Enterovirus infection linked with risk of islet autoimmunity or type 1 diabetes

"Our data strengthen the rationale for the development of vaccines targeting diabetogenic enterovirus types, specifically those within Enterovirus B," the researchers wrote.

Enteroviruses are routinely detected with molecular methods within large cohorts at risk for type 1 diabetes. Sonia R Isaacs, University of New South Wales, Sydney, NSW, Australia, and colleagues aimed to examine the association between enterovirus infection and islet autoimmunity or type 1 diabetes development by conducting a systematic review and meta-analysis.

For this purpose, the research team searched online databases for controlled observational studies from inception until Jan 1, 2023. Case-control or cohort studies were eligible if the detection was made of enterovirus RNA or protein in people with outcomes of islet autoimmunity or type 1 diabetes. Studies in pregnancy or other diabetes types were excluded.

Three reviewers independently performed data extraction and appraisal which involved author contact and deduplication. Study quality was evaluated with the National Health and Medical Research Council and the Newcastle-Ottawa Scale levels of evidence. Pooled and subgroup meta-analyses were done in RevMan version 5.4, with random effects models and Mantel-Haenszel odds ratios.

The authors reported the following findings:

· The search returned 3266 publications, with 897 full texts screened. Following deduplication, 113 eligible records corresponded to 60 studies (40 type 1 diabetes; nine islet autoimmunity; 11 both), comprising 12077 participants (5981 cases; 6096 controls).

· Study design and quality varied, generating substantial statistical heterogeneity.

· Meta-analysis of 56 studies showed associations between enteroviruses and islet autoimmunity (OR 2·1, n=18), type 1 diabetes (OR 8·0, n=48), or within 1 month of type 1 diabetes (OR 16·2, n=28).

· Detection of either multiple or consecutive enteroviruses was associated with islet autoimmunity (OR 2·0, n=8).

· Detection of Enterovirus B was associated with type 1 diabetes (OR 12·7, n=15).

"These findings highlight the association between enteroviruses and islet autoimmunity or type 1 diabetes," the researchers wrote. "Our data strengthen the rationale for the development of vaccines that target diabetogenic enterovirus types, specifically those within Enterovirus B."

"There is a need for prospective studies of early life to elucidate the role of enterovirus type, timing, and infection duration on the islet autoimmunity initiation and progression to type 1 diabetes," they concluded.

Reference:

Isaacs SR, Roy A, Dance B, Ward EJ, Foskett DB, Maxwell AJ, Rawlinson WD, Kim KW, Craig ME. Enteroviruses and risk of islet autoimmunity or type 1 diabetes: systematic review and meta-analysis of controlled observational studies detecting viral nucleic acids and proteins. Lancet Diabetes Endocrinol. 2023 Jun 27:S2213-8587(23)00122-5. doi: 10.1016/S2213-8587(23)00122-5. Epub ahead of print. PMID: 37390839.