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非靶向代谢组学揭示了印度糖尿病患者中支链氨基酸、葡萄糖和脂肪代谢的改变与冠状动脉疾病的发生有关。

Untargeted metabolomics reveals altered branch chain amino acids, glucose and fat metabolism contributing to coronary artery disease among Indian diabetic patients.

作者信息

Adela Ramu, Kasarla Siva Swapna, Saquib Najmuddin, Gupta Sonu Kumar, Bajpai Sneh, Kumar Yashwant, Banerjee Sanjay K

机构信息

Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research, Guwahati-781101, Assam, India.

Non-Communicable Diseases Group, Translational Health Science and Technology Institute (THSTI), Faridabad-121001, Haryana, India.

出版信息

Mol Omics. 2023 May 9;19(4):321-329. doi: 10.1039/d2mo00320a.

DOI:10.1039/d2mo00320a
PMID:36752683
Abstract

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterised by increased blood glucose levels. Patients with T2DM have a high risk of developing atherosclerotic coronary artery disease (CAD). CAD with T2DM has a complex etiology and the understanding of the pathophysiology of coronary artery disease (CAD) in the presence of diabetes is poor. Here, we have used LC-MS/MS-based untargeted metabolomics to unveil the alterations of metabolites in the serum of South-Indian patients diagnosed with T2DM, CAD and T2DM along with CAD (T2DM-CAD) compared with the healthy subjects (CT). Using untargeted metabolomics and network-based approaches, a set of metabolites highly co-expressed with T2DM-CAD pathogenesis were identified. Our results revealed that these metabolites belong to essential pathways such as amino acid metabolism, fatty acid metabolism and carbohydrate metabolism. The candidate metabolites identified by metabolomics study are branch chain amino acids, L-arginine, linoleic acid, L-serine, L-cysteine, fructose-6-phosphate, glycerol, creatine and 3-phosphoglyceric acid, and explain the pathogenesis of T2DM-assisted CAD. The identified metabolites could be used as potential prognostic markers to predict CAD in patients diagnosed with T2DM.

摘要

2型糖尿病(T2DM)是一种以血糖水平升高为特征的慢性代谢紊乱疾病。T2DM患者发生动脉粥样硬化性冠状动脉疾病(CAD)的风险很高。合并T2DM的CAD病因复杂,目前对糖尿病患者冠状动脉疾病(CAD)病理生理学的了解尚浅。在此,我们采用基于液相色谱-串联质谱的非靶向代谢组学方法,揭示了与健康受试者(CT)相比,被诊断为T2DM、CAD以及同时患有T2DM和CAD(T2DM-CAD)的南印度患者血清中代谢物的变化。利用非靶向代谢组学和基于网络的方法,鉴定出一组与T2DM-CAD发病机制高度共表达的代谢物。我们的结果表明,这些代谢物属于氨基酸代谢、脂肪酸代谢和碳水化合物代谢等重要途径。代谢组学研究鉴定出的候选代谢物有支链氨基酸、L-精氨酸、亚油酸、L-丝氨酸、L-半胱氨酸、6-磷酸果糖、甘油、肌酸和3-磷酸甘油酸,并解释了T2DM合并CAD的发病机制。所鉴定出的代谢物可作为潜在的预后标志物,用于预测被诊断为T2DM的患者是否患有CAD。

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