Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Eur J Endocrinol. 2021 Mar;184(3):383-394. doi: 10.1530/EJE-20-1121.
The alpha-glucosidase inhibitor acarbose is believed to reduce plasma glucose by delaying hydrolysis of carbohydrates. Acarbose-induced transfer of carbohydrates to the distal parts of the intestine increases circulating glucagon-like peptide 1 (GLP-1). Using the GLP-1 receptor antagonist exendin(9-39)NH2, we investigated the effect of acarbose-induced GLP-1 secretion on postprandial glucose metabolism in patients with type 2 diabetes.
In a double-blinded, placebo-controlled, randomized, crossover study, 15 participants with metformin-treated type 2 diabetes (age: 57-85 years, HbA1c: 40-74 mmol/mol) were subjected to two 14-day treatment periods with acarbose or placebo, respectively, separated by a 6-week wash-out period. At the end of each period, two randomized 4-h liquid mixed meal tests with concomitant infusion of exendin(9-39)NH2 and saline, respectively, were performed.
Compared to placebo, acarbose increased postprandial GLP-1 concentrations and decreased postprandial glucose. We observed no absolute difference in the exendin(9-39)NH2-induced increase in postprandial glucose excursions between placebo and acarbose periods, but relatively, postprandial glucose was increased by 119 ± 116% (mean ± s.d.) during exendin(9-39)NH2 infusion in the acarbose period vs a 39 ± 27% increase during the placebo period (P = 0.0163).
We confirm that acarbose treatment stimulates postprandial GLP-1 secretion in patients with type 2 diabetes. Using exendin(9-39)NH2, we did not see an impact of acarbose-induced GLP-1 secretion on absolute measures of postprandial glucose tolerance, but relatively, the effect of exendin(9-39)NH2 was most pronounced during acarbose treatment.
α-葡萄糖苷酶抑制剂阿卡波糖被认为通过延迟碳水化合物的水解来降低血糖。阿卡波糖诱导碳水化合物向肠道远端转移会增加循环胰高血糖素样肽 1（GLP-1）。使用 GLP-1 受体拮抗剂 exendin(9-39)NH2，我们研究了阿卡波糖诱导的 GLP-1 分泌对 2 型糖尿病患者餐后葡萄糖代谢的影响。
在一项双盲、安慰剂对照、随机、交叉研究中，15 名接受二甲双胍治疗的 2 型糖尿病患者（年龄：57-85 岁，HbA1c：40-74mmol/mol）分别接受为期 14 天的阿卡波糖或安慰剂治疗，其间间隔 6 周洗脱期。在每个时期结束时，分别进行两次随机的 4 小时液体混合餐测试，并同时输注 exendin(9-39)NH2 和生理盐水。
与安慰剂相比，阿卡波糖增加了餐后 GLP-1 浓度并降低了餐后血糖。我们观察到在安慰剂和阿卡波糖期之间，exendin(9-39)NH2 诱导的餐后葡萄糖波动增加没有绝对差异，但相对而言，在阿卡波糖期，exendin(9-39)NH2 输注期间餐后血糖增加了 119±116%（平均值±标准差），而在安慰剂期增加了 39±27%（P=0.0163）。
我们证实阿卡波糖治疗可刺激 2 型糖尿病患者餐后 GLP-1 分泌。使用 exendin(9-39)NH2，我们没有看到阿卡波糖诱导的 GLP-1 分泌对餐后葡萄糖耐量的绝对测量值有影响，但相对而言，在阿卡波糖治疗期间，exendin(9-39)NH2 的作用最为明显。
