Early Metabolic Abnormalities in Adolescents with Polycystic Ovarian Syndrome (PCOS)

Abstract 538 Endocrinology I Poster Symposium, Saturday, 5/1

Recent evidence suggests that hyperinsulinemia may play an important role in the pathogenesis of PCOS by stimulating androgen overproduction. The aim of the present study was to investigate if hyperinsulinemia precedes and leads to insulin resistance or insulin resistance is the primary derangement resulting in compensatory hyperinsulinemia. Therefore, we studied a group of adolescent females with recent onset PCOS in an effort to detect the earliest metabolic abnormalities. Thirteen girls with PCOS (age 12.3±0.7 yrs) were studied in comparison with seven nonhyperandrogenemic girls (age 11.5±0.5 yrs) (CN). The 2 groups were matched for % body fat (43.4±1.3 and 45.7±1.5%) determined by dual energy x-ray absorptiometry and for intra-abdominal fat (77.7±16.0 and 71.4±19.4 cm²) measured by CT scan. All subjects underwent a 3-hr hyperinsulinemic (80 mu/m²/min) -euglycemic clamp to determine in vivo insulin mediated glucose disposal (Rd), and a 2-hr hyperglycemic clamp (225 mg/dl) to determine first (1PI) and second phase insulin (2PI) secretion. Fasting hepatic glucose production (HGP) was determined with the use of [6,6-²H₂]glucose. Indirect calorimetry was used to measure glucose (GOX) and fat oxidation. Results are (mean±SEM): (NOXGD: nonoxidative glucose disposal). (Table)

Table 1 No caption available.

There were no differences in 1PI and 2PI between PCOS and CN (1PI:338.3±57.8 and 210.4±43.4 µu/ml; 2PI: 351.9±49.4 and 271.4±73.1 µu/ml, respectively), and no difference in HGP. However, glucose disposition index (product of insulin sensitivity X 2PI) was lower in PCOS (450±54 vs 646±82 mg/kg/min, p=0.05). In a multiple regression analysis both total testosterone and fat mass independently explained 71% of the variance in Rd among patients but not CN.

In summary, the earliest metabolic abnormality in PCOS is decreased insulin sensitivity with no discernable differences in insulin secretion. The lower glucose disposition index in PCOS compared with CNs suggests that PCOS adolescents may be at increased risk for impaired glucose tolerance and/or diabetes.