Reduced Carbohydrate Diet Intervention for PCOS

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Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome affecting 5-10% of women of reproductive age. It is characterized by elevated circulating insulin, reduced insulin sensitivity, infertility, hyperandrogenism, and a multitude of symptoms that result in a decreased quality of life. The elevated insulin characteristic of PCOS is likely to play a major role in its pathogenesis by reducing insulin sensitivity and stimulating testosterone (T) production and increasing its free fraction. Although many women with PCOS are overweight/obese (10-50%), those who are non-obese suffer from the same symptoms as their obese counterparts. Thus, it is likely that the metabolic disturbances associated with PCOS predispose to weight gain, which in turn exacerbates PCOS by worsening insulin resistance. Manipulation of dietary glycemic load (GL) may lower insulin and improve both reproductive and metabolic outcomes. No study has tested the efficacy of a eucaloric (weight-maintenance) lower GL diet among non-obese women with PCOS. The Specific Aim of this proposal is to determine if a eucaloric, lower GL diet is more effective than a eucaloric, standard (STD) diet in improving reproductive and metabolic outcomes of non-obese women with PCOS. We hypothesize that, in the absence of weight change, the lower GL diet will be more effective in decreasing insulin secretion, increasing insulin sensitivity, decreasing ectopic adipose tissue, decreasing inflammation, and improving reproductive health. Further, the lower GL diet will increase satiety and decrease hunger, effects mediated via gut hormones. This project has been reduced in scope to accommodate the 2-yr funding period associated with the ARRA. It will focus on Specific Aim 1 (of 2 original aims) in non-obese women, and will lay the ground work for Specific Aim 2, which will be conducted in the renewal phase. Development of a diet that optimizes reproductive and metabolic health among women with PCOS will reduce reliance on pharmacologic treatments and improve quality of life, even in the absence of weight loss. This project is novel in being the first to conduct a highly controlled nutrition intervention in non-obese women with PCOS under weight stable conditions, utilizing robust measures of insulin sensitivity and β-cell function (mathematical modeling); fat distribution (CT scan for visceral fat, MRS for intramyocellular lipid); inflammation; satiety and the gut hormone profile (ghrelin, GLP-1); and the reproductive-endocrine axis. The results from this study can be used as a starting point from which to explore optimal diets for overweight women with PCOS. Principal Investigator/Program Director (Last, First, Middle): Gower, Barbara Ann PHS 398/2590 (Rev. 09/04) Page Continuation Format Page Diet intervention (8-week, cross-over design) Reduced-GL STD Carbohydrate:40% 55% Low GL menu items Moderate/high GL menu items Glycemic load differential: 31% (average over menu cycle) Protein: 30% 15% Fat: 30% (<10% 30% (<10% saturated fat) saturated fat)