TEDDY - The Environmental Determinants of Diabetes in the Young

Epidemiologic patterns suggest that viruses, nutrition, toxic agents or socioeconomic
psychosocial factors may contribute to the etiology alone or in combination. Elucidation is
confounded by the long interval between exposure and onset of clinical disease, as well as
the interaction of multiple genes and/or insults, which appear to interact in a complex
manner. Numerous studies have investigated environmental influences but have yielded
conflicting results. This may be in part due to the failure to account for genetic
susceptibility, begin observation at early ages or in utero, and/or monitor subjects long
term and frequently.

Hypotheses:

1. Initiation of persistent beta-cell autoimmunity and progression from beta-cell
autoimmunity to diabetes is increased with:

1. Exposure to a trigger factor during pregnancy, such as infections, preeclampsia,
blood incompatibility, or birth weight.

2. Differences in the timing of the introduction and/or the type of dietary
constituents that include exposure to cereals or gluten, exposure to cow's milk
during infancy and/or childhood, and short duration of breast- feeding;

3. Lower intake of serum 25 hydroxyvitamin D in early infancy, vitamin E,
anti-oxidants (e.g., carotenoids, ascorbic acid, selenium, or omega-3 fatty acids);

4. Higher frequency of specific (e.g., enterovirus, rotavirus, or bacterial)
infections, or non-specific childhood infections including those that exhibit
molecular mimicry;

5. Increased exposure to routine childhood immunizations and their timing;

6. Environmental factors that may be contained in drinking water (e.g., low
concentrations of zinc or high concentrations of nitrates, or lower pH levels);

7. Exposure to household pets, and various allergies;

8. Excessive weight gain;

9. Increased psychological stress.

2. The risk of persistent beta-cell autoimmunity is lower in children from the general
population than in offspring or siblings of T1DM patients when stratifying for the HLA
DR-DQ genotype and exposure to environmental triggers.

3. The interaction of HLA DR-DQ genotype with exposure to dietary or infectious factors
leads to increased incidence of beta-cell autoimmunity and T1DM.

4. We expect that in some families study participation will be associated with affective
(anxiety, depression) and behavioral responses (e.g. actions to prevent possible T1DM).

Inclusion Criteria:

- Newborns with high risk HLA in the general population or having a first- degree
relative affected with T1DM

- Newborns are less than 4 months of age

Exclusion Criteria:

- Have an illness or birth defect that precludes long-term follow-up or involves use of
treatment that may alter the natural history of diabetes (e.g. steroids or insulin)

- Refuses to have blood and stool samples stored at the NIDDK Repository