Age-related Islet Autoantibody Incidence in Offspring of Patients With Type 1 Diabetes

Diabetologia. 2012 Jul;55(7):1937-43. doi: 10.1007/s00125-012-2472-x.

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 high-risk 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 diabetes associated autoimmunity in genetically at-risk children and should be targeted for effective primary prevention strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Child
  • Child of Impaired Parents*
  • Child, Preschool
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Germany / epidemiology
  • HLA-D Antigens / genetics
  • HLA-D Antigens / immunology*
  • Humans
  • Incidence
  • Infant
  • Longitudinal Studies
  • Male
  • Polymerase Chain Reaction
  • Prediabetic State / epidemiology
  • Prediabetic State / genetics
  • Prediabetic State / immunology*

Substances

  • Autoantibodies
  • HLA-D Antigens