RESUMO
BACKGROUND: Chronic heart failure (CHF) is associated with insulin resistance, indicating impairment in the control of energy metabolism. Insulin resistance in CHF relates to symptomatic status and independently predicts poor prognosis. We sought to determine whether insulin sensitivity is related to skeletal muscle strength in patients with CHF, taking into account muscle size and perfusion. METHODS: Quadriceps muscle size (square centimetre cross-sectional area at mid-femur level, computed tomography), isometric quadriceps muscle strength [absolute (in N) and strength per unit muscle area (N/cm2 )], resting-leg blood flow (plethysmography) and maximal oxygen consumption (treadmill exercise test) were measured in 33 patients with CHF (left ventricular ejection fraction 28 ± 3.2%, mean ± Standard Error of the mean (SEM)) and 20 healthy controls. Insulin sensitivity was assessed by intravenous glucose tolerance tests and minimal modelling analysis. RESULTS: Right quadriceps strength (-27.0%, P < 0.0001), strength per muscle area (-18.0%, P < 0.003) and insulin sensitivity (-64.2%, P < 0.001) were lower in patients with CHF. The correlation between insulin sensitivity and absolute muscle strength was significant in the CHF group (r = 0.54, P = 0.001) and borderline in controls (r = 0.47, P = 0.06). This association remained significant between insulin sensitivity and strength per muscle area (CHF: r = 0.52, P < 0.01; controls: r = 0.62, P < 0.05). In stepwise regression analyses in CHF, only insulin sensitivity emerged as a predictor of strength per unit area of muscle [standardized coefficient (SC) = 0.45, P = 0.006; diuretic dose, SC = -0.31, P = 0.051; R2 = 0.37, P = 0.001], while age, left ventricular ejection fraction, maximal oxygen consumption, fasting glucose and insulin and blood flow were excluded. In controls, only insulin sensitivity remained in the final regression model (SC = 0.62, P = 0.004; R2 = 0.39, P = 0.004). CONCLUSIONS: The myofibril contractile function of the quadriceps, i.e. functional quality of skeletal muscle, is strongly related to insulin sensitivity in patients with CHF and in healthy controls, independently of muscle size. Therapies aimed at improving insulin sensitivity in patients with CHF may clarify whether this relationship is causal.
RESUMO
AIMS: Patients with chronic heart failure (CHF) have an increased catabolic state that affects both muscle and adipose tissue (AT), and may ultimately result in cardiac cachexia. Increased plasma levels of ANP might contribute to increased lipid mobilization and oxidation in CHF. We tested the hypothesis that increased plasma ANP levels are associated with an increased catabolic (lipolytic) state of white AT in patients with CHF. METHODS AND RESULTS: After an overnight fast, AT metabolism was studied by microdialysis in patients with CHF and healthy controls of a similar age and body composition (both n = 8). AT glycolytic and lipolytic activities were assessed at rest (fasting) and after an oral glucose load (oGL). Fasting and post-prandial profiles of serum glucose, insulin, and free fatty acids and of dialysate glucose did not differ significantly between patients and controls. In contrast, fasting dialysate lactate and glycerol levels were two-fold higher in patients vs. controls (lactate, 0.51 ± 0.10 and 0.26 ± 0.06 mmol/L, P < 0.01; glycerol, 116 ± 18 and 50 ± 8 µmol/L, P < 0.001), indicating increased AT glycolytic and lipolytic rates in patients. After an oGL, dialysate lactate increased â¼2- and 2.5-fold, whereas dialysate glycerol decreased by â¼60% and 50% in patients vs. controls, but metabolite levels were always significantly higher in patients vs. controls (all P < 0.05). Plasma ANP levels were increased in patients and significantly correlated with adipose tissue dialysate glycerol. CONCLUSION: In patients wiuth CHF, there is a direct correlation between plasma ANP levels and increased AT catabolic (lipolytic) state. This might contribute to AT wasting and the development of cardiac cachexia in patients with CHF.
