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Cord blood insulinoma-associated protein 2 autoantibodies are associated with increased risk of type 1 diabetes in the population-based Diabetes Prediction in Skåne study



The aim of this study was to examine the effect of cord blood autoantibodies on the risk for type 1 diabetes in children followed prospectively from birth.


The Diabetes Prediction in Skåne (DiPiS) study consists of 35,853 children from the general population born during 2000–2004. Samples were collected at birth and analysed for HLA genotypes and autoantibodies to glutamate decarboxylase 65 (GAD65), insulin and insulinoma-associated protein 2 (IA-2). After adjusting for HLA, sex, maternal age and parental type 1 diabetes, independent associations with risk of diabetes were assessed using multivariate Cox proportional hazards models.


In total, 151 children (0.4%) had developed type 1 diabetes by the end of 2013 at a median age of 5.8 years (0.8–12.2 years). In the multivariate analysis, the presence of IA-2 autoantibodies (IA-2A) in cord blood (HR 6.88, 95% CI 1.46,32.4; p = 0.003), but not maternal diabetes (HR 1.38, 95% CI 0.24,7.84; p = 0.71), was associated with risk of developing type 1 diabetes. No increased risk could be seen for the presence of autoantibodies to GAD65 or insulin.


Our study indicates that the presence of cord blood IA-2A superimposes maternal diabetes and other cord blood islet autoantibodies as a predictor of type 1 diabetes development in the child. These findings may be of significance for future screening and study protocols on type 1 diabetes prediction.

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Fig. 1



Better Diabetes Diagnosis


Dried blood spot


Diabetes Prediction in Skåne


Glutamic acid decarboxylase 65 autoantibodies


Insulin autoantibodies


Insulinoma-associated protein 2 autoantibodies


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We thank all the participating parents and children in the DiPiS study. We thank Å. Lernmark for support and valuable comments on the manuscript. The members of the DiPiS study group are: C. Andersson, R. Bennet, I. Jönsson, M. Ask, J. Bremer, C. Brundin, C. Cilio, C. Hansson, G. Hansson, S. Ivarsson, B. Jonsdottir, Å Lernmark, B. Lindberg, B. Lernmark, Z. Mestan, A. Ramelius, I. Wigheden, U.-M. Carlsson (Department of Clinical sciences Malmö, Lund University, Sweden) A. Carlsson (Department of Clinical sciences Lund, Lund University, Sweden), E. Cedervall (Department of Paediatrics, Ängelholm hospital, Sweden), B. Jönsson (Department of Paediatrics, Ystad Hospital, Sweden), K. Larsson (Department of Paediatrics, Kristianstad Central Hospital, Sweden) and J. Neiderud (Department of paediatrics, Helsingborg Hospital, Sweden).


Our research is supported in part by the Swedish Research Council (grant no. 14064 to Åke Lernmark), JDRF, Swedish Childhood Diabetes Foundation, Swedish Diabetes Association, Nordisk Insulin Fund, SUS funds, Lion Club International, district 101-S, SUS foundations and the Skåne County Council Foundation for Research and Development.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

ML analysed the data and wrote the manuscript. KL was involved in the study design and critically revised the manuscript for important intellectual content. CL provided statistical support, database management and contributed to and edited the manuscript. HEL designed the study, was involved in data collection, interpreted data and contributed to and edited the manuscript. All authors gave final approval of the version to be published. ML is responsible for the integrity of the work as a whole.

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Correspondence to Markus Lundgren.

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Lundgren, M., Lynch, K., Larsson, C. et al. Cord blood insulinoma-associated protein 2 autoantibodies are associated with increased risk of type 1 diabetes in the population-based Diabetes Prediction in Skåne study. Diabetologia 58, 75–78 (2015).

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  • GAD65 autoantibodies
  • IA-2 autoantibodies
  • Insulin autoantibodies
  • Paediatric
  • Prediction
  • Type 1 diabetes