Serum insulin but not leptin is associated with spontaneous and growth hormone (GH)-releasing hormone—stimulated GH secretion in normal volunteers with and without weight loss

Weight loss in humans is associated with elevated hypothalamic-pituitary growth hormone (GH) secretion. This study evaluates the effects of weight loss on the hypothalamic-pituitary (GH-releasing hormone [GHRH]-GH) axis in 14 normal-weight (body mass index [BMI], 25 ± 1 Kg/m 2) subjects, of whom half had undergone a diet-induced weight loss of 14% ± 2% (mean ± SEM). Insulin-like growth factor-1 (IGF-1), insulin, oral glucose tolerance, leptin, and GH pulse patterns were determined in both groups after weight maintenance for 1 week. Of note, we tested the effects of recent weight loss (3 months) and not a recent dietary intake, since both groups ingested a normal calorie diet for 2 days in the Clinical Research Center (CRC) prestudy. Serum insulin (3.8 ± 0.7 v 9.0 ± 0.9 μU/mL, P < .01) and C-peptide (0.44 ± 0.06 v 0.59 ± 0.04 mg/mL, P < .05) were significantly lower in the weight loss group. Serum leptin was not different. Endogenous GH pulse height (11.9 ± 4.8 v 1.3 ± 0.1 μg/L, P < .05), area per GH pulse ([AUC] 57 ± 28 v 6 ± 1 μg/L, P < .05), and mean GH (3.91 ± 0.76 v 0.85 ± 0.16 μg/L, P < .01) were increased in the weight loss group. The serum insulin level was inversely associated with the mean GH concentration ( r = −.678, P < .01) and GH pulse height ( r = −7.33, P < .01). In addition to spontaneous GH secretion, the GHRH-stimulated GH pulse height (41.8 ± 18.1 v 7.1 ± 1.6 μg/L, P < .05) and AUC (161 ± 35 v 46 ± 13 μg/L/min, P < .05) were also increased in the weight loss group. The insulin concentration was also inversely correlated with the GHRH-stimulated GH pulse height ( r = −.718, P < .01). The leptin concentration was correlated with the BMI ( r = .554, P < .05) and body fat ( r = .744, P < .01), but not with GH secretion. In summary, even though these patients were on a normal calorie diet, a history of recent weight loss in young men and women of normal weight and health can be associated with a significant increase in spontaneous GH pulse height and GHRH-stimulated pulse height. Weight loss was also associated with a reduced serum insulin level. The observed increase in GH secretion may be secondary to the reduction in insulin or alterations of other factors acting at the site of the pituitary.