Ketel IJ, Stehouwer CD, Serné EH, Korsen TJ, Hompes PG, Smulders YM, de Jongh RT, Homburg R, Lambalk CB Obese but not normal-weight women with polycystic ovary syndrome are characterized by metabolic and microvascular insulin resistance. [JOURNAL ARTICLE] J Clin Endocrinol Metab 2008 Jul 1.
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: To investigate if 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 BMI-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 (AUC) to ACh and SNP- curves 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=.02). In contrast, normal-weight women with PCOS had similar insulin sensitivity compared to 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 to 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 in 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.
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