Oksa A, Gajdos M, Fedelesová V, Spustová V, Dzúrik R
Department of Clinical Pharmacology, Institute of Preventive and Clinical Medicine, Bratislava, Slovakia.
J Cardiovasc Pharmacol. 1994 Jan;23(1):79-86. doi: 10.1097/00005344-199401000-00010.
Data of 52 patients, 29 women and 23 men aged 32-68 years (mean age 47 years) with essential hypertension, participating in three open therapeutic trials with either enalapril, lisinopril, or perindopril were evaluated to assess the effects of angiotensin-converting enzyme (ACE) inhibition on glucose and lipid metabolism. The 75-g oral glucose tolerance test (oGTT) was performed, and plasma glucose and insulin levels, as well as total cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides levels were determined before and after the 8- to 12-week treatment. Minor differences in the blood pressure (BP)-lowering effect and metabolic response were obtained with the ACE inhibitors studied; only lisinopril improved glucose tolerance significantly; blood lipids were not changed by any drug. The entire patient population showed only a slight reduction in 1-h postload glucose after treatment. More obvious improvement in glucose tolerance was evident in hypertensive patients who were glucose intolerant and/or insulin resistant (GI/IR, 53.8% of all), however. This subgroup also showed a slight but not significant increase in HDL-cholesterol and a decrease in triglycerides levels. Only a slight change or no change in plasma glucose, insulin, and lipid values was noted in hypertensive patients with normal glucose tolerance (NGT) and insulin sensitivity. These favorable effects were expressed only after ACE inhibitor monotherapy, but not when hydrochlorothiazide was added. The results indicate that a lack of stratification of hypertensive patients with regard to glucose tolerance or insulin sensitivity could be a confounding factor in evaluation of metabolic effects of ACE inhibitors.
对52例年龄在32至68岁(平均年龄47岁)的原发性高血压患者的数据进行了评估,这些患者中29例为女性,23例为男性,他们参与了三项分别使用依那普利、赖诺普利或培哚普利的开放性治疗试验,以评估血管紧张素转换酶(ACE)抑制对葡萄糖和脂质代谢的影响。进行了75克口服葡萄糖耐量试验(oGTT),并在8至12周治疗前后测定了血浆葡萄糖和胰岛素水平,以及总胆固醇、高密度脂蛋白(HDL)胆固醇和甘油三酯水平。在所研究的ACE抑制剂中,血压(BP)降低效果和代谢反应存在微小差异;只有赖诺普利显著改善了葡萄糖耐量;任何药物均未改变血脂。整个患者群体在治疗后1小时负荷后血糖仅略有降低。然而,在葡萄糖不耐受和/或胰岛素抵抗的高血压患者(GI/IR,占所有患者的53.8%)中,葡萄糖耐量有更明显的改善。该亚组还显示HDL胆固醇略有但不显著增加,甘油三酯水平降低。葡萄糖耐量正常(NGT)和胰岛素敏感的高血压患者血浆葡萄糖、胰岛素和脂质值仅略有变化或无变化。这些有益效果仅在ACE抑制剂单药治疗后出现,而在加用氢氯噻嗪时则未出现。结果表明,高血压患者在葡萄糖耐量或胰岛素敏感性方面缺乏分层可能是评估ACE抑制剂代谢作用的一个混杂因素。