Obese but not normal-weight women with polycystic ovary syndrome are characterized by metabolic and microvascular insulin resistance

Context: Polycystic ovary syndrome ( PCOS) and obesity are associated with diabetes and cardiovascular disease, but it is unclear to what extent PCOS contributes independently of obesity. Objective: The objective of the study was to investigate whether insulin sensitivity and insulin's effects on the microcirculation are impaired in normal-weight and obese women with PCOS. Design and Population: Thirty-five women with PCOS ( 19 normal weight and 16 obese) and 27 age- and body mass index-matched controls ( 14 normal weight and 13 obese) were included. Metabolic Insulin sensitivity ( isoglycemic-hyperinsulinemic clamp) and microvascular insulin sensitivity [ endothelium dependent ( acetylcholine [ACh])] and endothelium-independent [ sodium nitroprusside ( SNP)] vasodilation with laser Doppler flowmetry was assessed at baseline and during hyperinsulinemia. Main Outcome Measures: Metabolic insulin sensitivity (M/I value) and the area under the response curves to ACh and SNP curves were measured to assess microcirculatory function at baseline and during insulin infusion ( microvascular insulin sensitivity). Results: Obese women were more insulin resistant than normal-weight women ( P < 0.001), and obese PCOS women were more resistant than obese controls ( P = 0.02). In contrast, normal-weight women with PCOS had similar insulin sensitivity, compared with normal-weight women without PCOS. Baseline responses to ACh showed no difference in the four groups. ACh responses during insulin infusion were significantly greater in normal-weight PCOS and controls than in obese PCOS and controls. PCOS per se had no significant influence on ACh responses during insulin infusion. During hyperinsulinemia, SNP-dependent vasodilatation did not significantly increase, compared with baseline in the four groups. Conclusion: PCOS per se was not associated with impaired metabolic insulin sensitivity in normal-weight women but aggravates impairment of metabolic insulin sensitivity in obese women. In obese but not normal-weight women, microvascular and metabolic insulin sensitivity are decreased, independent of PCOS. Therefore, obese PCOS women in particular may be at increased risk of metabolic and cardiovascular diseases.