Circulating Metabolic Biomarkers Are Consistently Associated With Type 2 Diabetes Risk in Asian and European Populations

Abstract

Context: While Asians have a higher risk of type 2 diabetes (T2D) than Europeans for a given body mass index (BMI), it remains unclear whether the same markers of metabolic pathways are associated with diabetes.

Objective: We evaluated associations between metabolic biomarkers and incidence of T2D in 3 major Asian ethnic groups (Chinese, Malay, and Indian) and a European population.

Methods: We analyzed data from adult males and females of 2 cohorts from Singapore (n = 6393) consisting of Chinese, Malays, and Indians and 3 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 glycemic 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 Phet ≥ 0.05) and largely consistent for the Asian and European populations (Phet ≥ 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.

Keywords: HDL; LDL; NMR; aromatic amino acids; branched-chain amino acids; cholesterol; fatty acids; glycoprotein acetyls; inflammation; lipoprotein; metabolomics; triglycerides; type 2 diabetes.