Diabetes issues in women and children: polycystic ovary syndrome.

Abstract

At the American Diabetes Postgraduate Course in New York, NY, on 12 January 2003, a number of important topics relating women’s health and diabetes were reviewed. Andrea Dunaif, Chicago, IL, discussed the polycystic ovary syndrome (PCOS), pointing out its frequency in the population and association with type 2 diabetes. PCOS is associated with a 40% decrease in insulin sensitivity (1) and with evidence of relative β-cell dysfunction (2). PCOS is a major risk factor for type 2 diabetes in adolescents (3) and in premenopausal women (4), with ∼40% of individuals with PCOS developing impaired glucose tolerance (IGT) or type 2 diabetes, a rate similar to that seen among Pima Indians. Among women with oligomenorrhea (menses ≤6/year), 77% have PCOS and 33% (vs. 7.7% of control subjects) have glucose intolerance. Using menstrual cycle length ≥40 days as a proxy marker, the Nurses Health Study data showed a 2.18-fold increase in risk of diabetes among women with long cycles (5). The same dataset showed a menstrual cycle ≥40 days to be associated with a 1.53-fold increase in coronary heart disease (CHD) risk (6). Thus, the disease “has substantial health consequences” and represents an important target population for diabetes prevention. Dunaif humorously suggested that as PCOS represents an expression of the metabolic syndrome in women, it should be called “Syndrome XX.” The mechanisms of insulin resistance may include specific genetic abnormalities. Postbinding abnormality in insulin signaling can be shown, with abnormal autophosphorylation of the insulin receptor and of insulin receptor substrate (IRS)-1. Tyrosine phosphorylation is decreased and serine phosphorylation increased at both of these receptors, leading to a decrease in the metabolic actions of insulin. Dunaif noted that cytochrome P450c17 is involved in ovarian androgen synthesis and activated by a serine kinase that may play a role in the abnormal insulin receptor and …