ANTIHYPERTENSIVE THERAPY AND INSULIN SENSITIVITY - DO WE HAVE TO REDEFINE THE ROLE OF BETA-BLOCKING-AGENTS

Essential hypertension is, at least in many subjects, associated with a decrease in insulin sensitivity, whereas glycemic control is (still) normal. Metaanalyses of hypertension intervention studies revealed di fferent efficacy of treatment on cerebral (cerebrovascular accidents [ CVA]) and cardiac (coronary heart disease [CHD]) morbidity and mortali ty. Although CVA were reduced to an extent similar to that anticipated , the decrease in CHD was less than expected. These differences are li kely to be caused by the different impact of concomitant cardiovascula r risk factors, such as dyslipidemia, impaired glucose tolerance, and noninsulin-dependent diabetes mellitus on CHD and CVA. Frequently thes e cardiovascular risk factors are ineffectively controlled in hyperten sive patients, and moreover, some of the widely used antihypertensive agents have unfavorable side effects and further deteriorate these par ticular metabolic risk factors. Therefore, the metabolic side effects of antihypertensive treatment have received more attention. During the past few years, studies demonstrated that most antihypertensive agent s modify insulin sensitivity in parallel with alterations in the ather ogenic lipid profile, alpha(1)-Blockers and angiotensin converting enz yme inhibitors were shown to either have no impact on or even improve insulin resistance and the profile of atherogenic lipids, whereas most of the calcium channel blockers were found to be metabolically inert. The diuretics and beta-adrenoreceptor antagonists further decrease in sulin sensitivity and worsen dyslipidemia. The mechanisms by which bet a-adrenoreceptor antagonist treatment exert its disadvantageous effect s are not fully understood, but several possibilities exist: significa nt body weight gain, reduction in enzyme activities (muscle lipoprotei n lipase and lecithin cholesterol acyltransferase), alterations in ins ulin clearance and insulin secretion, and, probably most important, re duced peripheral blood now due to increase in total peripheral vascula r resistance. Recent metabolic studies found beneficial effects of the newer vasodilating beta-blockers, such as dilevalol, carvedilol and c eliprolol, on insulin sensitivity and the atherogenic risk factors. In many hypertensive patients, elevated sympathetic nerve activity and i nsulin resistance are a deleterious combination. Although conventional beta-blocker treatment was able to take care of the former, the latte r got worse; the newer vasodilating beta-blocker generation seems to b e capable of successfully treating both of them. Am J Hypertens 1998;1 1:1258-1265 (C) 1998 American Journal of Hypertension, Ltd.