HYPERINSULINEMIA AND DECREASED INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1 ARE COMMON FEATURES IN PREPUBERTAL AND PUBERTAL GIRLS WITH A HISTORY OF PREMATURE PUBARCHE

The fasting insulin resistance index, mean blood glucose, mean serum i nsulin (MSI), early insulin response to glucose, glucose uptake rate i n peripheral tissues, and insulin sensitivity indexes in response to a standard oral glucose tolerance test; serum insulin-like growth facto r I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGFBP-3, and sex hormone binding-globulin (SHBG) levels; and the free androgen indexes were ev aluated in 98 girls with premature pubarche [PP; prepubertal (B1; n = 32), early pubertal (B2; n = 27), midpubertal (B3; n = 23), and postme narchal(B5; n = 16)] and in 86 Tanner stage-and bone age-matched contr ols. We ascertained whether hyperinsulinemia is already present in PP girls before or during pubertal development and whether these patients show a similar pattern of growth factor secretion as normal girls. Bo dy mass indexes did not differ significantly between patients and cont rols within the same pubertal stage. MSI levels showed a significant i ncrease with pubertal onset in all subjects, as expected. Patients sho wed significantly higher MSI values than controls at all Tanner stages (P < 0.03, P = 0.03, P = 0.03, and P < 0.05 for B1, B2, B3, and B5, r espectively); higher insulin response to glucose at B1, B2, and B3 (P < 0.03, P = 0.03, and P < 0.05, respectively); higher glucose uptake r ate in peripheral tissues at B1 and B2 (P < 0.04 and P = 0.02, respect ively); and a later rise in insulin sensitivity compared to controls. PP girls also showed lower IGFBP-1 levels at B1 and B5 (P < 0.01 and P = 0.02, respectively), lower SHBG concentrations at B5 (P < 0.0005), and higher free androgen indexes at B1, B3, and B5 (P < 0.01,P < 0.05, and P < 0.001, respectively) compared to controls. Among others, sign ificant correlations between SHBG and MSI levels (r = -0.49; P < 0.000 1) and between SHBG and IGFBP-1 levels (r = 0.41; P < 0.0001) were fou nd in all subjects. Hyperinsulinemia, increased early insulin response s to glucose, increased glucose uptake rate in peripheral tissues, ele vated free androgen indexes, and decreased SHBG and IGFBP-1 levels are present in most girls with PP from childhood. These findings lend str ong support to the concept that PP is not a benign condition, and long term follow-up of these patients into adulthood is recommended. The p ossible causal role of hyperinsulinemia in adrenal and/or ovarian andr ogen hypersecretion remains to be established.