Abstract
BackgroundAn ability to switch between primarily oxidizing fat in the fasted state to carbohydrate in the fed state, termed metabolic flexibility, is associated with insulin sensitivity. Metabolic flexibility has been explored previously in women with polycystic ovary syndrome (PCOS), yet the independent or synergistic contributions of androgen excess and/or insulin resistance is not yet known. Therefore, the purpose of this article was to characterize metabolic flexibility in women with PCOS compared to women of normal BMI, obesity, or type 2 diabetes (T2DM).MethodsEighty-six weight-stable women; thirty with either PCOS (n = 30), or fifty-six with obesity (n = 12), T2DM (n = 27), or normal BMI (n = 17) underwent a hyperinsulinemic euglycemic clamp and indirect calorimetry to measure insulin sensitivity and substrate oxidation via indirect calorimetry, respectively.ResultsAll analyses were adjusted for differences in age, ethnicity, and BMI between groups. Women with PCOS were less metabolically flexible compared to healthy women with obesity (p < 0.0001), normal BMI (p < 0.0001), but after controlling for glucose disposal rate, were similar to women with T2DM (p = 0.99). When dividing women with PCOS above and below the mean cutoff for insulin resistance, the insulin resistant women with PCOS had lower rates of non-oxidative glucose metabolism (p = 0.0001), higher levels of percent free testosterone (p = 0.04), a higher free androgen index (p = 0.006), more visceral adipose tissue (p = 0.02), and were less metabolically flexible (p = 0.007).ConclusionsWomen with T2DM were as metabolically inflexible as women with PCOS. When stratifying women with PCOS into those who are metabolically flexible and inflexible, the women who are inflexible display greater amounts of visceral fat and androgen excess. The inability to alter substrate use given the physiological stimulus may lead to subsequent increases in adiposity in women with PCOS thereby further worsening the insulin resistance.Trial registration numberClinical Trials.gov, NCT01482286. Registered 30 November 2011.
Highlights
An ability to switch between primarily oxidizing fat in the fasted state to carbohydrate in the fed state, termed metabolic flexibility, is associated with insulin sensitivity
We hypothesized that metabolic flexibility in women with polycystic ovary syndrome (PCOS) will be attenuated in comparison to women with a normal BMI and women with obesity with normal menstrual cycles, and, given that androgen excess is unique to PCOS, metabolic flexibility will be more blunted than for women with type 2 diabetes mellitus (T2DM)
Insulin sensitivity (GDR) normalized for fat-free mass was not different between women with PCOS and obesity (p = 0.25) whereas it was significantly lower in women with T2DM (p < .0001) but highest in women with normal BMI as compared to the other three groups (p < 0.0001)
Summary
An ability to switch between primarily oxidizing fat in the fasted state to carbohydrate in the fed state, termed metabolic flexibility, is associated with insulin sensitivity. In comparison to women with normal menstrual cycles, women with PCOS have been shown to have a similar degree of metabolic flexibility [11] or to be less metabolically flexible [12] Neither of these two reports are compelling because the underlying pathology of insulin resistance between women with PCOS and controls matched for age, adiposity (BMI), and varying degrees of insulin sensitivity is likely different. No studies have attempted to disentangle the role of the disordered, metabolic and hormonal phenotype of PCOS with metabolic flexibility The purpose of this cross-sectional study was to assess metabolic flexibility in women with PCOS in comparison to women with regular menstrual cycles and normal BMI, obesity, or T2DM. We hypothesized that metabolic flexibility in women with PCOS will be attenuated in comparison to women with a normal BMI and women with obesity with normal menstrual cycles, and, given that androgen excess is unique to PCOS, metabolic flexibility will be more blunted than for women with T2DM
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