Identification of infants with increased type 1 diabetes genetic risk for enrollment into Primary Prevention Trials—GPPAD‐02 study design and first results

• DOI: 10.1111/pedi.12870
• Publication Date: 2019-06-13T10:48:35Z
• Authors: Christiane Winkler; Florian Haupt; Martin Heigermoser; Jose Zapardiel‐Go...; Jasmin Ohli; Theresa Faure; Evdokia Kalideri; Angela Hommel; Petrina Delivani; Reinhard Berner; Olga Kordonouri; Frank Roloff; Thekla von dem Berge; Karin Lange; Mariusz Oltarzewski; Ryszard Glab; Agnieszka Szypowska; Matthew D. Snape; Manu Vatish; John A. Todd; Helena E. Larsson; Anita Ramelius; Jeanette Å. Kördel; Kristina Casteels; Jasmin Paulus; Anette G. Ziegler; Ezio Bonifacio
• Keywords: Male; type 1 diabetes; CHILDREN; Autoimmunity; Pediatrics; Polymorphism, Single Nucleotide; Endocrinology & Metabolism; Islets of Langerhans; 03 medical and health sciences; Neonatal Screening; Risk Factors; Humans; Genetic Predisposition to Disease; Genetic Testing; Autoantibodies; Beta-cell Autoantibodies ; Genetic Risk For Type 1 Diabetes ; Type 1 Diabetes; 0303 health sciences; Science & Technology; genetic risk for type 1 diabetes; Patient Selection; Type 1 Diabetes: Pathophysiology and Prevention; Infant, Newborn; Infant; ddc:; 3. Good health; Europe; Primary Prevention; Diabetes Mellitus, Type 1; Research Design; beta-cell autoantibodies; AUTOANTIBODIES; Female; Life Sciences & Biomedicine; Preliminary Data

Primary prevention of type 1 diabetes (T1D) requires intervention in genetically at-risk infants. The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) has established a screening program, GPPAD-02, that identifies infants with a genetic high risk of T1D, enrolls these into primary prevention trials, and follows the children for beta-cell autoantibodies and diabetes. Genetic testing is offered either at delivery, together with the regular newborn testing, or at a newborn health care visits before the age of 5 months in regions of Germany (Bavaria, Saxony, Lower Saxony), UK (Oxford), Poland (Warsaw), Belgium (Leuven), and Sweden (Region Skåne). Seven clinical centers will screen around 330 000 infants. Using a genetic score based on 46 T1D susceptibility single-nucleotide polymorphisms (SNPs) or three SNPS and a first-degree family history for T1D, infants with a high (>10%) genetic risk for developing multiple beta-cell autoantibodies by the age of 6 years are identified. Screening from October 2017 to December 2018 was performed in 50 669 infants. The prevalence of high genetic risk for T1D in these infants was 1.1%. Infants with high genetic risk for T1D are followed up and offered to participate in a randomized controlled trial aiming to prevent beta-cell autoimmunity and T1D by tolerance induction with oral insulin. The GPPAD-02 study provides a unique path to primary prevention of beta-cell autoimmunity in the general population. The eventual benefit to the community, if successful, will be a reduction in the number of children developing beta-cell autoimmunity and T1D.