Identification of Metabolites Associated with Onset of CAD in Diabetic Patients Using CE-MS Analysis: A Pilot Study

Aim: Coronary artery disease (CAD) is the result of a complex metabolic disorder caused by various environmental and genetic factors. Metabolomics is a potential tool for identifying biomarkers for better risk classification and for understanding the pathophysiological mechanisms of CAD. With this background, we performed a pilot study to identify metabolites associated with the future onset of CAD in patients with type 2 diabetes. Methods: Sixteen subjects who suffered from CAD event during the observation period and 39 non-CAD subjects who were matched to the CAD subjects for Framingham Coronary Heart Disease Risk Score, diabetes duration, and HbA1c were selected. Capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) was used to perform non-targeted metabolome analysis of serum samples collected in 2005. Results: A total of 104 metabolites were identified. Unsupervised principal component analysis (PCA) did not to reveal two distinct dusters of individuals. However, a significant association with CAD was found for 7 metabolites (pelargonic acid, glucosamine:galactosamine, thymine, 3-hydroxybutyric acid, creatine, 2-aminoisobutyric acid, hypoxanthine) and the levels of all these metabolites were significantly lower in the CAD group compared with the non-CAD group. Conclusions: We identified 7 metabolites related to long-term future onset of CAD in Japanese patients with diabetes. Further studies with large sample size would be necessary to confirm our findings, and future studies using in vivo or in vitro models would be necessary to elucidate whether direct relationships exist between the detected metabolites and CAD pathophysiology.