Serum Metabolomics Study of Gliclazide-Modified-Release-Treated Type 2 Diabetes Mellitus Patients Using a Gas Chromatography–Mass Spectrometry Method

摘要

Sulfonylureas are one of the commonly used drugs in type 2 diabetes mellitus (T2DM) but with considerable incidence of monotherapy failure. However, the mechanism of patients’ drug response is unclear, and suitability evaluation biomarkers are in urgent need for precision medicine. In this study, a pseudotargeted gas chromatography–mass spectrometry method was employed to investigate the serum metabolic profiling of 66 significant responders and 24 nonsignificant responders at baseline and 16 weeks after gliclazide modified-release (MR) monotherapy. Clinical improvements in blood glucose level and insulin sensitivity were closely associated with the alterations of TCA cycle, ketone body metabolism, lipid oxidation, branched-chain amino acid catabolism, and gut flora metabolism. The different baseline metabolic profiling observed in the two groups implied that patients with lower dyslipidemia level may be more suitable for sulfonylurea therapy. The biomarker panel consisting of HbA_(1c), 5,8,11,14,17-eicosapentaenoic acid, methyl 8,11,14-eicosatrienoate, and methyl hexadecanoate shows a very good prediction ability for the suitability of gliclazide treatment, and it may be meaningful in personalized medicine of T2DM patients by sulfonylurea therapy.