Common group of viruses strongly linked to type 1 diabetes

A common group of viruses is strongly associated with type 1 diabetes (T1D), according to new research presented at the annual meeting of the European Association for the Study of Diabetes in Stockholm, Sweden (September 19-23).

The Australian analysis found that individuals with T1D were eight times more likely to have an enterovirus infection than those without T1D.

T1D is the most common form of diabetes in children and its incidence has increased worldwide in recent decades. In people with the condition, the immune system attacks and destroys the insulin-producing beta cells in the pancreas, preventing the body from producing enough of the hormone to properly regulate blood sugar.

Over time, high blood sugar levels can damage the heart, eyes, feet and kidneys and shorten life expectancy. In addition, diabetic ketoacidosis, a condition that often presents with the diagnosis of T1D and where harmful substances called ketones build up in the blood, can be life-threatening if not treated early.

What exactly triggers the immune system’s attack remains controversial, but it’s thought to be a combination of a genetic predisposition and one or more environmental triggers, such as a virus infection.

Some of the strongest evidence for virus involvement points toward the enteroviruses. This common group of viruses includes viruses that cause polio and hand, foot, and mouth disease (HFMD), as well as other types that cause milder, cold-like symptoms.

Vaccines that seek to reduce the incidence of T1D by preventing enterovirus infection are already in clinical trials1 and confirmation of the role of enteroviruses would support this and other work for the primary prevention of T1D.

To explore the association more deeply, Sonia Isaacs, of the Department of Pediatrics and Child Health, School of Clinical Medicine, University of New South Wales, Australia, and colleagues conducted a systematic review and meta-analysis of existing research on the topic.

The meta-analysis – the largest in its field – included data from 12,077 participants (ages 0-87 years) from 60 controlled observational studies found in the PubMed and Embase databases.

5,981 of the participants had T1D or islet autoimmunity (which typically progresses to T1D). The remaining 6,096 participants had neither condition.

Enterovirus RNA or protein, a sign of current or recent infection, was detected in blood, stool or tissue samples using a range of advanced and highly sensitive molecular techniques.

Those with islet autoimmunity were twice as likely to test positive for enteroviruses as those without islet autoimmunity.

The risk of enterovirus infection was eight times greater in people with T1D than in people without T1D.

Most importantly, individuals with T1D were more than 16 times more likely to get an enterovirus infection in the month after their T1D diagnosis, than those without T1D.

The researchers conclude that there is a clear link between enterovirus infection and both islet autoimmunity and T1D.

Ms Isaacs added: “These findings provide further support for ongoing work to develop vaccines to prevent the development of islet autoimmunity and thereby reduce the incidence of T1D.”

There are several theories about how enteroviruses increase the risk of developing T1D. For example, it is thought that their interaction with certain genes may be important.

Ms Isaacs explains: “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.

“The number, timing and duration and even location of enterovirus infections can also be important. The ‘leaky gut’ hypothesis suggests that viruses originating from the gut may travel along with activated immune cells to the pancreas, where mild, persistent infection and resulting inflammation can trigger an autoimmune response.

“Virus infections are also proposed to act in conjunction with other factors, such as diet, imbalances in the gut microbiome and even exposure to chemicals that can occur in the womb (during pregnancy) or early childhood. There is still a lot to learn.”

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