Abstract
CONTEXT: We previously reported an association between lysophosphatidylinositol (LPI) (16:1) and risk for type 2 diabetes in a Chinese population using an untargeted analysis. OBJECTIVE: To examine the overall associations of LPIs and their related metabolites, such as nonesterified fatty acids (NEFAs) and acylcarnitines, with incident and prevalent type 2 diabetes using a targeted approach. DESIGN AND SETTING: A case-control study was nested within the Singapore Chinese Health Study. Cases and controls were individually matched by age, sex, and date of blood collection. We used both liquid and gas chromatography tandem mass spectrometry to measure serum metabolite levels at baseline, including 8 LPIs, 19 NEFAs, and 34 acylcarnitines. Conditional logistic regression models were used to estimate the associations between metabolites and diabetes risk. PARTICIPANTS: Participants included 160 incident and 144 prevalent cases with type 2 diabetes and 304 controls. MAIN OUTCOME MEASURE: Incident and prevalent type 2 diabetes. RESULTS: On the basis of a false discovery rate <0.1, we identified 37 metabolites associated with prevalent type 2 diabetes, including 7 LPIs, 18 NEFAs, and 12 acylcarnitines, and 11 metabolites associated with incident type 2 diabetes, including 2 LPIs and 9 NEFAs. Two metabolites, LPI (16:1) and dihomo-γ-linolenic acid, showed independent associations with incident type 2 diabetes and significantly enhanced the risk prediction. CONCLUSIONS: We found several LPIs and NEFAs that were associated with risk for type 2 diabetes and may improve our understanding of the pathogenesis. The findings suggest that lipid profiles could aid in diabetes risk assessment in Chinese populations.