Early Metabolic Abnormalities in Adolescent Girls with Polycystic Ovarian Syndrome

Objective: To investigate insulin sensitivity and secretion in young adolescent girls with childhood onset polycystic ovarian syndrome (PCOS) and to identify the early metabolic derangement(s).

Study Design: Twelve obese girls with PCOS (age 12.0+/-0.7 years) were compared with 10 obese nonhyperandrogenic girls (control group). The groups were matched for age, percent body fat, and abdominal fat. All subjects underwent a 3-hour hyperinsulinemic (80 mu/m(2)/min)-euglycemic clamp to determine in vivo insulin sensitivity and a 2-hour hyperglycemic clamp (225 mg/dL) to determine insulin secretion. Fasting hepatic glucose production was determined with the use of [6,6-(2)H(2)]glucose.

Results: Fasting glucose and hepatic glucose production were comparable between the 2 groups, but fasting insulin was 2-fold higher in the PCOS group. The fasting glucose to insulin ratio was lower in the PCOS group versus the control group (1.9+/- 0.3 vs 3.1+/-0.3, P =.02). During the hyperinsulinemic-euglycemic clamp, insulin sensitivity was lower in the PCOS group (1.4+/-0.2 vs 2.7+/-0.3 mg/kg/min per microu/mL, P =.002). During the hyperglycemic clamp, insulin secretion was significantly higher in the PCOS group. Insulin sensitivity correlated negatively with fasting insulin (r = -0.71, P =.0002) and positively with the fasting glucose to insulin ratio (r = 0.79, P<.0001).

Conclusion: Adolescent girls with PCOS have profound metabolic derangements detected early in the course of the syndrome, including (1) approximately 50% reduction in peripheral tissue insulin sensitivity, (2) evidence of hepatic insulin resistance, and (3) compensatory hyperinsulinemia. These observations may predict an increased risk of type 2 diabetes mellitus in adolescents with PCOS.