Key result
Adding metabolic, proteomic, and genomic biomarkers significantly improves CAD detection in East Asians with T2D.
Why the study?
CAD is a major cause of morbidity and mortality in T2D, and researchers aimed to discover associated metabolomic and proteomic signatures and evaluate their incremental value in CAD identification.
Does the addition of integrated metabolomic, proteomic, and genomic biomarkers to traditional clinical risk factors improve the identification of prevalent coronary artery disease in East Asians with type 2 diabetes?
Cross-Sectional (n=4,329)
Does the addition of integrated metabolomic, proteomic, and genomic biomarkers to traditional clinical risk factors improve the identification of prevalent coronary artery disease in East Asians with type 2 diabetes?
Effect estimate: AUC 0.775 to 0.841
p-value: p=0.016
The integration of metabolomic, proteomic, and genomic biomarkers significantly improves the identification of prevalent coronary artery disease in East Asian patients with type 2 diabetes compared to traditional clinical risk factors alone.
May enhance CAD identification in East Asian T2D; leaves open prospective validation before practice change.
Introduction and Objective: Coronary artery disease (CAD) is a major cause of morbidity and mortality in type 2 diabetes (T2D). We aimed to discover metabolomic and proteomic signatures associated with CAD in people with T2D and to assess their incremental value in CAD identification. Methods: We generated targeted serum metabolomic profiles (392 features) using mass spectrometry in a hospital-based cohort of 3,929 Koreans with T2D. Proteomics (Olink Explore HT, 5,416 features) was available in a subset (n=888). CAD identification was done in an independent validation set (n=400), and polygenic risk score (PRS) was calculated using transancestry meta-analysis of East Asian and European CAD genome-wide association studies. Results: Participants had a mean age of 62 years, and 59% were male. In the derivation set (n=3929), 323 participants had CAD at baseline. Cross-sectional analyses adjusted for age and sex identified 29 endogenous metabolites associated with prevalent CAD (PFDR < 0.05). The top 3 significant metabolites were 4-hydroxybenzoate, propylurofuranic acid and 12-hydroxyeicosatetraenoic acid, with enrichment in arginine and proline metabolism. Proteomic analyses in a subset (n=880) identified 17 proteins associated with prevalent CAD, with enrichment in PI3K-AKT-mTOR signaling. Among these, 12 proteins were nominally associated with incident myocardial infarction in UK Biobank (top 3: NPPB, MDK, APOM). Incorporation of these metabolic and proteomic markers and CAD PRS into a model including traditional clinical risk factors significantly improved identification of prevalent CAD in the validation set (AUC 0.775 to 0.841; P = 0.016 by DeLong's test). When added individually, the largest contribution was observed for metabolites (ΔAUC = 0.040), followed by CAD PRS (ΔAUC = 0.019) and proteins (ΔAUC = 0.016). Conclusion: This study demonstrates that integrated metabolomic, proteomic and genomic biomarkers may improve risk stratification for cardiovascular complications in individuals with T2D. Disclosure H. Lee: None. M. Kho: None. B. Ham: None. J. Choi: None. J. Lee: None. J. Park: None. Y. Jo: None. S. Lee: None. S. Choi: None. M. Moon: None. H. Lee: None. S. Lee: None. S. Kwak: None. Funding Seoul National University Hospital Phase III (Postdoctoral fellowship) grant of the SNU-SNUH Physician Scientist Training Program (800-20240636), Korean Ministry of Food and Drug Safety (23212MFDS202), Korean Ministry of Science and ICT (RS-2023-00262002)
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Lee et al. (2026) conducted a cross-sectional in Coronary artery disease in type 2 diabetes (n=4,329). Integrated metabolomic, proteomic, and genomic biomarkers vs. Traditional clinical risk factors alone was evaluated on Identification of prevalent CAD (AUC 0.775 to 0.841, p=0.016). Incorporating metabolic, proteomic, and genomic biomarkers into a clinical model significantly improved identification of prevalent CAD in East Asians with T2D (AUC 0.775 to 0.841; P=0.016).
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