788599","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 cardiometabolic perspective on post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID.","authors":"Francisco Westermeier, Etheresia Pretorius, Eva Untersmayr, Romina Bertinat, Nuno Sepúlveda, Enrique Fisman","doi":"10.1186/s12933-026-03316-8","DOIUrl":"10.1186/s12933-026-03316-8","url":null,"abstract":"<p><p>Post-exertional malaise (PEM), the defining feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is increasingly recognized in individuals with Long COVID. Although traditionally viewed as symptom exacerbation and/or emergence of new symptoms following exertion, PEM may reflect disrupted coordination across interconnected physiological systems operating over distinct post-exertional timescales. Such disruption may result in altered post-exertional physiological trajectories that contribute to multisystem manifestations and potential cardiometabolic consequences. This perspective outlines a conceptual approach for investigating PEM through longitudinal assessment of post-exertional physiological trajectories while considering disease severity and underlying cardiometabolic health, including obesity and type 2 diabetes. Integrating these dimensions may help contextualize post-exertional responses, inform future longitudinal cardiometabolic profiling, facilitate patient stratification, and provide a framework for future mechanistic and interventional studies in ME/CFS and Long COVID.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788569","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":"Correction: Associations of cumulative exposure and dynamic trajectories of the triglyceride-total cholesterol-body weight index with new-onset cardiometabolic multimorbidity in middle-aged and older Chinese adults: evidence from a nationwide prospective cohort study.","authors":"Xiao Chen, Chaochao Wang, Qi Huang, Yuan Luo, Zhe Wu, Jing Chen, Haibo Gong","doi":"10.1186/s12933-026-03321-x","DOIUrl":"10.1186/s12933-026-03321-x","url":null,"abstract":"","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720102","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}