Identification of infants with increased type 1 diabetes (T1D) risk for enrollment into Primary Oral Insulin Trial POInT

Background: Primary prevention of type 1 diabetes (T1D) requires early intervention in genetically at-risk infants. Neonates and infants who are at increased risk to develop type 1 diabetes can be identified using genetic markers. The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) has established a screening program, GPPAD-02, that identifies infants who have a high risk of T1D, enroll these children into the primary oral insulin trial (POInT), and follow and monitor them for islet autoantibodies and diabetes.

Methods: Genetic testing is offered either at delivery, together with the regular newborn testing, or at a pediatric baby-visit before the age of 4 months in regions of Germany, UK, Poland, Belgium and Sweden. Using a genetic score based on 46 T1D susceptibility SNPs and the first degree-family history for T1D, infants with a high (>10%) genetic risk for multiple beta-cell autoantibodies by the age of 6 years are identified.

Results: Since October 2017, 11,465 infants participated in the screening, including 247 (2.15%) with a first-degree family history of T1D (FDR). The T1D associated HLA risk genotypes DR3/DR4-DQ8 and DR4-DQ8/DR4-DQ8 were present, respectively, in 224 (2.0%) and 95 (0.85%) children from the general population (GP), and in 13 (5.3%) and 5 (2%) FDR children. In total, 166 (1.45%) infants had a high genetic risk (>10%) and are eligible for enrollment into POInT including 96 (0.86%) GP and 70 (28.3%) FDR children. The median genetic risk score in eligible infants was 14.56 as compared to 10.08 in the non-eligible children.

In conclusion, the first results of the GPPAD-02 study showed that screening for genetic risk in newborns on a population-based level is feasible.