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Diabetes, Vol 48, Issue 3 460-468, Copyright © 1999 by American Diabetes Association
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
AG Ziegler, M Hummel, M Schenker and E Bonifacio
Diabetes Research Institute and 3rd Medical Department, Krankenhaus Munchen-Schwabing, Germany. anziegler@lrz.uni-muenchen.de
The temporal development of autoantibodies was studied in 1,353 offspring
of parents with type 1 diabetes. Islet cell antibodies (ICAs) and
autoantibodies 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 had islet autoimmunity other than maternally acquired antibodies,
which were shown to influence antibody prevalence up to age 6 months.
Antibodies detected thereafter were likely to represent a true de novo
production, since prevalences were the same for offspring from mothers and
fathers with diabetes, antibodies detected at 9 months were almost always
confirmed in the 2-year sample and were associated with an increased
likelihood of having or developing other antibodies. By 2 years of age,
autoantibodies appeared in 11% of offspring, 3.5% having more than one
autoantibody. IAAs were detected most frequently, and few had
autoantibodies in the absence of IAAs. In 23 offspring 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 antibodies and changes in
levels, including decline of IAAs at older age, was frequent. Nine
children, all with IAAs and ICAs, developed diabetes. Overall cumulative
risk for disease by 5 years of age was 1.8% (95% CI 0.2-3.4) and 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.

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