title: Spironolactone, not furosemide, improved insulin resistance in patients with chronic heart failure.
abstract: OBJECTIVE
  Insulin resistance plays an important role in the pathophysiology in chronic heart failure (CHF). Diuretics generally have harmful effects on glucose metabolism, however, the effect of mineral corticoid receptor blockers on insulin resistance in CHF is unclear. This study aimed to evaluate the effects of the aldosterone blocker spironolactone, in comparison with furosemide, on insulin resistance in CHF patients.
  
  
  METHODS
  The effect of spironolactone (25mg/day) and furosemide (20mg/day) on IR for 16 weeks each was analyzed in 16 CHF patients using a double-blind, placebo-controlled, randomized cross-over study design.
  
  
  RESULTS
  Plasma BNP and left ventricular ejection fraction were improved with both treatments (furosemide: p=0.02 and p=0.009, respectively, spironolactone: p=0.03 and p=0.007, respectively). Fasting plasma glucose was not changed; however, plasma insulin levels decreased and insulin sensitivity (by homeostasis model assessment: HOMA-IR) improved with spironolactone as compared to furosemide (p<0.0005). TNF-α, IL-6 and MCP-1 decreased with spironolactone (p=0.002, p=0.02 and p=0.02 vs. baseline, respectively), but not with furosemide. Matrix metalloproteinase (MMP)-2 and MMP-9 were decreased with spironolactone (p=0.003 and p=0.04 vs. baseline, respectively), but not furosemide. Changes in TNF-α, IL-6 and MCP-1 levels after spironolactone treatment were significantly correlated with changes in HOMA-IR (r=0.61, r=0.55 and r=0.65, respectively; p=0.01, p=0.03 and p=0.01, respectively). Furthermore, changes in MMP-2 and MMP-9 levels were significantly correlated with changes in HOMA-IR (r=0.58 and r=0.58, respectively; p=0.02 and p=0.02, respectively).
  
  
  CONCLUSIONS
  Spironolactone, not furosemide, improved insulin resistance in CHF patients probably by the inhibition of inflammatory cytokines and MMPs.
authors.affiliation: Division of Clinical Laboratory, Tottori University Hospital, Yonago, Japan. Electronic address: ko-36@umin.ac.jp.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Ogino
authors.affiliation: Department of Cardiovascular Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Kinugasa
authors.affiliation: Department of Cardiovascular Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Cardiovascular Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medicine, Yonago, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hisatome
authors.affiliation: Division of Applied Cachexia Research, Department of Cardiology, Campus Virchow-Klinikum Charite Universitätsmedizin, Berlin, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: Center for Stroke Research Berlin, Charite Universitätsmedizin, Berlin, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Doehner
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005665:Furosemide / Q000494:pharmacology / Q000627:therapeutic use*; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D013148:Spironolactone / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D013148:Spironolactone; D005665:Furosemide
keywords: Aldosterone; Diabetes; Heart failure; Inflammatory cytokine; Insulin resistance; Matrix metalloproteinase