Children with type 1 diabetes are nearly 10 times as likely to have a particular viral infection than children without diabetes, BBC News has reported.
This news is based on a high-quality review of the findings of 26 studies that assessed how common an enterovirus infection is among people with and without type 1 diabetes. The enterovirus group of viruses includes polio and coxsackie viruses, which are believed to be the viruses most likely linked to type 1 diabetes. The review findings indicate a clear relationship, with the odds of having an enterovirus infection in people with type 1 diabetes almost 10 times greater than in unaffected individuals. However, as the researchers importantly note, the review cannot prove that the virus causes diabetes as the studies cannot confirm that infection occurred before the onset of diabetes.
This research supports previous studies that have identified enteroviruses as being linked to type 1 diabetes. There is now a need to assess the relationship between the virus and diabetes over time to determine whether there really is a cause-and-effect relationship between the two.
Where did the story come from?
The study was carried out by researchers from the University of New South Wales in Sydney, the University of Sydney and research hospitals in New South Wales, Australia. It received no specific grants from any funding agency in the public, commercial or not-for-profit sectors. The study was published in the peer-reviewed British Medical Journal.
BBC News accurately reported this study.
What kind of research was this?
This systematic review and meta-analysis searched global literature to identify studies examining an association between enterovirus and type 1 diabetes. Type 1 diabetes is an autoimmune disease, where the body produces antibodies that attack the beta cells of the pancreas, which normally make insulin. These antibodies cause the body to mount an immune response against the beta cells The person is then unable to produce insulin and needs lifelong insulin replacement. Type1 diabetes differs from type 2 diabetes, which is caused by the body’s tissues becoming less sensitive to the effects of insulin.
Though there is a strong hereditary component to type 1 diabetes, young people with no family history of type 1 diabetes can develop the condition. Enteroviruses - a group of several viruses, including polio and coxsackie viruses - are the most widely studied viruses believed to have a possible link to type 1 diabetes. Previous studies have demonstrated that blood from people with type 1 diabetes contains antibodies against enteroviruses, as well as proteins and a type of genetic material called RNA related to enteroviruses. However, the link has not been consistent across all studies, and this review aimed to gather the evidence to investigate whether enterovirus infection increases the risk of autoimmunity against pancreatic cells or type 1 diabetes.
While a systematic review with meta-analysis is the best way to identify and combine studies that have addressed this question, such a review is inherently limited due to the differences between the methods of the individual studies.
What did the research involve?
The researchers examined medical literature databases for cohort or case-control studies (published up to 2010) which had used reliable molecular methods to detect enterovirus RNA or viral protein in blood, stool or tissue samples from people with diabetes or pre-diabetic conditions (where autoimmunity against pancreas cells was identified but the person had not yet developed diabetes).
To be included in the review, studies also had to provide risk figures (odds ratios) expressing the chance of detecting enterovirus in people with pre-diabetes versus the chance in people with no diabetes, or in people with diabetes versus no diabetes.
What were the basic results?
In total, 24 case-control studies and two study abstracts (not full publications) met the inclusion criteria. These studies included 4,448 participants (1,931 cases with diabetes or pre-diabetes, and 2,517 controls without diabetes). Most studies defined the condition of pre-diabetes as testing positive for at least one autoantibody associated with type 1 diabetes. Most studies were in children, though some included adults up to the age of 53. When combining the studies, there was high variability between the outcomes they assessed and their study results (statistical heterogeneity), so the researchers used methods that would give them more conservative results.
When they combined the results of 23 studies in a meta-analysis, the researchers found that the odds of having had enterovirus infection were almost 10 times greater in people with diabetes than in controls without diabetes (odds ratio [OR] 9.8, 95% confidence interval [CI] 5.5 to 17.4). Combining the results of nine studies showed that the odds of having had an enterovirus infection in people with type 1 diabetes-related autoimmunity against pancreas cells were almost four times those of controls (OR 3.7, 95% CI 2.1 to 6.8).
How did the researchers interpret the results?
The researchers concluded that there is a significant association between enterovirus infection and type 1 diabetes or diabetes-related autoimmunity. They say that larger prospective studies would be needed to establish a “clear temporal link” between enterovirus infection and the development of autoimmunity and type 1 diabetes (i.e. to establish which came first).
This high-quality systematic review combined the findings of 26 observational studies that investigated whether enterovirus infection is detected in people with and without type 1 diabetes and diabetes-related immune responses against the pancreas. The review only included studies that used reliable molecular methods to detect the virus. The findings demonstrate a clear relationship, with the people with type 1 diabetes almost ten times as likely as controls to have evidence of enterovirus infection.
Points to note include:
- As the researchers mention, though this review has demonstrated that enterovirus appears to be associated with type 1 diabetes and related immunity, it cannot prove that this virus causes diabetes. The studies cannot establish whether the person contracted the virus before diabetes was established or whether they were infected with the virus when they already had diabetes.
- The studies were heterogeneous, which means they had widely different methods, inclusions and follow-up assessments. As such, there is some inherent inaccuracy in combining their results. While the size of the association between diabetes and enterovirus was expressed as an odds ratio of 9.8, the true size of the ratio is likely to fall within a wide range (somewhere between 5.5 and 17.4). This indicates that there may be some imprecision in the study’s estimate, and that this may not be the true size of the risk.
- This study focused specifically on enterovirus infection in the individual, and cannot tell us the influence of other risk factors for type 1 diabetes. In particular, the effect of maternal infection with enterovirus on the risk of diabetes in their child is unknown. Currently, a family history of type 1 diabetes or other autoimmune diseases is the most firmly established risk factor for the condition.
- It is worth noting that this study is relevant to type 1 diabetes only, not type 2 diabetes.
This research supports previous studies which have identified enteroviruses as being linked to type 1 diabetes. Further large prospective cohort studies would be needed to see whether exposure to this viral group, in addition to other infective and non-infective environmental causes, could increase the risk of developing type 1 diabetes.