The determinants of insulin sensitivity, β-cell function, and glucose tolerance are different in patients with polycystic ovary syndrome than in women who do not have hyperandrogenism

Abstract

To evaluate the pathogenetic mechanisms underlying abnormal glucose tolerance in polycystic ovary syndrome (PCOS). Case-control study. Academic hospital. One hundred twelve patients with PCOS and 86 nonhyperandrogenic control women of similar age and body mass index (BMI). An oral glucose tolerance test (OGTT) served to explore glucose tolerance and to calculate insulin sensitivity, insulin secretion, and insulin disposition indexes. Frequency of abnormal glucose tolerance, indexes of insulin sensitivity, secretion and disposition, and markers of inflammation, androgen excess, and iron stores. Obesity and age, but not PCOS, were associated with an increased frequency of abnormal glucose tolerance and diabetes. An imbalance between insulin resistance and secretion--translated into decreased insulin disposition index--predicted abnormal glucose tolerance in patients with PCOS and controls, yet these women differed in the factors associated with decreased insulin disposition. In patients with PCOS, hyperandrogenism, chronic inflammation, and family history of diabetes contributed to insulin resistance as the main pathogenetic mechanism. In nonhyperandrogenic women, familial aggregation of defective insulin secretion, adiposity, and increased body iron stores explained most of the decrease in insulin disposition. In addition to a major influence of obesity and age, the mechanisms underlying abnormal glucose tolerance are different in patients with PCOS compared with women who do not have hyperandrogenism.