Although the exact mechanisms that lead to the development of PCOS are not clear it has been shown that insulin resistance and compensatory hyperinsulinemia possess the central role in the pathophysiology of the syndrome. Women with PCOS have both basal and glucose-stimulated hyperinsulinemia compared with weight-matched women and the high levels of insulin are thought to mediate the development of hyperandrogenemia, anovulation, and infertility. At the same time, insulin resistance and compensatory hyperinsulinemia are responsible for the cardiovascular risk factors. The hyperinsulin-ism correlates with the hyperandrogenism and occurs independent of obesity (180,181).
The insulin resistance in at least 50% of PCOS women appears to be related to excessive serine phosphorylation of the insulin receptor (182). This abnormality is caused by a factor extrinsic to the insulin receptor, which is presumably a serine/threonine kinase. Serine phosphorylation appears to modulate the activity of P450c17, which is a key regulatory enzyme that regulates androgen biosynthesis explaining the hyperandrogenism. A second possible mechanism, perhaps in those who do not have the above defect, may be abnormal signaling at the receptor substrate-1 (IRS-1) level as a result of diminished activity of phosphatidylinositol-3 kinase (PI3K) (183). It has also been suggested that women with PCOS have a deficiency of a chiroinositol containing phosphoglycan that mediates the action of insulin. Treatment with D-chiroinositol improved ovulatory function and decreased serum androgen concentrations, BP, and plasma triglyceride concentrations (184).
Women with PCOS are at a greater risk for abnormal glucose tolerance and type 2 diabetes mellitus as compared with age- and weight-matched populations of women without PCOS. In a study that included 122 women with PCOS, glucose tolerance was abnormal in 45%: 35% had IGTand 10% had type 2 diabetes (185). In a subset of 25 women that were re-studied 2.4 years after the initial evaluation it was shown that the conversion from IGT to diabetes mellitus was accelerated as compared to the women without PCOS. The increased risk for IGT and type 2 diabetes occurs at all weight levels and at a young age and additionally, PCOS itself may be a more important risk factor that ethnicity or race for glucose intolerance in young women (186). Perimenopausal women with a history of PCOS are also at a higher risk for developing type 2 diabetes as compared to women without a history of PCOS (187).
Women with PCOS should periodically have an oral glucose tolerance test and must be closely followed and monitored for the development of IGT or diabetes. The basal and 2 hour, glucose-stimulated levels rather than the fasting glucose levels alone are required for such screening (188).
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