Islet Autoantibody Seroconversion in the DPT-1 Study: Justification for repeat screening throughout childhood

Pediatrics Epidemiology Center, University of South Florida, Tampa, Florida, USA.
Diabetes care (Impact Factor: 8.42). 02/2011; 34(2):358-62. DOI: 10.2337/dc10-1494
Source: PubMed


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.
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.
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).
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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    • "Type 1 diabetes (T1D) is characterized by immune-mediated destruction of the insulin-secreting í µí»½ cells in the pancreatic islets as a result of an unknown trigger mechanism. It is, however, well known that development of clinical disease is preceded by an asymptomatic latent period during which immune reactions against the insulin-secreting cell autoantigens can be demonstrated [1] [2] [3]. In this context, biochemically detectable autoantibodies against insulin (IAA), glutamic acid decarboxylase (GADA), insulinoma-associated antigen 2 (IA-2A), and Zn-transporter 8 (ZnT8A) as well as their counterpart immunofluorescent anti-islet antibodies (ICA) serve as reliable biomarkers for T1D development. "
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