Abstract 3153: Adipocyte Dysfunction Contributes to Metabolic Abnormalities in Acute Decompensated Heart Failure

Abstract

Patients with chronic heart failure (HF) develop metabolic abnormalities including a catabolic state, weight loss and cachexia that are associated with adipocyte dysregulation. Several factors, such as inflammatory cytokines and neurohormones, that regulate adipocytes are known to be elevated in ADHF. Therefore, we hypothesized that in acute decompensation (ADHF) there is marked dysregulation of adipocyte function as reflected by circulating adipocytokines including visfatin, a recently described adipocytokine. Methods: Plasma was obtained from 41 patients with ADHF (EF 27 ± 14, BMI 32 ± 6), 25 patients with chronic stable HF (EF 27 ± 18, BMI 28 ± 5), and 21 control subjects (EF 63 ± 3, BMI 31 ± 6) without HF. Levels of NT-proBNP, visfatin, adiponectin, resistin, leptin, insulin, IGF-1 and TNFα were measured by ELISA. Insulin resistance was assessed by HOMA-IR quotient. Results: NT-proBNP was 330 ± 28 fmol/mL in control (Con) patients, elevated to 704 ± 86 fmol/mL in chronic HF and elevated further to 1774 ± 206 fmol/mL in ADHF. Adiponectin was 14.9 ± 3 ng/mL in Con, increased to 28.9 ± 5.7 (p < 0.05) in stable HF, and increased further to 42.9 ± 2.8 ng/mL in ADHF (p < 0.05). Likewise, visfatin was 16.9 ± 3.5 ng/mL in Con, increased to 43.4 ± 9.5 (p < 0.05) in stable HF, and increased further to 79.9 ± 4.6 ng/mL ng/mL in ADHF (p < 0.05). Leptin and resistin were not elevated in chronic stable HF, whereas in ADHF, leptin (9.6 ± 1.0 vs 3.7 ± 0.6 ng/mL; p < 0.0001) and resistin (11.6 ± 1.3 vs 5.7 ± 0.9 ng/mL; p < 0.01) were both elevated compared to Con. Insulin resistance was present in chronic stable HF (24.5 ± 2.2 μU/mL*mg/dL) and increased further in ADHF (32.9 ± 2.0 vs; p < 0.001 vs. Con). In contrast, IGF-1 or insulin were unchanged in the three groups. In patients with ADHF, visfatin, resistin and insulin resistance all correlated with TNFα (p < 0.05 for all). Conclusion: In ADHF there is marked dysregulation of adipocytes as evidenced by elevated blood levels of several adipocytokines, including adiponectin, visfatin, leptin and resistin, and paralleled by worsening insulin resistance. TNFα may contribute to both adipocyte dysregulation and insulin resistance. Metabolic dysfunction in ADHF is associated with elevated adipocytokines that have important effects on insulin signaling.