Endocrinology Department, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Endocrinol (Lausanne). 2023 Jan 4;13:1097612. doi: 10.3389/fendo.2022.1097612. eCollection 2022.
As metabolic remodeling is a pathological characteristic in type 2 diabetes (T2D), we investigate the roles of newly developed long-acting glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as dulaglutide and liraglutide on metabolic remodeling in patients with recent-onset T2D.
We recruited 52 cases of T2D and 28 control cases in this study. In the patient with T2D, 39 cases received treatment with dulaglutide and 13 cases received treatment with liraglutide. Using untargeted metabolomics analysis with broad-spectrum LC-MS, we tracked serum metabolic changes of the patients from the beginning to the end of follow-up (12 week).
We identified 198 metabolites that were differentially expressed in the patients with T2D, compared to the control group, in which 23 metabolites were significantly associated with fasting plasma glucose. Compared to pre-treatment, a total of 46 and 45 differentially regulated metabolites were identified after treatments with dulaglutide and liraglutide, respectively, in which the most differentially regulated metabolites belong to glycerophospholipids. Furthermore, a longitudinal integration analysis concurrent with diabetes case-control status revealed that metabolic pathways, such as the insulin resistance pathway and type 2 diabetes mellitus, were enriched after dulaglutide and liraglutide treatments. Proteins such as GLP-1R, GNAS, and GCG were speculated as potential targets of dulaglutide and liraglutide.
In total, a metabolic change in lipids existed in the early stage of T2D was ameliorated after the treatments of GLP-1RAs. In addition to similar effects on improving glycemic control, remodeling of glycerophospholipid metabolism was identified as a signature of dulaglutide and liraglutide treatments.
由于代谢重构是 2 型糖尿病（T2D）的一种病理特征，我们研究了新开发的长效胰高血糖素样肽-1 受体激动剂（GLP-1RAs）如度拉糖肽和利拉鲁肽在近期诊断为 T2D 的患者中的代谢重构中的作用。
我们在这项研究中招募了 52 例 T2D 患者和 28 例对照者。在 T2D 患者中，39 例接受了度拉糖肽治疗，13 例接受了利拉鲁肽治疗。我们采用广谱 LC-MS 进行非靶向代谢组学分析，追踪患者从随访开始到结束（12 周）的血清代谢变化。
我们在 T2D 患者中鉴定出 198 种与对照组相比差异表达的代谢物，其中 23 种代谢物与空腹血糖显著相关。与治疗前相比，度拉糖肽和利拉鲁肽治疗后分别鉴定出 46 种和 45 种差异调节代谢物，其中最显著差异调节的代谢物属于甘油磷脂。此外，对糖尿病病例对照状态进行纵向整合分析显示，度拉糖肽和利拉鲁肽治疗后，胰岛素抵抗途径和 2 型糖尿病等代谢途径得到了富集。GLP-1R、GNAS 和 GCG 等蛋白被推测为度拉糖肽和利拉鲁肽的潜在靶点。
总的来说，T2D 早期存在的脂质代谢变化在 GLP-1RA 治疗后得到了改善。除了对改善血糖控制的相似作用外，甘油磷脂代谢的重塑被确定为度拉糖肽和利拉鲁肽治疗的特征。
