Metabonomic variations in the drug-treated type 2 diabetes mellitus patients and healthy volunteers.
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, HbA1c, 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.
Bao
Yuqian
Y
Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center of Diabetes, Shanghai, China.
Zhao
Tie
T
Wang
Xiaoyan
X
Qiu
Yunping
Y
Su
Mingming
M
Jia
Weiping
W
Jia
Wei
W
D002219:Carbamates / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D008239:Lysine / Q000097:blood / Q000378:metabolism; D055432:Metabolomics; D008687:Metformin / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use; D014527:Uric Acid / Q000097:blood / Q000378:metabolism; D014633:Valine / Q000097:blood / Q000378:metabolism
D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D014527:Uric Acid; D019344:Lactic Acid; C072379:repaglinide; D008687:Metformin; D014633:Valine; D008239:Lysine