April 21, 2015 -- Swallowing a daily dose of insulin is safe, and it may act like a vaccine to prevent type 1 diabetes, a small new study shows.
If the results can be repeated in larger and longer trials, the approach may one day be used to help young children at high risk of the disease avoid getting diabetes.
The condition affects about 3 million adults and children in the U.S. And no one is sure why, but like allergies and other kinds autoimmune conditions, it's on the rise. One study found the rates of type 1 diabetes in children under age 5 had climbed 70% between 1995 and 2004.
The immune system’s assault on the islet cells happens in several steps. Before the body attacks those cells, it makes proteins that mistakenly flag insulin as foreign and dangerous. In a sense, the body becomes allergic to itself.
Blood tests can spot this early immune breakdown. Right now they aren’t routinely given, though, because doctors don’t have a way to stop the process once it starts.
But scientists wondered if giving children insulin the way you might treat someone with a food allergy -- by feeding them tiny amounts of the problem food to build up a tolerance -- might prevent the attack.
Defusing the Assult
Researchers say when proteins are introduced to the body through the mouth or nose, or when they’re absorbed through the skin, the immune system learns to see them as safe and will later tolerate them.
“The immune system in these places is there to learn to turn itself off, not on,” says researcher Ezio Bonifacio, PhD, a professor of diabetes at the Center for Regenerative Therapies in Dresden, Germany.
One risk in this approach, though, has been that the insulin might cause a dangerous drop in blood sugar.
Studies in mice bred to get type 1 diabetes have shown that insulin can defuse the immune attack and prevent diabetes, without any effect on blood sugar. But previous studies that have tried the same approach in people were less successful. Experts think it might be because the insulin was given too late in the type 1 disease process or at too low a dose.
“We know that once the process has started, it’s pretty hard to turn it off,” Bonifacio says.
In the new study, “we’re giving the oral insulin at this very early stage when the immune system is learning,” he says. And his team found evidence that the immune system was turning itself down in response to the challenge.
The researchers enrolled 25 children who were at high risk of getting type 1, because they had both a strong family history and genes linked to the disease. But their bodies had not yet begun the immune attack that leads to diabetes.
Fifteen of the kids, who ranged in age from 2 to 7, ate a daily dose of powdered insulin sprinkled on food. The other 10 ate food sprinkled with a placebo. The insulin doses ranged from 2.5 milligrams to 67.5 milligrams, and the kids took it for a time period ranging from 3 to 18 months.
People who inject insulin to control their blood sugar might take a dose in the range of 10 “units,” Bonifacio says. The children in the study on the highest insulin dose were swallowing a daily equivalent of about 3,000 units.
Despite the high dose, none of the children in the study got dangerously low blood sugar, which was one fear at the start.
“Less than 1% of the insulin is absorbed into the bloodstream,” Bonifacio says.
Five of six kids who were on the highest dose had an immune response to the insulin. Those responses seemed to suggest that the immune system was learning to tolerate the protein, not to attack.
More Research Needed
This is the first time that scientists have been able to demonstrate that a treatment given before someone gets type 1 diabetes can impact the immune system in a way that might protect against the disease, says Julia Greenstein, PhD, vice president of Discovery Research at the Juvenile Diabetes Research Foundation, one of the organizations that funded the study.
Despite the intriguing result, researchers say more work is needed before they’ll know if this approach can head off the disease.
Researchers are planning a new trial to study the highest dose of insulin. That will start later this year. They expect to have results by 2017. A prevention trial, which will attempt to show that the treatment can stop or delay the development of type 1 diabetes, will take 8 or 9 years, Bonifacio says.
The study is published in the Journal of the American Medical Association.