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

Author:
  • Christiane Winkler
  • Florian Haupt
  • Martin Heigermoser
  • Jose Zapardiel-Gonzalo
  • 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 Kördel
  • Kristina Casteels
  • Jasmin Paulus
  • Anette G. Ziegler
  • Ezio Bonifacio
Publishing year: 2019
Language: English
Publication/Series: Pediatric Diabetes
Document type: Journal article
Publisher: Wiley-Blackwell

Abstract english

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.

Keywords

  • Pediatrics
  • Endocrinology and Diabetes
  • beta-cell autoantibodies
  • genetic risk for type 1 diabetes
  • type 1 diabetes

Other

Epub
  • Paediatric Endocrinology
  • Diabetes and Celiac Unit
  • ISSN: 1399-543X
E-mail: anita [dot] ramelius [at] med [dot] lu [dot] se

Biomedical analyst

Diabetes and Celiac Unit

+46 40 39 19 06

91:10:067

Jan Waldenströms gata 35, Malmö

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Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00