Mixed Bag: Islet-cell transplants offer good and bad news

Several years after receiving experimental transplants of insulin-making cells, most people with diabetes still need daily insulin shots, a new study finds. But the transplanted cells that thrive in their new hosts prevent sudden drops in blood sugar that come without warning, a life-changing improvement for some patients.

People with type 1, or juvenile-onset, diabetes lose their insulin-making pancreatic cells when their immune systems attack the clusters, or islets, housing these cells. In a procedure called islet transplantation, physicians take islet cells from a cadaver and infuse them into the portal vein of a patient’s liver, where the new cells start making insulin. That indispensable hormone orchestrates sugar metabolism.

In a study published in 2000 by researchers in Edmonton, Alberta, islet transplantation seemed to have cured seven patients with diabetes (SN: 9/2/00, p. 156: Transplanted Hopes).

Now, in the Sept. 28 New England Journal of Medicine, an international team led by the Alberta researchers reports that only 6 of 36 type 1 diabetes patients receiving islet transplants no longer needed insulin injections about 3.5 years later. That suggests that in most of the patients, the transplanted cells couldn’t produce a full complement of insulin. The reason may be that the number of cells delivered to the liver was too small, the recipients’ immune systems killed too many of the cells, or the cells simply died, say the researchers.

Nevertheless, study coauthor A.M. James Shapiro, a transplant surgeon at the University of Alberta in Edmonton, is heartened by the findings. “Insulin independence isn’t the be-all and end-all in these patients,” he says.

Indeed, the participants were chosen because, despite taking the best available medicines, they had had dangerous episodes of suddenly plummeting blood sugar. The drops came without the shakiness, sweating, and racing heartbeat that usually alert a person to low blood sugar, or hypoglycemia. As a result, some of the patients couldn’t drive cars or care for children.

The researchers found that 24 of the 36 participants retained some functional islet cells from the transplants, and all 24 were subsequently free of severe blood sugar crashes.

Even a small number of transplanted cells “increases insulin concentrations second by second,” delivering a trickle of the hormone that appears to prevent the crashes in the participants, Shapiro says. “This allowed a return to some kind of seminormal existence [and] has had a huge impact on their lives,” he says.

Side effects of the transplant procedure stemmed from the immune-suppressing drugs that the patients needed to prevent rejection of the islet cells. Some participants developed pneumonia, a drop in white blood cell counts, chest pain, fever, mouth ulcers, diarrhea, headaches, anemia, nausea, or a combination of complaints. Scientists plan to look for regimens for immune suppression with fewer side effects.

“This is not a procedure that’s ready for prime time in the vast majority of people with type 1 diabetes,” says endocrinologist Judith E. Fradkin of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md. However, she adds, “we shouldn’t write it off.”

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