Walnuts vs. Walnut-Oil, Glucose Homeostasis, PCOS

描述（由申请人提供）：我们的总体目标是研究饮食脂肪酸组成对多囊卵巢综合征（PCOS）妇女葡萄糖稳态的影响。这种常见的疾病影响十六分之一的妇女，并导致胰岛素抵抗和增加患糖尿病的风险。治疗胰岛素抵抗和随之而来的高胰岛素血症，可改善卵巢功能，提高生育能力。由于流行病学和实验研究表明，用不饱和脂肪替代膳食中的饱和脂肪可提高胰岛素敏感性，因此建议这些妇女增加坚果、种子和鱼油中的多不饱和脂肪（PUFA）摄入量。这个建议不是基于证据的。 我们最近研究了富含PUFA的坚果核桃对PCOS患者胰岛素中葡萄糖稳态的影响。出乎意料的是，核桃的摄入量增加了空腹和口服葡萄糖耐量试验期间的血糖。这一发现的临床结果取决于潜在的机制：如果血糖升高是由于胰腺功能受损，这可能会加速糖尿病的发展。另一方面，如果是由于胰腺葡萄糖传感器重新设置为更高的阈值，则这可以通过减少胰腺葡萄糖的浓度而使PCOS患者受益。 高胰岛素血症根据我们的初步观察，我们预计后一种机制可能是有效的。 这一订正提案的假设是： 1.富含PUFA的核桃，而不是富含MUFA的杏仁，改变了PCOS患者的葡萄糖稳态。 2.核桃中富含PUFA的油成分是葡萄糖稳态变化的原因。 3.核桃油对葡萄糖稳态的影响不同于鱼油。 这一假设将在96例PCOS患者中进行检验。在最初的习惯性饮食控制阶段之后，患者将被随机分配到平行设计干预中食用杏仁，核桃，核桃油或鱼油。将研究葡萄糖稳态的变化。 这项初步研究将确定不同富含PUFA的食物的有利和不利影响，并确定在未来的临床试验中测试的最有益的干预措施。拟议的研究将通过测试具有成本效益的营养干预措施来预防糖尿病，心血管疾病风险和年轻女性不孕症的发展做出重要贡献-这是一个研究不足的人群。

DESCRIPTION (provided by applicant): 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.