沙格列汀对2型糖尿病Nesfatin-1分泌及代谢调节的临床研究

Effect of Saxagliptin on regulation of nesfatin-1 secretion and metabolism in type 2 diabetes mellitus patients

摘要:

目的  沙格列汀能有效改善2型糖尿病（T2DM）糖代谢，Nesfatin-1是摄食行为和能量代谢调节的重要因子。为探讨沙格列汀对T2DM患者Nesfatin-1分泌调节及糖脂代谢、血压调节的作用，观察其治疗前后Nesfatin-1水平变化，并与同期其他非二基肽酶-4（DPP-4）抑制剂治疗患者进行比较。方法  门诊治疗的T2DM患者102例（男∶女=48:54），其中治疗组51例（男∶女=24∶27）使用包含沙格列汀口服降糖药物；同期51例（男∶女=24∶27）未使用DPP-4抑制剂治疗的T2DM患者作为对照组。观察和比较基线及3、6和12个月时Nesfatin-1、C-肽（C-P）、稳态β细胞功能评价指数（HOMA-β）、稳态胰岛素评价指数（HOMA-IR）、糖化血红蛋白A1c（HbA1c）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、体重指数（BMI）及血压变化。结果  治疗组血清Nesfatin-1分泌上调，C-P水平升高，显著改善HOMA-IR、HOMA-β以及糖脂代谢，降低BMI和血压。单因素直线回归分析显示，Nesfatin-1与HOMA-β、C-P以及HDL-C呈正相关，与其他指标呈负相关。结论  沙格列汀能促进T2DM患者Nesfatin-1分泌，有效改善胰腺β细胞功能、胰岛素抵抗及糖脂代谢，降低BMI和调节血压。沙格列汀可以通过上调Nesfatin-1分泌，在T2DM患者中发挥潜在的重要作用。

Abstract:

Objective To investigate the effect of Saxagliptin on regulating nesfatin-1 secretion and metabolism by observing the levels of the nesfatin-1 and other parameters in type 2 diabetes mellitus (T2DM) patients before and after Saxagliptin treatment. Methods A total of 102 T2DW participants (M : F = 48 : 54) were investigated. The 51 patients (M : F = 24 : 27) in the treatment group were treated with oral glucose-lowering drugs including Saxagliptin, the 51 patients (M : F = 24 : 27) in the control group were treated with oral glucose-lowering agents excluding all DPP-4 inhibitors. Serum nesfatin-1, C-peptide, HOMA-β function, HOMA-IR, HbA1c, LDL-C, HDL-C, BMI and blood pressure at baseline and in 3, 6 and 12 months of treatment were observed and compared. Results Saxagliptin significantly up-regulated nesfatin-1 secretion, increased serum C-peptide; improved HOMA-IR, HOMA-β function, glucose and lipid metabolisms; and reduced BMI and blood pressure. Simple linear regression analysis revealed that serum nesfatin-1 was positively correlated with HOMA-β function, C-peptide and HDL-C, while negatively correlated with the rest parameters. Conclusions Saxagliptin could up-regulate nesfatin-1 secretion, ameliorate islet β-cell's function and insulin resistance as well as the glucose and lipid metabolisms, lower BMI and blood pressure in patients with type 2 diabetes mellitus. As one of the DPP-4 inhibitors, Saxaglitin has the potential to play fundamental roles in type 2 diabetes mellitus by up-regulating nesfatin-1 secretion besides lowering glucose through inhibiting the degradation of GLP-1.