Insulin-Mediated Substrate Utilization in Women with the Different Phenotypes of PCOS: Role of Androgens.

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Few studies have explored in vivo insulin action on substrate utilization in women with PCOS. In particular, no data are available in women with different PCOS phenotypes. The aim of the study was to evaluate insulin action on glucose (Gox) and lipid (Lox) oxidation, non-oxidative glucose metabolism (Gnonox), and serum free fatty acid (FFA) in different PCOS phenotypes.One hundred and eighty-seven non-diabetic women with PCOS, diagnosed according to the Rotterdam criteria. Data from a historical sample of 20 healthy women were used as reference values.Whole body substrate utilization data were obtained by the hyperinsulinemic euglycemic clamp associated with indirect calorimetry. Serum androgens were assessed by liquid chromatography-mass spectrometry and equilibrium dialysis.During hyperinsulinemia, the increase of Gox (Δ Gox), Gnonox, as well as the suppression of Lox (Δ Lox) and serum FFA (Δ% FFA) were altered in each PCOS phenotype. Moreover, Gnonox and Δ% FFA were lower in women with the classic phenotype than in those with the ovulatory or the normoandrogenic phenotypes, and Δ Gox was lower in women with the classic than in those with the ovulatory phenotype. In multivariate analysis fat mass and free testosterone were independent predictors of Δ Gox, Gnonox and Δ% FFA, whereas only fat mass predicted Δ Lox.In women with PCOS, regardless of their phenotypes, insulin-mediated substrate utilization is impaired. This phenomenon is greater in subjects with the classic phenotype. Free testosterone plays an independent role on insulin action abnormalities on glucose and lipid metabolism.


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Authors: Flavia Tosi, Michela Villani, Matteo Migazzi, Giulia Faccin, Sabrina Garofalo, Tom Fiers, Jean-Marc Kaufman, Enzo Bonora, Paolo Moghetti

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