Enterovirus RNA in Blood Is Linked to the Development of Type 1 Diabetes
- Sami Oikarinen1,
- Mika Martiskainen1,
- Sisko Tauriainen1,
- Heini Huhtala2,
- Jorma Ilonen3,4,
- Riitta Veijola5,
- Olli Simell6,
- Mikael Knip7,8 and
- Heikki Hyöty1,9
- 1Department of Virology, Medical School, University of Tampere, Tampere, Finland;
- 2School of Public Health, University of Tampere, Tampere, Finland;
- 3Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland;
- 4Immunogenetics Laboratory, University of Turku, Turku, Finland;
- 5Department of Pediatrics, University of Oulu, Oulu, Finland;
- 6Department of Pediatrics, University of Turku, Turku, Finland;
- 7Department of Pediatrics, Tampere University Hospital, Tampere, Finland;
- 8Hospital for Children and Adolescents and Folkhälsan Research Center, University of Helsinki, Helsinki, Finland;
- 9Department of Clinical Microbiology, Centre of Laboratory Medicine, Tampere University Hospital, Tampere, Finland.
- Corresponding author: Sami Oikarinen, .
OBJECTIVE To assess whether the detection of enterovirus RNA in blood predicts the development of clinical type 1 diabetes in a prospective birth cohort study. Further, to study the role of enteroviruses in both the initiation of the process and the progression to type 1 diabetes.
RESEARCH DESIGN AND METHODS This was a nested case-control study where all case children (N = 38) have progressed to clinical type 1 diabetes. Nondiabetic control children (N = 140) were pairwise matched for sex, date of birth, hospital district, and HLA-DQ–conferred genetic susceptibility to type 1 diabetes. Serum samples, drawn at 3- to 12-month intervals, were screened for enterovirus RNA using RT-PCR.
RESULTS Enterovirus RNA–positive samples were more frequent among the case subjects than among the control subjects. A total of 5.1% of the samples (17 of 333) in the case group were enterovirus RNA–positive compared with 1.9% of the samples (19 of 993) in the control group (P < 0.01). The strongest risk for type 1 diabetes was related to enterovirus RNA positivity during the 6-month period preceding the first autoantibody-positive sample (odds ratio 7.7 [95% CI 1.9–31.5]). This risk effect was stronger in boys than in girls.
CONCLUSIONS The present study supports the hypothesis that enteroviruses play a role in the pathogenesis of type 1 diabetes, especially in the initiation of the β-cell damaging process. The enterovirus-associated risk for type 1 diabetes may be stronger in boys than in girls.
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- Received March 2, 2010.
- Accepted September 25, 2010.
- © 2011 by the American Diabetes Association.
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