A unique cohort of newborns at increased risk of insulin-dependent diabetes mellitus (IDDM) has been assembled to study the natural history of beta-cell autoimmunity (a precursor to IDDM). The investigators state that further follow-up of this cohort is a perfect opportunity to investigate the impact of antioxidants on the appearance and remission of beta-cell autoimmunity in a cost-effective manner and greatly increase our knowledge regarding diet and IDDM risk in a population of infants and children at risk for IDDM. The proposed study has the following specific aims: (1) to collect complete dietary profiles of 567 children at risk for IDDM, from birth to age 7 years, prospectively measuring infant and early childhood exposures to antioxidants and nitrates; (2) in a case-cohort study, to measure levels of antioxidants in plasma collected prospectively since birth in children who develop beta-cell autoimmunity and in those who do not; and (3) in a case-cohort study, to measure markers of oxidative stress, such as F2-isoprostanes, in the plasma of children who develop beta-cell autoimmunity and in those who do not. The primary outcome, autoantibodies to specific beta-cell autoantigens, will be analyzed at the ages of 9 months, 15 months, and 2, 3, 4, 5, 6, and 7 years. The investigators will examine the role of dietary intake of antioxidants in the risk of beta-cell autoimmunity using the whole cohort of 567 individuals. They will also conduct a case-cohort study, in which plasma levels of ascorbic acid, alpha- and gamma-tocopherol, retinol and beta-carotene, and F2-isoprostanes (a marker of oxidative stress) are measured in a cohort of 230 subjects containing 55 cases of beta-cell autoimmunity and 175 non-autoimmune children. The subjects who develop autoimmunity will be followed with blood draws every 3-6 months to monitor the maintenance of autoimmunity, conversion to IDDM, or remission of autoimmunity. Children who do not develop autoimmunity will have annual blood draws. The primary research questions will focus on what components (or combination of components), dose or timing of antioxidant intake, plasma levels of antioxidants and oxidative stress are associated with the appearance and remission of beta-cell autoimmunity.
Showing the most recent 10 out of 39 publications
