Addition of losartan to angiotensin-converting enzyme inhibitors improves insulin resistance in patients with chronic heart failure treated without β-blockers

Circ J. 2010 Nov;74(11):2346-52. doi: 10.1253/circj.cj-10-0395. Epub 2010 Sep 4.

Abstract

Background: Angiotensin II and insulin resistance (IR) have clinical implications in the pathophysiology of chronic heart failure (CHF). However, it is still unclear whether the combination of an angiotensin-receptor blocker and angiotensin-converting enzyme inhibitor (ACEI) improves IR in CHF patients who do not receive β-blockers. Thus, the aim of the present study was to evaluate the effects of losartan on glucose metabolism and inflammatory cytokines in CHF patients treated with ACEI but not β-blockers.

Methods and results: The effect of losartan treatment for 16 weeks on IR was analyzed in 16 CHF patients in a randomized crossover trial. Insulin level and homeostasis model IR index (HOMA-IR) decreased significantly (P<0.05), but fasting plasma glucose did not change significantly. Serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 levels were significantly decreased with losartan (P<0.05). Furthermore, the changes in IL-6 and MCP-1 levels were significantly correlated with the reduction in HOMA-IR (P<0.05), but the change in TNF-α levels was not significantly correlated.

Conclusions: The addition of losartan to ACEI therapy improved IR and decreased inflammatory cytokines in CHF patients who did not receive β-blockers.

Trial registration: ClinicalTrials.gov NCT00663377.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Aged
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Chemokine CCL2 / blood
  • Chronic Disease
  • Cross-Over Studies
  • Drug Therapy, Combination
  • Enalapril / therapeutic use
  • Female
  • Heart Failure / blood
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Imidazolidines / therapeutic use
  • Inflammation Mediators / blood
  • Insulin / blood
  • Insulin Resistance*
  • Interleukin-6 / blood
  • Japan
  • Lisinopril / therapeutic use
  • Losartan / therapeutic use*
  • Male
  • Middle Aged
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Adrenergic beta-Antagonists
  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Biomarkers
  • Blood Glucose
  • CCL2 protein, human
  • Chemokine CCL2
  • IL6 protein, human
  • Imidazolidines
  • Inflammation Mediators
  • Insulin
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Enalapril
  • imidapril
  • Lisinopril
  • Losartan

Associated data

  • ClinicalTrials.gov/NCT00663377