More Proof that Small Daily Insulin Injections Can Delay or Prevent Type 1 Diabetes
Latest results lend new urgency to screening for "pre-diabetes" and enrolling individuals in nationwide clinical trial
BOSTON — June, 2000 — New research shows that small daily doses of injected insulin given to individuals likely to develop type 1 diabetes may prevent the disease for as long as eight years, according to researchers at Joslin Diabetes Center in Boston.
Results of the study, which follows up on patients enrolled in a pilot type 1 prevention study begun in the early 1990s, show that six out of 15 young people at high risk for type 1 diabetes who took daily insulin injections have not developed the disease. Some of them have been followed for nearly eight years.
These results lend new focus to the importance of a nationwide clinical trial now being conducted to see if type 1 or juvenile diabetes can be delayed or prevented in the relatives of someone who already has type 1 diabetes. They also create a need in the immediate future for developing less costly means of screening the general public for type 1 diabetes, as 85 percent of those individuals diagnosed with type 1 diabetes each year have no relatives with the disease.
"These new results suggest that relatives of someone with type 1 diabetes who have been hesitant to be tested to see if they are developing type 1 diabetes should not sit-on-the-fence any longer," said Tihamer Orban, MD, of Joslin Diabetes Center, who will report on the study. "There is now real hope that we can prevent the disease, or significantly delay the development of the disease, hopefully giving young people at least several years of disease-free time."
The Joslin researchers, jointly with researchers at the Barbara Davis Center for Childhood Diabetes in Denver, CO, will report this week on the results of this study, and on a Centers for Disease Control and Prevention study involving researchers at Joslin and other institutions in which they are testing a method for using a paper screening tool for type 1 diabetes in the general population. The reports were presented Sunday, June 11, at the national meeting of the American Diabetes Association in San Antonio, Texas.
What causes type 1 diabetes?
Scientists believe type 1 diabetes is caused by a malfunction in the body’s disease-fighting immune system which results in the destruction of the body’s insulin producing cells. In the early 1980s, researchers at Joslin along with other research groups identified markers for so-called "pre-diabetes" in the blood. These markers (antibodies) could be detected up to eight years in advance of an individual developing clinical symptoms of diabetes. Joslin researchers then began testing insulin injections as a means of possibly preventing or delaying the development of diabetes in "pre-diabetics" who had been identified through screening of the immediate relatives of someone who already had type 1 diabetes.
Began in early 1990s
In 1993, Joslin researchers published a small study showing that insulin injections had prevented the development of diabetes in several pre-diabetics, even though sophisticated mathematical models demonstrated that the individuals should have already developed the disease.
As a result of this study, the federal government agreed to fund the nationwide Diabetes Prevention Trial-Type 1 (DPT-1) which since the mid-1990s has been screening 80,000 immediate relatives of someone with type 1 diabetes to identify those individuals in the process of developing type 1 diabetes. Pre-diabetes patients identified have then been randomized into programs where they would receive injected insulin, oral insulin or no treatment, to see if diabetes could be delayed or prevented.
The most recent study is relatively small — 31 young people, now all in their 20s. It is the outgrowth of a small pilot study conducted jointly by Joslin and Children’s Hospital in Boston which was first reported in the medical literature in 1993. At that time, researchers had enrolled 12 young people, five of whom received insulin. All were related to someone with type 1 diabetes and had markers in their blood (antibodies) which suggested that they were in the process of developing type 1 diabetes themselves and would have the disease within three years. In 1993 the researchers reported that one of five individuals who were given small doses of daily insulin injections developed diabetes, while all seven individuals who were untreated developed type 1 diabetes. The 1993 results were so promising that the federal government agreed to start the DPT-1 nationwide, multi-center study to determine whether giving insulin by injection or orally could prevent or delay the disease.
The pilot study continued to enroll individuals until the DPT-1 began, however, ultimately enrolling the total of 31 individuals who are now being reported on. The participants were divided into four groups. One group of eight received a five-day course of insulin by intravenous injection annually. Seven were enrolled in a group that received small daily insulin shots. Eight were enrolled in a group that combined daily shots with the annual intravenous insulin. Eight others received no treatment. The average follow-up time in the study was 3 years. Other researchers involved with the pilot study at Joslin include Richard A. Jackson, MD, and Alyne Ricker, MD The Denver researchers include H. Peter Chase, MD, and George S. Eisenbarth, MD.
Six of 15 diabetes free
So far in the pilot study, six out of 15 of the children given insulin shots either alone, or in combination with annual insulin IV regimen, do not have diabetes. In the control group, which received no treatment, all eight developed diabetes. "Therefore, the study shows insulin shots prevent or delay the onset of type 1 diabetes," Dr. Orban said. As expected, the researchers found increased insulin antibodies in patients who took the shots compared to those who received only the IV.
"Even though this is a very small study, the results are highly significant," Dr. Orban said. "The prevention or delay may be related to an insulin immune effect — somewhat similar to the way allergy shots increase tolerance to antigens. We will continue to follow this group and look more closely at this antibody response to see what mechanism brings about this apparent protection."
Why is even a delay of a few years helpful to those at risk of developing type 1 diabetes?
Not only would a delay give the young person more disease-free time, but scientists know that the older a child is when they develop type 1, the more able the child is to manage the disease psychosocially, Dr. Orban said. A delay also can help minimize complications from diabetes down the road, and perhaps could even one day delay the disease until a cure is found.
New ways to test sought for pre-diabetes
With the promise of being able to delay or prevent type 1 diabetes, the researchers are investigating ways to more easily and quickly identify those at risk. "Eighty-five percent of newly diagnosed type 1 patients have no family history of the disease. Therefore, there are thousands of people at risk for type 1 hiding in the general population," said Dr. Orban. "We want to find a way to identify them sooner and more quickly."
He and his colleagues at Joslin, the Barbara Davis Center and at other institutions also will be reporting on their study to develop a paper test screening method to detect those at risk for developing type 1 diabetes and other autoimmune disorders, including celiac disease (gluten wheat allergy). This study being conducted under the auspices of the US Centers for Disease Control and Prevention uses a simple drop of blood from a fingerprick to test for the disease. If successful, such a test would enable mass screenings to identify more quickly those at risk for type 1 and several other immune disorders.
Joslin was one of the first labs in the nation to work on such a test. Now the project is in phase 3 of development and the effort is to make the screening test suitable for the general public's use. "The antibodies precede the diabetes for several years. The antibodies are very good predictors of who will develop type 1," Dr. Orban said.
