Plasma Metabolomic Profiles in Association with Type 2 Diabetes Risk and Prevalence in Chinese Adults

Metabolomic studies have identified several metabolites associated with type 2 diabetes (T2D) in populations of European ancestry. East Asians, a population of particular susceptibility to T2D, were generally not included in previous studies. We examined the associations of plasma metabolites with risk and prevalence of T2D in 976 Chinese men and women (40-74 years of age) who were participants of two prospective cohort studies and had no cardiovascular disease or cancer at baseline. Sixty-eight prevalent and 73 incident T2D cases were included. Non-targeted metabolomics was conducted that detected 689 metabolites with known identities and 690 unknown metabolites. Multivariable logistic and Cox regressions were used to evaluate the associations of standardized metabolites with diabetes risk and prevalence. We identified 36 known metabolites and 10 unknown metabolites associated with prevalent and/or incident T2D at false discovery rate <0.05. The known metabolites are involved in metabolic pathways of glycolysis/gluconeogenesis, branched-chain amino acids, other amino acids, fatty acids, glycerophospholipids, androgen, and bradykinin. Six metabolites showed independent associations with incident T2D: 1,5-anhydroglucitol, mannose, valine, 3-methoxytyrosine, docosapentaenoate (22:5n3), and bradykinin-hydroxy-pro(3). Each standard deviation increase in these metabolites was associated with a 40-150 % change in risk of developing diabetes (30-80 % after further adjustment for glucose). Risk prediction was significantly improved by adding these metabolites in addition to known T2D risk factors, including central obesity and glucose. These findings suggest that hexoses, branched-chain amino acids, and yet to be validated novel plasma metabolites may improve risk prediction and mechanistic understanding of T2D in Chinese populations.