Kazuhide Ogino1, Yoshiharu Kinugasa2, Masahiko Kato2, Kazuhiro Yamamoto2, Ichiro Hisatome3, Stefan D Anker4, Wolfram Doehner5. 1. Division of Clinical Laboratory, Tottori University Hospital, Yonago, Japan. Electronic address: ko-36@umin.ac.jp. 2. Department of Cardiovascular Medicine, Faculty of Medicine, Tottori University, Yonago, Japan. 3. Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medicine, Yonago, Japan. 4. Division of Applied Cachexia Research, Department of Cardiology, Campus Virchow-Klinikum Charite Universitätsmedizin, Berlin, Germany. 5. Center for Stroke Research Berlin, Charite Universitätsmedizin, Berlin, Germany.
Abstract
BACKGROUND/ OBJECTIVES: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.
RCT Entities:
BACKGROUND/ OBJECTIVES: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 CHFpatients. METHODS: The effect of spironolactone (25mg/day) and furosemide (20mg/day) on IR for 16 weeks each was analyzed in 16 CHFpatients 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 CHFpatients probably by the inhibition of inflammatory cytokines and MMPs.
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