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 [6,6-6-H-2(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 hyper insulinemic-euglycemic clamp, insulin sensitivity was lower in the PCOS group (1.4 +/- 0.2 vs 2.7 +/- 0.3 mg/kg/min per muu/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) <similar to>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.