The etiology of Type 1 (autoimmune) diabetes involves both genetic and environmental influences of roughly equal magnitude. Large cooperative arrangements pooling many patient samples have aided in identification of several of the causative genetic polymorphisms. Identification of environmental factors has been more difficult, but should also benefit from a cooperative approach. The Diabetes Evaluation in Washington (DEW-IT) study is a 32,000 subject population-based screening program, which will identify more than 6,000 young children at elevated genetic risk of future diabetes. Combining subject groups with similarly sized population-based screening studies in the US and elsewhere should make it possible to achieve sufficient sample sizes and statistical power to identify common environmental triggers. We propose to follow subjects at high genetic risk (DEW-IT family and DEW-IT general cohorts) through three putative disease stages: a) seroconversion to single antibody positivity to one of GAD, ICA512/IA2, and insulin, b) progression from one to multiple defined autoantibodies, and c) development of low beta cell function (fasting C-peptide) or clinical diabetes. First degree relatives will be followed sequentially through all stages, but stages b) and c) will be augmented by antibody-positive genetically-at-risk children from the general DEW-IT cohort, prior to intense environmental sampling. Frequent patient sampling will include serum, PBMC, throat swabs, hair, urine and stool. We will also survey children on food intake, vaccinations, allergies, illnesses and other stressors. Environmental sampling will also include selected foodstuffs identified in patient diaries. Genotyping will include HLA DR-DQ and 10 other known diabetes risk loci, as well as 10 other loci designed to detect polymorphisms at beta cell genes known to mitigate toxic exposures. Trios, including both parents, will be collected for TDT analyses. Measured environmental exposures include enteroviruses, dietary mycotoxins, environmental toxins selected by the CDC, and exposures proposed by other sites. Disease progression will be analyzed with respect to gene effects, environmental effects, and gone x environment effects. Disease staging, sample collection and analyses, and statistical approach will follow the consensus approach developed by the consortium. The overall goal is to identify environmental factors initiating and/or propagating the pathogenesis of childhood autoimmune diabetes.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-8 (O2))
Program Officer
Akolkar, Beena
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Pacific Northwest Research Institute
United States
Zip Code
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

Showing the most recent 10 out of 83 publications