利拉鲁肽对肥胖2型糖尿病患者胰高血糖素分泌功能的影响

Effect of liraglutide on glucagon secretion in obese type 2 diabetic patients

目的探讨利拉鲁肽对肥胖2型糖尿病(T2DM)患者胰高血糖素分泌功能的影响。方法多中心、前瞻性、自身对比研究,根据入排标准选取T2DM患者24例,行12周利拉鲁肽治疗,分别比较治疗前及治疗后空腹、餐后30、60、120min胰高血糖素水平。结果治疗12周后,胰高血糖素整体水平下降,其中餐后30min和60min下降明显[(220±79)ng/L比(203±77)ng/L、(248±119)ng/L比(203±82)ng/L,P值均<0.05];胰高糖素曲线下面积明显减少(438±190比389±153,P<0.05)。治疗后C肽整体水平升高,尤以餐后30、60、120min明显[(1.53±1.02)nmol/L比(2.03±1.29)nmol/L、(1.93±1.19)nmol/L比(2.48±1.75)nmol/L、(2.36±1.47)nmol/L比(2.96±1.84)nmol/L,P值均<0.05];C肽曲线下面积明显增加(3.6±2.2比4.6±2.9,P<0.05);空腹血糖(FPG)、餐后2h血糖(2hPG)及糖化血红蛋白均较前下降,差异均有统计学意义(t=7.559,5.103,6.780,P值均<0.05);腰围、体重指数较前下降,差异均有统计学意义(t=5.275,6.910,P值均<0.05);胰岛素用量较前减少约55.1%,差异有统计学意义(t=3.023,P<0.05)。结论利拉鲁肽通过抑制胰高血糖素分泌,降低血糖,同时可以减轻体重、改善T2DM患者胰岛细胞功能、减少胰岛素用量。

Objective To investigate the effect of liraglutide on glucagon release in obese type 2 diabetes (T2DM). Methods A multi-center, prospective, and self-comparison study was conducted in four hospitals in Qingdao. Twenty-four patients with T2DM were selected and treated with liraglutide for 12 weeks. Glucagon levels before and after treatment were detected before and 30 min, 60 min and 120 min after meals. Results After 12 weeks of treatment, the overall level of glucagon decreased, in which the differences in glucagon levels at 30 min [(220±79) ng/L vs. (203±77) ng/L, P<0.05] and 60 min [(248±119) ng/L vs. (203±82)ng/L, P<0.05] reached significance, respectively, comparing to those before treatment. The area under the curve of glucagon after treatment was significantly lower than that before treatment (438±190 vs. 389±153, P<0.05). In contrast, after treatment, the overall level of C-peptide increased, especially the levels at 30 min [(1.53±1.02) nmol/L vs.(2.03±1.29) nmol/L], 60 min [(1.93±1.19) nmol/L vs. (2.48±1.75) nmol/L] and 120 min [(2.36±1.47) nmol/L vs. (2.96±1.84) nmol/L], all P<0.05. The area under C-peptide curve increased significantly (3.6±2.2 vs. 4.6±2.9, P<0.05). Fasting plasma glucose, postprandial 2 h plasma glucose and glycosylated hemoglobin A1c were all lower than before, and the differences were statistically significant (P<0.05). Waist circumference and body mass index were significantly lower than before (P<0.05). The amount of insulin used for the treatment decreased by approximately 55.1% compared with that before liraglutide, and the difference was statistically significant (P<0.05). Conclusions Liraglutide inhibits glucagon secretion and lowers blood glucose. It can also reduce body weight, improve islet cell function and reduce insulin use in T2DM.