A new systematic review has presented strong evidence the development of type 1 diabetes is linked to infection by enterovirus, a large group of common viruses. The findings build on a growing hypothesis linking the viruses to type 1 diabetes, with vaccines currently in development targeting the most likely viral strains.
The suggestion an enterovirus infection can trigger type 1 diabetes goes back more than 50 years, to a report published in 1969 that linked new-onset diabetes to recent infections with an enterovirus called Coxsackie B. Since then there have been a number of different studies published digging into this link, and the results have been frustratingly inconsistent.
A key 2011 study offered the first systematic review on the subject, focusing on modern molecular testing techniques (such as PCR tests). It found a clinically significant association between enterovirus infection and type 1 diabetes.
This new investigation, yet to be peer-reviewed and published but presented recently at the European Association for the Study of Diabetes annual meeting, is from the same research group and updates those 2011 findings to include more data and more advanced molecular diagnostic techniques.
The research encompassed data from 60 controlled observational studies, covering around 12,000 subjects. In general, those with type 1 diabetes were eight times more likely to have traces of an enterovirus infection.
More specifically, looking at studies with data on new-onset diabetes patients, the research found that within the first month of diagnosis patients were 16 times more likely to present evidence of enterovirus infection. The association was even stronger in those with either a genetic predisposition to type 1 diabetes or a relative with the disease.
"Our study found that people with T1D who had both genetic risk and a first-degree relative with T1D were 29 times more likely to have an enterovirus infection,” explained Sonia Isaacs, lead researcher on the project.
One of the challenges in understanding this viral association with diabetes is the enterovirus genus includes a large assortment of different viruses. To date, there are well over 80 different enteroviruses known to cause disease in humans.
For example, the three main species of rhinovirus linked to many cases of the common cold are part of the enterovirus virus genus. However, some enteroviruses are less innocuous. The three main types of poliovirus are also part of the enterovirus genus, as are the viruses that cause hand, foot and mouth disease in children. Other enteroviruses have been linked to myocarditis and encephalitis.
So which specific enteroviruses are associated with type 1 diabetes?
Prior studies have frequently homed in on a sub-group of enteroviruses dubbed Coxsackie B. There are six types of Coxsackie B enteroviruses, and researchers have estimated this group may account for a quarter of all enterovirus infections.
A team of researchers in Europe has already developed a single vaccine designed to target all six Coxsackie B enteroviruses. Human trials are underway and the goal is to create a vaccine that reduces a child’s risk of developing type 1 diabetes.
The new findings do somewhat back up the links between Coxsackie B and diabetes, with the highest associations being linked to enterovirus species encompassing those sub-types. However, the relationship may be a little broader, with enterovirus species A and C also showing links to diabetes development.
Isaacs is clear in pointing out these findings do not suggest enterovirus infections are the sole cause of type 1 diabetes. Instead, it seems likely a number of other factors need to line up for the virus to possibly trigger the development of diabetes.
"Virus infections are also proposed to work in combination with other factors such as diet, imbalances in the gut microbiome and even chemical exposures which may occur in utero (during pregnancy) or early childhood,” speculated Isaacs. “The number, timing and duration and even the site of enterovirus infections may also be important.”
The burgeoning evidence linking enterovirus infection to type 1 diabetes recalls recent research finding infections with the Epstein-Barr virus (EBV) can trigger the development of multiple sclerosis (MS). In that instance the research found not all EBV infections will cause MS but all MS cases are potentially preceded by EBV infections.
Type 1 diabetes is likely a much more heterogeneous disease than MS. Nevertheless, if some kind of enterovirus infection plays a key role triggering the condition in some people then preventing those infections could lead to a substantial reduction in new cases. Speaking to Medscape, diabetes researcher Kamlesh Khunti said the best patient population to target future studies based on these new findings would be those at high genetic risk of type 1 diabetes with close relatives already diagnosed with the condition.
"I think that's the group to go for because the association is so highly correlated,” said Kunti, who did not work on this new study. “Are there methods by which we can reduce this risk with either antivirals or vaccinations? I think that needs to be tested."
Source: Diabetologia