Circulating Metabolites and the Development of Type 2 Diabetes in Chinese Adults.
Bragg F., Kartsonaki C., Guo Y., Holmes M., Du H., Yu C., Pei P., Yang L., Jin D., Chen Y., Schmidt D., Avery D., Lv J., Chen J., Clarke R., Hill M., Li L., Millwood I., Chen Z.
OBJECTIVE: To assess prospective associations of circulating metabolites with the risk of type 2 diabetes (T2D) among Chinese adults. RESEARCH DESIGN AND METHODS: A case-cohort study within the 8-year prospective China Kadoorie Biobank comprised 882 participants with incident T2D and 789 subcohort participants. Nuclear magnetic resonance metabolomic profiling quantified 225 metabolites in stored baseline plasma samples. Cox regression related individual metabolites with T2D risk, adjusting for potential confounders and fasting time. RESULTS: After correction for multiple testing, 163 metabolites were significantly associated with the risk of T2D (P < 0.05). There were strong positive associations of VLDL particle size, the ratio of apolipoprotein B-to-apolipoprotein A-1, branched-chain amino acids, glucose, and triglycerides with T2D, and inverse associations of HDL-cholesterol, HDL particle size, and relative n-3 and saturated fatty acid concentrations. CONCLUSIONS: In Chinese adults, metabolites across diverse pathways were independently associated with T2D risk, providing valuable etiological insights and potential to improve T2D risk prediction.