Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose

Todd S. Perlstein, Robert R. Henry, Kieren J. Mather, Michael R. Rickels, Nicola I. Abate, Scott M. Grundy, Yabing Mai, Jeanine B. Albu, Jennifer B. Marks, James L. Pool, Mark A. Creager

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

AngII (angiotensin II) may contribute to cardiovascular risk in obesity via adverse effects on insulin sensitivity and endothelial function. In the present study, we examined the effects of ARB (angiotensin receptor blocker) therapy (losartan, 100 mg/day) on insulin sensitivity and endothelial function in 53 subjects with stage I hypertension, abdominal obesity and impaired fasting glucose. The study design was a randomized double-blinded parallel design placebo-controlled multicentre trial of 8 weeks duration. We used the hyperinsulinaemic-euglycaemic clamp technique to measure insulin sensitivity (expressed as the 'M/I' value) and RH-PAT (reactive hyperaemiaperipheral arterial tonometry) to measure endothelial function. Additional measures included HOMA (homoeostasis model assessment)-B, an index of pancreatic β-cell function, and markers of inflammation [e.g. CRP (C-reactive protein)] and oxidative stress (e.g. F 2-isoprostanes). ARB therapy did not alter insulin sensitivity [5.2 (2.7) pre-treatment and 4.6 (1.6) post-treatment] compared with placebo therapy [6.1 (2.9) pre-treatment and 5.3 (2.7) post-treatment; P value not significant], but did improve the HOMA-B compared with placebo therapy (P=0.05). ARB therapy also did not change endothelial function [RH-PAT, 2.15 (0.7) pre-treatment and 2.11 (0.7) post-treatment] compared with placebo therapy [RH-PAT, 1.81 (0.5) pre-treatment and 1.76 (0.7) post-treatment; P value not significant]. Markers of inflammation and oxidative stress were not significantly changed by ARB therapy. In conclusion, ARB therapy did not alter peripheral insulin sensitivity or endothelial function in this cohort of patients with essential hypertension, abdominal obesity and impaired fasting glucose, but did improve pancreatic β-cell function.

Original languageEnglish (US)
Pages (from-to)193-202
Number of pages10
JournalClinical science
Volume122
Issue number4
DOIs
StatePublished - Feb 2012
Externally publishedYes

Keywords

  • Angiotensin II
  • Clinical trial
  • Hypertension
  • Insulin signalling
  • Obesity
  • Vascular function

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose'. Together they form a unique fingerprint.

  • Cite this

    Perlstein, T. S., Henry, R. R., Mather, K. J., Rickels, M. R., Abate, N. I., Grundy, S. M., Mai, Y., Albu, J. B., Marks, J. B., Pool, J. L., & Creager, M. A. (2012). Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose. Clinical science, 122(4), 193-202. https://doi.org/10.1042/CS20110284