促胰岛素分泌肽融合蛋白对T2DM患者胰岛素敏感性改善研究

Improvement of insulin sensitivity in T2DM patients by glucagon-like peptide fusion protein

目的:为了定量考察促胰岛素分泌肽融合蛋白(exendin-4-IgG4-Fc,E4F4)给予12周对2型糖尿病(type 2 diabetes mellitus,T2DM)患者胰岛素敏感性的改善情况,本研究拟在E4F4给药前及给药后的标准面餐耐量试验(meal tolerance test,MTT)数据基础上,建立E4F4群体口服葡萄糖微小模型,分析低剂量(2.7 mg)给药12周是否可显著改善2型糖尿病患者的胰岛素敏感性。方法:收集本研究16位受试者中给药前或给药后完成MTT的血糖、胰岛素浓度值,采用NONMEN 7.2软件以非线性混合效应模型分别对给药前后数据进行群体口服葡萄糖微小模型的构建,以获得给药前后胰岛素敏感性参数(insulin sensitive,IS)值,使用GraphPad Prism 8.0对给药前后IS值进行统计学分析,以观察该药对胰岛素敏感性的改善作用。结果:将给药前后IS进行非参数检验,显示给药前后IS差异具有统计学意义(P=0.02),给药后胰岛素敏感性显著高于给药前的基线值。结论:E4F4低剂量治疗2型糖尿病患者12周后,患者胰岛素敏感性得到了改善,可为该全新生物制剂药效提供参考。

AIM:In order to quantitatively examine the improvement of insulin sensitivity(IS)in patients with type 2 diabetes mellitus(T2DM)when exendin-4-IgG4-Fc(E4F4)was given for 12 weeks,the present study was conducted to establish E4F4 population oral glucose minimal models based on the meal tolerance test(MTT)data of E4F4 pre-and post-dosing,and to analyze whether low-dose(2.7 mg)administration for 12 weeks significantly improved insulin sensitivity in patients with T2DM.METHODS:Blood glucose and insulin concentrations were collected among 16 subjects in the study who completed MTT before or after dosing.Nonlinear mixed-effects model construction for the population oral glucose minimal models was performed using NONMEN 7.2 software using pre-and post-dosing data,respectively.The insulin sensitivity parameters obtained from the models before and after the administration of the drug were statistically analyzed using GraphPad Prism 8.0.RESULTS:Nonparametric test of IS before and after dosing showed statistical difference(P=0.02),and insulin sensitivity after dosing was significantly higher than the baseline value before dosing.CONCLUSION:12 weeks of low-dose E4F4 treatment in patients with type 2 diabetes mellitus resulted in an improvement in insulin sensitivity.This study provides a pharmacodynamic basis for the efficacy of this novel biologic.