A large study of metabolomics reveals common and distinct metabolic biomarkers for type 2 diabetes, coronary heart disease, and stroke

Abstract We aimed at examining the shared and unique associations of metabolites with multiple cardiometabolic diseases, including type 2 diabetes (T2D), coronary heart disease (CHD), and stroke. In this study, a total of 168 plasma metabolites were measured by high-throughput nuclear magnetic resonance spectroscopy among 98 162 participants free of T2D, CHD, and stroke at baseline. Cox proportional hazard models estimated hazard ratios for a 1-SD increase in metabolite concentration levels, and false discovery rate (at 10%) was used to correct for multiple comparisons. Over 12.1 years of follow-up on average, 3463 T2D, 6186 CHD, and 1892 stroke events were recorded. Most lipoprotein metabolites were associated with risks of T2D and CHD but not with the risk of stroke, with stronger associations for T2D than for CHD. Phospholipids within intermediate-density lipoprotein or large low-density lipoprotein particles showed positive associations with CHD and inverse associations with T2D. Metabolites indicating very small very low-density lipoprotein, histidine, creatinine, albumin, and glycoprotein acetyls were associated with risks of all 3 conditions. This large-scale metabolomics study revealed common and distinct metabolic biomarkers for T2D, CHD, and stroke, providing instrumental information to possibly implement precision medicine for preventing and treating these conditions.