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Epigenetic biomarkers predict macrovascular events in individuals with type 2 diabetes

García-Calzón, Sonia LU ; Maguolo, Alice LU orcid ; Eichelmann, Fabian ; Edsfeldt, Andreas LU orcid ; Perfilyev, Alexander LU orcid ; Maziarz, Marlena LU orcid ; Lindström, Axel LU orcid ; Sun, Jiangming LU orcid ; Briviba, Monta and Schulze, Matthias B. , et al. (2025) In Cell Reports Medicine
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Cell Reports Medicine
publisher
Cell Press
ISSN
2666-3791
DOI
10.1016/j.xcrm.2025.102290
language
English
LU publication?
yes
additional info
doi: 10.1016/j.xcrm.2025.102290
id
0b896fad-e4a4-457a-bb50-e97a88d98b03
date added to LUP
2025-08-08 14:55:41
date last changed
2025-08-08 15:12:55
@article{0b896fad-e4a4-457a-bb50-e97a88d98b03,
  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.}},
  author       = {{García-Calzón, Sonia and Maguolo, Alice and Eichelmann, Fabian and Edsfeldt, Andreas and Perfilyev, Alexander and Maziarz, Marlena and Lindström, Axel and Sun, Jiangming and Briviba, Monta and Schulze, Matthias B. and Klovins, Janis and Ahlqvist, Emma and Gonçalves, Isabel and Ling, Charlotte}},
  issn         = {{2666-3791}},
  language     = {{eng}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports Medicine}},
  title        = {{Epigenetic biomarkers predict macrovascular events in individuals with type 2 diabetes}},
  url          = {{http://dx.doi.org/10.1016/j.xcrm.2025.102290}},
  doi          = {{10.1016/j.xcrm.2025.102290}},
  year         = {{2025}},
}