Persistent Apparent Pancreatic β-Cell Defects in Premenarchal PCOS Relatives

Context: 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. Objective: We sought to prospectively assess insulin sensitivity and secretion and to measure reproductive hormone levels using sensitive techniques. Design, Setting, and Participants: Twelve premenarchal FDR girls and 10 control girls of comparable age, Tanner stage, and body mass index were studied at an academic medical center. Interventions: Frequently sampled intravenous glucose tolerance tests and oral glucose tolerance tests were performed. Main Outcome Measures: Reproductive hormone levels, lipid profiles, glucose tolerance, and frequently sampled iv glucose tolerance test parameters of insulin sensitivity and secretion were investigated. Results: 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. Conclusions: DI is decreased in peripubertal FDR girls, and this decrease persists as puberty progresses. These findings suggest that beta-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.