Type 1 diabetes (T1DM) is one of the most common and severe chronic diseases in children and is increasing in incidence. T1DM risk is modified by both genetic and environmental factors. The objective of this study is to identify environmental factors, which promote or attenuate the initiation of islet autoimmunity and progression to T1DM. Our hypothesis is that an immature gut is a primary defect in T1DM and that some environmental agents which enter the organism via the gut can modify diabetes risk. We hypothesize that dietary gluten is one of these agents, and that its presence in the immature gut can provoke inflammation and lead to islet autoimmunity in genetically susceptible individuals. Accordingly, reduction of the incidence of islet autoimmunity and T1DM could be achieved by delaying the introduction of gluten into the diet until the gut is mature. This will be investigated through an intensive prospective study from birth of offspring or siblings of patients with T1DM. Neonates will be selected for the high risk (>20%) T1DM (HLA DR3/4-DQ2/8 or DR4/4-DQ8/8) or celiac disease (DR3/3) genotypes. A total of 140 neonates will be recruited and followed with collection of 3 monthly blood and urine samples, fortnightly stool samples and life style questionnaires, and 3 day food records up to the age of 3 years. Neonates will be randomized into one of two arms with gluten introduction at 6 mo or 12 mo. Outcome markers will be the development of islet autoantibodies, TIDM and CD-associated antibodies, and antibodies to food antigens. This clinical center and study will contribute all samples, data and questionnaire material to a consortium for the identification of T1DM environmental triggers. The consortium will establish a prospectively collected bank of cell, serum, RNA, DNA, stool, and urine specimens for international collaborative studies to address this problem with sufficient statistical power. Within the consortium, we will examine gluten exposure and immune responses to foods. Ancilliary studies will be performed to determine the natural history of autoantibody responses to islet autoantigens and whether T1D-associated autoimmunity is preceded by more wide-spread immune irregularities. If successful this consortium will identify environmental factors, which can be manipulated in order to reduce T1DM incidence.

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
Diabetes Research Institute
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 76 publications