Year: 2018
Type: article
Study design: Observational Study
Abstract: 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. 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). Eighty-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. All 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). Women 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. Clinical Trials.gov, NCT01482286 . Registered 30 November 2011.
Source: Nutrition & Metabolism
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,590
Funders: University of Virginia, Louisiana Clinical and Translational Science Center, National Institutes of Health, Nutrition Obesity Research Center, University of North Carolina, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G305254594, G3667826151, G3892861298, G4022818887, G4370236196, G4465362182, G5593137216, G5850863802, Effects of weight and insulin sensitivity on reproductive function in PCOS, Role of FGF21 in Protein Leverage and Placenta Function during Pregnancy, G738160294, Clinical and Basic Studies in Polycystic Ovarian Syndrome, G8477750575, G9000252454, G9000311072, Louisiana Clinical and Translational Science Center, Pennington/Louisiana NORC
OpenAlex ID: W2896817059