目的:胆汁酸螯合剂是降胆固醇药物,这也改善了2型糖尿病患者的血糖控制。降糖作用背后的机制尚不清楚,但已提出由胰高血糖素样肽-1(GLP-1)分泌增加介导。这里,我们研究了司维拉姆对2型糖尿病患者的降糖作用,包括GLP-1的任何作用.
方法:在随机分组中,双盲,安慰剂对照,交叉研究,15名接受二甲双胍单药治疗的2型糖尿病患者接受了两个为期17天的胆汁酸螯合剂司维拉姆和安慰剂治疗期,分别,以随机顺序进行,并插入至少6周的洗脱期。在每个治疗期的第15天和第17天,参与者在实验日进行了4小时的液体膳食测试,并同时输注了exendin(9-39)NH2或生理盐水.
结果:与安慰剂相比,司维拉姆改善了胰岛素敏感性(通过胰岛素抵抗的稳态模型评估)和β细胞对葡萄糖的敏感性,并降低了空腹和餐后血浆葡萄糖浓度.在两个治疗阶段,与生理盐水相比,exendin(9-39)NH2可增加餐后血糖波动,但两个治疗期之间无绝对或相对差异.相比之下,exendin(9-39)NH2消除了司维拉姆诱导的β细胞葡萄糖敏感性改善。
结论:胆汁酸螯合剂司维拉姆改善了胰岛素敏感性和β细胞对葡萄糖的敏感性,但使用GLP-1受体拮抗剂exendin(9-39)NH2,我们未能检测到2型糖尿病患者的GLP-1介导的司维拉姆降糖作用.然而,显示司维拉姆诱导的β细胞对葡萄糖敏感性的改善是GLP-1依赖性的.
OBJECTIVE: Bile acid sequestrants are cholesterol-lowering drugs, which also improve glycaemic control in people with type 2 diabetes. The mechanism behind the glucose-lowering effect is unknown but has been proposed to be mediated by increased glucagon-like peptide-1 (GLP-1) secretion. Here, we investigated the glucose-lowering effects of
sevelamer including any contribution from GLP-1 in people with type 2 diabetes.
METHODS: In a randomized, double-blind, placebo-controlled, crossover study, 15 people with type 2 diabetes on metformin monotherapy underwent two 17-day treatment periods with the bile acid sequestrant sevelamer and placebo, respectively, in a randomized order and with an interposed wash-out period of minimum 6 weeks. On days 15 and 17 of each treatment period, participants underwent experimental days with 4-h liquid meal tests and application of concomitant infusion of exendin(9-39)NH2 or saline.
RESULTS: Compared with placebo,
sevelamer improved insulin sensitivity (assessed by homeostatic model assessment of insulin resistance) and beta-cell sensitivity to glucose and lowered fasting and postprandial plasma glucose concentrations. In both treatment periods, exendin(9-39)NH2 increased postprandial glucose excursions compared with saline but without absolute or relative difference between the two treatment periods. In contrast, exendin(9-39)NH2 abolished the
sevelamer-induced improvement in beta-cell glucose sensitivity.
CONCLUSIONS: The bile acid sequestrant
sevelamer improved insulin sensitivity and beta-cell sensitivity to glucose, but using the GLP-1 receptor antagonist exendin(9-39)NH2 we were not able to detect a GLP-1-mediated glucose-lowering effect of sevelamer in individuals with type 2 diabetes. Nevertheless, the
sevelamer-induced improvement of beta-cell sensitivity to glucose was shown to be GLP-1-dependent.