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

Stephan Jacob, Kristian Rett, Erik J. Henriksen

Research output: Contribution to journalReview articlepeer-review

188 Scopus citations


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 noninsulin-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. α1-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 β- adrenoreceptor antagonists further decrease insulin sensitivity and worsen dyslipidemia. The mechanisms by which β-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 β-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 β-blocker treatment was able to take care of the former, the latter got worse; the newer vasodilating β-blocker generation seems to be capable of successfully treating both of them.

Original languageEnglish (US)
Pages (from-to)1258-1265
Number of pages8
JournalAmerican Journal of Hypertension
Issue number10 I
StatePublished - Oct 1998


  • Antihypertensive treatment
  • Cardiovascular disease
  • Carvedilol
  • Celiprolol
  • Dilevalol
  • Essential hypertension
  • Insulin sensitivity
  • Vasodilating β- blocker

ASJC Scopus subject areas

  • Internal Medicine


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