Identification of Plasma Inositol and Indoxyl Sulfate as Novel Biomarker Candidates for Atherosclerosis in Patients with Type 2 Diabetes. - Findings from Metabolome Analysis Using GC/MS

• Published in: Journal of Atherosclerosis and Thrombosis Vol. 27; no. 10; pp. 1053 - 1067
• Main Authors: Kazuo Omori, Naoto Katakami, Shoya Arakawa, Yuichi Yamamoto, Hiroyo Ninomiya, Mitsuyoshi Takahara, Taka-aki Matsuoka, Hiroshi Tsugawa, Masahiro Furuno, Takeshi Bamba, Eiichiro Fukusaki, Iichiro Shimomura
• Format: Journal Article
• Language: Japanese
• Published: Japan Atherosclerosis Society 2020
• ISSN: 1340-3478

[Aim :] An identification of the high-risk group of atherosclerotic cardiovascular disease (CVD) is important in the management of patients with diabetes. Metabolomics is a potential tool for the discovery of new biomarkers. With this background, we aimed to identify metabolites associated with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). [Methods :] A total of 176 patients with T2DM who have never had a CVD event and 40 who were survivors of coronary artery disease (CAD) events were enrolled. Non-targeted metabolome analysis of fasting plasma samples was performed using gas chromatography coupled with mass spectrometry (GC/MS) highly optimized for multiple measurement of blood samples. First, metabolites were screened by analyzing the association with the established markers of subclinical atherosclerosis (i.e., carotid maximal intima-media thickness (max-IMT) and flow-mediated vasodilation (FMD) ) in the non-CVD subjects. Then, the associations between the metabolites detected and the history of CAD were investigated. [Result :] A total of 65 annotated metabolites were detected. Non-parametric univariate analysis identified inositol and indoxyl sulfate as significantly (p<0.05) associated with both max-IMT and FMD. These metabolites were also significantly associated with CAD. Moreover, inositol remained to be associated with CAD even after adjustments for traditional coronary risk factors. [Conclusions :] We identified novel biomarker candidates for atherosclerosis in Japanese patients with T2DM using GC/MS-based non-targeted metabolomics.