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Submitted on March 18, 2008
Accepted on June 25, 2008
Division of Reproductive Medicine, Department of Obstetrics & Gynaecology, and Department of Internal medicine, de Boelelaan 1117, Amsterdam, The Netherlands; Department of Internal Medicine, Academic Hospital Maastricht, P. Debyelaan 25, Maastricht, The Netherlands
* To whom correspondence should be addressed. E-mail: ijg.ketel{at}vumc.nl.
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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| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |