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
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 :
Vatanen, Tommi; Franzosa, Eric A; Schwager, Randall et al. (2018) The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature 562:589-594
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
Riikonen, Anne; Hadley, David; Uusitalo, Ulla et al. (2018) Milk feeding and first complementary foods during the first year of life in the TEDDY study. Matern Child Nutr 14:e12611
Elding Larsson, Helena; Lynch, Kristian F; Lönnrot, Maria et al. (2018) Pandemrix® vaccination is not associated with increased risk of islet autoimmunity or type 1 diabetes in the TEDDY study children. Diabetologia 61:193-202
Koletzko, Sibylle; Lee, Hye-Seung; Beyerlein, Andreas et al. (2018) Cesarean Section on the Risk of Celiac Disease in the Offspring: The Teddy Study. J Pediatr Gastroenterol Nutr 66:417-424
Stanfill, Bryan A; Nakayasu, Ernesto S; Bramer, Lisa M et al. (2018) Quality Control Analysis in Real-time (QC-ART): A Tool for Real-time Quality Control Assessment of Mass Spectrometry-based Proteomics Data. Mol Cell Proteomics 17:1824-1836

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