Prediction of Type 1 Diabetes in the General Population

  1. Hans K. Åkerblom, MD, PHD1
  1. 1Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland;
  2. 2Folkhälsan Research Center, University of Helsinki, Helsinki, Finland;
  3. 3Department of Pediatrics, Tampere University Hospital, Tampere, Finland;
  4. 4Department of Pediatrics, University of Oulu, Oulu, Finland;
  5. 5Department of Health and Functional Capacity, National Institute for Health and Welfare, Helsinki, Finland;
  6. 6Department of Clinical Physiology, University of Turku and Turku University Central Hospital, Turku, Finland;
  7. 7Department of Medicine, University of Turku, Turku Finland.
  1. Corresponding author: Professor Mikael Knip, mikael.knip{at}hus.fi.

Abstract

OBJECTIVE To evaluate the utility of GAD antibodies (GADAs) and islet antigen-2 antibodies (IA-2As) in prediction of type 1 diabetes over 27 years in the general population and to assess the 6-year rates of seroconversion.

RESEARCH DESIGN AND METHODS A total of 3,475 nondiabetic subjects aged 3–18 years were sampled in 1980, and 2,375 subjects (68.3%) were resampled in 1986. All subjects were observed for development of diabetes to the end of 2007. GADAs and IA-2As were analyzed in all samples obtained in 1980 and 1986.

RESULTS A total of 34 individuals (1.0%; 9 developed diabetes) initially had GADAs and 22 (0.6%; 9 developed diabetes) IA-2As. Seven subjects (0.2%) tested positive for both autoantibodies. The positive seroconversion rate over 6 years was 0.4% for GADAs and 0.2% for IA-2As, while the inverse seroconversion rates were 33 and 57%, respectively. Eighteen subjects (0.5%) developed type 1 diabetes after a median pre-diabetic period of 8.6 years (range 0.9–20.3). Initial positivity for GADAs and/or IA-2As had a sensitivity of 61% (95% CI 36–83) for type 1 diabetes. Combined positivity for GADAs and IA-2As had both a specificity and a positive predictive value of 100% (95% CI 59–100).

CONCLUSIONS One-time screening for GADAs and IA-2As in the general childhood population in Finland would identify ∼60% of those individuals who will develop type 1 diabetes over the next 27 years, and those subjects who have both autoantibodies carry an extremely high risk for diabetes. Both positive and inverse seroconversions do occur over time reflecting a dynamic process of β-cell autoimmunity.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • See accompanying editorial on p. 1403.

  • Received June 7, 2009.
  • Accepted February 3, 2010.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

| Table of Contents