title: Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp.
abstract: OBJECTIVE
  What is the prevalence of insulin resistance (IR) and the contributions of intrinsic and extrinsic IR in women diagnosed with polycystic ovary syndrome (PCOS) according to the Rotterdam criteria?
  
  
  CONCLUSIONS
  We report novel clamp data in Rotterdam diagnosed PCOS women, using World Health Organization criteria for IR showing that women with PCOS have a high prevalence of IR, strengthening the evidence for an aetiological role of IR in both National Institutes of Health (NIH) and Rotterdam diagnosed PCOS in lean and overweight women.
  
  
  BACKGROUND
  PCOS is a complex endocrine condition with a significant increased risk of gestational diabetes and type 2 diabetes.
  
  
  METHODS
  Using a cross-sectional study design, 20 overweight and 20 lean PCOS (Rotterdam criteria), 14 overweight and 19 lean body mass index (BMI)-matched control non-PCOS women underwent clinical measures of IR after a 3-month withdrawal of insulin sensitizers and the oral contraceptive pill.
  
  
  METHODS
  In an academic clinic setting, glucose infusion rate (GIR) on euglycaemic-hyperinsulinaemic clamp was investigated as a marker of insulin sensitivity.
  
  
  RESULTS
  PCOS women were more IR than BMI-matched controls (main effect for BMI and PCOS; P < 0.001). IR was present in 75% of lean PCOS, 62% of overweight controls and 95% of overweight PCOS. Lean controls (mean ± SD; GIR 339 ± 76 mg min⁻¹ m⁻²) were less IR than lean PCOS (270 ± 66 mg min⁻¹ m⁻²), overweight controls (264 ± 66 mg min⁻¹ m⁻²) and overweight PCOS (175 ± 96 mg min⁻¹ m⁻²). The negative relationship between BMI and IR reflected by GIR was more marked in PCOS (y = 445.1 - 7.7x, R² = 0.42 (P < 0.0001) than controls (y = 435.5 - 4.6x, R² = 0.04 (P < 0.01)).
  
  
  CONCLUSIONS
  The study did not use glucose tracer techniques to completely characterize the IR, as well as the lack of matching for body composition and age.
  
  
  CONCLUSIONS
  IR is exacerbated by increased BMI, supporting intrinsic IR in PCOS. BMI impact on IR is greater in PCOS, than in controls, irrespective of visceral fat, prioritizing lifestyle intervention and the need for effective therapeutic interventions to address intrinsic IR and prevent diabetes in this high-risk population.
  
  
  BACKGROUND
  This investigator-initiated trial was supported by grants from the National Health & Medical Research Council (NHMRC) Grant number 606553 (H.J.T., N.K.S. and S.K.H.) as well as Monash University and The Jean Hailes Foundation. H.J.T. is an NHMRC Research Fellow. N.K.S. is supported through the Australian Government's Collaborative Research Networks (CRN) programme. A.E.J. is a Jean Hailes and NHMRC scholarship holder. The authors declare that there is no conflict of interest associated with this manuscript.
authors: School of Sport and Exercise Science,  Victoria University, Melbourne,  Australia.
authors: Nigel K
authors: NK
authors: Stepto
authors: Samantha
authors: S
authors: Cassar
authors: Anju E
authors: AE
authors: Joham
authors: Samantha K
authors: SK
authors: Hutchison
authors: Cheryce L
authors: CL
authors: Harrison
authors: Rebecca F
authors: RF
authors: Goldstein
authors: Helena J
authors: HJ
authors: Teede
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D015992:Body Mass Index; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005498:Follicular Phase; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance; D009765:Obesity / Q000150:complications*; D010044:Outpatient Clinics, Hospital; D050177:Overweight / Q000150:complications*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D017410:Practice Guidelines as Topic; D011236:Prediabetic State / Q000453:epidemiology / Q000209:etiology*; D015995:Prevalence; D014739:Victoria / Q000453:epidemiology; D055815:Young Adult