Spironolactone, not furosemide, improved insulin resistance in patients with chronic heart failure

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 (25 mg/day) and furosemide (20 mg/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.