Advanced

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

, ; Winkler, Christiane; Haupt, Florian; Heigermoser, Martin; Zapardiel-Gonzalo, Jose; Ohli, Jasmin; Faure, Theresa; Kalideri, Evdokia; Hommel, Angela and Delivani, Petrina, et al. (2019) In Pediatric Diabetes
Abstract

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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
@article{2128e684-68e6-463c-a6fb-c529d50c6281,
  abstract     = {<p>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 (&gt;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.</p>},
  author       = {,  and Winkler, Christiane and Haupt, Florian and Heigermoser, Martin and Zapardiel-Gonzalo, Jose and Ohli, Jasmin and Faure, Theresa and Kalideri, Evdokia and Hommel, Angela and Delivani, Petrina and Berner, Reinhard and Kordonouri, Olga and Roloff, Frank and von dem Berge, Thekla and Lange, Karin and Oltarzewski, Mariusz and Glab, Ryszard and Szypowska, Agnieszka and Snape, Matthew D. and Vatish, Manu and Todd, John A. and Larsson, Helena E. and Ramelius, Anita and Kördel, Jeanette and Casteels, Kristina and Paulus, Jasmin and Ziegler, Anette G. and Bonifacio, Ezio},
  issn         = {1399-543X},
  keyword      = {beta-cell autoantibodies,genetic risk for type 1 diabetes,type 1 diabetes},
  language     = {eng},
  publisher    = {Wiley-Blackwell},
  series       = {Pediatric Diabetes},
  title        = {Identification of infants with increased type 1 diabetes genetic risk for enrollment into Primary Prevention Trials—GPPAD-02 study design and first results},
  url          = {http://dx.doi.org/10.1111/pedi.12870},
  year         = {2019},
}