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

Abstract

To the Editor: Multiple islet autoantibodies mark a pre-clinical stage of type 1 diabetes, with 70% progression to clinical diabetes within 10 years of seroconversion [1]. Broad application of screening for multiple islet autoantibodies may, therefore, become an attractive instrument to identify asymptomatic type 1 diabetes and prevent severe metabolic disarrangements and ketoacidosis. In contrast to multiple islet autoantibodies, only a minority of children who are, and remain, single islet autoantibody-positive develop type 1 diabetes within 10 years of follow-up. 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. Here we analysed the prospectively followed German BABYDIAB/BABYDIET birth cohort [2, 5] to address this. Children in the BABYDIAB/BABYDIET studies were routinely tested for islet autoantibodies at the ages of 9 months and 2 years, and every 3 years thereafter; children who were positive for one or more islet autoantibodies were tested every 6 months. In a subgroup of children with high genetic risk participating in the BABYDIET intervention study, routine testing for islet autoantibodies was carried out at 3 month intervals from the age of 3 months to 3 years and annually thereafter. Persistent islet autoantibody positivity was defined as a positive result for the same islet autoantibody in at least two consecutive samples. A total of 227 children (114 boys) in the cohort developed persistent islet autoantibodies. Of these, 62 (27.3%) were multiple islet autoantibody positive already at their seroconversion sample and had a median age at seroconversion of 2.2 years (interquartile range [IQR] 1.97–5.02 years). The remaining 165 were single islet autoantibody positive at seroconversion and had a median age at seroconversion of 5.01 years (IQR 1.89–8.13 years, p=0.01). A total of 55 (25.2%) children transitioned from single to multiple islet autoantibodies during 8 years of follow-up. The longest observed period of multiple islet autoantibody positivity was 7.36 years after the seroconversion sample. The rate of Anette-Gabriele Ziegler and Ezio Bonifacio share senior authorship. R. Chmiel : E. Z. Giannopoulou :C. Winkler : P. Achenbach : A.<G. Ziegler (*) Institute of Diabetes Research, Helmholtz Zentrum Munchen, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universitat Munchen, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany e-mail: anette-g.ziegler@helmholtz-muenchen.de