Insulin Sensitivity, Insulin Secretion, and Metabolic and Hormonal Parameters in Healthy Women and Women With Polycystic Ovarian Syndrome

摘要

As many as one in five women with polycystic ovarian syndrome (PCOS) who undergo oral glucose tolerance testing exhibit impaired tolerance and may be at risk of developing type 2 diabetes. A defect in transduction of insulin receptors might lead to insulin resistance in some women with PCOS. This study was an attempt to gauge the contributions of body mass and a family history of type 2 diabetes to insulin status in 15 lean (LPCOS) and 28 obese (OPCOS) women, compared with 17 lean and 17 obese control women, all of whom underwent a 75-gm oral glucose tolerance test. The insulin sensitivity index (M/I) was estimated using the euglycemic, hyperinsulinemic clamp technique. Criteria for PCOS included polycystic ovaries in addition to menstrual dysfunction or clinical manifestations of hyperandrogenism.Compared with their respective control subjects, both the LPCOS and OPCOS groups had a higher waist/hip ratio, more hirsutism, and greater average ovarian volumes. The LPCOS women tended to be hyperinsulinemic and to have impaired insulin sensitivity, but only in OPCOS women were these trends significant. Early phase insulin secretion (but not early phase C-peptide secretion) was higher in PCOS women than in control subjects (Figs. 1 and 2) . M/I was significantly lower in OPCOS women than in obese control subjects (Fig. 3). Both glucose oxidation and glucose nonoxidation indices were significantly reduced. In women with PCOS, neither early phase insulin nor C-peptide secretion was influenced by a family history of type 2 diabetes. One-hour glucose and insulin concentrations during tolerance testing were significantly higher in obese than in lean control women, and the obese women had lower M/I indices.Fig. 1. Glucose and insulin concentrations (mean ± SE) during oral glucose tolerance test (OGTT) in the subjects of the study (controls, ○; polycystic ovarian syndrome, •). *P .05, **P .01 compared with obese control. (Used by permission of Oxford University Press.)Fig. 2. Early phase secretions of insulin and C-peptide in lean and obese subjects. LC = lean control; LPCOS = lean polycystic ovarian syndrome; OC = obese control; and OPCOS = obese polycystic ovarian syndrome. *P = .015 compared with OC. (Used by permission of Oxford University Press.)Fig. 3. Mean (± SE) insulin sensitivity index (M/I), glucose oxidation (black section), and nonoxidation (hatched section) indices expressed as &mgr;mol/kg/min/mIU/liter during the euglycemic, hyperinsulinemic clamp. *Not significant (M/I) compared with LC (glucose oxidation index: not significant; glucose nonoxidation index: not significant) and P .001 (M/I) compared with OPCOS (both glucose oxidation and non-oxidation indices: P .001). **P = .04 (M/I) compared with OC (glucose oxidation index: P = .002; glucose nonoxidation index: P = .05). ***P .001 (M/I) compared with OC (both glucose oxidation and nonoxidation indices: P .001). For calculation of M/I see Materials and Methods. (Used by permission of Oxford University Press.)This study demonstrated markedly impaired insulin sensitivity in obese women with PCOS. It would seem that obesity (especially abdominal obesity) contributes to an important degree to the development of insulin resistance in this setting. Whether hyperinsulinemia results from primarily impaired insulin action, primary abdominal obesity, or defective &bgr;-cell function remains to be determined.Hum Reprod 2000;15:1266–1274