Metabonomic Characteristics of Myocardial Diastolic Dysfunction in Type 2 Diabetic Cardiomyopathy Patients

Mingyu Hao; Jianxin Deng; Xiaohong Huang; Haiyan Li; Huiting Ou; Xiangsheng Cai; Jiajie She; Xueting Liu; Ling Chen; Shujuan Chen; Wenlan Liu; Dewen Yan

doi:10.3389/fphys.2022.863347

Metabonomic Characteristics of Myocardial Diastolic Dysfunction in Type 2 Diabetic Cardiomyopathy Patients

Front Physiol. 2022 May 9:13:863347. doi: 10.3389/fphys.2022.863347. eCollection 2022.

Authors

Mingyu Hao^{1

2}, Jianxin Deng¹, Xiaohong Huang¹, Haiyan Li¹, Huiting Ou¹, Xiangsheng Cai³, Jiajie She^{2

4}, Xueting Liu¹, Ling Chen¹, Shujuan Chen¹, Wenlan Liu⁵, Dewen Yan¹

Affiliations

¹ Department of Endocrinology, Shenzhen Clinical Research Center for Metabolic Diseases, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center of Shenzhen University, Shenzhen, China.
² Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
³ Institute of Translational Medicine, University of Chinese Academy of Science-Shenzhen Hospital, Shenzhen, China.
⁴ The First Affiliated Hospital of Shenzhen University, Reproductive Medicine Centre, Shenzhen Second People's Hospital, Shenzhen, China.
⁵ Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen University First Affiliated Hospital, Shenzhen, China.

Abstract

Diabetic cardiomyopathy (DCM) is one of the most essential cardiovascular complications in diabetic patients associated with glucose and lipid metabolism disorder, fibrosis, oxidative stress, and inflammation in cardiomyocytes. Despite increasing research on the molecular pathogenesis of DCM, it is still unclear whether metabolic pathways and alterations are probably involved in the development of DCM. This study aims to characterize the metabolites of DCM and to identify the relationship between metabolites and their biological processes or biological states through untargeted metabolic profiling. UPLC-MS/MS was applied to profile plasma metabolites from 78 patients with diabetes (39 diabetes with DCM and 39 diabetes without DCM as controls). A total of 2,806 biochemical were detected. Compared to those of DM patients, 78 differential metabolites in the positive-ion mode were identified in DCM patients, including 33 up-regulated and 45 down-regulated metabolites; however, there were only six differential metabolites identified in the negative mode including four up-regulated and two down-regulated metabolites. Alterations of several serum metabolites, including lipids and lipid-like molecules, organic acids and derivatives, organic oxygen compounds, benzenoids, phenylpropanoids and polyketides, and organoheterocyclic compounds, were associated with the development of DCM. KEGG enrichment analysis showed that there were three signaling pathways (metabolic pathways, porphyrin, chlorophyll metabolism, and lysine degradation) that were changed in both negative- and positive-ion modes. Our results demonstrated that differential metabolites and lipids have specific effects on DCM. These results expanded our understanding of the metabolic characteristics of DCM and may provide a clue in the future investigation of reducing the incidence of DCM. Furthermore, the metabolites identified here may provide clues for clinical management and the development of effective drugs.

Keywords: diabetes; diabetic cardiomyopathy (DCM); metabolic profiles; metabonomics; serum metabolites.