Insulin-Mediated Substrate Use in Women With Different Phenotypes of {PCOS}: the Role of Androgens

Context: Few studies have explored in vivo insulin action on substrate use in women with PCOS. In particular, no data are available in women with different PCOS phenotypes.Objective: The aim of the study was to evaluate insulin action on glucose (Gox) and lipid (Lox) oxidation, nonoxidative glucose metabolism (Gnonox), and serum free fatty acids (FFAs) in different PCOS phenotypes.Methods: Participants included 187 nondiabetic 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 use data were obtained by the hyperinsulinemic euglycemic clamp associated with indirect calorimetry. Serum androgens were assessed by liquid chromatography-mass spectrometry and equilibrium dialysis.Results: During hyperinsulinemia, the increase of Gox (Delta Gox), Gnonox, as well as the suppression of Lox (Delta Lox) and serum FFA (Delta% FFA) were altered in each PCOS phenotype. Moreover, Gnonox and Delta% FFA were lower in women with the classic phenotype than in those with the ovulatory or the normoandrogenic phenotypes, and Delta Gox was lower in women with the classic than in those with the ovulatory phenotype. In multivariable analysis fat mass and free testosterone were independent predictors of Delta Gox, Gnonox, and Delta% FFA, whereas only fat mass predicted Delta Lox.Conclusion: In women with PCOS, regardless of phenotype, insulin-mediated substrate use is impaired. This phenomenon is greater in individuals with the classic phenotype. Free testosterone plays an independent role in insulin action abnormalities in glucose and lipid metabolism.