Study of the effect of changing glucose, insulin, and insulin-like growth factor-I levels on serum corticosteroid binding globulin in lean, obese, and obese subjects with glucose intolerance

Abstract

We have previously described that serum corticosteroid binding globulin (CBG) concentrations are associated with insulin secretion. The present study was designed to evaluate the effects of changing insulin concentrations, both endogenous and after exogenous insulin administration, on circulating CBG levels in vivo. Serum CBG concentrations were measured during an insulin-modified frequently sampled intravenous (IV) glucose tolerance test (FSIVGT) in 14 lean and 19 obese otherwise healthy subjects with varying degrees of glucose tolerance. Acute insulin response to glucose (AIRg) correlated significantly with serum CBG concentrations at time 0 ( r = [minus ].38, P = .029), 22 minutes ( r = [minus ].41, P = .01), 50 minutes ( r = [minus ].41, P = .01), and 180 minutes ( r = [minus ].39, P = .02). Insulin sensitivity (S I) was not associated with serum CBG concentration at time 0 ( r = [minus ].16, P = not significant [NS]), but correlated significantly with CBG concentration at 22 minutes ( r = [minus ].41, P = .02) and 50 minutes ( r = [minus ].35, P = .048) of the FSIVGT. In lean subjects, serum CBG concentration decreased significantly after IV insulin from 37.9 [plusmn] 5.4 to 35.4 [plusmn] 3 mg/L ( P = .02) and returned to basal levels thereafter. In contrast, obese, glucose-tolerant subjects had lower CBG levels than lean and obese glucose intolerant subjects (33.8 [plusmn] 3.0 v 37.9 [plusmn] 5.4 and 39.8 [plusmn] 4.4 mg/L, respectively), and their serum CBG concentrations remained unchanged during FSIVGT. Mean serum-free insulin-like growth factor-I (IGF-I) concentrations steadily declined from 1.21 [plusmn] 0.81 to 0.8 [plusmn] 0.36 [mu ]g/L during the FSIVGT, and this effect was restricted to lean subjects. Basal serum-free IGF-I did not correlate with CBG levels at time 0, but correlated inversely with the serum CBG concentrations at 22 minutes ( r = [minus ].36, P = .04). Stepwise multivariant analysis showed that AIRg ( P = .035) and S I ( P = .046), but not free IGF-I levels, independently contributed to 28% of CBG variance at 22 minutes. These results suggest that insulin, but not IGF-I, constitutes an important negative regulator of CBG liver synthesis. Endogenous and exogenous insulin do not affect serum CBG concentrations in insulin-resistant obese subjects with preserved or decreased insulin secretion. Obese glucose-tolerant subjects are hypothesized to exhibit tonically inhibited serum CBG levels. In contrast, in lean subjects, the higher the insulin secretion the lower the serum CBG concentration. The mechanisms of this CBG inhibitory effect exerted by insulin and its implication on cortisol homeostasis and fat distribution in humans await further investigations.