Metabonomic Variations in the Drug-Treated Type 2 Diabetes Mellitus Patients and Healthy Volunteers
Metabonomic Variations in the Drug-Treated Type 2 Diabetes Mellitus Patients and Healthy Volunteers
复制标题
DOI：
10.1021/pr800643w
复制
发表时间：
2009-04-01
影响因子：
4.4
通讯作者：
Jia, Wei
中科院分区：
文献类型：
--
作者：
Bao, Yuqian;Zhao, Tie;Jia, Wei
2型糖尿病（T2 DM）的病理发展和药物干预涉及下游低分子量代谢产物（包括脂质和氨基酸）以及碳水化合物（如葡萄糖）表达的改变。目前，用于T2 DM治疗临床评估的少量标志物可能不足以反映病理生理学的全球变化。在本研究中，对74例新诊断为T2 DM并接受瑞格列奈、二甲双胍或罗格列酮单药治疗48周的患者进行了代谢组学研究，以确定与T2 DM和药物治疗相关的代谢变异。分别于治疗24周和48周空腹过夜和餐后2 h采集血清，监测空腹血糖（FPG）、餐后2 h血糖（2 hPG）、糖化血红蛋白（HbA（1c））等生化指标。气相色谱/质谱联用多变量统计分析用于确定与T2 DM相关的总体血清代谢物与健康对照相比的变化以及对药物治疗的反应。糖尿病受试者中显著改变的血清代谢物包括缬氨酸、麦芽糖、谷氨酸、尿酸盐、丁酸盐和长链脂肪酸（C16：0、C18：1、C18：0、十八烷酸盐和花生四烯酸盐）增加，以及葡萄糖醛酸内酯、赖氨酸和乳酸盐减少。三种治疗均能将T2 DM患者血清中高水平的谷氨酸下调至较低水平，但罗格列酮治疗能够逆转更多异常水平的代谢物，如缬氨酸、赖氨酸、葡萄糖醛酸内酯、C16：0、C18：1、尿酸盐和十八烷酸盐，表明罗格列酮比其他两种药物更有效地改变T2 DM患者的代谢。
The pathological development and the drug intervention of type 2 diabetes mellitus (T2DM) involve altered expression of downstream low molecular weight metabolites including lipids and amino acids, and carbohydrates such as glucose. Currently, a small number of markers used for clinical assessment of T2DM treatment may be insufficient to reflect global variations in pathophysiology. In this study, a metabonomic study was performed to determine metabolic variations associated with T2DM and the drug treatments on 74 patients who were newly diagnosed with T2DM and received a 48 week treatment of a single drug, repaglinide, metformin or rosiglitazone. Fasting overnight and 2 h postprandial blood serum of patients were collected at 24 and 48 weeks to monitor the biochemical indices (FPG, 2hPG, HbA(1c), etc.). Gas chromatography/mass spectrometer coupled with multivariate statistical analysis was used to identify the alteration of global serum metabolites associated with T2DM as compared to healthy controls and responses to drug treatment. Significantly altered serum metabolites in diabetic subjects include increased valine, maltose, glutamate, urate, butanoate and long-chain fatty acid(C16:0,C18:1, C18:0, octadecanoate and arachidonate), and decreased glucuronolactone, lysine and lactate. All of the three treatments were able to down-regulate the high level of glutamate to a lower level in serum of T2DM patients, but rosiglitazone treatment was able to reverse more abnormal levels of metabolites, such as valine, lysine, glucuronolactone, C16:0, C18:1, urate, and octadecanoate, suggesting that it is more efficient to alter the metabolism of T2DM patients than the other two drugs.