The Environmental Determinants of Diabetes in the Young (TEDDY) study was initiated in 2004 by six clinical centers in the United States and Europe, and screened 424,732 newborns to enroll 8,669 children (2525 in Sweden) at increased HLA risk for type 1 diabetes (T1D). The primary objective of our multi-center, prospective cohort study in this renewal application is the identification of infectious agents, dietary factors, and other environmental exposures that may trigger or protect against the development of islet autoimmunity and T1D as well as celiac disease, a common co-morbidity to T1D. Enrolled infants are followed four times per year until age 4 and twice a year thereafter until age 15. In 2013, the youngest children will be 3 and the oldest 8 years of age. So far, 425 children (145 in Sweden) have developed persistent islet autoantibodies and 117 (30 in Sweden) have developed T1D.
The specific aims of this renewal application are to: 1) Follow the TEDDY cohort of 8,669 high-risk children for development of islet autoimmunity and diabetes and celiac disease for 5 more years;2) Collect all planned biological specimens and epidemiological data according to the standard TEDDY protocol with continued high retention and compliance and close monitoring of sample and data quality;3) Perform planned laboratory analyses at appropriate times using a nested case-control study design to answer specific scientific questions and hypotheses pertinent to the TEDDY study goals;4) Analyze and publish laboratory and epidemiological data in collaboration with the TEDDY Data Coordinating Center (funded by a separate UC4 contract), and 5) Guide the ongoing TEDDY project by participation of Sweden TEDDY clinic investigators and staff in the work of the study Steering Committee and sub-committees.
These aims are crucial to the long-term scientific goals to A) to identify environmental factors that trigger or protect against the development of defined islet autoantibodies (against insulin, GAD65, IA-2 as well as ZnT8) or clinical T1D;B) to assess potential gene-environment interactions affecting development of islet autoimmunity or T1D, and to gain insight on mechanisms;and C) to collect and bank specimens for studies of T1D pathogenesis and development of biomarkers for T1D prediction. A successful study outcome should allow better understanding of the etiology and pathogenesis of islet autoimmunity and T1D, thereby guiding development of new strategies to prevent, delay, or reverse the disease.

Public Health Relevance

Type 1 diabetes is the most common chronic disease among children and young adults. The disease is increasing worldwide and is posing an increasing problem for affected families and health care systems. The prevalence of type 1 diabetes in the individuals younger than 20 years of age has increased by 23%, from 2001 to 2009. The life-time risk now is greater than 1% both in North America and Europe. Thanks to research such as The Environmental Determinants of Diabetes in the Young (TEDDY) study surprising new knowledge is available. It has been known for years that the disease is autoimmune i.e. the child's own immune system is attacking the pancreatic islet cells that make insulin. What has been found is that autoantibodies against beta cells appear already at 1-3 years of age. This is called islet autoimmunity and without symptoms a child may have islet autoimmunity for months and rather years before diabetes is diagnosed. The first goal in TEDDY is to find triggers of islet autoimmunity. This first part of TEDDY is well underway since 425 children in TEDDY have islet autoimmunity. Advanced technologies will be used on the many samples that have been collected since 3 months of age to find why islet autoimmunity appeared in some but not all TEDDY children. The second part of TEDDY is to continue to follow children with islet autoimmunity to find factors that promote or protect the children from diabetes. This second part of TEDDY is also well underway as 119 children have been diagnosed with diabetes. TEDDY is already furthering our understanding on how environmental factors, including virus infections and diet, may affect islet autoimmunity. The aim of the TEDDY study is eventually to prevent type 1 diabetes that affects 1.5 million people in the U.S. and accounts for $15-20 billion in health care cost. Prevention of diabetes would eliminate the burden of illness and late complications that plaque the life of type 1 diabetes patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
High Impact Research and Research Infrastructure Cooperative Agreement Programs—Multi-Yr Funding (UC4)
Project #
2UC4DK063861-11
Application #
8510746
Study Section
Special Emphasis Panel (ZDK1-GRB-S (J2))
Program Officer
Spain, Lisa M
Project Start
2003-03-01
Project End
2018-05-31
Budget Start
2013-06-05
Budget End
2018-05-31
Support Year
11
Fiscal Year
2013
Total Cost
$5,729,698
Indirect Cost
$423,533
Name
Lund University
Department
Type
DUNS #
350582417
City
Lund
State
Country
Sweden
Zip Code
SE-22-100
Hummel, Sandra; Beyerlein, Andreas; Tamura, Roy et al. (2017) First Infant Formula Type and Risk of Islet Autoimmunity in The Environmental Determinants of Diabetes in the Young (TEDDY) Study. Diabetes Care 40:398-404
Smith, Laura B; Lynch, Kristian F; Kurppa, Kalle et al. (2017) Psychological Manifestations of Celiac Disease Autoimmunity in Young Children. Pediatrics 139:
Beyerlein, Andreas; Uusitalo, Ulla M; Virtanen, Suvi M et al. (2017) Intake of Energy and Protein is Associated with Overweight Risk at Age 5.5 Years: Results from the Prospective TEDDY Study. Obesity (Silver Spring) 25:1435-1441
Lee, Hye-Seung; Krischer, Jeffrey P (2017) A new framework for prediction and variable selection for uncommon events in a large prospective cohort study. Model Assist Stat Appl 12:227-237
Hagopian, William; Lee, Hye-Seung; Liu, Edwin et al. (2017) Co-occurrence of Type 1 Diabetes and Celiac Disease Autoimmunity. Pediatrics 140:
Krischer, Jeffrey P; Lynch, Kristian F; Lernmark, Åke et al. (2017) Genetic and Environmental Interactions Modify the Risk of Diabetes-Related Autoimmunity by 6 Years of Age: The TEDDY Study. Diabetes Care 40:1194-1202
Roth, Roswith; Baxter, Judith; Vehik, Kendra et al. (2017) The feasibility of salivary sample collection in an international pediatric cohort: The the TEDDY study. Dev Psychobiol 59:658-667
Krischer, Jeffrey P; Liu, Xiang; Lernmark, Åke et al. (2017) The Influence of Type 1 Diabetes Genetic Susceptibility Regions, Age, Sex, and Family History on the Progression From Multiple Autoantibodies to Type 1 Diabetes: A TEDDY Study Report. Diabetes 66:3122-3129
Yang, J; Tamura, R N; Uusitalo, U M et al. (2017) Vitamin D and probiotics supplement use in young children with genetic risk for type 1 diabetes. Eur J Clin Nutr 71:1449-1454
Köhler, Meike; Beyerlein, Andreas; Vehik, Kendra et al. (2017) Joint modeling of longitudinal autoantibody patterns and progression to type 1 diabetes: results from the TEDDY study. Acta Diabetol 54:1009-1017

Showing the most recent 10 out of 78 publications