Circulating metabolic biomarkers are consistently associated with type 2 diabetes risk in Asian and European populations

Jowy Yi Seah, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; Singapore 117549, Singapore.
Yueheng Hong, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; Singapore 117549, Singapore.
Anna Cichońska, Nightingale Health Ltd, Mannerheimintie 164a, 00300 Helsinki, Finland.
Charumathi Sabanayagam, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore.
Simon Nusinovici, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore.
Tien Yin Wong, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore.
Ching-Yu Cheng, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore.
Pekka Jousilahti, Department of Public Health Solutions, Finnish Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland.
Annamari Lundqvist, Department of Public Health Solutions, Finnish Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland.
Markus Perola, Department of Public Health Solutions, Finnish Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland.
Veikko Salomaa, Department of Public Health Solutions, Finnish Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland.
E Shyong Tai, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; Singapore 117549, Singapore.
Peter Würtz, Nightingale Health Ltd, Mannerheimintie 164a, 00300 Helsinki, Finland.
Rob M. van Dam, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; Singapore 117549, Singapore.
Xueling Sim, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; Singapore 117549, Singapore.

Document Type

Journal Article

Publication Date

4-7-2022

Journal

The Journal of clinical endocrinology and metabolism

DOI

10.1210/clinem/dgac212

Keywords

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

Abstract

CONTEXT: 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. OBJECTIVE: 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 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.

Department

Exercise and Nutrition Sciences

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