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DOI: 10.1055/s-0034-1375061
Seroconversion incidence of high and low risk antibody phenotypes in genetically at-risk children for type 1 diabetes
Objective: To identify periods of high seroconversion incidence of islet autoantibody phenotypes associated with progression to type 1 diabetes (T1D).
Methods: Islet and thyroid autoantibody incidence per 1000 person-years was calculated in 2441 genetically at-risk children at age 9 months and 2, 5, 8, 11, 14 and 18 years. High-risk autoantibody phenotypes included multiple antibodies, high affinity single antibodies to insulin (IAA) and single antibodies to truncated glutamic acid decarboxylase (GADA) or high affinity single GADA. Low-risk phenotypes included low affinity single IAA and low affinity or truncated(-) single GADA.
Results: Multiple antibody incidence was high at ages 9 months and 2 years (15.4 and 15.8 per 1000 years, respectively) and decreased thereafter (5.4 at 5 years, 2.4 at 8 years, 1.4 at 11 years, 0.9 at 14 years and 0.0 at 18 years). The peak incidence of high-risk single antibodies was at age 9 months (high affinity IAA) or 2 years (high-risk GADA). Low-risk autoantibody seroconversion incidence had no early peak. TPO seroconversion incidence peaked during adolescence (incidence per 1000 years: 12.9 at 14 years). T1D susceptible HLA class II genotypes markedly affected the seroconversion incidence of high-risk autoantibody phenotypes, but not the incidences of low-risk phenotypes or TPO. Genotypes of minor T1D susceptibility genes influenced the incidence of high-risk antibody and TPO seroconversion.
Conclusions: Seroconversion incidence of high-risk autoantibody phenotypes peaks between ages 9 months and 2 years in genetically at-risk children. Emphasis on this age period should be considered for disease pathogenesis, preclinical staging of T1D and primary prevention trials.