Antihypertensive therapy and insulin sensitivity: Do we have to redefine the role of β-blocking agents?

Abstract

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 different efficacy of treatment on cerebral (cerebrovascular accidents [CVA]) and cardiac (coronary heart disease [CHD]) morbidity and mortality. Although CVA were reduced to an extent similar to that anticipated, the decrease in CHD was less than expected. These differences are likely to be caused by the different impact of concomitant cardiovascular risk factors, such as dyslipidemia, impaired glucose tolerance, and non-insulin-dependent diabetes mellitus on CHD and CVA. Frequently these cardiovascular risk factors are ineffectively controlled in hypertensive patients, and moreover, some of the widely used antihypertensive agents have unfavorable side effects and further deteriorate these particular 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 agents modify insulin sensitivity in parallel with alterations in the atherogenic lipid profile. Alpha1-blockers and angiotensin converting enzyme 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 insulin sensitivity and worsen dyslipidemia. The mechanisms by which beta-adrenoreceptor antagonist treatment exert its disadvantageous effects are not fully understood, but several possibilities exist: significant body weight gain, reduction in enzyme activities (muscle lipoprotein lipase and lecithin cholesterol acyltransferase), alterations in insulin clearance and insulin secretion, and, probably most important, reduced peripheral blood flow due to increase in total peripheral vascular resistance. Recent metabolic studies found beneficial effects of the newer vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors. In many hypertensive patients, elevated sympathetic nerve activity and insulin resistance are a deleterious combination. Although conventional beta-blocker treatment was able to take care of the former, the latter got worse; the newer vasodilating beta-blocker generation seems to be capable of successfully treating both of them.

Insulin Resistance, Inflammatory Biomarkers, and Adipokines in Patients with Chronic Kidney Disease

“…In addition, it improved glucose sensitivity. These data confirmed previous observations in humans and experimental animals without renal disease that showed that RAS blockers are able to ameliorate the metabolic adverse effects that are observed in MS (33)(34)(35)(36)(37)(38). However, to our knowledge, this is the first study to analyze the effect of ARB on IR that is associated with kidney disease.…”

“…Besides changes in hemodynamic forces, additional mechanisms could be involved in the beneficial effects of olmesartan on IR because not all of the antihypertensive drugs ameliorate insulin sensitivity (35,36): In fact, ␣ blockers, ACEI, and angiotensin II receptors antagonists are the ones that have been shown to improve it. By contrast, diuretics and ␤ blockers worsen insulin sensitivity.…”

Mechanisms of obesity-induced hypertension

“…b-blockers may cause impaired lipid and glucose metabolism and should not be used as first choice therapy in obese hypertensive patients unless required by specific indications. 86,87 However, these effects seem to be less pronounced with the new vasodilating b-blockers such as carvedilol and nebivolol. 88 First choice drugs for the obesity-induced hypertension are the Ang receptor antagonists and the ACE-inhibitors both associated with a lower incidence of diabetes 85 and favorable effects on left ventricular hypertrophy and nephropathy.…”

Effect of Beta - Blockers on Insulin Resistance in Patients with Hypertension and Metabolic Syndrome after 6 Months of Treatment

“…At the same time, according to the purpose of the analysis Jasob et al (1998), which combines a number of studies on treatment of hypertension with the use of beta-blockers, it appears that some of them may even increase the sensitivity of peripheral tissues to insulin [6].…”