Epigenetic biomarkers predict macrovascular events in individuals with type 2 diabetes
Year: 2025
Type: article
Study design: Observational Study
Abstract: Prediction of incident macrovascular events (iMEs) in individuals with type 2 diabetes (T2D) remains suboptimal. We aim to discover blood-based epigenetic biomarkers predicting iMEs in 752 newly diagnosed individuals with T2D, among whom 102 developed iMEs during follow-up. 461 DNA methylation sites, e.g., near ARID3A , GATA5 , HDAC4 , IRS2 , and TMEM51 , associate with iMEs. Using cross-validation, a methylation risk score (MRS) containing 87 sites predicts iMEs with an area under the curve (AUC) of 0.81 and an AUC of 0.84 for the combination of MRS and clinical risk factors, better than SCORE2-Diabetes (Systematic Coronary Risk Evaluation 2-Diabetes), UKPDS (United Kingdom Prospective Diabetes Study), Framingham, and polygenic risk scores (AUCs = 0.54–0.62). This epigenetic biomarker has a negative predictive value of 95.9% and improves the classification of iMEs with continuous net reclassification improvement (NRI) showing 90.2% improvement versus clinical factors. Atherosclerotic versus non-atherosclerotic aortas show 78 differentially methylated sites. We validate 32 sites in EPIC-Potsdam and 43 in OPTIMED cohorts, including an MRS (AUC = 0.80). Together, blood-based epigenetic biomarkers predict iMEs better than clinical risk factors, supporting its future clinical use. • Blood-based epigenetic biomarker predicts macrovascular events at type 2 diabetes diagnosis • The epigenetic biomarker tool outperforms established clinical cardiovascular risk scores • DNA methylation markers also show biological relevance in human aortic and carotid plaques • The epigenetic biomarker may support future precision medicine strategies in type 2 diabetes García-Calzón et al. identify a blood-based epigenetic biomarker tool that helps predict future cardiovascular disease, which individuals with type 2 diabetes are more likely to develop. Their findings support the use of epigenetic biomarkers to improve risk stratification and guide more personalized prevention strategies in diabetes care.
Source: Cell Reports Medicine
Institutions: Lund University, Instituto de Salud Carlos III, Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, Navarre Institute of Health Research, Skåne University Hospital, Universidad de Navarra, German Center for Diabetes Research, German Institute of Human Nutrition, Latvian Biomedical Research and Study Centre, University of Potsdam, University of Latvia
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: Marie Curie, Stiftelsen för Strategisk Forskning, Bundesministerium für Bildung und Forschung, Lunds Universitet, Svenska Sällskapet för Medicinsk Forskning, Hjärt-Lungfonden, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Ministerio de Ciencia e Innovación, Diabetesförbundet, Novo Nordisk Fonden, Region Skåne, Skånes universitetssjukhus, Medicinska fakulteten, Umeå Universitet, H2020 Marie Skłodowska-Curie Actions, Deutsches Zentrum für Diabetesforschung
Awards: G1150796042, The vulnerable atherosclerotic plaque: mechanisms of development and techniques for imaging, G1371075171, G1524398354, G1590297379, G1815081691, Diabetes subclassification - new genes and novel mechanisms, G2515376675, Epigenetic biomarkers for prediction of vascular complications and response to treatment in subjects with diabetes, G3184054503, Can our epigenetics findings be translated to diabetes patients?, G477451934, G5706130723, The vulnerable atherosclerotic plaque: mechanisms of development and tools for its identification, Vulnerable atherosclerotic plaque: underlying mechanisms and novel tools for its detection, Epigenetics for precision medicine and future therapies in type 2 diabetes, G7000675311, LUDC-IRC för individanpassad medicin i diabetes, G7700986924, G7957046100, Apoptosis and efferocytosis as mechanisms of impaired fibrotic tissue repair in diabetes associated vascular complications
OpenAlex ID: W4413055626