The Relationship Between Diabetes and Enteroviruses

Contributed by Guest Blogger: Charlie Gray ‘11

Enteroviruses are a genus of positive sense, single-stranded RNA viruses which include poliovirus, coxsackie A & B, echovirus, and enterovirus. These viruses can cause a variety of symptoms ranging from the common cold and conjunctivitis to paralytic poliomyelitis. Researchers have also found an association between enteroviruses and type 1 diabetes, a disease whose incidence has increased over the past 25 years at an annual rate of 3%, a rate that cannot be explained simply by genetics.

In a recently published paper, Wing-Chi G Yeung and his colleagues conduct a systematic review of controlled studies that use molecular virological methods in an effort to compile what is currently known about the association between enteroviruses and type 1 diabetes, and to aggregate their results. Their meta-analysis included 34 papers, 30 of which used reverse transcriptase PCR or in situ hybridization to detect the enterovirus RNA; the other four used immunostaining for the enterovirus capsid protein, vp1, on autopsy pancreas specimens. Although the studies varied in age distribution, most investigated children and adolescents (i.e. less than 16).

Yeung and his colleagues found a strong association between enterovirus infection and diabetes, with a 9 fold increase in the risk of infection in diabetic individuals. They conclude that their meta-analysis of these previous observational studies do provide support to the growing collection of findings that individuals with type 1 diabetes have increased odds of suffering from an enterovirus infection.

Despite Yeung et al.’s findings, there was quite a bit of variation in the designs and methods used in the various studies that the authors analyzed. Only 10 of the 34 studies matched for three or more potential confounding factors such as age, genetic risk, geographical location and sampling time. In addition, the studies varied greatly in the site selection from which they collected samples (e.g., serum, stool, throat swabs). Enteroviruses invade cells and replicate at mucosal surfaces; therefore, detection rates could be significantly higher in samples that were obtained from the gastrointestinal tract.

Although this paper does provide evidence for a diabetes-enterovirus link, it does leave several questions for future research. It is unclear how strong the association between enterovirus infection and diabetes is, and if the other factors such as geographic location and genetics may influence the observation of enterovirus infection and diabetes. For example, previous studies have examined varying HLA (a gene encoding an important immune system protein) genotypes and how certain genotypes can modify the association between enterovirus infection and diabetes; however, those results have provided conflicting evidence. Therefore, further study is needed to determine how these confounding factors affect one another and the enterovirus-diabetes link.