Association between the Insulin Resistance of Puberty and the Insulin-Like Growth Factor-I/Growth Hormone Axis

To test the hypothesis that the relative insulin resistance of puberty is associated with changes in IGF-I levels, we compared IGF-I, IGF binding protein-3 (IGFBP-3), and IGFBP-1 levels to insulin resistance M(lbm), milligrams glucose used per kilogram of lean body mass (LBM) per minute measured during euglycemic, hyperinsulinemic clamp studies in 342 children and adolescents. IGF-I levels rose and fell during the Tanner stages of puberty in a pattern that closely followed the rise and fall of insulin resistance. IGF-I levels were significantly related to M(lbm) in boys (P = 0.0006) and girls (P = 0.02). IGF-I was significantly related to fasting insulin levels only in girls (P = 0.006; boys, P = 0.26), and this relation was significantly influenced in girls by body fat (P = 0.007), with the strongest association between IGF-I and fasting insulin seen in thin girls. IGFBP-1 correlated negatively with insulin resistance in both boys (P = 0.0004) and girls (P = 0.04), whereas IGFBP-3 correlated positively with insulin resistance in boys (P = 0.0004) but not girls (P = 0.85). These data suggest that the GH/IGF-I axis is an important contributor to the insulin resistance of puberty.