Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes - The 2-year analysis of the German BABYDIAB study

The temporal development of autoantibodies was studied in 1,353 offspring o f parents with type 1 diabetes. Islet cell antibodies (ICAs) and autoantibo dies to insulin (IAAs), glutamic acid decarboxylase, and IA-2 were measured at birth, 9 months, 2 years, and 5 years of age. At birth, no offspring ha d islet autoimmunity other than maternally acquired antibodies, which were shown to influence antibody prevalence up to age 6 months. Antibodies detec ted thereafter were likely to represent a true de novo production, since pr evalences were the same for offspring from mothers and fathers with diabete s, antibodies detected at 9 months were almost always confirmed in the S-ye ar sample and were associated with an increased Likelihood of having or dev eloping other antibodies. By 2 Sears of age, autoantibodies appeared in 11% of offspring, 3.5% having more than one autoantibody IAAs were detected mo st frequently and few had autoantibodies in the absence of IAAs. in 23 offs pring with multiple islet autoantibodies, IAAs preceded other antibodies in 10 cases and were first detected concurrently with other antibodies in 12 and after detection of other antibodies in 1. Development of additional ant ibodies and changes in levels, including decline of IAAs at older age, was frequent. Nine children, all with IAAs and ICAs, developed diabetes. Overal l cumulative risk for disease by 5 years of age was 1.8% (95% CI 0.2-3.4) a nd was 50% (95% CI 19-81) for offspring with more than one autoantibody in their 2-year sample. Autoimmunity associated with childhood diabetes is an early event and a dynamic process. Presence of IAAs is a consistent feature of this autoimmunity, and IAA detection can identify children at risk.