Eriksson J W, Jansson P A, Foley K, Lithell H
Lundberg Laboratory for Diabetes Research, Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
J Hypertens. 1996 Dec;14(12):1469-75. doi: 10.1097/00004872-199612000-00014.
To compare the effects of the alpha 1-blocker bunazosin retard and the beta 1-blocker atenolol (Uniloc) on insulin sensitivity and glucose and lipid homeostasis in patients with type-2 diabetes and hypertension.
Patients with controlled type-2 diabetes (non-insulin-dependent diabetes mellitus), treated by diet or oral sulphonylurea derivatives, and with mild-to-moderate hypertension were include in a randomized, parallel group, double-blind, multicentre study. After a single-blind placebo run-in period lasting 4-6 weeks, the patients were treated either with bunazosin retard or with atenolol for a further 16 weeks including an initial dose titration period to achieve blood pressure control. Treatment involved 3, 6 or 12 mg bunazosin retard tablets or 25, 50 or 100 mg atenolol tablets, administered orally once a day and prescribed according to blood pressure response. The euglycaemic hyper-insulinaemic clamp technique was used to assess insulin sensitivity both after the placebo period and after the active treatment. A total of 95 patients was enrolled in the study (placebo phase). Forty-eight patients were withdrawn from the placebo phase, mainly due to their blood pressures being outside the required range (seated diastolic blood pressure 90-114 mmHg) and 47 patients were allocated randomly to active treatment. Of these, 23 were administered bunazosin retard and 24 atenolol. All evaluations were on an intention-to-treat basis.
Insulin sensitivity assessed as glucose utilization during the clamp was significantly higher following bunazosin retard compared with following atenolol administration (3.52 +/- 0.27 versus 2.86 +/- 0.19 units of metabolic clearance rate of glucose index, P < 0.05). The insulin level attained during clamps (infusion rate 56 mU/m2 per min) was higher (P < 0.05) following atenolol (117 +/- 5 mU/l) than it was following bunazosin retard administration (102 +/- 5) or placebo (108 +/- 3), possibly due to an impaired insulin clearance. Compared with placebo, atenolol treatment resulted in significantly increased glucosylated haemoglobin whereas bunazosin retard had no significant effect. The two drugs did not show any consistent differences in lipid profile or fibrinogen and plasminogen activator inhibitor 1 levels. During the study seven serious adverse events were reported and one was reported shortly after completion of the study. All except one were classified as not related to the study drug and five of them occurred during placebo treatment. The non-serious side effects were in general considered to be either unrelated to the test drugs or expected effects of the two respective drug classes. Both bunazosin retard and atenolol displayed acceptable safety profiles.
Bunazosin retard treatment in hypertensive non-insulin-dependent diabetes mellitus patients appears to be associated with a slightly higher insulin sensitivity than is atenolol.
比较α1受体阻滞剂缓释布那唑嗪与β1受体阻滞剂阿替洛尔（优律克）对2型糖尿病合并高血压患者胰岛素敏感性及糖脂稳态的影响。
将通过饮食或口服磺脲类衍生物治疗且病情得到控制的2型糖尿病（非胰岛素依赖型糖尿病）合并轻至中度高血压患者纳入一项随机、平行组、双盲、多中心研究。经过为期4 - 6周的单盲安慰剂导入期后，患者再接受16周的缓释布那唑嗪或阿替洛尔治疗，包括初始剂量滴定期以实现血压控制。治疗采用3、6或12 mg缓释布那唑嗪片或25、50或100 mg阿替洛尔片，每日口服一次，并根据血压反应进行处方。采用正常血糖高胰岛素钳夹技术在安慰剂期和积极治疗后评估胰岛素敏感性。共有95例患者纳入研究（安慰剂期）。48例患者退出安慰剂期，主要原因是其血压超出要求范围（坐位舒张压90 - 114 mmHg），47例患者被随机分配至积极治疗组。其中，23例接受缓释布那唑嗪治疗，24例接受阿替洛尔治疗。所有评估均基于意向性分析。
与阿替洛尔给药后相比，缓释布那唑嗪给药后在钳夹期间评估的胰岛素敏感性（以葡萄糖利用率表示）显著更高（葡萄糖代谢清除率指数的代谢清除率单位为3.52±0.27对2.86±0.19，P<0.05）。在钳夹期间达到的胰岛素水平（输注速率为56 mU/m²每分钟），阿替洛尔给药后（117±5 mU/l）高于缓释布那唑嗪给药后（102±5）或安慰剂组（108±3）（P<0.05），这可能是由于胰岛素清除受损。与安慰剂相比，阿替洛尔治疗导致糖化血红蛋白显著升高，而缓释布那唑嗪无显著影响。两种药物在血脂谱、纤维蛋白原和纤溶酶原激活物抑制剂1水平方面未显示出任何一致的差异。在研究期间报告了7例严重不良事件，在研究完成后不久又报告了1例。除1例之外，所有事件均被分类为与研究药物无关，其中5例发生在安慰剂治疗期间。一般认为非严重副作用与受试药物无关或为两种相应药物类别的预期效应。缓释布那唑嗪和阿替洛尔均显示出可接受的安全性。
在高血压非胰岛素依赖型糖尿病患者中，缓释布那唑嗪治疗似乎比阿替洛尔具有略高的胰岛素敏感性。
