Fogari R, Zoppi A, Corradi L, Lazzari P, Mugellini A, Lusardi P
Department of Internal Medicine and Therapeutics, University of Pavia, Italy.
Br J Clin Pharmacol. 1998 Nov;46(5):467-71. doi: 10.1046/j.1365-2125.1998.00811.x.
The aim of this study was to compare the effects of the ACE-inhibitor lisinopril and the angiotensin II receptor antagonist losartan on insulin sensitivity in the treatment of non diabetic hypertensives.
Twenty-five non diabetic subjects with mild to moderate hypertension, 11 females and 14 males, aged 44-63 years, after a 4-week wash-out period on placebo, were randomized to receive lisinopril 20 mg once daily or losartan 50 mg once daily for 6 weeks. Following another 4-week wash-out period, patients were crossed to the alternative regimen for further 6 weeks. At the end of the placebo and of the active treatment periods, blood pressure (BP) was measured (by standard mercury sphygmomanometer, Korotkoff I and V) and insulin sensitivity was assessed by the euglycaemic hyperinsulinaemic clamp technique. Glucose infusion rate (GIR) during the last 30 min of clamp and total glucose requirement (TGR) were evaluated.
Both lisinopril and losartan significantly reduced SBP (by a mean of 20.2 and 17.2 mmHg, respectively) and DBP (by a mean of 15.2 and 12.3 mmHg, respectively), with no difference between the two treatments. GIR, used as an indicator of insulin sensitivity, was significantly increased by lisinopril (+1.5 mg min(-1) kg(-1), P<0.05 vs baseline) but not by losartan (+0.42 mg min(-1) kig(-1), NS), the difference between the two drugs being statistically significant (P<0.05). TGR was increased by lisinopril (+7.3 g, P<0.05 vs baseline), whereas losartan did not significantly modify it (+1.9 g, NS).
In conclusion, with all cautions due to an absence in this study of a randomized placebo phase, our findings suggest that lisinopril improved insulin sensitivity whereas losartan did not affect it.
本研究旨在比较血管紧张素转换酶抑制剂赖诺普利和血管紧张素II受体拮抗剂氯沙坦在治疗非糖尿病高血压患者时对胰岛素敏感性的影响。
25名轻度至中度高血压的非糖尿病受试者,11名女性和14名男性,年龄44 - 63岁,在服用安慰剂4周洗脱期后,随机分为两组,一组每天服用一次20毫克赖诺普利,另一组每天服用一次50毫克氯沙坦,持续6周。在另一个4周洗脱期后,患者交叉接受另一种治疗方案,再持续6周。在安慰剂期和积极治疗期结束时,测量血压(通过标准汞柱血压计,柯氏音I期和V期),并通过正常血糖高胰岛素钳夹技术评估胰岛素敏感性。评估钳夹最后30分钟的葡萄糖输注率(GIR)和总葡萄糖需求量(TGR)。
赖诺普利和氯沙坦均显著降低收缩压(分别平均降低20.2和17.2 mmHg)和舒张压(分别平均降低15.2和12.3 mmHg),两种治疗之间无差异。作为胰岛素敏感性指标的GIR,赖诺普利使其显著增加(+1.5毫克·分钟⁻¹·千克⁻¹,与基线相比P<0.05),而氯沙坦未使其增加(+0.42毫克·分钟⁻¹·千克⁻¹,无统计学意义),两种药物之间的差异具有统计学意义(P<0.05)。赖诺普利使TGR增加(+7.3克,与基线相比P<0.05),而氯沙坦未使其显著改变(+1.9克,无统计学意义)。
总之,鉴于本研究缺乏随机安慰剂对照阶段,需谨慎对待,我们的研究结果表明赖诺普利可改善胰岛素敏感性,而氯沙坦对其无影响。