Drug Found to Slow Onset of Diabetes
Scientists have delayed the onset of full-blown Type 1 diabetes in young people for at least a year with a two-week drug treatment that blocked a specific part of the youths’ immune systems.
Patients taking the drug continued to produce their own insulin and required fewer and smaller insulin shots than those who were not treated, according to a study published today in the New England Journal of Medicine. Previous studies have shown that diabetics who continue to produce at least some insulin have better control of their blood-sugar levels and far fewer devastating side effects, such as blindness and loss of nerve sensation.
These results are “remarkable,” said Dr. Robert Goldstein, chief scientific officer of the Juvenile Diabetes Research Foundation.
“For the first time, it has been shown that progression of the destructive autoimmune response can be stopped with few side effects and [insulin production] preserved,” he said.
But a second, much larger, study also published today in the New England Journal of Medicine showed that another once-promising approach to preventing the disease--giving regular insulin shots to children in an effort to block the onset of diabetes--does not work.
Type 1 diabetes, which affects at least 1 million Americans, is an autoimmune disease in which a person’s own immune system destroys the pancreas cells that normally produce insulin. Once those cells have died, the insulin must be supplied by daily injections.
Over the last decade, researchers have made great progress in detecting the early signs of such an autoimmune attack, enabling them to identify people who are at high risk of developing the disease. Identifying them while they still have some insulin production makes it possible to consider interventions to block the disease process.
Brute-force approaches, such as shutting down the immune system with steroids and other immune-suppressing drugs, have been shown to delay the onset of full-blown diabetes, but the severe side effects produced by the drugs proved worse than the disease itself.
Researchers have thus been searching for other ways to trick the immune system into breaking off its attack.
Researchers from UC San Francisco and Columbia University attacked the problem using a new drug with the unlikely name of hOKT3-gamma-1 (ala-ala). This artificial antibody, developed by Dr. Jeffrey Bluestone of UCSF, attacks the immune cells that are targeted at pancreatic cells.
“It sets up a regulatory network that keeps these cells in check,” preventing them from destroying pancreas cells, Bluestone said.
The team led by Bluestone and Dr. Kevin Herold of Columbia University studied 12 patients, ages 7 to 27, who had recently been diagnosed with diabetes.
For two weeks, the patients received daily injections of the antibody.
Twelve carefully matched patients who had also been diagnosed with diabetes did not receive the drug and served as controls.
One year after the treatment, nine of the 12 patients who received the antibody had little, if any, loss of their ability to secrete insulin. In contrast, 10 of the 12 in the other group had a significant loss of insulin production.
The treated patients also showed improvements in other clinical symptoms of the disease, the team reported.
The new drug will now be studied in at least 80 more patients, Bluestone noted. The drug will be administered at the beginning of the study, at six months, and after one year in the hopes that a stronger, more prolonged response will be observed.
But researchers cautioned against undue optimism about the drug, citing the disappointing results with insulin injections.
That approach looked very promising in animal studies and in a small human trial similar to the new antibody study.
The idea was that the injected insulin would allow the body’s own insulin-secreting cells to “rest,” thereby making them less susceptible to the immune attack.
To test this idea, a network of researchers in the United States and Canada screened more than 84,000 relatives of diabetics, looking for patients in the early stages of the disease.
They ultimately identified 339 children, with an average age of about 12, who had at least a 50% chance of developing diabetes in the next five years.
Half were given twice-daily doses of insulin, while the rest were merely observed. After nearly four years in the study, 69 of those receiving insulin had developed diabetes, compared to 70 of those in the observation group.
In other words, the intervention didn’t work, said Dr. Jay S. Skyler of the University of Miami, who headed the study.
Skyler noted that his group had encountered some difficulty in enrolling patients in the study because many physicians were already administering insulin to the potential subjects based on the results of the small preliminary study and the results in animals.
That is why it was important to conduct the larger study, he said: “The history of medicine is littered with wrong conclusions drawn from pilot studies.”
Although researchers were disappointed at the study’s findings, they were encouraged by the fact that the team was able to identify people at high risk of diabetes and make an effort to intervene.
Even though this particular study was not successful, researchers now have a clinical network in place to conduct future studies of other potential treatments.
“The landmark importance of his trial is related not to the outcome, but to the fact that it could be conducted at all,” according to Dr. Edwin A.M. Gale of the University of Bristol in England.
“It was a really important trial because it enabled us to get together a consortium of people across North America to work together on common protocols to try to prevent diabetes,” said Dr. Francine R. Kaufman of USC, president-elect of the American Diabetes Assn. “It was a beginning. Now we can go on to look at other drugs.”
Meanwhile, two other major prevention studies are nearing conclusion.
A European group has been administering the antioxidant nicotinamide to high-risk children and is expected to report their findings in September.
The North American network is also conducting a second large insulin study in which the hormone is consumed orally.
The idea of this approach, which has also proved successful in animals, is that exposure of the hormone to the broad variety of immune cells in the gut will interfere with the autoimmune attack.
Those results are not expected for another year.
