口服降糖药物对初诊T2DM胰高血糖素样肽1及相关因素的影响

Effects of Oral Antidiabetic Treatments on GLP-1 and Function of β Cells in Newly Diagnosed T2DM

目的观察二甲双胍、格列吡嗪联合降糖对初诊2型糖尿病(T2DM)的胰高血糖素样肽1(GLP-1)及相关因素的影响。方法以初诊T2DM 40例为试验组,分别于口服药物治疗前及治疗4周后,均进行OGTT试验(需禁食10 h),测定0、30、120 min各时间点的血糖水平,并检测相应的血清GLP-1、C肽、胰岛素等指标,以健康者30例作为对照组,观察两组各指标差异,计算HOMA胰岛素分泌及抵抗指数,并比较试验组治疗前后的各指标变化,分析口服药物联合降糖治疗对初诊2型糖尿病(T2DM)的GLP-1水平的影响。结果试验组的GLP-1水平低于对照(P<0.05)。口服降糖治疗各时间点前后比较,血糖及其曲线下面积(AUCg)降低(P<0.05);胰岛素、C肽及其曲线下面积(AUCins、AUCc-p)升高(P<0.05);HOMA-IR(胰岛素抵抗指数)降低(P<0.05),HOMA-IS(胰岛素分泌指数)、△INS_(30)/G_(30)、△INS_(120)/G_(120)升高(P<0.05)。与治疗前比较,治疗组各时间点GLP-1水平及AUCglp(GLP-1曲线下面积)升高(P<0.05),接近对照组曲线。结论初诊T2DM GLP-1水平低于正常;口服降糖治疗后其水平升高,接近正常水平。胰岛素、C肽及AUCins、AUCc-p、HOMA-IS、HOMA-IR等明显改善,提示β细胞功能恢复,胰岛素抵抗减轻。笔者认为,β细胞功能明显改善及胰岛素抵抗减轻,可能与高糖毒性的解除等因素有关。

Objective To Observe the effect of oral glucose lowering drugs （glipizide and metformin） on the GLP-1 level of newly diagnosed type 2 diabetes mellitus （T2DM） and its relationship with the function of β cells. Methods As 40 cases of newly diagnosed T2DM to be experimental group, OGTT （to be fast 10h） were tested before and after oral antidiabetic treatment. Levels of blood glucose, GLP-1, C-peptide and insulin were measured at 0, 30, 120 minutes with 30 healthy subjects served as the control group. Then,we analyzed each index of the experimental group, calculated HOMA insulin secretion and insulin resistance index.Testing of GLP-1 levels and comparation in newly diagnosed T2DM were done before and after treatment. Results GLP-1 levels of the treatment group were significantly lower than the control （P〈0.05）. Before and after four weeks treatment of Glipizide and metformin, blood glucose at each time point, and glucose area under the curve （AUCg） were statistically significant decreased （P〈0.05）. Insulin and C-peptide at each time point, and the AUC （AUCins, AUCc-p） were increased （P〈0.05）. HOMA-IR was statistically decreased compared with pretherapy （P〈0.05）. HOMA-IS and AINS30/G30, A INS120/G120 were significantly increased （P〈0.05）. Compared with pretherapy, GLP-1 levels at each time point and AUCglp （area under the GLP-1 curve） elevated in the experimental group （P〈0.05）, closed to the control group curve. Conclusions The level of GLP-1 was lower than normal in newly diagnosed T2DM. After oral hypoglycemic therapy, the level of GLP-1 increased, which was closed to normal level. Insulin, C-peptide and AUCins, AUCc-p, HOMA- IS and HOMA-IR were significantly improved, suggesting that β-cell function recovery, insulin resistance. The author believes that improvement of β-cell function and insulin resistance, may be related to the removal of high glucose toxicity and other factors.