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Islets could be the key to a cure for diabetes
At 43, she is trim, fit and energetic. She camps, hikes and runs marathons on Maui in the Hawaiian Islands, where she lives and is a nurse. But she was in Minneapolis at the University of Minnesota Medical Center last month to receive an infusion of cells taken from the pancreas of a deceased donor.

The experimental procedure, which has been tried in about 1,000 patients worldwide, aims to restore Rohde's ability to produce insulin.

In recent years, scientific understanding of diabetes has expanded markedly. Studies have shown keeping blood sugar levels as close to normal as possible can help prevent or delay many of the complications of the disease.

At the same time, scientists have been working on ways to go beyond just treating the disease, all the way to prevention and a cure.

"We've had a tremendous amount of progress in diabetes in recent years," says Jay Skyler of the Diabetes Research Institute at the University of Miami.

And more is coming.

"We're at a stage now where we can sense that we can lick this thing," he says. "We're going to get there."

Type 1 diabetes is caused by the immune system's destruction of insulin-producing cells in the pancreas, known as beta cells. It affects about 10 percent of the nearly 21 million Americans with diabetes. About 90 percent have type 2, which is caused by the body's inability to make enough insulin or to use it efficiently.

Since she was diagnosed at age 28 with type 1 diabetes, Rohde has been taking daily insulin shots and has been able to be active and healthy. But three years ago, she began to lose the ability to sense when her blood sugar was falling too low. This condition of hypoglycemia can cause loss of consciousness, coma and death if left untreated. Rohde's inability to sense it, known as hypoglycemic unawareness, progressively has gotten worse.

"It's so subtle," she says. "One way I can tell is I feel indecisiveness. I lose focus. You don't necessarily pass out, but you can."

It's especially dangerous for someone who lives alone, as Rohde does, because it can occur during sleep.

"The trouble with hypoglycemia is you don't wake up," she says.

She set two alarm clocks, hoping that would help, but she has awakened to neighbors pounding on her door because the clocks were ringing for hours.

She has fallen and broken her nose, had three car accidents, twice was taken by ambulance from the gym and has, in a state of semi-awareness, nearly walked out of the grocery store without paying.

"It's so embarrassing," she says. "It just busted my spirit."

Transplants hold hope


Rohde is taking part in a clinical trial at the University of Minnesota designed to confirm earlier study results on the effectiveness of islet transplants in reducing or eliminating the need for insulin injections and the observation that in 95 percent of cases, the procedure also restores a person's ability to sense low blood sugars.

Transplants of human islets, tiny organs in the pancreas that contain several kinds of cells, including the beta cells that produce insulin, have been studied since the 1960s.

The technology took a leap forward in 2000 when Canadian researchers reported seven patients whose diabetes could not be controlled with medication were able to go off insulin for up to a year after they received transplants of thousands of islets taken from two donor pancreases.

Researchers have been performing islet transplants, working to refine the process. Results have been mixed. In many cases, more than one transplant has been needed, and in time, most patients have had to resume daily insulin injections.

Bernhard Hering, director of the Islet Transplant Program at the Diabetes Institute for Immunology and Transplantation at the University of Minnesota, says that by using innovative immune therapies, researchers have improved long-term results. Three patients at the center have been insulin-independent for seven years, he says.

Now, a major study about to begin here and at six other research centers in the United States, Canada and Sweden that are part of the Clinical Islet Transplantation Consortium will focus on improving islet transplants in people with type 1 diabetes who have had kidney transplants and already are on immune suppressants.

If successful, Hering says, "it is fair to assume that within a few years from now, this will be an approved treatment for type 1 diabetes. The doctor (will be able) to prescribe human islets like he prescribes insulin."

Ultimately, the procedure also may help patients with type 2 diabetes, he says, because these patients also have fewer islets than people without diabetes.

Source needed


But before that can happen, a plentiful supply of islets, which now come from donated organs, has to be found. Scientists are studying ways to produce islets using stem cells or genetic engineering. Hering and colleagues are looking to pigs as a source.

"We believe pig islets are at the forefront because we and others have shown (they) can reverse diabetes in monkeys for six months or longer," Hering says.

Donor animals are being developed, and human testing could begin in the next couple of years.

Research, much of it sponsored by the National Institutes of Health, is taking place on several fronts.

Among the goals is identifying causes of diabetes. All forms are thought to result from a genetic predisposition triggered by some kind of environmental exposure. In type 2 diabetes, obesity and lack of exercise contribute to the body's inability to produce enough insulin or to use it effectively. The trigger that causes the autoimmune process in type 1 diabetes is unknown.

In a study called TEDDY (The Environmental Determinants of Diabetes in the Young), researchers at six centers in the USA and Europe are following more than 7,000 children with type 1 diabetes until age 15, looking at their exposure to infectious agents, dietary factors and other potential triggers.

In another study, TRIGR (Trial to Reduce Insulin-Dependent Diabetes Mellitus in the Genetically at Risk), scientists in 15 countries are investigating whether proteins in cow's milk could trigger type 1 diabetes in babies who are genetically susceptible. TRIGR is following 2,161 children for 10 years.

A dozen centers are testing treatments for type 2 diabetes in children in a five-year study called TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth). The study is enrolling 750 children and teens who will get either metformin alone, metformin with Avandia or metformin with intensive diet and exercise.

 

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