DIFFERENTIAL EFFECT OF CHRONIC TREATMENT WITH 2 BETA-BLOCKING-AGENTS ON INSULIN SENSITIVITY - THE CARVEDILOL-METOPROLOL STUDY

Background Hypertensive patients frequently show resistance to insulin -stimulated glucose uptake and hyperinsulinemia. Diuretics and beta-ad renoceptor blocking agents have been found to decrease insulin sensiti vity, whereas alpha(1)-blockers and angiotensin converting enzyme inhi bitors seem to improve it. Objective To compare the effects of a 3 mon ths' antihypertensive treatment with carvedilol, a non-selective beta- adrenoceptor blocker with alpha(1)-blocking properties, with the beta( 1)-selective receptor blocker metoprolol on insulin sensitivity in non -diabetic hypertensive patients. Design A multicenter double-blind ran domized study. Subjects and methods Seventy-two non-diabetic hypertens ive patients were randomly assigned to treatment with either carvedilo l or metoprolol. An isoglycemic, hyperinsulinemic glucose clamp was co nducted before and after 12 weeks of treatment; the metabolic clearanc e rate for glucose was taken as an indicator of insulin sensitivity. R esults The two groups did not differ in age, sex, body mass index, blo od pressure or lipids, and treatment effectively lowered blood pressur e. In both groups, insulin sensitivity was impaired at baseline. After metoprolol treatment, insulin sensitivity further decreased significa ntly by about 14%, whereas it increased after carvedilol. There was al so a decrease in high-density lipoprotein and an increase in triglycer ides levels in patients in the metoprolol-treated group, whereas these parameters remained unchanged in patients in the carvedilol-treated g roup. Conclusion This study confirms previous findings of a reduction in insulin sensitivity after chronic metoprolol treatment. Carvedilol treatment, however, resulted in a slight increase in insulin resistanc e and a better lipid profile. We thus demonstrate that a beta-blocker with alpha(1)-blocking properties has favorable effects on glucose met abolism, suggesting a potentially important role of peripheral blood f low in regulating glucose uptake. These findings imply that beta-block er treatment, when combined with alpha(1)-blocking activity has advant ageous effects on insulin sensitivity and lipids and could therefore b e suitable for patients with the metabolic syndrome.