Now This Is \m/O.o\m/ - RocKStaR
By Michelle Fay Cortez
Sept. 28 (Bloomberg) -- Patients with complications from the most severe form of diabetes may benefit from transplants of pancreatic cells that produce insulin, even if it doesn't free them from a lifetime of insulin shots, researchers said.
The first study showing islet cell transplants can be widely performed appears in the Sept. 28 New England Journal of Medicine. Of 36 patients treated in North America and Europe since the procedure was first introduced in 2000, 16 no longer needed daily insulin injections one year later and 10 had better control of the disease. The transplanted cells didn't survive in the remaining 10 patients, giving them no benefit.
The procedure isn't yet the cure Canadian researchers were hoping for when they initially presented their approach. The doctors showed insulin-making pancreas cells, called islets, from donor cadavers can be transplanted into only a select group of diabetics. The hope is that the treatment can be improved to allow many people with type 1 diabetes to live without daily shots of the hormone.
``Even for those who weren't completely free of insulin, the degree of sugar control was phenomenal,'' said James Shapiro, director of the transplant program at the University of Alberta and a pioneer of the technique. ``You just can't achieve that degree of control'' with ``injected insulin.''
Up to 2 million Americans have type 1 diabetes, where the body destroys islet cells in the pancreas that make insulin to convert blood sugar to energy. Without it, sugar builds up in the blood and damages nerves, blood vessels, eyes and organs like the kidneys.
20 Million Americans
Type 2 diabetes, where the body doesn't properly use insulin, affects nearly 20 million Americans, according to the National Institutes of Health. Both diseases can cause organ damage, though the complications generally occur earlier in life among those with type 1 as that form of the disease usually arises in children.
The study included patients who had repeated bouts with low blood sugar, a potentially deadly condition that can trigger fatigue, confusion and convulsions. While most people can tell when their blood sugar falls, some diabetics become desensitized to the condition.
The Immune Tolerance Network, supported by the NIH and the Juvenile Diabetes Research Foundation, funded the research. The drugs used to suppress the patients' immune systems to prevent rejection of the transplanted islet cells were provided free of charge by their manufacturers.
Drugs
Patients received Tokyo-based Astellas Pharma Inc.'s Prograf, Madison, New Jersey-based Wyeth's Rapamune and Zenapax from Roche Holding AG in Basel, Switzerland. The mix of drugs was tailored by the Canadian researchers to reduce the toxicity for the transplanted cells. Additional studies are planned with newer drugs, including Bristol-Myers Squibb Co.'s experimental belatacept.
Thirty patients needed more than one transplant of islet cells, which were injected into a large vein that leads into the liver. The problem with low blood sugar, called hypoglycemia, abated in all the patients who had even a small amount of surviving cells in the liver, where they nested and immediately began producing insulin, Shapiro said.
There are two major limitations with the transplants: side effects and the need for repeat transfusions of the cells, said Christopher Saudek, director of the Johns Hopkins Diabetes Center and past president of the American Diabetes Association. For now, the approach should be used only in research, he said.
`Major Challenges'
The researchers ``have shown there are major challenges left before this could become a practical approach to treating diabetes,'' Saudek said in a telephone interview today. ``Most of these people had two or three donor pancreases, and that becomes a huge challenge when you consider the waiting list overall'' for donated organs, he said.
Side effects included reductions in infection-fighting white blood cells, pneumonia, mouth sores, anemia and ulcers. Some patients had a decline in kidney function, likely because of the toxic effects of immune system-suppressing drugs, underscoring the need for better therapy, the researchers said.
In most cases, the transplanted islet cells burned out with time in a process called metabolic exhaustion. After two years, just five patients were still free of daily insulin injections. In addition, less than half of the pancreases tested yielded enough islet cells for a transplant.
``Islet transplantation is at a crossroads,'' wrote Jonathan S. Bromberg and Derek LeRoith from the Mount Sinai School of Medicine in New York in an editorial. ``It is clear that poor long-term results, high costs and the relatively high incidence'' of side effects make it hard to argue for expanding its use, they wrote.
Blood Sugar
``Nonetheless, the dramatic discoveries and successful dissemination of information in a relatively short period encourage us to believe these advances will continue apace,'' they said.
Controlling blood sugar with just a few transplanted cells is significant, said Nancy Bridges, chief of the transplant immunobiology branch at the National Institute of Allergy and Infectious Diseases. Repeating the 2000 study at numerous institutions in the U.S. and Europe was essential, she said.
``It's of limited usefulness to patients if it can be done only at one place in the world,'' Bridges said. ``It's crucial to demonstrate that the same results can be achieved by other people,'' she said.
The goal is to continue improving the transplant methods so more patients can get off insulin altogether, she said.
``This is just the beginning,'' Shapiro said in a telephone interview. ``It provides durable hope for people with diabetes that there is more than just injected insulin around the corner that will make a real difference in this disease, and will hopefully one day provide a cure.''
Scientists want to perfect the transplants so that someday they can use islets grown in the lab from stem cells. That prospect is years away as researchers have yet to figure out how to turn stem cells extracted from embryos into islets.
To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net