Islet Transplantation Promising for Type 1 Diabetes

A large clinical study testing the Edmonton Protocol, an approach to islet transplantation, shows that the procedure benefits some patients with severe complications of type 1 diabetes.

Of the nearly 21 million Americans with diabetes, about 5-10% have type 1. In type 1 diabetes, the body’s immune system attacks and destroys islets, the clusters of cells in the pancreas that produce insulin, which the body needs to use glucose (sugar) as a source of energy. Without insulin, glucose can’t enter cells where the body can use it. High levels of glucose accumulate in the blood, causing injury to nerves and blood vessels.

Without insulin shots, type 1 diabetes is fatal. Even with injections, however, people with type 1 diabetes can’t perfectly control their blood sugar. Most eventually develop complications such as heart disease and damage to the eyes, nerves and kidneys.

Pancreas transplants have allowed many people with type 1 diabetes to achieve total insulin independence. However, the procedure isn’t routinely done in patients with type 1 diabetes because it’s a major surgery. Even without complications, it requires several weeks of recovery. Recipients must stay on powerful drugs that suppress the immune system so that the body doesn’t reject the transplanted pancreas. The drugs make people more vulnerable to infection and can cause other side effects such as kidney damage.

Since the 1970s, doctors have been experimenting with a less invasive procedure. Islets are isolated from the pancreas of a deceased donor and infused into a patient's portal vein, a large vessel that carries blood into the liver. Once in the liver, the islets settle in small blood vessels, begin sensing blood sugar and produce insulin to control it. In 2000, a team led by Dr. James Shapiro of the University of Alberta in Edmonton, Canada, reported that seven patients had achieved insulin independence after islet transplantation. The procedure came to be known as the Edmonton Protocol.

In the September 28, 2006, issue of The New England Journal of Medicine, Shapiro and his colleagues reported on a larger trial to further test the Edmonton protocol. The study was organized by the Immune Tolerance Network, a consortium supported by NIH and the Juvenile Diabetes Research Foundation International. Thirty six adult volunteers at nine sites in North America and Europe received up to three infusions of islets. Each recipient had type 1 diabetes for more than five years and had severe problems controlling their blood sugar.

A year after the final treatment, 44% of the recipients no longer needed insulin injections, and an additional 28% had partial islet function. Insulin independence didn’t persist indefinitely for most recipients, however. Less than a third of those who’d been freed from insulin injections after one year remained so by two years. Nevertheless, those with functioning islets had improved control of their diabetes, even though they still needed insulin. They also no longer had episodes of hypoglycemia unawareness, a condition in which a person doesn’t recognizes the early symptoms of low blood sugar.

The researchers say further research will now be needed to improve and prolong the effects of the procedure.