Plasma metabolomic signatures of obesity and risk of type 2 diabetes

Abstract Objective The mechanisms linking obesity to type 2 diabetes (T2D) are not fully understood. This study aimed to identify obesity‐related metabolomic signatures (MESs) and evaluated their relationships with incident T2D. Methods In a nested case‐control study of 2076 Chinese adults, 140 plasma metabolites were measured at baseline, linear regression was applied with the least absolute shrinkage and selection operator to identify MESs for BMI and waist circumference (WC), and conditional logistic regression was applied to examine their associations with T2D risk. Results A total of 32 metabolites associated with BMI or WC were identified and validated, among which 14 showed positive associations and 3 showed inverse associations with T2D; 8 and 18 metabolites were selected to build MESs for BMI and WC, respectively. Both MESs showed strong linear associations with T2D: odds ratio (95% CI) comparing extreme quartiles was 4.26 (2.00‐9.06) for BMI MES and 9.60 (4.22‐21.88) for WC MES (both p ‐trend < 0.001). The MES‐T2D associations were particularly evident among individuals with normal WC: odds ratio (95% CI) reached 6.41 (4.11‐9.98) for BMI MES and 10.38 (6.36‐16.94) for WC MES. Adding MESs to traditional risk factors and plasma glucose improved C statistics from 0.79 to 0.83 ( p < 0.001). Conclusions Multiple obesity‐related metabolites and MESs strongly associated with T2D in Chinese adults were identified.