Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies
OPEN ACCESS- Wing-Chi G Yeung, medical student1,
- William D Rawlinson, professor12,
- Maria E Craig, associate professor234
- 1Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia
- 2Virology Research, POWH and UNSW Research Laboratories, Prince of Wales Hospital, Randwick, NSW 2031
- 3The Children’s Hospital at Westmead, Institute of Endocrinology and Diabetes, Sydney
- 4Discipline of Paediatrics and Child Health, University of Sydney, Sydney
- Correspondence to: M Craig, Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Australia m.craig@unsw.edu.au
Abstract
Objective To review the association between current enterovirus infection diagnosed with molecular testing and development of autoimmunity or type 1 diabetes.
Design Systematic review and meta-analysis of observational studies, analysed with random effects models.
Data sources PubMed (until May 2010) and Embase (until May 2010), no language restrictions, studies in humans only; reference lists of identified articles; and contact with authors.
Study eligibility criteria Cohort or case-control studies measuring enterovirus RNA or viral protein in blood, stool, or tissue of patients with pre-diabetes and diabetes, with adequate data to calculate an odds ratio and 95% confidence intervals.
Results The 24 papers and two abstracts (all case-control studies) that met the eligibility criteria included 4448 participants. Study design varied greatly, with a high level of statistical heterogeneity. The two separate outcomes were diabetes related autoimmunity or type 1 diabetes. Meta-analysis showed a significant association between enterovirus infection and type 1 diabetes related autoimmunity (odds ratio 3.7, 95% confidence interval 2.1 to 6.8; heterogeneity χ2/df=1.3) and clinical type 1 diabetes (9.8, 5.5 to 17.4; χ2/df=3.2).
Conclusions There is a clinically significant association between enterovirus infection, detected with molecular methods, and autoimmunity/type 1 diabetes. Larger prospective studies would be needed to establish a clear temporal relation between enterovirus infection and the development of autoimmunity and type 1 diabetes.