Pollare T, Lithell H, Selinus I, Berne C
Department of Geriatrics, Uppsala University, Sweden.
BMJ. 1989 Apr 29;298(6681):1152-7. doi: 10.1136/bmj.298.6681.1152.
To compare the effects of metoprolol and atenolol on carbohydrate and lipid metabolism and on insulin response to an intravenous glucose load.
Randomised, double blind, double dummy, controlled crossover trial.
University Hospital, Uppsala, Sweden.
60 Patients with primary hypertension (diastolic blood pressure when resting supine 95-119 mm Hg on at least two occasions during four to six weeks of treatment with placebo) randomised to receive either metoprolol (n = 30) or atenolol (n = 30) during the first treatment period.
Placebo was given for a run in period of four to six weeks. Metoprolol 100 mg twice daily or atenolol 25 mg twice daily was then given for 16 weeks. The two drugs were then exchanged and treatment continued for a further 16 weeks.
Evaluation of effects of treatment with metoprolol and atenolol on glucose, insulin, and lipid metabolism and glucose disposal mediated by insulin.
Reduction of blood pressure was similar and satisfactory during treatment with both drugs. Glucose uptake mediated by insulin was measured during a euglycaemic hyperinsulinaemic clamp to evaluate patients' sensitivity to insulin. Glucose uptake decreased from 5.6 to 4.5 mg/kg/min when patients were taking metoprolol and from 5.6 to 4.9 mg/kg/min when they were taking atenolol. Both drugs caused a small increase in fasting plasma insulin and blood glucose concentrations and glycated haemoglobin concentration. Despite decreased sensitivity to insulin the increase in insulin concentration in response to an intravenous glucose tolerance test was small, suggesting inhibition of release of insulin. Very low density lipoprotein and low density lipoprotein triglyceride concentrations were increased with both drugs and high density lipoprotein cholesterol concentration was decreased. Low density lipoprotein cholesterol concentration was not affected.
Long term use of metoprolol and atenolol causes metabolic abnormalities that may be related to the increased incidence of diabetes in patients with hypertension who are treated pharmacologically. These results may help to explain why the two drugs have failed consistently to reduce the incidence of coronary heart disease in several large scale studies.
比较美托洛尔和阿替洛尔对碳水化合物及脂质代谢以及静脉注射葡萄糖负荷后胰岛素反应的影响。
随机、双盲、双模拟、对照交叉试验。
瑞典乌普萨拉大学医院。
60例原发性高血压患者（在服用安慰剂进行4至6周治疗期间，至少两次静息仰卧位舒张压为95 - 119 mmHg），在第一个治疗期随机接受美托洛尔（n = 30）或阿替洛尔（n = 30）治疗。
在为期4至6周的导入期给予安慰剂。随后给予美托洛尔100 mg每日两次或阿替洛尔25 mg每日两次，持续16周。然后交换两种药物，并继续治疗16周。
评估美托洛尔和阿替洛尔治疗对葡萄糖、胰岛素和脂质代谢以及胰岛素介导的葡萄糖处置的影响。
两种药物治疗期间血压下降情况相似且令人满意。在正常血糖高胰岛素钳夹试验期间测量胰岛素介导的葡萄糖摄取，以评估患者对胰岛素的敏感性。服用美托洛尔时，葡萄糖摄取从5.6降至4.5 mg/kg/min，服用阿替洛尔时从5.6降至4.9 mg/kg/min。两种药物均导致空腹血浆胰岛素、血糖浓度和糖化血红蛋白浓度略有升高。尽管对胰岛素的敏感性降低，但静脉葡萄糖耐量试验后胰岛素浓度的升高幅度较小，提示胰岛素释放受到抑制。两种药物均使极低密度脂蛋白和低密度脂蛋白甘油三酯浓度升高，高密度脂蛋白胆固醇浓度降低。低密度脂蛋白胆固醇浓度未受影响。
长期使用美托洛尔和阿替洛尔会导致代谢异常，这可能与高血压患者药物治疗后糖尿病发病率增加有关。这些结果可能有助于解释为何在几项大规模研究中这两种药物一直未能降低冠心病的发病率。
