Obese But Not Normal-Weight Women With Polycystic Ovary Syndrome Are Characterized by Metabolic and Microvascular Insulin Resistance

Abstract

A high proportion of women with the polycystic ovary syndrome (PCOS) are obese. It is unclear whether normal-weight women with PCOS are at a greater risk of diabetes and cardiovascular disease than obese women without PCOS. It is also unclear whether risks of diabetes and cardiovascular disease in obese women and those with PCOS are additive. To determine whether the risk of diabetes and cardiovascular disease in PCOS is independent of the risk associated with obesity, this prospective controlled study compared insulin sensitivity and microvascular function in normal-weight and obese women with and without PCOS. The 4 PCOS groups were comprised of 19 normal-weight and 16 obese women with PCOS, and 14 normal-weight and 13 obese women controls without PCOS matched for age and body mass index. Before and after insulin infusion to produce hyperinsulinemia, metabolic insulin sensitivity (M/I value) was measured by means of the isoglycemic hyperinsulinemic clamp, and microvascular insulin sensitivity was assessed by analysis of microvascular endothelium-dependent and independent vasodilatation using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) in combination with laser Doppler flowometry in the skin. For the latter, area under the response curves to Ach and SNP were measured. Analysis of metabolic insulin sensitivity showed that both groups of obese women had a significantly lower M/I value than normal-weight women (P ≤ 0.001) and that obese PCOS women had a lower M/I value than obese controls (P ≤ 0.02). In contrast, there was no difference in the M/I value between normal-weight PCOS women and controls. Before insulin infusion, there was no significant difference in microvascular responses to Ach among the 4 groups. During insulin infusion, Ach responses were significantly reduced in obese compared with normal-weight women; a similar difference was found for normal-weight women with or without PCOS. Compared to baseline values, SNP-dependent vasodilatation was not increased during insulin infusion in the 4 groups (P = ns). This report is the first to show that normal-weight women with PCOS may be at relatively normal risk of metabolic and cardiovascular disease and that obese woman with PCOS may be at increased risk. The investigators conclude from these findings that the focus of management in women with PCOS should be on weight control.