A Body Making War on Itself

By David Bjerklie

When health professionals talk about the growing diabetes epidemic, they are usually referring to Type 2 diabetes. But that doesn't mean that Type 1, which afflicts up to 1 million Americans, is under much better control. While both types of diabetes concern the relationship between insulin and glucose, there are important differences in the progression of the disease and its treatment. The key distinction is that Type 2 diabetes involves an inability to utilize the insulin the body has, while Type 1 is an autoimmune disease in which the body attacks the islet cells in the pancreas that produce insulin.

The Type 1 disease has a strong genetic predisposition, but that alone doesn't explain why people get it. Researchers believe that an environmental trigger is also necessary. Among the prime suspects are viral infections like the Coxsackie B virus. The theory is that the immune system gets fired up to ward off a viral infection, then turns its attention to pancreatic islet cells because a protein on the cell surface is chemically similar to the virus.

Once 90% of the islet cells are destroyed, the body is no longer able to regulate blood-sugar levels and the patient develops the classic symptoms of diabetes. At this point, the patient needs insulin injections to survive. Even with insulin, though, the complications of Type 1 disease can take a terrible toll. By age 55, for example, 35% of victims have died of a heart attack. Kidney failure is also common, and after 15 years of the disease, 80% of Type 1 diabetics have sustained significant eye damage.

That's what Type 1 patients had to look forward to in the past. The good news is that there are now better treatments, including more effective preparations of insulin, closer monitoring of blood sugar and earlier intervention for complications. Even more promising are current attempts to make an end run around the disease. A case in point is Gary Kleiman, 50, who has had two kidney transplants and lost most of his eyesight since being diagnosed at age 6. Today Kleiman is one of 300 patients worldwide who have received a transplant of pancreatic islet cells. For the first time since age 6, Kleiman does not need insulin injections. "It's been an amazing journey," he says. "Several of my very special friends with Type 1 didn't make it this far. They died at ridiculously young ages--in their 30s and 40s."

Kleiman's physician, Dr. Camillo Ricordi of the Diabetes Research Institute at the University of Miami, is one of the pioneers who have refined islet-cell transplants. And while a pancreatic-cell transplant may sound like a cure, Ricordi is quick to point out that it is not. First, there is the challenge of preventing a patient's body from rejecting the transplanted cells, and second, there is the challenge of shutting off the immune response that still wants to kill off islet cells.

Even if these obstacles are surmounted, there remains the problem of finding donors. "Because we have only 6,000 [dead] organ donors a year, there's no way we can fulfill the need for the millions that could benefit," says Ricordi. "And even if we could figure out a way to harvest cells from live donors, that's likely to only increase the number of transplants from a few thousand to tens of thousands."

This, says Ricordi, is why doctors need to develop alternative sources of insulin-producing cells. Researchers are exploring such possibilities as turning embryonic stem cells into unlimited numbers of insulin-producing cells, or using adult stem cells obtained from the patient's own bone marrow or liver or pancreatic tissue to do the same. Others are trying to harvest islet cells from genetically modified pigs and even from fish that have been engineered to produce human insulin.

Researchers believe they have cured Type 1 diabetes in mice, but they have yet to translate that success to humans, although they hope to begin trials soon. A real cure may remain elusive, but as scientists learn more about this complicated disease, they will continue to design more effective treatments. Given the grave health concerns that Type 1 diabetics still face, those treatments can't come soon enough. --By David Bjerklie