Serum leptin concentrations correlate to plasma insulin concentrations independent of body fat content in chronic renal failure

Background. The ob gene product leptin is secreted by fat cells and reflects the content of fat in the body. Leptin and insulin concentrations as well as body weight are interrelated and a direct correlation has been found between these concentrations in humans with normal renal function. Markedly elevated serum leptin concentrations have recently been reported in patients with chronic renal failure (CRF). The aim of the present study was to investigate the relation between serum leptin and plasma insulin in patients with advanced CRF. Methods. Serum leptin, plasma insulin, as well as body fat content (determined with dual-energy X-ray absorptiometry) were determined in a cohort of 46 patients (mean age 54 +/- 2 years) with advanced CRF (creatinine clearance 8 +/- ml/min). Results. In 23 CRF patients with plasma insulin below the median value (14 mU/1), serum leptin concentrations were no higher than in healthy controls (8.0 +/- 1.2 vs 8.4 +/- 0.9 ng/ml). However, in CRF patients with plasma insulin >14mU/1 (n=23) the serum leptin concentrations were much higher (38.2 +/- 11.0 ng/ml; P<0.0001); In CRF patients, serum leptin (normalized for the per cent body fat content) correlated significantly (r = 0.64; P < 0.0001) with plasma insulin concentrations. However, the increase in plasma insulin was blunted in patients with very high serum leptin concentrations in relation to the per cent body fat content. Conclusions. The present results demonstrate that serum leptin concentrations are markedly elevated in CRF patients with higher plasma insulin than in those with lower plasma insulin concentrations. This suggests that insulin resistance and hyperinsulinaemia contribute to elevated serum leptin concentrations in CRF. The present results also demonstrate that, when circulating serum leptin concentrations are much higher in relation to the per cent body fat content, no additional increase in plasma insulin occurs. This latter observation suggests that the secretion of insulin by the pancreas is lower in hyperleptinaemic patients. Consequently, extremely elevated serum leptin may play a role in reducing glucose-stimulated insulin secretion and glucose intolerance in CRF.