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The Metabolic Syndrome and Insulin-Like Growth Factor I Regulation in Adolescent Obesity¹

Departments of Pediatrics and Internal Medicine and the Yale Children’s General Clinical Research Center, Yale University School of Medicine, New Haven, Connecticut 06520

Address all correspondence and requests for reprints to: S. Caprio, M.D., Department of Pediatrics, 333 Cedar Street, Yale University School of Medicine, New Haven, Connecticut 06520. E-mail: caprio{at}cdmas.med.yale.edu

Although low GH levels are commonly seen in obese adults and children, the effects of obesity on the insulin-like growth factor (IGF)/IGF-binding 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-I levels and IGFBP-1, -2, and -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), and 10 lean adults (22 ± 0.7 yr; BMI, 22 ± 0.7). Fasting plasma insulin levels were significantly greater in obese adolescents than in either lean group, whereas circulating IGFBP-1 levels were suppressed in an inverse relationship to basal insulin (r = -0.49; P < 0.01). Low IGFBP-1 levels were associated with normal to increased free IGF-I levels in obese adolescents, even though total IGF-I values were lower than those in lean adolescents. Basal GH and IGFBP-3 levels were also lower in obese vs. lean adolescents. Basal IGFBP-1 levels were markedly reduced in obese adolescents (14 ± 3 ng/mL) vs. those in adolescents and adults. No further suppression of IGFBP-1 levels was observed in the obese group during a two-step 8 and 40 mU/m² insulin clamp. In contrast, IGFBP-1 levels were promptly lowered in lean adults. Basal IGFBP-2 levels were significantly lower in both groups of adolescents vs. lean adults (P < 0.05), and IGFBP-2 levels did not change during euglycemic hyperinsulinemia. These data suggest that the compensatory hyperinsulinemia that characterizes adolescent obesity chronically suppresses levels of IGFBP-1, and low IGFBP-1 concentrations may serve to increase the bioavailability of free IGF-I, which may, in turn, contribute to lower circulating GH, total IGF-I, and IGFBP-3 concentrations.

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