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.
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