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. 2011 Feb;34(2):358-62.
doi: 10.2337/dc10-1494.

Islet autoantibody seroconversion in the DPT-1 study: justification for repeat screening throughout childhood

Kendra Vehik  1 , Michael J Haller, Craig A Beam, Desmond A Schatz, Diane K Wherrett, Jay M Sosenko, Jeffrey P Krischer; DPT-1 Study Group
Affiliations

Islet autoantibody seroconversion in the DPT-1 study: justification for repeat screening throughout childhood

Kendra Vehik et al. Diabetes Care. 2011 Feb.

Abstract

Objective: Although type 1 diabetes autoimmunity frequently begins in childhood, little is known about the relationship between age and autoimmunity development. Our aim was to determine the timing of seroconversion to diabetes-associated autoantibody (DAA) positivity and risk in first- and second-degree relatives of patients with type 1 diabetes.

Research design and methods: Study subjects were identified through the Diabetes Prevention Trial-Type 1 (DPT-1). Children 3-18 years of age (n = 42,447) were screened for DAAs; 1,454 were ICA positive (≥ 10 JDF units), 1,758 were GAD65 positive, and 899 were ICA512 positive at the time of initial screening. Subjects who were initially antibody negative (n = 39,212) were recalled for rescreening, and 11,813 returned for rescreening.

Results: DAA seroconversion occurred in 469 (4%) children; 258 seroconverted to ICA, 234 to GAD65, and 99 to ICA512. The median time to seroconversion was 2 years. The 2-year risk for DAAs was highest in early childhood. For each 1-year increase in age in this cohort, the risk of any autoantibody seroconversion (HR 0.95, 95% CI 0.92-0.97) decreased by 5%, and for any two autoantibodies risk decreased by 13% (0.87, 0.82-0.93).

Conclusions: Risk of autoantibody seroconversion among children followed in DPT-1 is age dependent. Younger children have the highest risk for DAAs, with the majority of children seroconverting by 13 years of age (75%). This suggests that annual screenings should be started in early childhood and continued through early adolescence to identify the majority of subjects at risk for type 1 diabetes and eligible for prevention trials.

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Figures

Figure 1
Figure 1
Two-year risk of autoantibody seroconversion by autoantibody and development of any autoantibody(s) by age (years). GAD65, gray dashed line; ICA, solid black line; ICA512, black dashed line; any autoantibody, black dotted line; and any two autoantibodies, solid gray line.
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References

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