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

J Clin Endocrinol Metab. 2008 Sep;93(9):3365-72. doi: 10.1210/jc.2008-0626. Epub 2008 Jul 1.

Abstract

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.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Pressure / drug effects
  • Blood Vessels / drug effects
  • Blood Vessels / physiology
  • Body Weight / physiology*
  • Endothelium, Vascular / drug effects
  • Female
  • Humans
  • Insulin / administration & dosage
  • Insulin / pharmacology
  • Insulin Resistance / physiology*
  • Nitroprusside / pharmacology
  • Obesity / complications*
  • Obesity / metabolism*
  • Obesity / physiopathology
  • Polycystic Ovary Syndrome / complications*
  • Polycystic Ovary Syndrome / metabolism
  • Polycystic Ovary Syndrome / physiopathology
  • Skin / blood supply
  • Skin / drug effects
  • Vasodilation / drug effects

Substances

  • Insulin
  • Nitroprusside