Effect of weight loss on free insulin-like growth factor-I in obese women with hyposomatotropism.

OBJECTIVE: It has been hypothesized that increased free insulin-like growth factor (IGF)-I levels generated from an increase in IGF-binding protein (IGFBP) protease activity could be the inhibitory mechanism for the decreased growth hormone (GH) secretion observed in obese subjects.

RESEARCH METHODS AND PROCEDURES: In this study, we determined basal and 24-hour levels of free IGF-I and -II, total IGF-I and -II, IGFBP-1, as well as basal IGFBP-2, -3, and -4, acid-labile subunit (ALS), IGFBP-1, -2, and -3 protease activity, and 24-hour GH release in obese women before and after a diet-induced weight loss. Sixteen obese women (age, 29.5+/-1.4 years) participated in a weight loss program and 16 age-matched non-obese women served as controls.

RESULTS: Circulating free IGF-I and 24-hour GH release were significantly decreased in obese women at before weight loss compared with non-obese women (1.29+/-0.12 vs. 0.60+/-0.09 microg/L; p<0.001 and 862+/-90 vs. 404+/-77 mU/24 hours; p<0.001, respectively). Free IGF-I and 24-hour GH release were not inversely correlated to each other. IGFBP-1 and -2 levels were decreased, whereas ALS, IGFBP-3 and -4, and IGFBP-1, -2, and -3 protease activity were similar in obese and non-obese women. Eight of the 16 obese women achieved an average weight loss of 30+/-5 kg during 26 to 60 weeks of dieting. After the considerable weight loss, significant differences in free IGF-I, GH release, and IGFBP-1 and -2 levels were no longer present between previously obese and non-obese women.

DISCUSSION: We showed that circulating free IGF-I is markedly decreased in severely obese women and does not per se mediate the concomitant hyposomatotropism. The decreased levels of free IGF-I seem to be transient and restored to normal levels after weight loss.