Enterovirus Infection and Progression from Islet Autoimmunity to Type 1 Diabetes: The Diabetes and Autoimmunity Study in the Young (DAISY)

  1. Marian Rewers, MD, PhD (marian.rewers{at}
  1. 1 Division of Epidemiology, Norwegian Institute of Public Health, Oslo, NO-0403, Norway
  2. 2 Department of Virology, University of Tampere Medical School, Tampere, FIN-33520, Finland
  3. 3 Department of Microbiology, Center for Laboratory Medicine, Tampere University Hospital, Tampere, FIN-22520, Finland
  4. 4 Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, Colorado 80045, United States
  5. 5 Department of Epidemiology, University of Colorado School of Public Health, Aurora, Colorado 80045, United States
  6. 6 Department of Human Genetics, Roche Molecular Systems, Inc, Alameda, California 94501, United States


Aim: To investigate whether enterovirus infections predict progression to type 1 diabetes in genetically predisposed children repeatedly positive for islet autoantibodies.

Methods: Since 1993, DAISY has followed 2,365 genetically predisposed children for islet autoimmunity and type 1 diabetes. Venous blood and rectal swabs were collected every 3-6 months after seroconversion for islet autoantibodies (against glutamic acid decarboxylase, insulin or IA-2), until diagnosis of diabetes. Enteroviral RNA in serum or rectal swabs was detected using reverse transcriptase PCR with primers specific for the conserved 5′ non-coding region, detecting essentially all enterovirus serotypes.

Results: Of 140 children who seroconverted to repeated positivity for islet autoantibodies at a median age of 4.0 years, 50 progressed to type 1 diabetes during a median follow-up of 4.2 years. The risk of progression to clinical type 1 diabetes in the sample interval following detection of enteroviral RNA in serum (3 diabetes cases diagnosed among 17 intervals) was significantly increased compared to that in intervals following a negative serum enteroviral RNA test (33 cases diagnosed among 1064 intervals; hazard ratio: 7.02, 95% CI: 1.95-25.3, after adjusting for number of autoantibodies). Results remained significant after adjustment for ZnT8-autoantibodies, and after restriction to various subgroups. Enteroviral RNA in rectal swabs was not predictive of progression to type 1 diabetes. No evidence for viral persistence was found.

Conclusion: This novel observation suggests that progression from islet autoimmunity to type 1 diabetes may increase after an enterovirus infection characterized by the presence of viral RNA in blood.

  • Received June 22, 2010.
  • Accepted September 13, 2010.