Association of circulating metabolites with incident type 2 diabetes in an obese population from a national cohort

•Our study describes the difference of metabolome in obese group with incident type 2 diabetes.•Five metabolites including spermine are associated with incident type 2 diabetes.•Our study introduces alanine-to-glycine ratio as a predictive marker for type 2 diabetes. Obesity is the most common risk factor for type 2 diabetes. However, not all obese individuals develop diabetes. In the era of precision medicine, metabolomics may reveal the fundamental metabolic status of an individual. Our aim was to assess the association of metabolites with incident type 2 diabetes in obese individuals using Korean Genome and Epidemiology Cohort Study. Using 12 years of metabolomic data from 2,580 individuals, we performed a metabolomic study to define metabolically healthy obesity in an obese population (n = 704) with incident type 2 diabetes. Cox proportional hazards regression model and survival analysis were performed adjusted for the traditional risk factors of type 2 diabetes. Our study revealed that spermine, acyl-alkyl phosphatidylcholines (C34:3, C36:3, C42:1), hydroxy sphingomyelin (C22:2, C14:1), and sphingomyelin (C16:0) were associated with incident type 2 diabetes in obese individuals after the adjustment for risk factors and correction of multiple comparisons by Bonferroni method. Five metabolites (except hydroxy sphingomyelin C14:1 and sphingomyelin C16:0) were also significantly associated with incident type 2 diabetes in lean individuals. This study highlights the need for defining metabolically healthy obesity based on serum metabolites and elucidates potential biomarkers for type 2 diabetes in an obese population.