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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK049654-01A2
Application #
2016969
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Harris, Maureen I
Project Start
1997-06-20
Project End
2001-04-30
Budget Start
1997-06-20
Budget End
1998-04-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Frohnert, Brigitte I; Laimighofer, Michael; Krumsiek, Jan et al. (2018) Prediction of type 1 diabetes using a genetic risk model in the Diabetes Autoimmunity Study in the Young. Pediatr Diabetes 19:277-283
Lamb, Molly M; Frederiksen, Brittni; Seifert, Jennifer A et al. (2015) Sugar intake is associated with progression from islet autoimmunity to type 1 diabetes: the Diabetes Autoimmunity Study in the Young. Diabetologia 58:2027-34
Rønningen, Kjersti S; Norris, Jill M; Knip, Mikael (2015) Environmental Trigger(s) of Type 1 Diabetes: Why Is It So Difficult to Identify? Biomed Res Int 2015:847906
Lamb, Molly M; Miller, Melissa; Seifert, Jennifer A et al. (2015) The effect of childhood cow's milk intake and HLA-DR genotype on risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young. Pediatr Diabetes 16:31-8
Frederiksen, Brittni N; Kroehl, Miranda; BarĂ³n, Anna et al. (2015) Assessing age-related etiologic heterogeneity in the onset of islet autoimmunity. Biomed Res Int 2015:708289
Frederiksen, Brittni N; Seifert, Jennifer; Kroehl, Miranda et al. (2015) Timing of solid food introduction is associated with urinary F2-isoprostane concentrations in childhood. Pediatr Res 78:451-6
Hall, Katelyn; Frederiksen, Brittni; Rewers, Marian et al. (2015) Daycare attendance, breastfeeding, and the development of type 1 diabetes: the diabetes autoimmunity study in the young. Biomed Res Int 2015:203947
Norris, Jill M; Kroehl, Miranda; Fingerlin, Tasha E et al. (2014) Erythrocyte membrane docosapentaenoic acid levels are associated with islet autoimmunity: the Diabetes Autoimmunity Study in the Young. Diabetologia 57:295-304
Frederiksen, Brittni N; Steck, Andrea K; Kroehl, Miranda et al. (2013) Evidence of stage- and age-related heterogeneity of non-HLA SNPs and risk of islet autoimmunity and type 1 diabetes: the diabetes autoimmunity study in the young. Clin Dev Immunol 2013:417657
Lamb, Molly M; Simpson, Melissa D; Seifert, Jennifer et al. (2013) The association between IgG4 antibodies to dietary factors, islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young. PLoS One 8:e57936

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