The Environmental Determinants of Diabetes in the Young (TEDDY) study
Anette-Gabriele Ziegler, MD
Institute of Diabetes Research, Helmholtz Zentrum München, Munich, Germany Heikki Hyöty, MD, PhD
Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
The TEDDY study is defining the environmental determinants and natural history of islet autoimmunity and type 1 diabetes (T1D).
A 47 single polynucleotide polymorphism screening panel has defined a genetic risk score that can identify children from the general population having a 25-fold increase in the risk for islet autoimmunity.
Using this panel, seven clinical centres in Germany, UK, Poland, Belgium and Sweden will screen around 330,000 infants to identify those with a genetic high risk of T1D, enrol them in primary prevention trials and follow them for beta-cell autoantibodies and diabetes.
The interaction between genes and environmental factors, such as diet, has been hypothesised to play an important role in triggering type 1 diabetes (T1D). The mechanisms linking early feeding practices and development of T1D are not very well known, but may include immature and adverse immunological responses of the gut to complementary food, mucosal inflammation, and increased gut permeability. The TEDDY study is investigating these aspects.
Cumulative risk for IA is higher in children with a first-degree family history compared to the general population.
Genotyping of 47 single polynucleotide polymorphisms (SNPs) has defined a genetic risk score (GRS) combining HLA and non-HLA genes that identified children from the general population having >10% risk for IA (stage 1) by age 6 years, and 12% by age 10.
The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) has established a screening program, GPPAD-02, based on the 47 SNP GRS identified.
BTLN2 is a key gene associated with increased risk of T1D, and the BTNL2 high-risk allele is more frequent in children with first-degree family history.
The risk of IA decreases exponentially with age, with a half-life of 3.5 years in relatives and 2.2 years in the TEDDY population for those in the highest GRS quartile.
Early autoimmunity appears to be dominated by autoantibodies to insulin, and insulin first autoimmunity is higher in children with a DR4 high risk phenotype.
Maternal T1D protects from first appearing insulin autoimmunity, but less from GAD or later appearing autoimmunity.
BTNL2 genotyping improves risk stratification and increases the sensitivity of identifying stage I IA.
The TEDDY 47 SNP GRS identifies children from the general population having a 25-fold increase in the risk for IA.
Key messages/Clinical Perspectives
The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) is using high-throughput technology with the 47 SNP GRS for newborn screening to identify infants with a genetic high risk of T1D, enrol these into primary prevention trials and follow children for beta-cell autoantibodies and diabetes.
Seven clinical centres will screen around 330,000 infants in Germany, UK, Poland, Belgium and Sweden.
Winkler C, Haupt F, Heigermoser M, et al. Identification of infants with increased type 1 diabetes genetic risk for enrollment into Primary Prevention Trials-GPPAD-02 study design and first results. Pediatr Diabetes 2019 Sep;20(6):720-7
Presenter disclosure: The presenters has reported that no relationships exist relevant to the contents of this presentation.
Medical writer: Patrick Moore, PhD
Reviewer: Marco Gallo, MD
Local reviewers: Marco Gallo, MD (Italia); Anna Novials Sardá, MD, PhD (España); Eric Renard, MD, PhD (France); Peter Schwarz, MD, PhD (Deutschland)