Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
National Health and Medical Research Council (NHMRC), Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia.
Diabetes Obes Metab. 2019 May;21(5):1158-1167. doi: 10.1111/dom.13633. Epub 2019 Feb 14.
To evaluate the effects of the prandial glucagon-like peptide-1 receptor agonist lixisenatide on gastric emptying and blood pressure (BP) and superior mesenteric artery (SMA) blood flow, and the glycaemic responses to a 75-g oral glucose load in healthy people and those with type 2 diabetes (T2DM).
Fifteen healthy participants (nine men, six women; mean ± SEM age 67.2 ± 2.3 years) and 15 participants with T2DM (nine men, six women; mean ± SEM age 61.9 ± 2.3 years) underwent measurement of gastric emptying, BP, SMA flow and plasma glucose 180 minutes after a radiolabelled 75-g glucose drink on two separate days. All participants received lixisenatide (10 μg subcutaneously) or placebo in a randomized, double-blind, crossover fashion 30 minutes before the glucose drink.
Lixisenatide slowed gastric emptying (retention at 120 minutes, P < 0.01), attenuated the rise in SMA flow (P < 0.01) and markedly attenuated the decrease in systolic BP (area under the curve [AUC] 0-120 minutes, P < 0.001) compared to placebo in healthy participants and those with T2DM. Plasma glucose (incremental AUC 0-120 minutes) was greater in participants with T2DM (P < 0.005) than in healthy participants, and lower after lixisenatide in both groups (P < 0.001).
In healthy participants and those with T2DM, the marked slowing of gastric emptying of glucose induced by lixisenatide was associated with attenuation of the increments in glycaemia and SMA flow and decrease in systolic BP. Accordingly, lixisenatide may be useful in the management of postprandial hypotension.
评估肠促胰素类似物利西那肽对健康人和 2 型糖尿病(T2DM)患者胃排空和血压(BP)及肠系膜上动脉(SMA)血流的影响,以及对 75g 口服葡萄糖负荷的血糖反应。
15 名健康参与者(9 名男性,6 名女性;平均年龄±SEM 67.2±2.3 岁)和 15 名 T2DM 参与者(9 名男性,6 名女性;平均年龄±SEM 61.9±2.3 岁)在两天内分别接受放射性标记的 75g 葡萄糖饮料后 180 分钟测量胃排空、BP、SMA 流量和血浆葡萄糖。所有参与者在葡萄糖饮料前 30 分钟以随机、双盲、交叉方式接受利西那肽(10μg 皮下注射)或安慰剂。
与安慰剂相比,利西那肽在健康人和 T2DM 患者中均显著减慢胃排空(120 分钟时的残留率,P<0.01),减弱 SMA 血流的升高(P<0.01),显著减弱收缩压的下降(0-120 分钟时的曲线下面积[AUC],P<0.001)。T2DM 参与者的血糖(0-120 分钟时的增量 AUC)高于健康参与者(P<0.005),且两组中利西那肽后均降低(P<0.001)。
在健康参与者和 T2DM 患者中,利西那肽显著减缓葡萄糖的胃排空,与血糖和 SMA 血流的升高以及收缩压的降低减弱有关。因此,利西那肽可能对餐后低血压的管理有用。