Type 1 Diabetes Onset Strongly Linked to Enterovirus Infection Type, Timing

The link between enterovirus infection and type 1 diabetes appeared to be a strong one in a meta-analysis of molecular studies.

Across 48 abstracts on the topic, people with type 1 diabetes were nearly eight times more likely to have an enterovirus infection than those with normal pancreatic function (OR 7.99, 95% CI 4.92-13.00, P<0.00001), reported Sonia Isaacs, PhD candidate, of University of New South Wales in Australia, at the European Association for the Study of Diabetes (EASD) meeting.

People with islet autoimmunity were twice as likely (OR 2.07, 95% CI 1.30-3.31, P=0.002) to have had an enterovirus infection at any point in time, based on data from 18 studies.

Subgroup analysis of people who were diagnosed with the enterovirus within the past month found 16.22-fold higher odds (P<0.00001) of recent-onset type 1 diabetes, based upon 28 studies.

“This is very recent onset type 1 diabetes, and that was the highest risk group that we detected,” Isaacs said during a press conference.

Looking more closely at other subgroup criteria, she added that her group wanted to see what factors might be playing into this association between enterovirus and islet autoimmunity.

First, those who had any islet autoimmunity and eventually progressed to full-blown type 1 diabetes were over five times more likely to have an enterovirus infection than controls; this was a higher risk than those who had islet autoimmunity and never progressed to type 1 diabetes. When it came to timing, only infections at the time of or after islet autoimmunity seroconversion carried higher risk (OR 5.1), whereas the increased risk wasn’t significant for infections prior to seroconversion.

Those with a familial risk of type 1 diabetes — with the condition in a first-degree relative — also had a much higher risk for an enterovirus infection (OR 9.8), which Isaacs noted was higher than what was seen for the subgroup of participants recruited just based on carrying a high-risk HLA gene. But that being said, individuals who had the high-risk HLA gene and a familiar risk of type 1 diabetes had 141.1-times higher odds of prior enterovirus infection.

Having several enterovirus infections was also linked with a higher chance of islet autoimmunity (OR 2.0).

Specific type of enterovirus linked to risk of type 1 diabetes included:

• Enterovirus A: OR 3.7
• Enterovirus B: OR 12.7
• Enterovirus C: OR 13.8

“This is where the coxsackieviruses come from,” Isaacs pointed out. “Coxsackievirus B1 and B4 stood out.”

She added that the findings brings up the question of whether focus should shift towards enterovirus vaccinations and use of antivirals as a primary prevention strategy for type 1 diabetes. “There’s fantastic work being done in vaccination against the coxsackieviruses — they are including coxsackievirus B1 to 5.”

“If we can stop the enterovirus infection, will the incidence of type 1 diabetes be reduced? That’s the question for future studies,” she said.

Her group’s meta-analysis was an update to their previous systematic review and meta-analysis published in 2011 that included 26 studies on the topic. But within the past decade, there have been advancements in terms of molecular development for detecting viruses, like high-frequency sequencing and single-cell technology. With these advancements, it was time to update their prior review, said Isaacs.

For this new review, the researchers looked at published studies that identified enterovirus infection by looking for viral nucleic acid or protein in a human clinical sample — blood, stool, tissue, etc. — via molecular methods. There were a total of 56 studies included in the meta-analysis, representing data on over 12,000 participants.