Insulin sensitivity and secretion influence the relationship between growth hormone-binding-protein and leptin

BACKGROUND A direct relationship between body mass index (BMI), visceral ad ipose tissue, insulin levels and growth hormone-binding protein (GHBP) acti vity has consistently been reported. It was recently described that GHBP di rectly depends on serum leptin levels. Since leptin co-varies with insulin secretion and/or sensitivity, we aimed to study the influence of these vari ables on plasma GHBP activity. SUBJECTS In order to isolate the effects of obesity per se from those of in sulin secretion, three groups of subjects were prospectively studied: 14 le an, 10 obese and nine obese subjects with glucose intolerance. MEASUREMENTS The percentage of body fat was measured through bioelectric im pedance. Insulin sensitivity and secretion were determined through a freque ntly sampled intravenous glucose tolerance test with minimal model analysis . Serum leptin was measured by radioimmunoassay. GHBP activity was determin ed by the high performance liquid chromatography-gel filtration method. RESULTS Plasma GHBP activity was found to correlate with BMI (r = 0.65, P < 0.0001), fat mass (r = 0.51, P = 0.003), waist circumference (r = 0.64, P < 0.0001), waist-to-hip ratio (r = 0.42, P = 0.01), insulin sensitivity (S- I, r = - 0.61, P = 0.0001), insulin secretion (expressed as the acute insul in response to intravenous glucose, AIRg) (r = 0.48, P = 0.006) and leptin concentration (r = 0.49, P = 0.004). The associations with S-I (r = - 0.42, P = 0.02) and AIRg (r = 0.38, P = 0.03) persisted even after controlling f or fat mass. Since insulin secretion and insulin sensitivity usually covary in glucose tolerant subjects (an increased insulin secretion is necessary to compensate a decreased insulin sensitivity), we constructed a multiple l inear regression to predict GHBP activity. In this model, S-I (P = 0.005), AIRg (P = 0.02) and SD score-leptin (P = 0.03) independently contributed to 34, 10 and 8% of the variability in serum GHBP activity. CONCLUSIONS Our results suggest that plasma GHBP activity is simultaneousll y influenced by insulin secretion and sensitivity and leptin. Perhaps lepti n, through increased insulin secretion, might induce GHBP/GH secretion, exp laining the normal to high insulin-like growth factor (IGF)-I levels found in overnutrition.