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

• Published in: The journal of clinical endocrinology and metabolism 2008-09, Vol.93 (9), p.3365-3372
• Main Authors: Ketel, Iris J. G., Stehouwer, Coen D. A., Serné, Erik H., Korsen, Ted J. M., Hompes, Peter G. A., Smulders, Yvo M., de Jongh, Renate T., Homburg, Roy, Lambalk, Cornelis B.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Blood Pressure - drug effects; Blood Vessels - drug effects; Blood Vessels - physiology; Body Weight - physiology; Endocrinopathies; Endothelium, Vascular - drug effects; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Humans; Insulin - administration & dosage; Insulin - pharmacology; Insulin Resistance - physiology; Medical sciences; 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; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2008-0626

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.