Age-related islet autoantibody incidence in offspring of patients with type 1 diabetes

Abstract

Aims/hypothesis Seroconversion to islet autoantibodies precedes type 1 diabetes. This study aimed to identify periods of high seroconversion incidence, which could be targeted for mechanistic and therapeutic studies. Methods Incidence of islet autoantibodies was calculated in 1,650 genetically at-risk children followed with measurements of islet autoantibodies and thyroid autoantibodies at age 9 months and 2, 5, 8, 11, 14 and 17 years. Peak incidence periods were confirmed in a second cohort of 150 children followed until age 6 years with three-monthly samples up to age 3 years. Results Islet autoantibody incidence (per 1,000 person-years) was 18.5 until age 9 months, 21 from 9 months to 2 years and <10 for intervals after age 2 years. The second cohort confirmed peak incidence around age 9 months and demonstrated an absence of seroconversion before this age. Seroconversion to insulin autoantibodies occurred earlier than other autoantibodies (p<0.01 against glutamic acid decarboxylase [GAD]-, insulinoma-associated protein 2 [IA-2]-and zinc transporter 8 [ZnT8]-autoantibodies). Early peak seroconversion incidence was most evident in children with highrisk HLA DR3/4-DQ8 or DR4/4-DQ8 genotypes. Conclusion The age period 9 months to 2 years is associated with a high incidence of activation of type 1 diabetesassociated autoimmunity in genetically at-risk children and should be targeted for effective primary prevention strategies.

Islet autoantibody phenotypes and incidence in children at increased risk for type 1 diabetes

“…These findings suggest that susceptibility to autoimmunity against specific beta cell autoantigens occurs at distinct age periods. This study extends previous work from our own BABYDIAB study [3], the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study [14] and The Environmental Determinants of Diabetes in the Young (TEDDY) study [15]. It involved substantial follow-up of the cohort and uniquely characterised the islet autoantibodies at seroconversion and follow-up.…”

“…In accordance with the visit schedule, antibody incidence (per 1,000 person-years) was calculated from samples obtained within the age intervals 0-18 months (mean age of sample group, 0.85 years), 18-42 months (mean age of sample group, 2.0 years), 42-78 months (mean age of sample group, 5.0 years), 78-114 months (mean age of sample group, 8.0 years), 114-150 months (mean age of sample group, 11.0 years), 150-186 months (mean age of sample group, 14.0 years) and 186-204 months (mean age of sample group, 17.0 years), by dividing the number of children who had newly seroconverted to islet autoantibody positivity by the number of children followed at each interval [3]. SE calculations were based on the Cooper-Pearson methods.…”

“…These autoantibodies may develop throughout childhood, but seroconversion is most frequent from 6 months to 2 years of age [3]. Seroconversion typically involves IAA and/or GADA, and is often followed quickly by expansion to multiple islet autoantibodies [4], an event that defines an asymptomatic stage of type 1 diabetes.…”

Progression from single to multiple islet autoantibodies often occurs soon after seroconversion: implications for early screening

“…Nevertheless, many multiple islet autoantibody-positive children are likely to have transitioned from single to multiple islet autoantibodies. We [2,3], and others [4] have reported that multiple islet autoantibody-positive children frequently seroconvert in the first 2 years of life, but little is known of the timing of transition from single to multiple islet autoantibody positivity. This knowledge is important for the design of screening and re-screening strategies.…”

“…This knowledge is important for the design of screening and re-screening strategies. Here we analysed the prospectively followed German BABYDIAB/BABYDIET birth cohort [2,5] to address this.…”