Islet autoantibody levels predict progression to diabetes

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By Eleanor McDermid, Senior medwireNews Reporter

Levels of insulin autoantibodies (IAAs) and insulinoma-associated protein 2 autoantibodies (IA-2As) predict the onset of diabetes in young children with islet autoimmunity, show findings from the TEDDY study.

Most children who progressed to diabetes within 5 years of first islet autoantibody detection had at least two islet autoantibodies, were very young and had first-degree relatives with diabetes.

The TEDDY (The Environmental Determinants of Diabetes in the Young) study included 577 children who were persistently positive for at least one islet autoantibody, and 164 of these progressed to diabetes during a median 5 years of follow-up. In all, 88% of these children had at least two autoantibodies, and the cumulative risk of progression was 47% and 36% for children with three and two autoantibodies, compared with 11% for those with just one.

“[O]ur results support the notion that diabetes is likely to develop in most children with persistent multiple islet autoantibodies”, say Andrea Steck (University of Colorado School of Medicine, Aurora, USA) and study co-authors.

“However, the time of progression to diabetes can be highly variable. Therefore, factors that can predict the age at development of diabetes may have an important prognostic value for parents and providers, and may also be of use in interim analyses of prevention trials.”

Children who progressed to diabetes were significantly younger at first autoantibody detection than those who did not, at 1.3 versus 2.5 years of age, and were 1.6-fold more likely to have first-degree relatives with diabetes than those who did not progress.

After accounting for these factors, each 1-unit increase in log mean IAA level was associated with an 8.1-fold increased risk of developing diabetes during follow-up, and each 1-unit increase in log mean IA-2A level increased it 7.4-fold.

Glutamate decarboxylase 65 autoantibody levels did not influence diabetes risk, however, and neither did human leukocyte antigen genotype.

“On the other hand, the IAA is most often the initial antibody to become positive in young children”, the researchers write in Diabetes Care. “[T]his TEDDY cohort is still very young, and these antibody findings might be different in an older population.”

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