Dynamics in insulin resistance and plasma levels of adipokines in patients with acute decompensated and chronic stable heart failure

Abstract

Background: Patients with heart failure (HF) develop metabolic derangements including increased adipokine levels, insulin resistance, inflammation and progressive catabolism. It is not known whether metabolic dysfunction and adipocyte activation worsen in the setting of acute clinical decompensation, or conversely, improve with clinical recovery.

Methods and results: We assessed insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR), and measured plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), adiponectin, visfatin, resistin, leptin, and tumor necrosis factor (TNF) α in 44 patients with acute decompensated HF (ADHF) due to left ventricular (LV) systolic dysfunction and again early (<1 wk) and late (> 6 mo) after clinical recovery, in 26 patients with chronic stable HF, and in 21 patients without HF. NT-proBNP was not increased in control subjects, mildly elevated in patients with stable HF, markedly elevated in patients with ADHF, and decreased progressively early and late after treatment. Compared to control subjects, plasma adiponectin, visfatin, leptin, resistin, and TNF-α were elevated in patients with chronic stable HF and increased further in patients with ADHF. Likewise, HOMA-IR was increased in chronic stable HF and increased further during ADHF. Adiponectin, visfatin, and HOMA-IR remained elevated at the time of discharge from the hospital, but returned to chronic stable HF levels. Adipokine levels were not related to body mass index in HF patients. HOMA-IR correlated positively with adipokines and TNF-α in HF patients.

Conclusions: ADHF is associated with worsening of insulin resistance and elevations of adipokines and TNF-α, indicative of adipocyte activation. These metabolic abnormalities are reversible, but they temporally lag behind the clinical resolution of decompensated HF.

Figure 1. Serum Levels and Time Course of Neurohumoral Activation and Insulin Resistance in Patients with ADHF, CHF and controls

(A) Plasma levels of NT-proBNP in controls (n=21), patients with stable CHF (n=26) and acute decompensated HF (ADHF, n=44). (B) Dynamics in circulating levels of NT-proBNP from admission to the hospital and upon discharge and at clinical recovery (n=16). (C) Plasma levels of TNFα in controls, CHF and ADHF and (D) during in-hospital treatment and after recovery. (E) Insulin Resistance assessed by HOMA quotients in controls, CHF and ADHF and (F) changes in IR during in-hospital treatment and after recovery († p<0.05 vs. controls; ‡ p<0.01 vs. controls; $ p<0.05 vs. CHF; * p<0.05 vs. admission; § p<0.01 vs. admission; # p<0.05 vs. discharge).

Figure 2. Serum Levels and Time Course of Changes in Adipokines in Patients with ADHF, CHF and controls

Adiponectin (A), visfatin (C), leptin (E) and resistin (G) were detected in controls (n=21), patients with stable CHF (n=26) and acute decompensated CHF at admission (n=44) to the hospital. In a subgroup, all adipokines were assessed again at discharge and after recovery (B, D, F, H) (n=16) († p<0.05 vs. controls; ‡ p<0.01 vs. controls; $ p<0.05 vs. CHF; * p<0.05 vs. admission; § p<0.01 vs. admission; # p<0.05 vs. discharge).