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}


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.


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  • See accompanying editorial on p. 1403.

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

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