title: Metabolic inflexibility is a feature of women with polycystic ovary syndrome and is associated with both insulin resistance and hyperandrogenism.
abstract: BACKGROUND
  Metabolic inflexibility, ie, the impaired ability of the body to switch from fat to carbohydrate oxidation under insulin-stimulated conditions, is associated with insulin resistance. This alteration in metabolic plasticity can lead to organ dysfunction and is considered a key issue among the abnormalities of the metabolic syndrome. It is still unknown whether this phenomenon occurs in women with polycystic ovary syndrome (PCOS).
  
  
  OBJECTIVE
  Our objective was to examine whether metabolic inflexibility is a feature of PCOS women and whether hyperandrogenism may contribute to this phenomenon.
  
  
  METHODS
  Eighty-nine Caucasian women with PCOS were submitted to hyperinsulinemic-euglycemic clamp. Respiratory exchange ratios were evaluated at baseline and during hyperinsulinemia by indirect calorimetry to quantify substrate oxidative metabolism. Total testosterone was measured by liquid chromatography mass spectrometry and free testosterone by equilibrium dialysis.
  
  
  METHODS
  Outpatients were seen in a tertiary care academic center.
  
  
  METHODS
  Metabolic flexibility was assessed by the change in respiratory quotient upon insulin stimulation.
  
  
  RESULTS
  Sixty-five of the 89 PCOS women (73%) had increased serum free testosterone, 68 (76%) were insulin resistant, and 62 (70%) had an impaired metabolic flexibility. Comparison of hyperandrogenemic and normoandrogenemic women showed that the 2 subgroups were of similar age but differed in terms of several anthropometric and metabolic features. In particular, hyperandrogenemic women had greater body mass index (32.9 ± 1.0 vs 24.7 ± 0.9 kg/m(2), P < .001) and lower glucose utilization during the clamp (9.2 ± 0.4 vs 10.9 ± 0.7 mg/kg fat-free mass · min, P = .023) and metabolic flexibility (0.09 ± 0.06 vs 0.12 ± 0.01, P = .014). In univariate analysis, metabolic flexibility was associated with several anthropometric, endocrine, and metabolic features. In multivariate analysis, this feature was directly associated with baseline respiratory quotient and insulin sensitivity and inversely with free testosterone and free fatty acids concentrations under insulin suppression (R(2) = 0.634, P < .001).
  
  
  CONCLUSIONS
  Metabolic inflexibility is a feature of PCOS women. Both insulin resistance and androgen excess might contribute to this abnormality.
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, I-37126 Verona, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Di Sarra
authors.forename: Flavia
authors.initials: F
authors.lastname: Tosi
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bonin
authors.forename: Tom
authors.initials: T
authors.lastname: Fiers
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Kaufman
authors.forename: Chiara
authors.initials: C
authors.lastname: Signori
authors.forename: Francesca
authors.initials: F
authors.lastname: Zambotti
authors.forename: Marlene
authors.initials: M
authors.lastname: Dall'Alda
authors.forename: Beatrice
authors.initials: B
authors.lastname: Caruso
authors.forename: Maria Elisabetta
authors.initials: ME
authors.lastname: Zanolin
authors.forename: Enzo
authors.initials: E
authors.lastname: Bonora
authors.forename: Paolo
authors.initials: P
authors.lastname: Moghetti
mesh_terms: D000328:Adult; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D017588:Hyperandrogenism / Q000150:complications*; D007333:Insulin Resistance; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
chemical_list: D005230:Fatty Acids, Nonesterified; D013739:Testosterone