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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

Abstract

Aims/hypothesis

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.

Methods

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.

Results

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.

Conclusions/interpretation

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

Abbreviations

BDD:

Better Diabetes Diagnosis

DBS:

Dried blood spot

DiPiS:

Diabetes Prediction in Skåne

GADA:

Glutamic acid decarboxylase 65 autoantibodies

IAA:

Insulin autoantibodies

IA-2A:

Insulinoma-associated protein 2 autoantibodies

References

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Acknowledgements

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).

Funding

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). https://doi.org/10.1007/s00125-014-3394-6

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Keywords

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