Circulating metabolic biomarkers are consistently associated with incident type 2 diabetes in Asian and European populations – a metabolomics analysis in five prospective cohorts

Background While Asians have a higher risk of type 2 diabetes (T2D) than Europeans for a given BMI, it remains unclear whether the same markers of metabolic pathways are associated with diabetes. Objectives We evaluated associations between metabolic biomarkers and incident T2D in three major Asian ethnic groups (Chinese, Malay, and Indian) and a European population. Methods We analyzed data from adult males and females of two cohorts from Singapore (n = 6,393) consisting of Chinese, Malays and Indians, and three cohorts of European-origin participants from Finland (n = 14,558). We used nuclear magnetic resonance to quantify 154 circulating metabolic biomarkers at baseline and performed logistic regression to assess associations with T2D risk adjusted for age, sex, BMI and glycaemic markers. Results Of the 154 metabolic biomarkers, 59 were associated with higher risk of T2D in both Asians and Europeans ( P < 0.0003; Bonferroni-corrected). These included branched-chain and aromatic amino acids, the inflammatory marker glycoprotein acetyls, total fatty acids, monounsaturated fatty acids, apolipoprotein B, larger very low-density lipoprotein particle sizes, and triglycerides. In addition, 13 metabolites were associated with a lower T2D risk in both populations including omega-6 polyunsaturated fatty acids and larger high-density lipoprotein particle sizes. Associations were consistent within the Asian ethnic groups (all P het ≥ 0.05) and largely consistent for the Asian and European populations ( P het ≥ 0.05 for 128 of 154 metabolic biomarkers). Conclusion Metabolic biomarkers across several biological pathways were consistently associated with T2D risk in Asians and Europeans.