Hyperleptinaemia in chronic heart failure. Relationships with insulin.

Abstract

Leptin, a product of the ob gene, is known to increase energy expenditure. Given that chronic heart failure is a hypercatabolic state, we sought to determine whether congestive heart failure involves elevations in plasma leptin levels. Since leptin secretion is up-regulated by insulin, we also explored whether in congestive heart failure, a hyperinsulinaemic state, plasma leptin levels relate to plasma insulin levels. Male patients with weight-stable congestive heart failure (n = 25, aged 55.5 +/- 2.0, mean +/- SEM, body mass index = 27.4 +/- 0.8, radionuclide left ventricular ejection fraction = 29.3 +/- 3.0%) and 18 controls, matched for age, sex and body fat (dual energy X-ray absorptiometry), underwent measurement of fasting plasma leptin (radioimmunoassay) and insulin levels. Compared to controls, patients with congestive heart failure had higher plasma leptin [8.12 (-1.12, +1.31) vs 4.48 (-0.61, +0.70) ng.ml-1, mean +/- asymmetrical SEM, P = 0.003], 41.5% higher plasma leptin per percent body fat mass (P < 0.001), and higher fasting insulin levels [67.8 (-11.1, +13.3) vs 32.9 (-5.7, +6.9) pmol.l-1, P = 0.010]. In the congestive heart failure group, plasma leptin correlated with total body fat (r = 0.66) and fasting insulin (r = 0.68) (both P < 0.001). In multivariate regression analyses of the congestive heart failure group, fasting insulin (standardized coefficient = 0.41, P = 0.011) emerged as a predictor of plasma leptin levels, independent of total body fat (standardized coefficient = 0.73, P = 0.002, R2 = 0.66, P < 0.001). Plasma leptin levels are raised in patients with congestive heart failure. The observation of a positive relationship between plasma leptin and insulin concentrations suggests that the insulin-leptin axis may be related to the increased energy expenditure observed in patients with congestive heart failure.