Thomas H. Maugh II (Los Angeles Times)
Researchers in California and Florida have strong new evidence implicating a common class of viruses in causing Type 1 or insulin-dependent diabetes, a discovery that eventually could lead to ways of preventing the disease that affects as many as 1 million Americans.
Type 1 diabetes occurs when the body’s immune system attacks and destroys insulin-producing cells in the pancreas. Researchers know that only people with a specific genetic profile are susceptible to this autoimmune attack, but there has been debate about the identity of the agent that triggers the immune reaction.
Now, two studies in this month’s issues of the Journal of Experimental Medicine and the Journal of Clinical Investigation strongly implicate coxsackie viruses, polio-related viruses that cause upper respiratory infections.
One report shows that coxsackie viruses trigger diabetes in genetically susceptible mice but not in those that have a different genetic profile. The second demonstrates that the autoimmune reaction is triggered by a similarity between a coxsackie virus protein and a protein in the pancreas.
The two studies provide “a strong case of guilt by association,” said molecular biologist Daniel L. Kaufman of the University of California, Los Angeles.
“It’s only inferential data so far, but it’s pretty strong inferential data,” added Noel Maclaren of the University of Florida. “I think the case is really seriously beginning to build” that coxsackie viruses are the key triggering agent.
If the virus is shown to be a primary cause of the disease, vaccines against the virus probably could prevent diabetes, the researchers said. But “before we can start working on such a vaccine, we need to have a fairly clear smoking gun,” strongly confirming that the virus causes diabetes, said Joan Harmon, director of the Diabetes Research Program at the National Institutes of Health.
Researchers have a 30-year history of interest in coxsackie viruses as a diabetes cause. Epidemiological studies in the 1960s, for example, showed that coxsackie outbreaks in various regions were followed by an increased incidence of diabetes. Studies also showed that perhaps 60 percent of newly diagnosed diabetics had antibodies to the virus.
More recently, researchers such as Maclaren and his Florida colleague Mark Atkinson have demonstrated that people in the very earliest stages of diabetes have antibodies against a specific protein, subsequently shown by Kaufman and others to be an enzyme called glutamic acid decarboxylase or GAD.
Three years ago, Kaufman and Allen J. Tobin of UCLA demonstrated that a small segment of GAD is structurally similar to a segment of a coxsackie protein. Their interpretation was that when the immune system attacks this viral protein in fighting off a coxsackie infection, it also inadvertently attacks GAD, which is found on the surface of insulin-secreting pancreas cells. Ultimately the cells are destroyed and diabetes results.
Maclaren cautioned that coxsackie viruses may not be the cause of all type 1 diabetes. About one in every five diabetics, he noted, do not make an immune response to GAD, and their disease may have been triggered by some other agent. Possible triggers that have received a lot of attention include the nitrosamines used as a food preservative and a protein in cow’s milk.
“We’re really homing in on the cause of this disease,” said Richard Kahn, vice president for research at the American Cancer Society. “This could very well be the major, perhaps the only, environmental trigger for diabetes… .
Coupled with the progress in identifying people at risk, we’re getting very close to being able to prevent this disease from occurring.”