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 non-significant responders at baseline and 16-week 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 acids catabolism and gut flora metabolism. The different baseline metabolic profiling observed in the two groups implied patients with lower dyslipidemia level may be more suitable for sulfonylurea therapy. The biomarker panel consisting of HbA1c, 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, it may be meaningful in personalized medicine of T2DM patients by sulfonylurea therapy.

中文翻译：

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气相色谱-质谱法研究格列齐特缓释治疗的2型糖尿病患者的血清代谢组学

磺脲类药物是2型糖尿病（T2DM）中常用的药物之一，但是单药治疗失败的可能性很高。然而，患者药物反应的机制尚不清楚，适用性评估生物标志物迫切需要精密医学。在这项研究中，采用了伪靶向气相色谱-质谱法研究了格列齐特调释（MR）单一疗法后基线和16周时66位显着缓解者和24位非显着缓解者的血清代谢谱。血糖水平和胰岛素敏感性的临床改善与TCA周期，酮体代谢，脂质氧化，支链氨基酸分解代谢和肠道菌群代谢的改变密切相关。两组中观察到的基线代谢谱不同，表明血脂异常水平较低的患者可能更适合磺脲类药物治疗。由HbA1c，5,8,11,14,17-二十碳五烯酸，8,11,14-二十碳三烯酸甲酯和十六烷酸甲酯组成的生物标志物组显示出非常好的预测格列齐特治疗适应性的能力，这在个性化治疗中可能是有意义的磺脲类药物治疗T2DM患者的药物。