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Enterovirus infection and type I...


BMJ 2011; 2011; 342:d35 doi: 10.1136/bmj.d35 (Published 3 February 2011)

Cite this as: BMJ 2011; 2011; 342:d35

• Research

Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies

OPEN ACCESS

1. Wing-Chi G Yeung, medical student1, 
2. William D Rawlinson, professor12,
3. Maria E Craig, associate professor234

+Author Affiliations

1. ¹Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia
2. ²Virology Research, POWH and UNSW Research Laboratories, Prince of Wales Hospital, Randwick, NSW 2031
3. ³The Children’s Hospital at Westmead, Institute of Endocrinology and Diabetes, Sydney
4. ⁴Discipline of Paediatrics and Child Health, University of Sydney, Sydney

1. 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

• Accepted 25 October 2010

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.