THE METABOLIC SYNDROME AND INSULIN-LIKE-GROWTH-FACTOR-I REGULATION INADOLESCENT OBESITY

Although low GH levels are commonly seen in obese adults and children, the effects of obesity on the insulin-like growth factor (IGF)/IGF-bi nding protein (IGFBP) system have not been established. As GH and IGF- I normally increase during adolescence, we investigated the effects of obesity on circulating total and free IGF-E levels and IGFBP-1, -2, a nd -3 in 19 obese adolescents [14 +/- 1 yr old; body mass index (BMI), 34 +/- 3], 20 lean adolescents (14 +/- 1 yr old; BMI, 23 +/- 0.5), an d 10 lean adults (22 +/- 0.7 yr; BMI, 22 +/- 0.7). Fasting plasma insu lin levels were significantly greater in obese adolescents than in eit her lean group, whereas circulating IGFBP-1 levels were suppressed in an inverse relationship to basal insulin (r = -0.49; P < 0.01). Low IG FBP-1 levels were associated with normal to increased free IGF-I level s in obese adolescents, even though total IGF-I values were lower than those in lean adolescents. Basal GH and IGFBP-3 levels were also lowe r in obese vs. lean adolescents. Basal IGFBP-1 levels were markedly re duced in obese adolescents (14 +/- 3 ng/mL) vs. those in adolescents a nd adults. No further suppression of IGFBP-1 levels was observed in th e obese group during a two-step 8 and 40 mU/m(2) insulin clamp. In con trast, IGFBP-1 levels were promptly lowered in lean adults. Basal IGFB P-2 levels were significantly lower in both groups of adolescents vs, lean adults (P < 0.05), and IGFBP-2 levels did not change during eugly cemic hyperinsulinemia. These data suggest that the compensatory hyper insulinemia that characterizes adolescent obesity chronically suppress es levels of IGFBP-1, and low IGFBP-1 concentrations may serve to incr ease the bioavailability of free IGF-I, which may, in turn, contribute to lower circulating GH, total IGF-I, and IGFBP-3 concentrations.