The effects of miglitol on glucagon-like peptide-1 secretion and appetite sensations in obese type 2 diabetics
The effects of miglitol on glucagon-like peptide-1 secretion and appetite sensations in obese type 2 diabetics
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DOI：
10.1046/j.1463-1326.2002.00219.x
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发表时间：
2002-09-01
影响因子：
5.8
通讯作者：
Morley, JE
中科院分区：
文献类型：
--
作者：
Lee, A;Patrick, P;Morley, JE
背景资料：先前的研究报告称，在健康人群中，第一代α-葡萄糖苷酶抑制剂（AGI）（如伏格列波糖或阿卡波糖）给药可产生胰高血糖素样肽-1（GLP-1）（一种来自肠胰岛轴的肠促胰岛素激素）的过度和持续餐后反应。关于糖尿病患者AGI治疗后GLP-1的餐后释放知之甚少。GLP-1起着介导饱腹感的作用。任何能够显著提高GLP-1水平的药物理论上都可以减少饥饿感，增加饱腹感并限制食物摄入。目的：本研究旨在分析米格列醇（一种更强效、胃肠道副作用更少的第二代AGI）对膳食相关GLP-1分泌调节、胰岛素-葡萄糖动力学变化以及胃抑制多肽（GIP）释放的影响，另一种肠促胰岛素激素，在肥胖的2型糖尿病受试者中通过普通膳食刺激后。米格列醇的随后的影响食欲的感觉和食物intake也measured.Design：在总共，8肥胖型2糖尿病妇女随机接受治疗与100毫克米格列醇或安慰剂，每天三次，2天（共六个剂量）在一个双盲的方式。在每个治疗阶段（米格列醇或安慰剂）的第3天，在进食720 kcal早餐后3小时内定期测量GLP-1、GIP、胰岛素和葡萄糖。视觉模拟量表（VAS）的食欲评级被用来评估摄食行为每小时早餐前和每小时后6小时，直到午餐前。午餐时吃的金枪鱼三明治的数量被用来测量food consumption.Results：血浆GLP-1，葡萄糖，胰岛素和GIP水平在响应混合餐后进行了比较米格列醇和安慰剂治疗。米格列醇可有效增强餐后GLP-1释放并抑制血浆GIP分泌。在超重糖尿病受试者中，与安慰剂相比，米格列醇给药后混合餐的摄入诱导GLP-1显著升高。米格列醇给药后30 - 180 min所有时间点的GLP-1进餐相关升高均显著大于安慰剂给药后。米格列醇治疗组GLP-1的餐后增量曲线下面积约为安慰剂组的2倍。GLP-1水平在混合餐后120分钟达到最大值，并在3小时研究期的其余时间内稳步上升。在米格列醇治疗条件下，与安慰剂治疗条件下相比，早餐后GLP-1升高超过30%的8例受试者中有6例的30分钟进食期间午餐平均热量摄入比安慰剂治疗后低12%（p < 0.05）。相应地，平均评分显着降低饥饿的感觉，并显着更大的饱腹感下的米格列醇治疗，开始2和3小时，分别在午餐test.Conclusions：米格列醇诱导增强和延长GLP-1的释放在高生理浓度后，在血糖控制的糖尿病患者摄入普通膳食。米格列醇治疗后餐后GLP-1过度升高改变了进食行为和食物摄入，因此在肥胖2型糖尿病患者中具有调节食欲和稳定体重的潜在价值。
Background: Previous studies reported that administration of first generation alpha-glucosidase inhibitors (AGIs), such as voglibose or acarbose, produced exaggerated and sustained postprandial responses of glucagon-like peptide-1 (GLP-1), an incretin hormone from the enteroinsular axis, in healthy humans. Little is known about the postprandial release of GLP-1 after AGI therapy in diabetics. GLP-1 plays a role to mediate satiety. Any agent that substantially elevates GLP-1 levels may theoretically reduce hunger, increase satiation and limit food intake.Objectives: This study was performed to analyse the effect of miglitol, a more potent second generation AGI with fewer gastrointestinal side-effects, on the regulation of meal-related GLP-1 secretion and on the change of insulin-glucose dynamics as well as the release of gastric inhibitory polypeptide (GIP), another incretin hormone, after stimulation by an ordinary meal in obese type-2-diabetic subjects. Miglitol's subsequent influences on appetite sensations and food intake were also measured.Design: In total, 8 obese type-2-diabetic women were randomized to receive treatment with 100 mg of miglitol or placebo three times a day for 2 days (six doses total) in a double-blind fashion. On day 3 of each treatment period (miglitol or placebo), measurements of GLP-1, GIP, insulin and glucose were taken periodically during 3 h after eating a 720 kcal breakfast. Appetite ratings with visual analogue scales (VASs) were used to assess ingestive behaviour hourly just before breakfast and hourly after for 6 h until immediately before lunch. The number of tuna sandwiches eaten at lunch was used to measure food consumption.Results: The plasma GLP-1, glucose, insulin and GIP levels in response to the mixed meal were compared after the miglitol and placebo treatment. Miglitol effectively enhanced postprandial GLP-1 release and suppressed plasma GIP secretion. The ingestion of a mixed meal induced a remarkable rise in GLP-1 after miglitol as compared with placebo in overweight diabetic subjects. The meal-related rise in GLP-1 after miglitol was significantly greater at all time-points between 30 and 180 min than after the placebo. The postprandial incremental area under the curve for GLP-1 with miglitol treatment was about twofold that with the placebo. The GLP-1 level reached a maximum at 120 min after the mixed meal and steadily rose throughout the rest of the 3-h study period. In the miglitol-treated condition, the average caloric intake at lunch during a 30-min eating period was 12% lower (p < 0.05) as compared with that after the placebo in six out of the eight subjects who exhibited a GLP-1 rise after the breakfast meal by greater than 30% from the placebo-treated condition. Correspondingly, the average rating scores were significantly lower for hunger feelings and markedly greater for sensations of satiety under the miglitol treatment; beginning 2 and 3 h, respectively, before the lunch test.Conclusions: Miglitol induced an enhanced and prolonged GLP-1 release at high physiological concentrations after ingesting an ordinary meal in glycaemic-controlled diabetics. The excessive postprandial GLP-1 elevation after miglitol therapy modified feeding behaviour and food intake, and thereby has potential value in regulating appetite and stabilizing body weight in obese type-2-diabetic patients.