Longitudinal study of physiologic insulin resistance and metabolic changes of puberty

Cross-sectional studies have shown that 1) adolescents are insulin resistant compared with prepubertal children and adults, 2) pubertal insulin resistance is likely mediated by growth hormone (GH), and 3) pubertal insulin resistance is associated with increased fat oxidation and decreased glucose oxidation. The aim of this study was to assess the validity of these cross-sectional observations by performing a longitudinal study in normal children during the prepubertal and pubertal periods. Nine healthy, normal weight, prepubertal children underwent hyperinsulinemic-euglycemic and hyperglycemic clamp studies for evaluation of insulin sensitivity and insulin secretion. Children had repeat evaluations during puberty. Consistent with cross-sectional observations, this longitudinal study demonstrated that during puberty: 1) insulin sensitivity decreased by similar to 50%, 2) the decrease in insulin sensitivity was compensated by a doubling in insulin secretion, and 3) the decrease in insulin sensitivity was independent of changes in percentage of body fat. Puberty was associated with increased total body lipolysis and decreased glucose oxidation. A novel observation is the demonstration of similar to 50% decrease in adiponectin levels at the pubertal time point. These metabolic changes are proposed to be partially mediated by increased GH secretion and are consistent with the Randle cycle of competition between glucose and fat oxidation.