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-

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

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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 adjust-ments 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.

Original languageEnglish
Pages (from-to)1053-1067
Number of pages15
JournalJournal of atherosclerosis and thrombosis
Volume27
Issue number10
DOIs
Publication statusPublished - 2020

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical

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