Kazuo Omori1, Naoto Katakami1,2, Shoya Arakawa3, Yuichi Yamamoto1, Hiroyo Ninomiya1, Mitsuyoshi Takahara1,4, Taka-Aki Matsuoka1, Hiroshi Tsugawa5, Masahiro Furuno3, Takeshi Bamba6, Eiichiro Fukusaki3, Iichiro Shimomura1. 1. Department of Metabolic Medicine, Osaka University Graduate School of Medicine. 2. Department of Metabolism and Atherosclerosis, Osaka University Graduate School of Medicine. 3. Laboratory of Bioresource Engineering, Department of Biotechnology, Graduate School of Engineering, Osaka University. 4. Department of Diabetes Care Medicine, Graduate School of Medicine, Osaka University. 5. RIKEN Center for Sustainable Resource Science, Yokohama. 6. Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University.
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 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.
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.
Authors: Allison L O'Kell; Clive Wasserfall; Joy Guingab-Cagmat; Bobbie-Jo M Webb-Roberston; Mark A Atkinson; Timothy J Garrett Journal: Metabolomics Date: 2021-11-14 Impact factor: 4.290