Transplants for Diabetes Promising, Yet Limited
May 29, 2002 -- Can diabetes be transplanted away?
Judy Guggenheim hopes so. Guggenheim has uncontrollable diabetes. She must use a pump to get the insulin her body needs. She must test her blood 15 times a day, including twice in the middle of the night, every night. And even then, the level of sugar in her blood can plummet without warning.
A transplant of insulin-producing cells called islets (pronounced "eye"-lets) could change her life and perhaps even save it.
"It's going to save my life," Guggenheim told ABCNEWS' John McKenzie. "I can't count the number of times I've been in a coma because of my diabetes."
The transplantation of insulin-producing cells is producing miraculous results for a select group of patients with serious complications like Guggenheim's, experts say. Yet they are quick to add there are limitations to its more widespread use.
One million Americans have type I diabetes, the most severe form, in which the body's own immune system attacks insulin-producing cells. The diagnosis of what is also known as juvenile-onset diabetes requires lifelong insulin injections to manage the disease.
However, researchers are exploring alternative treatment options. One is transplantation into diabetics of either a whole pancreas, or, in a less-expensive, less-invasive procedure, just the islets.
Researchers from various institutions have reported success in transplanting islets into patients with severe complications from type I diabetes, many of whom have subsequently reduced or eliminated their dependence on insulin.
Too Few Donors
While many view islet transplantation as a significant medical advance, its use as a treatment or potential cure for all diabetics is limited.
"The No. 1 difficulty is that we don't have enough islets to transplant," says Dr. Robert Goldstein, chief scientific officer at the Juvenile Diabetes Research Foundation International in New York.
Islets are currently harvested from about 5,500 cadaver donors in the United States each year. Even then, certain cells from that relatively small number of donors may not be eligible. Illness and logistical factors can make organs unsuitable for transplantation, and reduce availability by as many as 2,000 donors.
"There are 30,000 new cases of type I diabetes each year, so 3,500 donors a year is just inadequate," says Dr. David Sutherland, head of the division of transplantation and director of the Diabetes Institute for Immunology and Transplantation at the University of Minnesota in Minneapolis.
And the supply may be limited even further, given that successful transplantation techniques, like that reported by researchers from the University of Alberta in Edmonton, Canada, required islet cells from multiple donors.
"If it takes all of the islets purified from one pancreas to be transplanted twice to help somebody, we have a diminishing-returns problem here," says Goldstein.
Lifelong Immunosuppression
A further limitation is the fact that while transplantation may reduce or eliminate the need for insulin injection, recipients of islet cells require lifelong immunosuppression to prevent rejection.
"Many people think that the price of immunosuppression is worth the cost of being a diabetic," says Sutherland. "It's an individual decision."
Yet the price of immunosuppression is quite high. Suppressed immune systems are ill-equipped to fight infection and are at an increased risk of developing cancer.
"As a potential cure for a 10-year-old with type I diabetes, this is not it," says Goldstein. "We can't give 10-year-olds lifelong immunosuppression — it's just too toxic. That's trading one bad disease for another."
This is why candidates for such transplantation are those with severe complications of the disease — such as severely low blood sugar that causes unconsciousness, seizures or impaired cognition — that are poorly controlled with insulin. Other candidates are those who require other transplants, such as a kidney, and would be given immunosupression anyway. Almost 5,000 of 5,700 pancreas transplants have been performed simultaneously with or following a kidney transplant between 1997 and 2001.
For others, some experts say that the trade-off is simply not worth the risk.
"It's one thing if you have a really bad disease for which you cannot do anything else, but here I am talking about somebody who is doing OK on insulin shots. Would I want to put them at that kind of risk?" says Goldstein.
Overcoming Barriers
Without these barriers, islet cell transplantation could well be the solution to a burgeoning diabetes problem, and scientists are currently working on ways to increase the supply of islet cells that are available for transplantation.
Research areas include xenotransplantation, in which islets from pigs are being explored for human use, the use of stem cells that are coaxed to develop into insulin-producing cells, and living donor transplants. However, none of these areas has produced the far-reaching results for which researchers have hoped, they acknowledge.
Another future goal, and one for all areas of transplantation, is to induce immune tolerance of transplanted organs.
"The idea is that if I can figure out how to show your body that the organ I am giving you is not foreign, and I can do that by instructing the immune system not to reject it, I can induce tolerance," explains Goldstein.
While these research goals are not immediately within reach, there is enthusiasm that they may not be all that far away, either, and that a cure for diabetes is on the horizon.
"[Success with islet cell transplants] has given us a tremendous platform to advance research quickly," says Goldstein. "Some very special people have had their lifestyle remarkably improved at the cost of immunosuppression and that's a wonderful medical achievement, but that's not a cure."
For Judy Guggenheim, within two days of entering the hospital for the transplant procedure, she was back home. And for the first time since she was a teenager, doctors say she has no sign of diabetes.
ABCNEWS' John McKenzie contributed to this report.