Giorda C, Appendino M, Mason M G, Imperiale E, Pagano G
Servizio di Diabetologia, Ospedale Maggiore, Chieri, Italy.
Metabolism. 1995 May;44(5):673-6. doi: 10.1016/0026-0495(95)90127-2.
The antihypertensive doxazosin is a selective alpha 1-adrenoceptor-blocking drug whose favorable impact on lipid metabolism is well known. A single-blind placebo-controlled crossover study was designed to determine whether antihypertensive treatment with doxazosin affects insulin sensitivity in diabetic, mildly hypertensive, non-obese patients. Twelve subjects (diastolic blood pressure, 98 +/- 1.5 mm Hg; body mass index, 25 +/- 0.6 kg/m2; hemoglobin A1c [HbA1c], 7.6% +/- 0.4%) who were not taking drugs and were treating diabetes only by diet were randomly assigned to placebo treatment for 6 weeks and then to doxazosin for the same period, or vice versa. The doxazosin dose (maximum, 12 mg/d) was increased to achieve a normotensive blood pressure (final diastolic pressure, 85 +/- 2 mm Hg, P < .05). A euglycemic (100 +/- 4 mg/dL) hyperinsulinemic (61 +/- 6 microU/mL) glucose clamp was performed at baseline and at the end of both placebo and doxazosin administration. Hepatic glucose production was measured by the isotope dilution technique using 3H-glucose. Body weights and HbA1c did not vary during the entire study. The basal mean glucose uptake and the insulin sensitivity index (2.3 +/- 0.3 mg/kg/min and 4 +/- 0.5 mg/kg/min per U/L x 100) remained unchanged during placebo administration (2.5 +/- 0.4 and 4 +/- 0.6, NS), but significantly increased during doxazosin treatment (3.3 +/- 0.4 and 5.6 +/- 0.7, P < .05). Hepatic glucose production showed no modification during both placebo and doxazosin. These data provide evidence that doxazosin improves insulin sensitivity in diabetic hypertensive patients, mainly through peripheral effects.
抗高血压药物多沙唑嗪是一种选择性α1肾上腺素能受体阻断药，其对脂质代谢的有益影响是众所周知的。一项单盲、安慰剂对照的交叉研究旨在确定多沙唑嗪抗高血压治疗是否会影响糖尿病、轻度高血压、非肥胖患者的胰岛素敏感性。12名未服用药物且仅通过饮食治疗糖尿病的受试者（舒张压为98±1.5mmHg；体重指数为25±0.6kg/m2；糖化血红蛋白[HbA1c]为7.6%±0.4%）被随机分配接受6周的安慰剂治疗，然后接受相同时间段的多沙唑嗪治疗，反之亦然。增加多沙唑嗪剂量（最大剂量为12mg/d）以达到正常血压（最终舒张压为85±2mmHg，P<.05）。在基线以及安慰剂和多沙唑嗪给药结束时进行了正常血糖（100±4mg/dL）高胰岛素血症（61±6μU/mL）葡萄糖钳夹试验。使用3H-葡萄糖通过同位素稀释技术测量肝葡萄糖生成。在整个研究过程中体重和HbA1c没有变化。在安慰剂给药期间，基础平均葡萄糖摄取和胰岛素敏感性指数（分别为2.3±0.3mg/kg/min和4±0.5mg/kg/min per U/L×100）保持不变（分别为2.5±0.4和4±0.6，无显著性差异），但在多沙唑嗪治疗期间显著增加（分别为3.3±0.4和5.6±0.7，P<.05）。在安慰剂和多沙唑嗪治疗期间，肝葡萄糖生成均未改变。这些数据证明多沙唑嗪主要通过外周作用改善糖尿病高血压患者的胰岛素敏感性。
