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Glucose Intolerance in Obese Adolescents with Polycystic Ovary Syndrome: Roles of Insulin Resistance and ß-Cell Dysfunction and Risk of Cardiovascular Disease¹

Division of Pediatric Endocrinology, Metabolism, and Diabetes Mellitus, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213

Address all correspondence and requests for reprints to: Silva A. Arslanian, M.D., Division of Endocrinology, Children’s Hospital of Pittsburgh, 3705 Fifth Avenue at DeSoto Street, Pittsburgh, Pennsylvania 15213. E-mail: arslans{at}chplink.chp.edu

The roles of insulin resistance and insulin secretion in the pathogenesis of glucose intolerance in polycystic ovary syndrome (PCOS) were evaluated in 11 adolescents with impaired glucose tolerance (IGT) and 10 with normal glucose tolerance (NGT). Hepatic glucose production and insulin-stimulated glucose disposal were measured using [6,6-²H₂]glucose and a 3-h hyperinsulinemic (80 mu/m²·min)-euglycemic clamp. First and second phase insulin secretions were evaluated during a hyperglycemic clamp. Automated blood pressure measurements were made to assess the nocturnal change in blood pressure.

Hepatic glucose production was significantly higher in IGT vs. NGT. Insulin-stimulated glucose disposal was not different between the two groups. The first phase insulin level was lower in IGT (207.9 ± 21.0 vs. 357.0 ± 62.9 µu/mL; P = 0.025; 1247 ± 126 vs. 2142 ± 377 pmol/L) without a difference in second phase insulin. The glucose disposition index (product of insulin sensitivity x first phase insulin) was lower in IGT vs. NGT (278 ± 40 vs. 567 ± 119 mg/kg·min; P = 0.023; 1546 ± 223 vs. 3249 ± 663 µmol/kg·min). The glucose disposition index correlated inversely with OGTT glucose concentrations at 30, 60, and 120 min. Adolescents with PCOS-IGT lacked the normal nocturnal decline in blood pressure.

We conclude that in obese adolescents with PCOS, glucose intolerance is associated with 1) decreased first phase insulin secretion, 2) decreased glucose disposition index, and 3) increased hepatic glucose production. These metabolic abnormalities are precursors of type 2 diabetes and are present early in the course of PCOS. Furthermore, the absence of nocturnal dipping in blood pressure may herald the early expression of cardiovascular disease risk in these adolescents.

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