Greta Nakonechny used to be a very ill woman suffering from complications of severe diabetes. Now she has a new kidney and new islets which produce so much insulin, she went off insulin therapy last August, and her blood sugar is normal. For a diabetic, that means health and freedom.

In 1990, another Edmontonian, Marge Heayn, became the first person in the world with severe Juvenile Diabetes to have long-term freedom from insulin therapy. Her transplated islets functioned well for two years, but she then required insulin therapy again, probably because she is on high doses of anti-rejection drugs to control rejection problems with her transplated kidney. Her transplated islets are still functioning and may produce all the insulin she needs when she is able to reduce the immunosuppression drugs.

These women were treated by the pioneer islet transplat team at the University of Alberta. Dr. Ray Rajotte, Dr. Garth Warnock, and Dr. Norm Kneteman. They are all world leaders in the field.

During the last six years, they carefully showed that transplanting human insulin-producing cells is safe and works. Now the research is entering an exciting second stage that will answer the question: Can islet transplatation efficiently and cost-effectively prevent the devastating complications of diabetes?

Marge Heayn and the other patients were chosen because they had severe diabetes along with kidney failure, and were already receiving a kidney transplant. This meant they would receive the very strong immunosuppressive drug neccesary for the kidney transplant. The idea was that it would be unethical and unwise to give patients immunosuppressive drugs only for experimental islet transplants before the procedure was proven effective.

With the first transplant, the U of A team showed that giving diabetics donor insulin-producing cells work. Recent lab research has solved the problem of the immunosuppressive drugs. The scientists have found that, when islets are cryopreservered, and placed in culture for a week before transplatation, they are less susceptible to rejection. This means lower doses of the anti-rejection drugs. This means lower doses of the anti-rejection drugs. All are, a great benefit because the drugs have undesireable side effects, and are very expensive. Once a tranplant is under control, it still costs an average of $15, 000 a year per patient for anti-rejection drugs. Lowering the dose would reduce costs dramatically.

Now the team is about to begin the second stage of the studies with a small group of patients who will require much lower doses of anti-rejection drugs.

Eight young adults have been recruited for the next transplants, and matched to eight control patients. They have previously had kidney transplants, but other complications are stable. Seven million islets have been harvested from donor pancreas, cryopreserced, and stored in a tissure bank. This time the islters will not be surgically transplanted. They will be injected into the patient's liver, using X-rays to guide the needle.

One of the disadvantages of islet transplants, compared to transplating the whole pancreas, is that three or four pancreases are needed to extract the thousands of islets required. The team expects to solve this problem with a new chemical that makes seperation of the cells easier. In the United States transplatation of the pancreas is more popular because it has a greater success rate. Once islet transplants are equally efficient, they will be preferable because less transplated tissure means fewer immunosuppressive drugs, and less surgery.

Dr. Ray Rajotte is working on ways to encapsulate the transplated islets so that the body does not see them as foreign and reject them.

Then there are the cocktails Dr. Rabinovitch and his colleagues are mixing up to stop the immune system from destroying the transplanted islets the way it destroyed the diabetic's own islets.


Intensive Therapy Works

Dr. Warnock stresses that islet transplants are designed for people who have diabetes and are sure to develop renal failure, blindness and other complications, so that they can receive the transplants before the complications occur. When gene tests can accurately predict who is likely to decelop complications, these people can be targeted for transplants.

But for now, Dr. Warnock wants all people with juvenile diabetes to know there is something they can do to prevent the disease from progressing: undergo intensive therapy. He explains, "Strict control of blood sugar matters. This has been proven scientifically and there are non-transplant ways of achieving it." A very intense, disciplined regime of careful diet, regular monitoring, insulin therapy, and exercise will control diabetes. Dr. Warnock urges patients to follow this, even though it is extraordinarily demanding.


This is Only Kindergarten

"Once the signals that regulate insulin production are known, maybe we could get an engineered beta cell in there that would bring insulin under control. Then I could take a biopsy of cells from a diabetic child, reconstitute those cells to what I think is an insulin-secreting cell line, and restore insulin production. I wouldn't need to worry about transplant rejection, and hopefully Alex(Rabinovitch) and Ray (Rajotte) will tell us how to control the autoimmunity," says Dr. Warnock.

"When you look ahead you realize that someday we'll look at what we're doing right now as kindergarten stuff," he adds. "We've never been in a better position to find an ideal way to reverse diabetes. I find that, as we encounter obstacles, we look back a year later and say, 'Gee, I wouldn't have thought I could overcome that !' But we do. We have to be persistent. It never seems like we're moving fast enough, but we have to be persistent."