Islet-cell transplants: the end of insulin shots?

by Debra Wood

Diabetes update: islet cell transplantation Islet-cell transplants could offer millions of people with diabetes the chance for life without daily insulin injections.

Listen carefully and you might hear the faint whisper of the word "cure" echoing through the minds of people with diabetes. That's because promising results from a small study at the University of Alberta in Edmonton, Canada, have sparked international interest.

"I'm functioning as a normal, nondiabetic with few if any of the restrictions and none of the constant juggling that is part of the day-to-day life of an insulin-dependent diabetic," says Edmonton lawyer Robert Teskey who had been injecting himself with insulin for 40 years before receiving an islet-cell transplant. "I've had a whole new lease on life. I view it as nothing short of a miracle," he says.

The "miracle"

Physicians at the University of Alberta have transplanted insulin-producing islet cells from donated pancreases into patients with severe, unstable diabetes. The recipients have maintained normal blood sugar levels without taking insulin shots.

"The patients who have had the transplant are cured of diabetes, but they do have to take antirejection drugs," says James Shapiro, MD, director of the university's Clinical Islet Transplant Program. "But," he cautions, "there are still a number of challenging steps forward before we're ready to take this treatment to the 130 million people around the world with diabetes."

Conquering the incurable

Considered incurable, diabetes mellitus causes high blood sugar levels due to the body's inability to produce or effectively use insulin, a hormone secreted by the pancreas that aids in storing or converting glucose from food into energy. Almost 16 million Americans have this disease, and about five million of them don't even realize they have it.

People with type 1 diabetes, formerly known as juvenile-onset diabetes, produce little or no insulin and require multiple daily injections of the hormone. People with type 2 diabetes either don't produce enough insulin or their bodies have difficulty putting the available insulin to work; about 40% of them require insulin injections. Age, obesity and sedentary lifestyles contribute to type 2 diabetes.

Diabetes is the leading cause of blindness, end-stage kidney failure and leg amputations, and it also increases the risk for heart disease, which is the number-one killer of men and women in America. Until now, people with diabetes who wanted to lower their chances of an early death or painful, debilitating complications had no choice but to inject themselves with insulin throughout the day, measure their blood sugar levels, watch their diet, and plan structured meals and activities.

"It's given me more freedom, control and self-confidence," says transplant recipient Mary Anna Kralj-Pokerznik, who for 18 years injected insulin as often as five or six times per day without obtaining stable glucose levels. "I can focus on what I am doing and not have to always think about whether it's time to take a blood test, eat a meal or take an injection. Now, I can do things like everybody else," she says.

The breakthrough

Research on islet-cell transplants began more than a quarter century ago, but most transplanted cells only functioned for a short time. Only about 8% of the patients who received the cells remained off insulin for at least a year.

"We had a major breakthrough when the protocol I designed really worked," Shapiro says. "The trick was to come up with a unique drug cocktail that was effective in stopping rejection, but didn't involve steroids, because steroids can cause diabetes. Making sure the islets were of the highest quality and being prepared to put enough of them into the patients pretty much guaranteed it would work."

The Edmonton Protocol includes transplanting cells immediately after removal from the donated pancreas, removing foreign proteins from the cells, and adding islets from a second pancreas if blood sugars start to rise. Doctors infuse the cells into the patient's liver during a simple procedure and the process carries less risk than an organ transplant.

Potential side effects

The antirejection medications, however, suppress the immune system and increase the patient's chances of developing cancer and infections.

"The possible problems with immunosuppressive drugs are just that a possibility. The difficulties I was having with diabetes were a certainty," says Teskey, who considers it an easy trade-off.

"We'd like to be able to do it with less drugs or with no antirejection drug at all," Shapiro says. "The advantage is we could treat children as soon as they were diagnosed with diabetes. We'd never have to put them on insulin. They'd go straight to a cell transplant, and it would be a cure."

Continuing research

The National Institutes of Health and the Juvenile Diabetes Foundation, with the sponsorship of the Immune Tolerance Network, are funding additional trials at 10 research centers in hopes of duplicating the Canadian results.

"Successful islet transplantation is as close to a cure as anyone is going to get. You can use the 'C-word' (cure) in discussing this. It's a huge advance," says R. Paul Robertson, MD, scientific director of the Pacific Northwest Research Institute, which is one of the transplant sites, and immediate-past chairman of the American Diabetes Association's Scientific Sessions.

Remaining hurdles

Lack of donated pancreases will limit the number of people who can receive islet-cell transplants. Robertson's team plans on transplanting cells from only one pancreas and giving the islets additional time to work. Modifying the protocol might help, but it's not the real solution. Shapiro believes an alternative tissue supply will be necessary before the treatment can be given to people with type 2 diabetes. He believes that to achieve the same results, these patients will require a greater number of islet cells.

With limited available organs, other scientists search for new sources of islet cells. Susan Bonner-Weir, PhD, a senior investigator at the Joslin Diabetes Center at Harvard Medical School, has cultivated human islet cells in the laboratory, and will test how they function in mice. Fred Levine, MD, PhD, at the University of California at San Diego Cancer Center has developed a human beta cell line that has secreted insulin. Until these or other new methods prove to be expedient, safe and effective, transplants will rely on donated organs.

Beyond their wildest dreams

"As someone on insulin, you never expect to be in any different situation; you never consider what life would be like without the juggling act," Teskey says. "In five or 10 years, we may be looking at a situation in which the world of type 1 diabetes has changed dramatically."