Type 1 diabetes can seemingly spring up out of nowhere; leaving many who are diagnosed asking if there was anything they could have done to prevent this. Unfortunately, there currently isn’t any way to safely prevent type 1 diabetes— and there are only a few factors to indicate a higher risk for one person versus another. But a national clinical trial is trying to leverage those factors to help families whose risk might be elevated.
Type 1 diabetes accounts for 5 to 10 percent of the 23 million cases of diabetes in America. Much of the disease remains mysterious, but researchers have determined that type 1 diabetes onset most likely has to do with a blend of genetics and environment.
“There are certain genes that predispose people,” said Jason Gaglia, M.D., M.M.Sc., Investigator in the section on Immunobiology at Joslin Diabetes Center. For the average American the chance of developing type 1 diabetes is only about 1 percent. But, that risk increases ten- to fifteen-fold if a parent or sibling has the disease.
But genetics isn’t the only thing at play. Research suggests the involvement of an environmental trigger. “But what that environmental factor is isn’t really clear,” said Dr. Gaglia. “It could be some type of viral exposure, it could be changes in diet, or the absence of a protective factor, but we ultimately do not know.”
The importance of an environmental trigger seems evident from the fact that the rate of type 1 diabetes diagnosis is rapidly rising. In fact, “the incidence of type 1 diabetes is increasing at a faster rate than the incidence of type 2 diabetes in children,” said Dr. Gaglia. “The genes have not been changing at a rate that’s fast enough to account for the increased incidence of type 1 diabetes. So it needs to be some environmental factor.”
While the trigger remains unknown, Joslin researchers like Dr. Gaglia are looking for reliable ways to pinpoint a particular individual’s risk. A national effort to catalogue people at risk, called Type 1 Diabetes TrialNet, is underway at many centers, including Joslin. Dr. Gaglia heads up the clinical trial’s efforts at Joslin.
Under TrialNet, clinical researchers look for signs of impending onset by testing the blood of immediate relatives of people diagnosed with type 1 diabetes.
“Diabetes can be thought of as a spectrum, and what we think of as clinical diabetes is only at the very end part of that spectrum, when you’ve lost so much insulin producing capacity that you can’t keep your blood sugars in check,” said Dr. Gaglia. “But earlier on in the process, things such as autoantibodies develop and those are what we use as markers of disease, and just because an individual develops autoantibodies doesn’t mean that they’re necessarily going to go on to progress to developing clinical type 1 diabetes.”
TrialNet screens for specific markers of autoimmunity. Finding one means the person has some degree of autoimmunity. This doesn’t guarantee the person will develop the disease; it only slightly elevates the risk. As the number of autoantibodies discovered increases, however, so do the prospects of developing clinical diabetes.
Researchers working under TrialNet aim to understand disease progression through these tests. But the researchers involved also give participants the opportunity to join other clinical trials attempting to prevent the progression towards type 1 diabetes.
“Basically, what we’ve seen is, in these more successful strategies to date, most of them delay progression by about six months,” said Dr. Gaglia. “But then, unfortunately after that six month point, the clinical course tends to continue at about the same rate as those who hadn’t been treated. It’s just shifted six months on the curve.”
Eventually, the researchers under TrialNet want to cure the disease. Understanding how the disease advances will allow them to figure out targeted therapies and treatments. Until then, TrialNet can offer peace of mind to some wondering about their risk for type 1 diabetes.