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. 2011 Sep;34(9):1897-901.
doi: 10.2337/dc11-0560. Epub 2011 Jul 12.

Development of autoantibodies in the TrialNet Natural History Study

Kendra Vehik  1 , Craig A Beam, Jeffrey L Mahon, Desmond A Schatz, Michael J Haller, Jay M Sosenko, Jay S Skyler, Jeffrey P Krischer; TrialNet Natural History Study Group
Affiliations

Development of autoantibodies in the TrialNet Natural History Study

Kendra Vehik et al. Diabetes Care. 2011 Sep.

Abstract

Objective: Understanding the relationship between age and islet autoantibody (Ab) seroconversion can establish the optimal screening interval(s) to assess risk for type 1 diabetes, identify subjects who can participate in prevention trials, and determine associated costs. This study assessed the rates of seroconversion to glutamic acid decarboxylase positive (GAD65(+)), insulin positive (mIAA(+)), and insulinoma-associated protein 2 positive (ICA512(+)) in a large cohort of relatives of type 1 diabetes probands undergoing Ab rescreening in the TrialNet Natural History Study.

Research design and methods: Of 32,845 children aged <18 years screened for Abs, 1,287 (3.9%) were GAD65(+), 778 (2.4%) were mIAA(+), 677 (2.1%) were ICA512(+), and 31,038 were Ab-negative. Ab-negative children were offered annual rescreening up to 18 years of age. Cox regression was used to estimate the risk for GAD65, mIAA, and ICA512 seroconversion. RESULTS There were 205 children who seroconverted to GAD65(+), 155 who seroconverted to mIAA(+), and 53 who seroconverted to ICA512(+) over 5.8 years of follow-up. The risk of mIAA (hazard ratio 0.89 [95% CI 0.85-0.92]) and GAD65 (0.96 [0.93-0.99]) seroconversion significantly decreased with increasing age (i.e., for each 1-year increase in age, the risk of seroconversion decreased by 11% [P < 0.0001] for mIAA and 4% [P = 0.04] for GAD65) across all ages. The cumulative Ab seroconversion was 2% for those <10 years of age versus 0.7% for those ≥10 years of age.

Conclusions: The risk of development of islet Abs declines with increasing age in type 1 diabetes relatives. These data support annual screening for children <10 years of age and one additional screening in adolescence.

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Figures

Figure 1
Figure 1
Flow diagram of study screens and Ab seroconversion (screen time points shown on rescreen scale from Time 0 [initial screen] to Time 5 [5 years of follow-up]).
Figure 2
Figure 2
The 2-year risks (A) and 3-year risks (B) of Ab seroconversion by Ab and development of any Ab(s) by age (years).
Figure 3
Figure 3
Cumulative Ab seroconversion by annual rescreen number by age (A) and cost of rescreening by age at initial screen (B).
See this image and copyright information in PMC

References

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    1. Vehik K, Haller MJ, Beam CA, et al. ; DPT-1 Study Group. Islet autoantibody seroconversion in the DPT-1 study: justification for repeat screening throughout childhood. Diabetes Care 2011;34:358–362 - PMC - PubMed
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