Markers of metabolic disease risk in Polycystic Ovary Syndrome — ASN Events

Markers of metabolic disease risk in Polycystic Ovary Syndrome (#184)

Samantha Cassar 1 , Helena J Teede 2 3 , Cheryce L Harrison 2 , Anju E Joham 2 , Samantha K Hutchison 2 , Rebecca F Goldstein 2 , Lisa J Moran 4 , Nigel K Stepto 1 2 5
  1. College of Sport and Exercise Science, Victoria University, Footscray, Victoria, Australia
  2. Women's Public Health Research, School of Public Health and Preventative Medicine, Monash University, Clayton, Victoria, Australia
  3. Diabetes and Vascular Medicine Unit, Monash Health, Clayton, Victoria, Australia
  4. The Robinson Institute, Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, University of Adelaide, North Adelaide, South Australia, Australia
  5. Institute of Sport and Active Living, Victoria University, Footscray, Victoria, Australia

Introduction: Polycystic ovary syndrome (PCOS) affects 12-21% of reproductive aged women1 2 and is associated with reproductive abnormalities, insulin resistance (IR) and elevated risk factors for cardiovascular disease and Type 2 diabetes3 4 5. The aetiology of PCOS remains controversial, with IR implicated in the pathophysiology of the condition6. Up to 85% of women with PCOS have some degree of IR that occurs independently of, yet is exacerbated by obesity7. The present study aimed to assess circulating biomarkers ghrelin, resistin, visfatin, glucagon-like peptide- 1 (GLP-1), leptin, plasminogen activator inhibitor-1 (PAI-1), gastric inhibitory polypeptide (GIP) and C-Peptide, as they play pivotal roles in body weight regulation, glucose homeostasis, insulin sensitivity and lipid metabolism, directly relevant to PCOS. Methods: In a mechanistic observational study, 84 premenopausal women with (n = 44) and without (n = 40) PCOS were recruited and further divided into groups based on PCOS and BMI status (lean control (n = 22), lean PCOS (n = 22), overweight control (n = 18) and overweight PCOS (n = 22). Hyperinsulinemic clamp studies and biomarker assays were completed. Results: Overall women with PCOS were more IR (clamp glucose infusion rate [mean±SD] 313±89 vs. 330±90 mg.min-1m2 P<0.05), had elevated testosterone, fasting androgen index and LDL:HDL ratio and lower fasting GIP levels (P<0.05). When investigating the relationships with PCOS and obesity, it was demonstrated that lean controls were the least IR, followed by lean PCOS (Effect size [ES] = 0.9), overweight controls (ES = 1.0) and overweight PCOS (ES = 2.0). C-peptide was elevated in the overweight PCOS group (0.3 ± 0.3 ng/ml) compared to lean control (0.2 ± 0.1 ng/ml; P = 0.02) and lean PCOS groups (0.1 ± 0.16 ng/ml; P=0.01). Lower ghrelin and higher leptin levels were found in overweight women irrespective of PCOS status compared to lean women. Glucose infusion rate, measured by the hyperinsulinemic clamp, predicted PAI1 and C-peptide levels, while BMI predicted leptin levels. Conclusion: The selected biomarkers measured to assess metabolic disease risk, appear more strongly associated with BMI status and insulin resistance than with PCOS status.

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  7. STEPTO, N. K., CASSAR, S., JOHAM, A. E., HUTCHISON, S. K., HARRISON, C. L., GOLDSTEIN, R. F. & TEEDE, H. J. 2013. Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp. Human reproduction, 28, 777-784
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