Diabetes cure being pioneered in Seattle

SEATTLE - On May 30, Elizabeth Kresse became the first person in the Northwest to receive an islet transplant. The tiny cells are working to cure her diabetes.

"This is big this is a life change. This is a new life ... and it's going to be a better life," said Kresse.

One week later, Jackie Westcott, and another type 1 diabetic, David Ellis, would be among the first patients anywhere to receive a combination kidney and islet transplant.

"I'll be limited for a while in what I can do, but after that, I'll be free to do what I want to do. It'll be great," said Westcott.

Now, less than two months later, all three patients are starting to produce their own insulin for the first time in years. But the procedure is not intended for those with mild to moderate diabetes.

"I think the attitude nationally is that the procedure is best designed for those patients that have major problems regulating glucose levels," said Paul Robertson, M.D., Pacific Northwest Research Center.

In type 1 diabetes, insulin-producing islet cells are destroyed so that the body becomes insulin-deficient. When islets are transplanted from a donated pancreas, they take up residence in the recipient's liver and secrete insulin to re-establish normal control of the body's blood sugar metabolism.

"The hope of a transplant is that if you can control the blood sugar, cure the diabetes, so these long term complications will not occur," said Robert Wilburn, M.D., Virginia Mason Hospital and Research Center.

All three will get a second islet transplant, which involves only a simple injection into the liver. The goal is to make these patients completely insulin free. At this point they have been able to cut their shots in half and have already noticed a difference.

"My energy level has gone way up now and I feel a lot more alert and able to do a lot more," said Ellis. "The transplants we have now successfully completed are only the first of 10 planned for this year. But the new things we learn will move us forward in providing hope for the millions of diabetes patients who are still waiting for the cure to their disease," said Dr. Robertson.

The procedure is not being done in children because of the anti-rejection drugs required. However, the future goal is to use stem cells so children can benefit before diabetes takes over their lives.

Patients who are interested in receiving islet transplantation sponsored by the HITS program should contact their physician to review together the three current protocols. The islet transplantation alone protocol involves individuals who are lean, have had type 1 diabetes greater than five years, have normal kidney function and significant problems with metabolic control of glucose levels.The simultaneous kidney and islet protocol involves individuals who are in need of kidney transplantation because of renal failure and who desire to have islets transplanted as well. The islets after kidney transplantation protocol involves individuals with a successful kidney transplant and who do not take steroids and have poor glucose control.

Diabetes is a chronic disease in which the body either cannot produce insulin or cannot properly use the insulin it does produce. Insulin is a hormone that is produced in the pancreas by islet cells. Insulin is the gatekeeper of glucose that allows glucose from our blood into our body's cells.

Glucose is the basic form of energy that our cells need to function. Type 1 diabetes is known as insulin dependent or Juvenile Onset Diabetes Mellitus. This means that the body produces no insulin.

People with Type 1 diabetes require daily injections of insulin in order to live. They must adhere to a strict regime of diet, physical activity, and monitoring in order to control their diabetes. This is done in an attempt to prevent complications such as blindness, kidney failure, stroke, gangrene, heart disease, severe pain from nerve involvement and impotence. Despite insulin, people with diabetes continue to develop these complications. FAQ about islet transplantation

Islets ("eye-lets") are groups of cells. Their mid-19th century discoverer, Paul Langerhans, called them islets because they look like small islands in a sea of other tissue. In the healthy pancreas, islets contain four types of cells essential to metabolism and the management of glucose levels in the blood. Though a normal adult pancreas contains approximately a million islets, they account for only 2-3% of the pancreas's tissue.

Beta cells-one of the four types of cells in pancreatic islets-produce the insulin needed for proper metabolism. In type 1 diabetes, beta cells are completely destroyed and thus unable to produce any insulin. In type 2 diabetes, they produce insulin erratically or deliver it ineffectively to the body. Properly functioning beta cells are able to return diabetic patients to normal insulin secretion and blood sugar control.

What is islet transplantation? Healthy islets are removed from a donor pancreas, purified, and then inserted by catheter into the liver of a diabetic patient. The collection and purification of the islets is technically complex, but the transplantation itself is relatively simple. It can be performed while the patient is fully conscious and may take less than an hour to complete. Following the transplant, patients take immunosuppressive drugs to keep their body from rejecting the new islets.

Pancreases have been transplanted successfully for many years as a treatment for patients with advanced diabetes. But pancreas transplantation is major surgery, undertaken usually only when the diabetes complications are so severe as to warrant the trauma and risk of the surgery. Islet transplantation is far simpler and faster. It can be performed on diabetes patients with far less risk and before the worst complications of the disease are able to develop. Or alternatively, on patients for whom glucose control is very difficult but for whom a whole pancreas transplant is deemed too risky.

The pancreas is anatomically more difficult to reach than the liver. So it is easier to infuse the islets through the portal vein of the liver than to inject them into the pancreas. The liver also provides an environment in which the islets can thrive and flourish.

Why aren't transplanted beta cells destroyed - as the recipient's own beta cells were - by the mechanisms that led to the patient's diabetes?

Type 1 diabetes is an autoimmune disease. For reasons not yet fully understood, the body's immune system kills its own beta cells. The beta cells infused by islet transplantation are not one's own, so the immune system does not respond to them in the same way. The ordinary rejection mechanism of the immune system does need to be controlled after islet transplantation, and therapy is given to block recurrence of type 1 diabetes.

A key recent discovery in islet transplantation is the combination of anti-rejection drugs that will protect transplanted islets without causing major side-effects to the patient. The removal of steroids from the anti-rejection drugs appears to reduce toxicity to both the islets and the patients.

HITS-Human Islet Transplantation in Seattle - is a consortium of six medical care and research facilities in the Northwest, collaborating together to advance islet transplantation as a cure for diabetes.

Two clinical studies of islet transplantation are currently being conducted by the Seattle group-one in which islets are transplanted alone; one in which patients receive both islet and kidney transplants at the same time. Both studies draw their procedures from one established at the University of Alberta in Edmonton, Canada, and called the "Edmonton Protocol."

Human islet transplantation has only recently achieved promising success. In 2000, doctors in Edmonton reported that a small number of diabetes patients continued to produce their own insulin, with no appreciable side effects, after islet transplantation. Nine sites in North America, Canada, and Europe were then selected to replicate the Edmonton procedure, to test its effectiveness on more patients in different treatment centers. The coordinating center for these various sites is the Immune Tolerance Network, a program established and sponsored by the National Institutes of Health. Seattle is one of the nine test sites.

· In the kidney-islet procedure, the islet transplant is similar to Edmonton's, but it is conducted in conjunction with kidney transplant surgery.

A small number of patients have been selected for the earliest HITS transplants. For islet only transplants, they are chosen by the Immune Tolerance Network from a pool of volunteer candidates. Then they are further screened by HITS to meet the stringent eligibility requirements of the research study. Participants in the kidney-islet program, are volunteers from among the kidney patients of participating HITS institutions. They too must meet strict health criteria to be included.

Among other requirements of age, weight, glucose levels, and health history, participating patients all have type 1 diabetes, all are adults, and, in spite of scrupulous diet and lifestyle control, all still experience extreme insulin failure. Where else are experimental islet transplants being conducted?

Under the general auspices of the Immune Tolerance Network, the Edmonton protocol is being tested by the University of Alberta, six research centers in the U.S., and medical centers in Italy, Germany, and Switzerland.

Islet transplantation is also being conducted independently at a number of other institutions in the U.S. and abroad.

Early results indicate that this is as effective as whole pancreas transplantation for the treatment of type 1 diabetes. But islet transplants from donor pancreases are sharply limited by the number of donors. Researchers are conducting promising beta cell and stem cell research that may make healthy islets widely available. With such resources, islet transplantation may become possible for millions of patients suffering from diabetes.

There are many pictures and diagrams at the linked site.

• More than 18 million Americans have diabetes

• Children with Type 1 diabetes must inject insulin every day.

• Type 2 diabetes (traditionally a disease of middle age) is approaching epidemic proportions in today's sedentary society.

• Fifty percent of Native Americans and Hispanics in the United States will develop diabetes.

• Diabetes is the leading cause of blindness in the U.S.

• 65 percent of kidney transplants in the U.S. are for diabetic patients

• Diabetes is a leading cause of heart attacks and cardiovascular disease

The statistics are horrible! I knew a wonderful woman in Seattle who died a hellish death from diabetes. She was young, intellingent, full of grace. Valerie Sieber. What an unspeakable fate she endured. I miss her.

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