DataSheet_1_The Changes of Lipidomic Profiles Reveal Therapeutic Effects of Exenatide in Patients With Type 2 Diabetes.doc

ObjectiveExenatide has been demonstrated beneficial effects on patients with type 2 diabetes mellitus (T2DM) regarding lipid metabolism. However, the potential mechanism remains unclear. We used a lipidomic approach to evaluate lipid changes in response to treatment with exenatide in T2DM patients.MethodsSerum lipidomic profiles of 35 newly diagnosed T2DM patients (before and after exenatide treatment) and 20 age-matched healthy controls were analyzed by ultrahigh-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry.ResultsA total of 45 lipid species including sphingomyelins (SMs), ceramides (CERs), lysophosphatidylcholines (LPCs), phosphatidylethanolamines (PEs), lysophosphatidylethanolamines (LPEs) and phosphatidylcholines (PCs) were identified in all participants. Compared to the healthy controls, 13 lipid species [SM (d18:1/18:0, d18:1/18:1), Cer (d18:1/18:0, d18:1/16:0, d18:1/20:0, d18:1/24:1), LPC (15:0, 16:0, 17:0), PC (19:0/19:0), LPE (18:0) and PE (16:0/22:6, 18:0/22:6)] were markedly increased in the T2DM group, while PE (17:0/17:0) and PC (18:1/18:0) were decreased (P < 0.05). The serum SM (d18:1/18:0, d18:1/18:1), LPC (16:0), and LPE (18:0) were significantly decreased after exenatide treatment, which was accompanied by the amelioration of lipids and glycemic parameters (TC, LDL-C, ApoA-I, FCP and HbA1c) in T2DM patients. The chord diagrams showed distinct correlation patterns between lipid classes and subclasses among healthy controls, T2DM patients before and after exenatide treatment.ConclusionOur results revealed that the therapeutic benefits of exenatide on T2DM might be involved in the improved lipid metabolism, especially SM, LPC, and LPE.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03297879.

目标：依那肽在2型糖尿病（T2DM）患者中已被证实对脂质代谢具有益处。然而，其潜在机制尚不明确。本研究采用脂质组学方法，评估依那肽治疗对T2DM患者脂质变化的影响。方法：通过超高效液相色谱-串联四极杆飞行时间质谱技术，分析了35名新诊断的T2DM患者（在接受依那肽治疗前后）和20名年龄匹配的健康对照者的血清脂质组学图谱。结果：在所有参与者中，共鉴定出45种脂质，包括鞘磷脂（SMs）、鞘氨醇（CERs）、溶血磷脂酰胆碱（LPCs）、磷脂酰乙醇胺（PEs）、溶血磷脂酰乙醇胺（LPEs）和磷脂酰胆碱（PCs）。与健康对照组相比，T2DM组中13种脂质（SM（d18:1/18:0, d18:1/18:1）、CER（d18:1/18:0, d18:1/16:0, d18:1/20:0, d18:1/24:1）、LPC（15:0, 16:0, 17:0）、PC（19:0/19:0）、LPE（18:0）和PE（16:0/22:6, 18:0/22:6））显著增加，而PE（17:0/17:0）和PC（18:1/18:0）则减少（P < 0.05）。依那肽治疗后，血清SM（d18:1/18:0, d18:1/18:1）、LPC（16:0）和LPE（18:0）显著降低，伴随着T2DM患者血脂和血糖参数（总胆固醇、低密度脂蛋白胆固醇、载脂蛋白A-I、非酯化脂肪酸和糖化血红蛋白A1c）的改善。弦图显示了健康对照组、T2DM患者在依那肽治疗前后脂质类别和亚类之间的独特相关性模式。结论：我们的研究结果揭示了依那肽对T2DM的治疗益处可能与改善脂质代谢有关，尤其是SM、LPC和LPE。临床试验注册：ClinicalTrials.gov，标识符NCT03297879。