Nutritional Etiology of Pre-Diabetic Autoimmunity

描述(申请人提供)：为了检查营养状况 糖尿病相关自身免疫和1型糖尿病的病因学，两个独特的 成群结队的儿童已经聚集在一起。第一个是出生队列中的 已知有患糖尿病风险的儿童，因为他们已被分型为 通过脐血筛查21,602名普通人群中糖尿病相关的人类白细胞抗原基因分型 人口中的孩子或2)他们是某种类型的人的兄弟姐妹或后代 糖尿病1例。这一群体从出生起就被遵循，以发展 糖尿病相关的自身免疫性疾病。第二个队列是测试过的儿童 至少有一种糖尿病自身抗体阳性，并随着时间的推移进行了跟踪， 确定转化为糖尿病、维持自身免疫力或 自身免疫力的缓解。到目前为止，这些的短期前瞻性后续行动 已经提供了新的重要信息，关于 维生素、抗氧化剂和氧化应激在1型糖尿病病因中的作用 糖尿病，以及数据表明脂肪酸的作用。在这 竞争性续签申请，这些队列将被跟踪五年 为了实现以下具体目标： 1.继续跟踪IDDM高危儿童从出生到11岁 多年，前瞻性地测量糖尿病相关自身抗体，饮食摄入量 抗氧化剂，硝酸盐；要完成，以足够的力量，已经 启动了研究抗氧化剂饮食摄入量的作用的队列研究， 硝酸盐和脂肪酸有引发β细胞自身免疫的风险。此外, 使用上述队列和数据，我们建议检查n-3的作用 和n-6多不饱和脂肪酸(PUFA)摄入对β细胞风险的影响 自身免疫力。 2.以足够的力量完成已经启动的病例队列研究 检查血浆和尿液中抗氧化剂和维生素的作用，以及 F2-异前列腺素(氧化应激的标志)与β细胞的风险 自身免疫力。此外，使用储存的样本和在此期间收集的样本 更新后，我们建议使用上述病例队列研究设计来 检测红细胞膜脂肪酸和血浆前列腺素的作用 有患上β细胞自身免疫的风险。 3.继续关注已形成β细胞自身免疫的儿童 (也就是自身免疫队列)用于饮食摄入量、血浆和尿液的测量 抗氧化剂，F2-异前列腺素；要完成，以足够的功率，已经 启动的队列研究将这些作为贝塔病毒缓解的预测因素 细胞自身免疫。此外，我们建议研究n-3和n-6的作用 多不饱和脂肪酸、前列腺素、红细胞膜脂肪酸和前列腺素 合酶2(PGS2)在β细胞自身免疫缓解中的表达

DESCRIPTION (provided by applicant): In order to examine the nutritional etiology of diabetes-related autoimmunity and type 1 diabetes, two unique cohorts of children have been assembled. The first is a birth cohort of children who have a known risk for diabetes because they 1) had been typed for diabetes related HLA genotypes through a cord blood screening of 21,602 general population children or 2) they are a sibling or offspring of someone with type 1 diabetes. This cohort is followed from birth for the development of diabetes-related autoimmunity. The second cohort is of children who have tested positive for at least one diabetes autoantibody and who are followed over time, to determine reasons for conversion to diabetes, maintenance of autoimmunity or remission of autoimmunity. To date, a short prospective follow-up of these cohorts has already provided new important information concerning the role of vitamins, anti-oxidants and oxidative stress in the etiology of type 1 diabetes, as well as data suggesting a role for fatty acids. In this competitive renewal application, these cohorts will be followed for five years in order to address the following specific aims: 1. To continue to follow the children at risk for IDDM from birth to age 11 years, prospectively measuring diabetes-related autoantibodies, dietary intake of anti-oxidants, nitrates; and to complete, with sufficient power, already initiated cohort studies examining the role of dietary intake of anti-oxidants, nitrates and fatty acids in the risk of beta cell autoimmunity. In addition, using the aforementioned cohort and data, we propose to examine the role of n-3 and n-6 polyunsaturated fatty acids (PUFA) intake on the risk of beta cell autoimmunity. 2. To complete, with sufficient power, already initiated case-cohort studies examining the role of plasma and urine antioxidants and vitamins, and F2-isoprostanes (a marker of oxidative stress) in risk of beta-cell autoimmunity. In addition, using stored samples and samples collected during the renewal, we propose to use the aforementioned case-cohort study design to examine the role of erythrocyte membrane fatty acids, and plasma prostaglandins in risk of beta-cell autoimmunity. 3. To continue to follow the children who have developed beta-cell autoimmunity (a.k.a. Autoimmune Cohort) for dietary intake, plasma and urine measures of anti-oxidants, F2-isoprostanes; and to complete, with sufficient power, already initiated cohort studies examining these as predictors of remission of beta cell autoimmunity. In addition, we propose to examine the role of n-3 and n-6 PUFA, prostaglandins, erythrocyte membrane fatty acids, and prostaglandin synthase 2 (PGS2 ) expression in the remission of beta cell autoimmunity.