Prevention of Post-Prandial Hypoglycemia Using n-3/n-6 PUFA in PCOS

描述（由申请人提供）：本提案是对PAR-04-087（GCRC补充和替代医学研究计划）的回应，并利用了加州大学戴维斯分校GCRC的资源。目的是确定必需和/或长链ω（n）-3多不饱和脂肪酸（PUFA）是否可以预防多囊卵巢综合征（PCOS）的餐后低血糖及其不利的内分泌后果。PCOS影响1/16的女性，并表现为胰岛素抵抗、高胰岛素血症、雄激素过多、多毛症、不孕症，并且通常伴有肥胖。治疗胰岛素抵抗和肥胖可改善卵巢功能和不孕症。我们证明PCOS患者经常发生餐后低血糖，这反过来又刺激皮质醇和肾上腺雄激素的分泌。由于这些激素促进向心性肥胖、胰岛素抵抗和可能的多毛症，因此预防餐后低血糖是非常有益的。我们以前的研究表明，n-3多不饱和脂肪酸补充剂可能有助于预防PCOS患者的餐后低血糖。假设是：在患有PCOS的女性中，必需和长链n-3 PUFA都可以预防餐后低血糖，但可能是通过不同的机制：鱼油中的长链n-3 PUFA减少胰岛素分泌，而亚麻籽油中的必需n-3 PUFA将胰腺葡萄糖传感器重新设置为更高的阈值。将采用随机、双盲、安慰剂对照、平行设计的干预方法，在90名PCOS女性患者中检验这一假设，干预分为两个阶段：I.导入期（4周）和II.干预（6周）。在导入期，所有受试者将接受安慰剂。在干预期间，参与者将被随机分配到3个治疗组：安慰剂、鱼油或亚麻籽油。将研究血糖、胰岛素敏感性、胰岛素分泌、胰腺储备和低血糖症状的变化。我们预期n-3 PUFA将预防低血糖，从而预防皮质醇和肾上腺雄激素的分泌。这项R21提案将确定在未来的大型临床试验中测试的最佳n-3 PUFA补充剂，以减少肥胖，中心性肥胖，胰岛素抵抗，多毛症以及患有PCOS的年轻女性患糖尿病和不孕症的风险-这是一个研究不足的人群。多囊卵巢综合征（PCOS）是一种常见的疾病，每16名女性中就有1名受到影响。在美国有近700万PCOS患者。这种疾病会导致不育、面部毛发生长，并增加肥胖、糖尿病和心脏病的风险。我们发现PCOS患者经常发生低血糖（低血糖）。反过来，低血糖会导致对糖的渴望和暴饮暴食，并增加导致肥胖和糖尿病的激素分泌。避免低血糖可以保护这些患者免于增加额外的体重和成为糖尿病患者。我们认为我们可以通过使用鱼油和/或亚麻籽油补充剂来实现这一目标。我们还不知道哪一种补品是更好的选择。我们的目的是确定最好的补充剂，可以防止低血糖症及其不良后果，在这些年轻妇女-一个研究不足的患者群体。

DESCRIPTION (provided by applicant): This proposal is in response to the PAR-04-087 (The GCRC Complementary and Alternative Medicine Research Program) and utilizes the resources of the UC Davis GCRC. The aim is to determine whether the essential and/or the long-chain omega (n)-3 polyunsaturated fatty acids (PUFAs) can prevent postprandial hypoglycemia and its unfavorable endocrine consequences in polycystic ovary syndrome (PCOS). PCOS affects 1 in 16 women and manifests with insulin resistance, hyperinsulinemia, androgen excess, hirsutism, infertility, and commonly with obesity. Treatment of insulin resistance and obesity improves ovarian function and infertility. We demonstrated that PCOS patients frequently develop postprandial hypoglycemia, which in turn stimulates secretion of cortisol and adrenal androgens. Since these hormones promote central obesity, insulin resistance and possibly hirsutism, prevention of postprandial hypoglycemia can be very beneficial. Our previous research suggests that n-3 PUFA supplementation may be useful in preventing postprandial hypoglycemia in PCOS. The hypothesis is: In women with PCOS, both the essential and the long-chain n-3 PUFAs can prevent postprandial hypoglycemia, but possibly through different mechanisms: The long-chain n-3 PUFAs from fish oil decrease insulin secretion, whereas the essential n-3 PUFA from flax seed oil re-sets the pancreatic glucose sensor to a higher threshold. This hypothesis will be tested in 90 women with PCOS using a randomized, double- blinded, placebo-controlled, parallel-design intervention that has two phases: I. Lead-in (4 weeks) and II. Intervention (6 weeks). During the lead-in period all participants will receive a placebo. During the intervention, the participants will be randomized to 3 treatment arms: placebo, fish oil or flax seed oil. Changes in blood glucose, insulin sensitivity, insulin secretion, pancreatic reserve and hypoglycemic symptoms will be investigated. We anticipate that n-3 PUFAs will prevent hypoglycemia, and thus secretion of cortisol and adrenal androgens. This R21 proposal will determine the best n-3 PUFA supplement to be tested in future large clinical trials in order to decrease obesity, central obesity, insulin resistance, hirsutism, and the risks for diabetes and infertility in young women with PCOS --an understudied population. Polycystic ovary syndrome (PCOS) is a common disease that affects 1 out of 16 women. There are almost 7 million PCOS patients in the USA. This disease causes infertility, facial hair growth, and increases the risk for obesity, diabetes and heart disease. We discovered that PCOS patients experience low blood sugars (hypoglycemia) frequently. In turn, hypoglycemia causes sugar craving and overeating, and increases secretion of the hormones that lead to obesity and diabetes. Avoiding hypoglycemia may protect these patients from gaining additional weight and becoming diabetic. We think we can achieve this goal by using fish oil and/or flax seed oil supplements. We do not know yet however which one of these supplements would be the better choice. Our aim is to identify the best supplement that can prevent hypoglycemia and its unwanted consequences in these young women-an under-studied patient population.