Koskinen MK, Mikk ML, Laine AP, et al. - In the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study in children with and without multiple autoantibodies, researchers explored the connections between first-phase insulin response (FPIR) and genetic variants outside the HLA DR-DQ region. Among 438 children who had one or more FPIR results available after seroconversion, the relationship between FPIR and class I alleles A*24 and B*39, and eight SNPs outside the HLA region were examined. To analyze repeated measurements of FPIR, Hierarchical linear mixed models were used. In children with multiple autoantibodies, there was a significant difference in the change in FPIR over time among children with various PTPN2 (rs45450798), FUT2 (rs601338), CTSH (rs3825932) and IKZF4 (rs1701704), genotypes in at least one version. In addition, the presence of the HLA class I A*24 allele was linked to steeper decline of FPIR over time in children with multiple autoantibodies. Some genetic variants outside the class II HLA region may have a significant effect on FPIR's longitudinal pattern.