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

Division of Reproductive Medicine, Department of Obstetrics and Gynaecology (I.J.G.K., T.J.M.K., P.G.A.H., R.H., C.B.L.) and Department of Internal Medicine (E.H.S., Y.M.S., R.T.d.J.), de Boelelaan, 1117 Amsterdam, The Netherlands; and Department of Internal Medicine (C.D.A.S.), Academic Hospital Maastricht, P. Debyelaan 25, 6202 AZ Maastricht, The Netherlands

Address all correspondence and requests for reprints to: Iris J. G. Ketel, de Boelelaan 1118, Room 0Z106, 1081 HV Amsterdam, The Netherlands. 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: 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.