Induction of insulin resistance by beta-blockade but not ACE-inhibition: long-term treatment with atenolol or trandolapril

Abstract

The effects on glucose metabolism by the beta-blocker atenolol and the angiotensin-converting enzyme (ACE)-inhibitor trandolapril were investigated in a randomised double-blind parallel group study of patients with primary hypertension. Twenty-six patients were treated with 50–100 mg atenolol and 27 patients with 2–4 mg trandolapril o.d. Intravenous glucose tolerance tests, euglycaemic hyperinsulinaemic clamps and serum lipid measurements were performed after 8 and 48 weeks of active treatment. After 48 weeks insulin sensitivity was reduced by 23% by atenolol while it remained unchanged during trandolapril treatment (+0.5%, P = 0.0010 for difference between treatments, ANCOVA). The effect on triglycerides (+22% vs −8.5%) and high-density lipoprotein cholesterol (−13% vs +0.7%) also differed significantly between atenolol and trandolapril. Results after 8 weeks were similar. Glucose tolerance was not affected by either drug. Atenolol reduced diastolic blood pressure (DBP) better than trandolapril (−15.3 mm Hg vs −6.6 mm Hg for supine DBP after 48 weeks, P = 0.012). The difference in effect on insulin sensitivity between the drugs corresponded to 25% of the baseline values of insulin sensitivity, and persisted over 48 weeks of treatment. The choice of antihypertensive treatment could influence the risk of diabetes associated with treated hypertension.