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

Kendra Vehik, Michael J. Haller, Craig A. Beam, Desmond A. Schatz, Diane K. Wherrett, Jay M Sosenko, Jeffrey P. Krischer

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 themajority of subjects at risk for type 1 diabetes and eligible for prevention trials.

Original languageEnglish
Pages (from-to)358-362
Number of pages5
JournalDiabetes Care
Volume34
Issue number2
DOIs
StatePublished - Feb 1 2011

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Autoantibodies
Class 8 Receptor-Like Protein Tyrosine Phosphatases
Type 1 Diabetes Mellitus
Autoimmunity
Seroconversion
Research Design
Antibodies

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Vehik, K., Haller, M. J., Beam, C. A., Schatz, D. A., Wherrett, D. K., Sosenko, J. M., & Krischer, J. P. (2011). Islet autoantibody seroconversion in the DPT-1 study: Justification for repeat screening throughout childhood. Diabetes Care, 34(2), 358-362. https://doi.org/10.2337/dc10-1494

Islet autoantibody seroconversion in the DPT-1 study : Justification for repeat screening throughout childhood. / Vehik, Kendra; Haller, Michael J.; Beam, Craig A.; Schatz, Desmond A.; Wherrett, Diane K.; Sosenko, Jay M; Krischer, Jeffrey P.

In: Diabetes Care, Vol. 34, No. 2, 01.02.2011, p. 358-362.

Research output: Contribution to journalArticle

Vehik, K, Haller, MJ, Beam, CA, Schatz, DA, Wherrett, DK, Sosenko, JM & Krischer, JP 2011, 'Islet autoantibody seroconversion in the DPT-1 study: Justification for repeat screening throughout childhood', Diabetes Care, vol. 34, no. 2, pp. 358-362. https://doi.org/10.2337/dc10-1494
Vehik, Kendra ; Haller, Michael J. ; Beam, Craig A. ; Schatz, Desmond A. ; Wherrett, Diane K. ; Sosenko, Jay M ; Krischer, Jeffrey P. / Islet autoantibody seroconversion in the DPT-1 study : Justification for repeat screening throughout childhood. In: Diabetes Care. 2011 ; Vol. 34, No. 2. pp. 358-362.
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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 themajority of subjects at risk for type 1 diabetes and eligible for prevention trials.",
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