Metabolic Inflexibility Is a Feature of Women With Polycystic Ovary Syndrome and Is Associated With Both Insulin Resistance and Hyperandrogenism

Author:

Di Sarra Daniela1,Tosi Flavia1,Bonin Cecilia2,Fiers Tom3,Kaufman Jean-Marc34,Signori Chiara2,Zambotti Francesca1,Dall'Alda Marlene1,Caruso Beatrice5,Zanolin Maria Elisabetta6,Bonora Enzo1,Moghetti Paolo1

Affiliation:

1. Departments of Endocrinology, Diabetes and Metabolism (D.D.S., F.T., F.Z., M.D., E.B., P.M.), I-37126 Verona, Italy

2. Obstetrics and Gynecology (C.B., C.S.), I-37126 Verona, Italy

3. Laboratory for Hormonology (T.F., J.-M.K.), B-9000 Ghent, Belgium

4. Department of Endocrinology (J.-M.K.), Ghent University Hospital, B-9000 Ghent, Belgium

5. Laboratory of Clinical Chemistry (B.C.), University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, I-37126 Verona, Italy

6. Department of Public Health and Community Medicine (M.E.Z.), University of Verona, I-37131 Verona, Italy

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/m2, 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 (R2 = 0.634, P < .001). Conclusions: Metabolic inflexibility is a feature of PCOS women. Both insulin resistance and androgen excess might contribute to this abnormality.

Publisher

The Endocrine Society

Subject

Biochemistry, medical,Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

Reference35 articles.

1. Fuel selection in human skeletal muscle in insulin resistance: a reexamination;Kelley;Diabetes,2000

2. The theoretical bases of indirect calorimetry: a review;Ferrannini;Metabolism,1988

3. Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss;Kelley;Am J Physiol,1999

4. Family history of diabetes links impaired substrate switching and reduced mitochondrial content in skeletal muscle;Ukropcova;Diabetes,2007

5. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications;Diamanti-Kandarakis;Endocr Rev,2012

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