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Metabolic inflexibility is a feature of women with polycystic ovary syndrome and is associated with both insulin resistance and hyperandrogenism

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Abstract
Context: 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. Design and Patients: 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. Setting: Outpatients were seen in a tertiary care academic center. Main Outcome Measure: 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.
Keywords
MITOCHONDRIAL DYSFUNCTION, HUMAN SKELETAL-MUSCLE, FREE TESTOSTERONE, FLEXIBILITY, SENSITIVITY, GLUCOSE, MECHANISMS, CRITERIA, OBESITY, HUMANS

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Chicago
Di Sarra, Daniela, Flavia Tosi, Cecilia Bonin, Tom Fiers, Jean Kaufman, Chiara Signori, Francesca Zambotti, et al. 2013. “Metabolic Inflexibility Is a Feature of Women with Polycystic Ovary Syndrome and Is Associated with Both Insulin Resistance and Hyperandrogenism.” Journal of Clinical Endocrinology & Metabolism 98 (6): 2581–2588.
APA
Di Sarra, D., Tosi, F., Bonin, C., Fiers, T., Kaufman, J., Signori, C., Zambotti, F., et al. (2013). Metabolic inflexibility is a feature of women with polycystic ovary syndrome and is associated with both insulin resistance and hyperandrogenism. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 98(6), 2581–2588.
Vancouver
1.
Di Sarra D, Tosi F, Bonin C, Fiers T, Kaufman J, Signori C, et al. Metabolic inflexibility is a feature of women with polycystic ovary syndrome and is associated with both insulin resistance and hyperandrogenism. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM. 2013;98(6):2581–8.
MLA
Di Sarra, Daniela, Flavia Tosi, Cecilia Bonin, et al. “Metabolic Inflexibility Is a Feature of Women with Polycystic Ovary Syndrome and Is Associated with Both Insulin Resistance and Hyperandrogenism.” JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 98.6 (2013): 2581–2588. Print.
@article{4121756,
  abstract     = {Context: 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.
Design and Patients: 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. Setting: Outpatients were seen in a tertiary care academic center.
Main Outcome Measure: 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 {\textlangle} .001) and lower glucose utilization during the clamp (9.2 +/- 0.4 vs 10.9 +/- 0.7 mg/kg fat-free mass . min, P {\textlangle} .023) and metabolic flexibility (0.09 +/- 0.06 vs 0.12 +/- 0.01, P {\textlangle} .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 {\textlangle} .001).
Conclusions: Metabolic inflexibility is a feature of PCOS women. Both insulin resistance and androgen excess might contribute to this abnormality.},
  author       = {Di Sarra, Daniela and Tosi, Flavia and Bonin, Cecilia and Fiers, Tom and Kaufman, Jean and Signori, Chiara and Zambotti, Francesca and Dall'Alda, Marlene and Caruso, Beatrice and Zanolin, Maria Elisabetta and Bonora, Enzo and Moghetti, Paolo},
  issn         = {0021-972X},
  journal      = {JOURNAL OF CLINICAL ENDOCRINOLOGY \& METABOLISM},
  keyword      = {MITOCHONDRIAL DYSFUNCTION,HUMAN SKELETAL-MUSCLE,FREE TESTOSTERONE,FLEXIBILITY,SENSITIVITY,GLUCOSE,MECHANISMS,CRITERIA,OBESITY,HUMANS},
  language     = {eng},
  number       = {6},
  pages        = {2581--2588},
  title        = {Metabolic inflexibility is a feature of women with polycystic ovary syndrome and is associated with both insulin resistance and hyperandrogenism},
  url          = {http://dx.doi.org/10.1210/jc.2013-1161},
  volume       = {98},
  year         = {2013},
}

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