Persistent apparent pancreatic β-cell defects in premenarchal PCOS relatives.

Abstract

Polycystic ovary syndrome confers an increased risk for type 2 diabetes in affected women as early as adolescence. First-degree relatives (FDRs) of affected women are at increased risk for associated reproductive and metabolic phenotypes. We sought to prospectively assess insulin sensitivity and secretion and to measure reproductive hormone levels using sensitive techniques. Twelve premenarchal FDR girls and 10 control girls of comparable age, Tanner stage, and body mass index were studied at an academic medical center. Frequently sampled intravenous glucose tolerance tests and oral glucose tolerance tests were performed. Reproductive hormone levels, lipid profiles, glucose tolerance, and frequently sampled iv glucose tolerance test parameters of insulin sensitivity and secretion were investigated. Disposition index (DI), insulin secretion corrected for insulin sensitivity, was decreased in FDR compared with control girls at baseline (P = .01), independent of dysglycemia. Decreases in DI persisted in FDR girls during the 2-year follow-up (P = .003). T levels were increased (P = .02) in FDR compared with control girls at baseline, but this difference did not persist because T levels increased in control girls. DI is decreased in peripubertal FDR girls, and this decrease persists as puberty progresses. These findings suggest that β-cell dysfunction is an early defect in glucose homeostasis preceding decompensation in glucose tolerance in FDR girls. T levels were increased in FDR girls earlier than previously reported, but these changes did not persist, suggesting an earlier onset of pubertal increases in glandular androgen secretion in FDR girls.