Women with PCOS demonstrate intrinsic insulin resistance on gold standard hyperinsulinaemic-euglycaemic clamp. — ASN Events

Women with PCOS demonstrate intrinsic insulin resistance on gold standard hyperinsulinaemic-euglycaemic clamp. (#131)

Nigel K Stepto 1 2 3 , Samantha Cassar 1 , Samantha K Hutchison 2 , Cheryce L Harrison 2 , Anju Joham 2 , Nicole Ng 2 , Rebecca Goldstein 2 , Benedit J Canny 4 , Helena J Teede 2 5
  1. Victoria University, Melbourne, VIC, Australia
  2. Women’s Public Health Research, School of Public Health and Preventative Medicine, Monash University, Clayton, VIC, Australia
  3. Institute of Sport Exercise and Active Living, Victoria University, Melbourne, VIC, Australia
  4. Department of Physiology, Monash University, Clayton, VIC
  5. Diabetes and Vascular Medicine Unit, Southern Health, Clayton, VIC, Australia

Introduction: Polycystic Ovary Syndrome (PCOS) is currently recognised as a complex and heterogeneous disorder comprising metabolic, endocrine and reproductive features, affecting 12-21% of reproductive aged women (1). It has been proposed that there is both an intrinsic PCOS related insulin resistance, which is compounded by extrinsic body mass index (BMI) related insulin resistance (2), however data to support this hypothesis is limited. We aimed to determine insulin sensitivity by hyperinsulinaemic-euglycaemic clamps in lean and overweight women with and without PCOS to explore this hypothesis.
Methods: 73 women were recruited from the community. Following written informed consent, 4 groups of women; 14 overweight women without PCOS and 20 overweight with PCOS (BMI> 27 kg/m2), 19 lean women without PCOS and 20 lean with PCOS (BMI<27 kg/m2) participated in the study. PCOS status was determined using the Rotterdam diagnostic criteria. After an overnight fast the participants underwent a 2 hour euglycaemic-hyperinsulinaemic clamp(3).
Results: The PCOS and control women were matched for BMI within the overweight (mean±SD; PCOS 35.4±6.0 vs. control 36.8±6.7 kg/m2) and lean (PCOS 22.8±2.1 vs. control 21.8±2.1 kg/m2) groups. Compared to lean controls: lean PCOS were 25% more insulin resistant (IR), overweight controls were 50% more IR and overweight PCOS were 95% more IR suggesting both a PCOS and weight related impact on IR. Specifically mean glucose infusion rates (GIR) were impaired in both the overweight (PCOS 174±96 vs. control 250±81 mg/min/m2; P=0.04) and lean (PCOS 269±67 vs. control 338±76 mg/min/m2; P=0.05) women with PCOS compared to matched controls.
Conclusion: We demonstrate for the first time, using the “gold standard” clamp technique, that lean women with PCOS have insulin resistance, compared to weight matched controls consistent with an intrinsic PCOS related insulin resistance that is further exacerbated by extrinsic BMI related IR.

This work was supported by NHMRC APP606553

  1. W. A. March et al., The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 25, 544 (Feb, 2010)
  2. H. J. Teede, S. K. Hutchison, S. Zoungas, The management of insulin resistance in polycystic ovary syndrome. Trends Endocrinol Metab 18, 273 (September, 2007).
  3. S. K. Hutchison et al., Effects of exercise on insulin resistance and body composition in overweight and obese women with and without polycystic ovary syndrome. J Clin Endocrinol Metab 96, E48 (Jan, 2011)