The Environmental Determinants of Diabetes in the Young (TEDDY) study was initiated in 2003 by six clinical centers in the United States and Europe, including ours, to identify infectious agents, dietary factors, or other environmental exposures that may trigger or protect against the development of islet autoimmunity and type 1 diabetes (T1D). Additional long-term scientific goals include assessment of potential gene-environment interactions affecting development of islet autoimmunity or T1D, gaining insight on triggering mechanisms through detailed multi-omics analyses, and sharing collected specimens with broader scientific community for studies of T1D pathogenesis and prevention. A total of 424,788 newborns were screened by HLA-DR,DQ genotyping to identify children at increased risk for T1D and 8,677 enrolled for quarterly follow-up until age 4 and semi-annually thereafter until age 15. Now, 13 years after enrollment began, 5731 (66%) remain actively engaged in the protocol. Our Georgia/Florida Clinical Center enrolled 966 TEDDY participants. As of 2/28/18, 62 of those have developed persistent confirmed islet autoantibodies and 24 have been diagnosed with T1D. Detailed analyses of biological samples from the entire cohort, along with even more comprehensive multi- omics analyses in selected individuals, will provide a rich dataset to complement the intensive collection of exposure data and highly efficient ascertainment of islet autoimmunity and T1D endpoints in the entire cohort.
Specific aims of this renewal application for this multi-center, prospective cohort study for the next 5 years are: 1. Follow the TEDDY cohort of high-risk children for development of islet autoimmunity, diabetes, celiac disease and autoimmune thyroid disease until 15 years of age; collect biological specimens and epidemiological data according to the study protocol. 2. Characterize genetic, epigenetic, transcriptomic, proteomic and metabolomic determinants of islet autoimmunity and T1D in the study participants. 3. Prospectively assess infectious, dietary and other environmental exposures of study participants as triggers of islet autoimmunity, promotors of progression to T1D, or both. A successful study outcome will provide a dataset unprecedented in depth and breadth, to help elucidate specific exposures and mechanisms serving in the etiology and pathogenesis of islet autoimmunity, T1D, and closely related autoimmune diseases. The results will support the development of new strategies to prevent, delay, or reverse the disease.

Public Health Relevance

The Environmental Determinants of Diabetes in the Young (TEDDY) Study is designed to intensively study high-risk children from infancy to 15 years of age, at six clinical centers across four countries (Finland, Sweden, Germany, and the USA in Georgia/Florida, Colorado, and Washington). The primary objective of this multi-center, prospective cohort study initiated in 2003 is the identification of infections agents, dietary factors, or other environmental exposures that trigger or protect against the development of islet autoimmunity and type 1 diabetes (T1D), including information on pathophysiological mechanisms. The knowledge gained will provide a solid foundation for the development of new strategies to prevent, delay, or reverse type 1 diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK063865-14
Application #
10016249
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Castle, Arthur
Project Start
2003-03-01
Project End
2023-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
14
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Augusta University
Department
Pathology
Type
Schools of Medicine
DUNS #
City
Augusta
State
GA
Country
United States
Zip Code
30912
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Stewart, Christopher J; Ajami, Nadim J; O'Brien, Jacqueline L et al. (2018) Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature 562:583-588
Sharma, Ashok; Liu, Xiang; Hadley, David et al. (2018) Identification of non-HLA genes associated with development of islet autoimmunity and type 1 diabetes in the prospective TEDDY cohort. J Autoimmun 89:90-100
Silvis, Katherine; Aronsson, Carin A; Liu, Xiang et al. (2018) Maternal dietary supplement use and development of islet autoimmunity in the offspring: TEDDY study. Pediatr Diabetes :
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Salami, Falastin; Lee, Hye-Seung; Freyhult, Eva et al. (2018) Reduction in White Blood Cell, Neutrophil, and Red Blood Cell Counts Related to Sex, HLA, and Islet Autoantibodies in Swedish TEDDY Children at Increased Risk for Type 1 Diabetes. Diabetes 67:2329-2336
Smith, Laura B; Liu, Xiang; Johnson, Suzanne Bennett et al. (2018) Family adjustment to diabetes diagnosis in children: Can participation in a study on type 1 diabetes genetic risk be helpful? Pediatr Diabetes 19:1025-1033
Uusitalo, Ulla; Lee, Hye-Seung; Andrén Aronsson, Carin et al. (2018) Early Infant Diet and Islet Autoimmunity in the TEDDY Study. Diabetes Care 41:522-530
Pitchika, Anitha; Vehik, Kendra; Hummel, Sandra et al. (2018) Associations of Maternal Diabetes During Pregnancy with Overweight in Offspring: Results from the Prospective TEDDY Study. Obesity (Silver Spring) 26:1457-1466

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