Key takeaways
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The TEDDY study followed more than 8,600 children at high genetic risk for developing type 1 diabetes mellitus (T1D).
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As this large study nears completion, investigators report on key findings of factors leading to T1D in children.
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TEDDY data reveals insights on genetic and environmental factors that may trigger islet autoimmunity and T1D, but questions still remain.
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Studies using an omics approach are already underway to help address remaining research gaps.
Research study background
This review highlights the most significant findings thus far from The Environmental Determinants of Diabetes in the Young (TEDDY) study. The large, multi-institutional prospective cohort study began in enrollment in 2004 and was conducted at six clinical centers in Finland, Germany, Sweden and the United States. TEDDY primarily seeks to identify triggers of islet autoimmunity, often the first sign preceding type 1 diabetes mellitus (T1D) in children, and understand the progression to Stage 3 clinical T1D. To date, more than 170 peer-reviewed investigations have been published from TEDDY data.
In over 425,000 newborns screened, the study recruited 8,676 eligible participants who had a high genetic risk for developing T1D. Participants were followed from three months of age until a diagnosis of T1D or age 15, whichever came first.
Experts from the Barbara Davis Center for Diabetes at the University of Colorado School of Medicine, the Digestive Health Institute at Children’s Hospital Colorado, Colorado School of Public Health and the other study centers contributed to this review. Key findings reported included insights on heterogeneity of islet autoimmunity, genetic factors, infectious agents, risks related to celiac disease autoimmunity (CDA), growth, dietary and psychosocial factors.
In T1D screenings, insulin autoantibodies (IAA) or glutamic acid decarboxylase antibodies (GADA), which target components of the insulin producing cells, usually appear first. If two or more islet autoantibodies appear, there is a nearly 100% chance that clinical symptomatic T1D will eventually develop. Islet autoimmunity can develop at any age during childhood but often begins before the age of 6 years.
Genetic factors interact with environmental factors in initiation of islet autoimmunity and progression to dysglycemia. Researchers developed genetic risk scores to identify individuals who may benefit most from islet autoantibody screening.
Species B enteroviruses (EVB) including Coxsackie B viruses are linked to higher odds for developing islet autoimmunity and usually target those with IAA as the first appearing autoantibody. Early-life antibiotic use was not associated with future islet autoimmunity or CDA.
TEDDY participants had annual screenings for tissue transglutaminase IgA antibodies, which are markers for CDA. Study data reveals the highest incidence of CDA occurs between ages 1 and 4 years.The cumulative incidence rates at 14 years of age in the TEDDY study reached 5.1% for IAA-first, 7.1% for GADA-first and 18.9% for CDA.
Weight gain during infancy was associated with an increased risk of islet autoimmunity, especially in those with GADA appearing first. Rapid height gain increased the risk of progression from GADA-first to clinical onset of T1D, while excessive energy intake is indirectly involved.
TEDDY data led to a new discovery that giving probiotics to infants in the first 28 days may lower the risk of developing islet autoimmunity, especially in those with the highest genetic risk for T1D.
Both maternal respiratory infections and job-related life events during pregnancy were associated with a reduced risk of IAA appearing first in children under 7 years old, primarily among those with the HLA-DR4-DQ8 haplotype.
These findings highlight the importance of gene–environmental interactions in the development of islet autoimmunity. This suggests multiple mechanisms are working together to create different pathways for a child to develop IAA-first or GADA-first. Study authors concluded that there is a distinct pattern of associated factors (IAA-first, GADA-first or both) that lead to the initiation of islet autoimmunity. Background factors that lead to the progression and clinical onset of T1D seem to point to early associations, although full data analyses have not yet been completed.
Relevance to future research
While TEDDY has provided insight into the role of environmental and genetic factors in the cause of T1D, many questions remain. Current studies using omics approaches aim to better characterize potential triggers and pathways leading to autoimmunity. Additional research is needed to determine if other viruses are linked to islet autoimmunity and if maternal virus antibodies in cord blood play a protective role. Future studies should also examine strategies to mitigate the annual 3-to-5% increase in T1D over the past four decades.
Featured researchers

Edwin Liu, MD
Director, Colorado Center for Celiac Disease and Taplin Endowed Chair for Celiac Disease
Digestive Health Institute
Children's Hospital Colorado
Professor
Pediatrics-Gastroenterology, Hepatology and Nutrition
University of Colorado School of Medicine

Marian Rewers, MD, PhD
Executive Director
Barbara Davis Center for Childhood Diabetes
University of Colorado Anschutz Medical Campus
Professor
Pediatrics-Barbara Davis Center
University of Colorado School of Medicine

Jill Norris PhD, MPH
Professor, Chair EPI Department
Epidemiology
University of Colorado School of Medicine
Patricia Gesualdo, MPH, RN
Senior research instructor
Pediatrics-Barbara Davis Center
University of Colorado School of Medicine

Andrea Steck, MD
Director, Pediatric Diabetes Division
Barbara Davis Center for Childhood Diabetes
Children's Hospital Colorado
Professor
Pediatrics-Barbara Davis Center
University of Colorado School of Medicine

Brigitte Frohnert, MD, PhD
Pediatric endocrinologist
Barbara Davis Center for Childhood Diabetes
Children's Hospital Colorado
Associate Professor
Pediatrics-Barbara Davis Center
University of Colorado School of Medicine