TEDDY Fails to Find Viral Trigger for Type 1 Diabetes

Marlene Busko

May 06, 2013

Researchers found no evidence that a viral infection caused rapid-onset type 1 diabetes in 24 children with a genetic susceptibility to the disease who participated in The Environmental Determinants of Diabetes in the Young (TEDDY) international study.

The TEDDY researchers had hypothesized that children with rapid-onset type 1 diabetes, which develops within 6 months from the appearance of anti-islet antibodies, would have viremia around the time when these autoantibodies were first detected. But this was not the case.

This finding "probably means that if it is a virus that starts this [progression toward type 1 diabetes], then it is well hidden," study author Ezio Bonifacio, MD, at Dresden University of Technology, in Germany, told Medscape Medical News in an email. "It could, of course, also mean that it is not a virus that does this, but we can't say this yet."

The study is published online May 6 in Diabetologia.

Does a Viral Infection Precede Type 1 Diabetes?

Patients with type 1 diabetes develop antibodies to proteins in their pancreatic islet beta cells, which gradually destroys their ability to form insulin. Enteroviruses have been implicated as possible triggers of this process, but studies in humans have been inconclusive, the authors write.

TEDDY, a prospective cohort study in 3 centers in the United States (Colorado, Georgia/Florida, and Washington) and 3 in Europe (Finland, Germany, and Sweden) is investigating the role of environmental factors such as viral infections, food, diet, vaccinations, drinking-water quality, and pollutants in type 1 diabetes.

From 2004 to 2010, TEDDY enrolled 8677 infants younger than 4.5 months who had a genetic predisposition to type 1 diabetes, including 932 with a first-degree family member with a history of the disease.

The children had blood samples taken every 3 months until they were 4 years old, to detect, among other things, when autoantibodies to islet cells occurred. A total of 355 participants developed islet autoantibodies, and 86 children progressed to type 1 diabetes by July 2011. Of these, 24 children developed type 1 diabetes within 6 months of the appearance of islet immunity (rapid-onset type 1 diabetes).

The researchers used next-generation nucleic-acid sequencing to determine whether viral sequences were present in plasma samples from 14 children with rapid-onset type 1 diabetes and 14 controls. The samples were from when the autoantibodies were first detected, when the children were 8 to 27 months old, and from 3 months earlier.

The sequencing test found viruses only in 1 patient (rhinovirus C), as well as in 3 controls (parvovirus, herpes virus, and GB virus).

The researchers then compared the 24 children with rapid-onset diabetes (patients) and 72 controls to investigate whether a gastrointestinal, respiratory, or other infection or fever was associated with a rapid progression to type 1 diabetes. All patients and 70 of 72 controls had reported at least 1 infection prior to the onset of diabetes, and the number of infections was similar in both groups.

Fever was less frequent in patients than in controls, which suggests "that a normal fever response is helpful in blocking the start of autoimmunity," but this would need to be confirmed in a larger sample, noted Dr. Bonifacio.

The authors acknowledge that the study was small and some viral infection episodes may have occurred at times other than when the blood samples were taken.

Complex Relationship, More Study Needed

This was a well-done study examining the complex relationship between viruses and type 1 diabetes, Matthias von Herrath, MD, professor at the La Jolla Institute for Allergy and Immunology, California, and vice president and head of the Novo Nordisk type 1 diabetes research and development center in Seattle, Washington, who was not involved in the study, told Medscape Medical News in an email.

Studies in "animal models show that viruses can accelerate as well as stop diabetes depending on viral strain, time of infection, and dose of infection," he added. Certain strains of enteroviruses are likely associated with human type 1 diabetes, as suggested by a meta-analysis by Maria Craig, MD, from the University of New South Wales, Sydney, Australia, and colleagues (BMJ. 2011;342:d35) and some emerging findings from the Network for Pancreatic Organ Donors with Diabetes (nPOD) consortium.

According to von Herrath, "It is not easy to associate any type of general viremia with human diabetes, and more detailed sampling during infectious events is likely needed [as well as] studies analyzing the pancreas directly, where possible."

The authors have reported no relevant financial relationships.

Diabetologia. Published online May 6, 2013.