Shimabukuro M, Higa N, Takasu N, Tagawa T, Ueda S
Second Department of Internal Medicine, Faculty of Medicine, University of Ryukus, Okinawa, Japan.
Diabet Med. 2004 Sep;21(9):983-6. doi: 10.1111/j.1464-5491.2004.01272.x.
This randomized crossover placebo-controlled study aimed to assess the efficacy of nateglinide, a phenylalanine-derived insulin secretagogue, on forearm endothelial function in diabetic subjects before and after an oral glucose load.
Forearm blood flow (FBF) was measured using strain-gauge plethysmography during reactive hyperaemia before and after an oral glucose load (75 g) with a prior use of placebo or nateglinide (90 mg) in 15 diet-treated Type 2 diabetic patients or age-matched controls with normal glucose tolerance.
The peak FBF response and total reactive hyperaemic flow (flow debt repayment: FDR), indices of resistance artery endothelial function, were decreased after an oral glucose load in diabetic patients, but unchanged in controls. Nateglinide administered to diabetic patients accelerated insulin secretion and reduced post-challenge plasma glucose, and also abolished the post-challenge impairment of endothelial function. The peak FBF and FDR were well correlated with 120-min glucose levels and 30-min insulinogenic index.
A single challenge of glucose was shown to impair endothelial function in diabetic patients, and the post-challenge endothelial dysfunction was improved by a prior use of nateglinide. Long-term effects of nateglinide on endothelial function in Type 2 diabetic patients need to be clarified in future studies.
本随机交叉安慰剂对照研究旨在评估苯丙氨酸衍生的胰岛素促分泌剂那格列奈对糖尿病患者口服葡萄糖负荷前后前臂内皮功能的疗效。
在15名接受饮食治疗的2型糖尿病患者或年龄匹配的糖耐量正常对照者中，先使用安慰剂或那格列奈（90毫克），然后在口服葡萄糖负荷（75克）前后，使用应变片体积描记法测量反应性充血期间的前臂血流量（FBF）。
糖尿病患者口服葡萄糖负荷后，阻力动脉内皮功能指标即FBF峰值反应和总反应性充血流量（血流债偿还：FDR）降低，但对照组无变化。给予糖尿病患者那格列奈可加速胰岛素分泌并降低餐后血糖，还消除了餐后内皮功能障碍。FBF峰值和FDR与120分钟血糖水平和30分钟胰岛素生成指数密切相关。
单次葡萄糖负荷显示会损害糖尿病患者的内皮功能，预先使用那格列奈可改善餐后内皮功能障碍。那格列奈对2型糖尿病患者内皮功能的长期影响有待未来研究阐明。
