Our overall aim is to investigate the effects of dietary fatty acid composition on glucose homeostasis in women with polycystic ovary syndrome (PCOS). This common disease affects one out of sixteen women and causes insulin resistance and increases the risk for diabetes. Treatment of insulin resistance, and consequent hyperinsulinemia, improves ovarian function and increases fertility. Since epidemiological and experimental studies indicate that replacement of the dietary saturated fats with unsaturated fats improves insulin sensitivity, these women are advised to increase polyunsaturated fat (PUFA) intake from nuts, seeds and fish-oil. This advice is not evidence based. ? ? We recently investigated the effects of a PUFA-rich nut, walnuts, on glucose homeostasis in an insulin in PCOS patients. Unexpectedly, walnut-intake increased plasma glucose both at fasting and during oral glucose tolerance test. The clinical consequence of this finding depends upon the underlying mechanism: If the rise in blood glucose is due to an impairment in pancreatic function, this can potentially accelerate development of diabetes. On the other hand, if it is due to re-setting of the pancreatic glucose-sensor to a higher threshold, this can benefit PCOS patients by reducing ? hyperinsulinemia. Based on our initial observations, we anticipate that the latter mechanism may be valid. ? ? The hypotheses of this revised proposal are: ? 1. PUFA-rich walnuts, but not MUFA-rich almonds, alter glucose homeostasis in PCOS patients. ? 2. The PUFA-rich oil component of the walnuts is responsible for the changes in glucose homeostasis. ? 3. Effects of walnut-oil on glucose homeostasis differ from those of the fish-oils. ? ? This hypothesis will be tested in 96 women with PCOS. After an initial habitual-diet control phase, patients will be randomized to consume almonds, walnuts, walnut-oil or fish-oil in a parallel-design intervention. Changes in glucose homeostasis will be investigated. ? ? This pilot study will identify the favorable as well as unfavorable effects of different PUFA-rich foods and determine the most beneficial intervention to be tested in future clinical trials. The proposed research will make important contributions by testing cost-effective nutrition interventions in forestalling the development of diabetes, cardiovascular disease risk, and infertility in young women--an understudied population. ? ?
