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

BMJ 2011; 342 doi: (Published 03 February 2011) Cite this as: BMJ 2011;342:d35
  1. Wing-Chi G Yeung, medical student1,
  2. William D Rawlinson, professor12,
  3. Maria E Craig, associate professor234
  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{at}
  • Accepted 25 October 2010


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.


  • Contributors: WGY performed the literature search, extracted, analysed, and interpreted the data, and drafted the article. MEC conceived and designed the review, helped extract and interpret the data, and revised the article critically for intellectual content. WDR revised the article critically for intellectual content and approved the final draft for publication. WDR is guarantor.

  • Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

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