title: Improved insulin sensitivity by the angiotensin receptor antagonist irbesartan in patients with systolic heart failure: a randomized double-blinded placebo-controlled study.
abstract: BACKGROUND
  Impaired insulin sensitivity is common in patients with chronic systolic heart failure (CHF) and contributes to symptomatic status and impaired prognosis. A specific metabolic effect to improve insulin sensitivity in diabetic patients has been reported for some but not all angiotensin II-receptor antagonists. We aimed to test the ancillary metabolic effect of irbesartan on insulin sensitivity in patients with CHF.
  
  
  METHODS
  In this placebo-controlled double-blinded study 36 non-diabetic patients with stable ischemic CHF (age 63 ± 9 years, peak VO(2) 16.6 ± 4.8 ml/kg/min, LVEF 32 ± 9%) were randomized to irbesartan 300 mg/d vs placebo on top of standard CHF therapy. Body composition (dual energy X-ray absorptiometry), clinical status, peripheral vasodilator capacity (plethysmography) and neuroendocrine and metabolic profiles were assessed. Primary endpoint was the change of whole body insulin sensitivity after 4 months of treatment assessed by intravenous glucose tolerance testing and minimal modeling.
  
  
  RESULTS
  Insulin sensitivity improved by 26% (p<0.001) in the irbesartan group, but not in the placebo group (treatment effect: 1.044 min(-1)·μU·ml(-1)·10(4); 95%CI 0.45 to 1.64, p=0.0026). Treatment effects on systolic and diastolic blood pressure were -11 (95%CI -21 to -1)mmHg and -8 (95%CI -15 to -3)mmHg, respectively. Peripheral vasodilator capacity improved by 14% (p=0.016). Change in insulin sensitivity correlated with increased vasodilator capacity (R=0.47, p=0.021). Body composition and clinical status were not different after 4 months of therapy. Also adiponectin, resistin, cytokine profile, and asymmetric dimethylarginine (ADMA) were not changed after this short-term intervention.
  
  
  CONCLUSIONS
  Therapy with irbesartan improved insulin sensitivity in patients with chronic heart failure. Improved peripheral vasodilator capacity may contribute to the metabolic effect. (Clinical trials identifier: NCT00347087).
authors.affiliation: Center for Stroke Research Berlin, Charite Universitätsmedizin Berlin, Germany. wolfram.doehner@charite.de
authors.forename: Wolfram
authors.initials: W
authors.lastname: Doehner
authors.forename: Johanna
authors.initials: J
authors.lastname: Todorovic
authors.forename: Cornelia
authors.initials: C
authors.lastname: Kennecke
authors.forename: Mathias
authors.initials: M
authors.lastname: Rauchhaus
authors.forename: Anja
authors.initials: A
authors.lastname: Sandek
authors.forename: Mitja
authors.initials: M
authors.lastname: Lainscak
authors.forename: Sophie
authors.initials: S
authors.lastname: van Linthout
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschöpe
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D054143:Heart Failure, Systolic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan