1 August 1996
A Potential New Diabetes Treatment Would Help Patients Grow New Pancreas Cells -- In Their ArmSTANFORD -- Researchers are preparing to test a potential treatment for juvenile-onset diabetes based on implanting fetal pancreas tissue into a patient's forearm. The treatment could eliminate patients' need for insulin shots by providing them with an internal, self-regulating insulin source.
The treatment stems from research in rats conducted at Stanford University School of Medicine, including a study led by surgical resident Dr. Gregg A. Adams, to be presented at the annual meeting of the American Society of Transplant Surgeons.
The Stanford researchers plan to begin testing the treatment in humans this summer.
Patients who undergo the procedure will need lifelong treatment with immunosuppressive drugs to prevent them from rejecting the implanted tissue. For this reason, the researchers are first testing the strategy on diabetic kidney transplant patients -- who must take immunosuppressants for the life of their kidney transplants.
Ultimately, all juvenile-onset diabetes patients may be eligible for the treatment, the researchers said, as long as fetal pancreas tissue is available, because the treatment's benefits may outweigh the drawback of life-long immunosuppression. The treatment could eventually replace the need for insulin injection, they said.
"If the treatment works, it will not only spare patients from the inconvenience of insulin injections but also -- and maybe more importantly -- from the harmful effects of sharp ups and downs in their blood sugar levels," said Dr. Donald Dafoe, an associate professor of surgery at Stanford and senior researcher on the project.
"Usually, even multiple insulin injections a day will not finely control delivery of insulin," said Dafoe, who with Adams plans to conduct the pilot human trial.
Normally, a healthy pancreas responds to changes in blood sugar level by secreting higher levels of insulin when needed, to help sugar enter cells so it can be used by the body as an energy source.
Juvenile-onset diabetes results when damaged cells in the pancreas can no longer produce enough insulin to control a person's blood sugar level. The disease, also called Type 1 diabetes, affects about a million people in the United States.
High blood sugar levels shorten diabetics' lives, damage their nerves and blood vessels, and increase their risk of stroke, heart attack and limb amputation because of gangrene.
The standard medical treatment for juvenile-onset diabetes includes insulin injections (usually about three a day), regular exercise and a low-sugar diet.
The use of an insulin pump, another treatment strategy, has not been universally successful, Dafoe added. The pump, which hangs on a belt outside the patient's body, delivers insulin through a needle inserted in the abdomen. The injection site, however, is prone to infection, and may restrict patients' lifestyle.
Clinicians have treated diabetes with implanted pancreas tissue in the past, but because the tissue failed to flourish, the procedures were not entirely successful.
"People have tried to transplant fetal pancreas for a number of years, with the first attempt in 1928, but have had no success," Adams said. The reason, he said, is that "fetal pancreas does not have the right growth factors to allow it to mature. So Dr. Dafoe and I looked at various growth factors to see if there is something we can add to the soup to tickle the pancreas tissue to grow."
In the new strategy, Adams and his colleagues hope to overcome that problem by treating the newly implanted tissue with a chemical called Insulin-like Growth Factor 1 (IGF1). In experiments in rats, IGF1 treatments helped pancreas cells proliferate and produce insulin.
At this week's meeting, Adams will discuss a similar experiment using rats, using a newly identified growth factor called ALR. His team found that nearly all 17 of the rats given fetal pancreas implants and treated with ALR were able to regulate their blood sugar levels, but that only one out of the 14 rats given no ALR were able to do so.
Though this experiment shows that ALR is quite effective at stimulating the pancreas cells to produce insulin, IGF1 appears to be as good or better, Adams said.
Adams presented this study Thursday, May 30, during the American Society of Transplant Surgeon's annual meeting, at the Wyndham Anatole Hotel, Dallas.
Adams and Dafoe collaborated on the rat study with Dr. Marcello Maestri, a transplant surgeon at the University of Pavia, Italy. The rat research was funded in part by the Juvenile Diabetes Foundation International and a Walter V. and Idun Berry Fellowship.
In the pilot human trial, involving 10 subjects, researchers plan to implant fetal pancreas tissue into the subjects' forearm muscles, creating a row of about 4 implantations on one arm of each subject. The researchers will use the forearm, Dafoe said, because it is easily accessible and has been used successfully for other types of implants.
"The procedure depends on just a simple incision. It's like planting a row of seed corn in the soil," Dafoe said.
The researchers will give half of the subjects IGF1 injections and compare the growth and function of transplanted fetal pancreas with those of the subjects who receive no IGF1.
Diabetic kidney transplant candidates interested in participating in the trial can contact Stanford's Multi-Organ Transplant Clinic (415) 725-9891.
Last Updated: Tuesday February 03, 2015 22:31:55
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