Monday, August 12, 2002

Islet cell transplants give diabetics hope


Experimental surgery done at University Hospital can transform lives

By Peggy O'Farrell pofarrell@enquirer.com
The Cincinnati Enquirer

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Les Clark and his wife Linda Freeman.
(Craig Ruttle photo)
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        When Les Clark was diagnosed with Type 1 diabetes at age 16, his doctors gave him a glass syringe, a hypodermic needle that had to be boiled before every use and a stone to sharpen the needle with.

        Now 55, Mr. Clark is waiting for a phone call that could mean the end of the disease he's worked to keep under control since he was a teenager.

        “Everything was so primitive back then, just in terms of being able to manage it or not manage it,” he says. He took a single shot a day of “long-acting” insulin (“It wasn't that long-acting,” he says dryly.) and tested his glucose levels via urine, not blood. Since the urine tests measured what his glucose levels had been eight hours ago, the results weren't very useful.

On waiting list

        The Mount Washington man is on the waiting list for an islet cell transplant, the implantation of pancreatic cells that produce insulin. The transplant is a promising experimental procedure that gives some diabetics the ability to produce their own insulin and lessens the disease's potential complications, which include heart disease, blindness and kidney and nerve damage.

        Mr. Clark, a registered nurse and certified diabetes educator, has been lucky in many ways. He hasn't suffered any of the devastating side effects diabetes can have. He's careful to monitor his blood sugar several times a day to make sure it doesn't spike too high or dip too low.

        He's the picture of cautious optimism: On one hip, he wears an insulin pump, a computerized device that constantly measures his blood glucose levels and administers insulin as needed via a small catheter implanted just under the skin. On the other, he wears a pager, so the transplant team at University Hospital can let him know when, and if, the procedure is a go. If the pager goes off, there's a chance he can give up the insulin pump, the constant blood testing and the perpetual feeling of being on the alert against his disease forever.

        There's no guarantee he'll get the transplant. The donor cells have to match on blood type and several tissue indicators.

        “(The pager) could go off at any minute, or it may never go off at all,” he says.

        University Hospital is one of six centers in the United States that have successfully completed the experimental procedure. Six patients have received islet cell transplants in Cincinnati, says Dr. Horacio Rilo, director of the cell transplant program at the University of Cincinnati.

More approvals

        UC was originally approved to perform the procedure on 12 patients for the trial. But recently, the Food and Drug Administration granted approval for 30 patients — including kidney transplant patients — to receive the transplants. Kidney failure is a real danger for patients with uncontrollable diabetes. If a patient who's already had to have a kidney transplant can receive an islet cell transplant, his or her odds of continued health are much improved.

        The procedure under study, called the Edmonton protocol, was developed at the University of Alberta in Canada and was first performed in 1999.

        Type 1 diabetes occurs when the body's immune system mistakenly attacks the pancreas and destroys its ability to produce enough insulin to regulate blood glucose levels.

        Islet cell transplants are straightforward procedures with, when successful, near-miraculous results. Islet cells — clusters of cells that produce insulin and other related hormones — are harvested from donor pancreases (most patients require two to three cadaver donors) and transplanted via catheter and a small incision into the recipient's liver.

        As with all organ transplants, donors and recipients must go through blood and tissue-type matching, says surgeon E. Steve Woodle, chief of the division of transplantation at UC.

        Results are mixed. For a small percentage of patients, the transplanted cells start producing enough insulin that the patient doesn't need injections or infusions of the hormone after the surgery. Some patients don't see any change after the procedure, either because they didn't receive enough islet cells or because their bodies rejected the transplant. And many patients still require insulin after the procedure, but in smaller amounts to keep their blood sugar under control.

        The procedure is new enough that doctors don't know how long the transplanted cells continue producing insulin. Theoretically, patients whose transplants were successful could need additional transplants in the future or they might have to return to drug therapy if the original transplant fails at some point down the road.

        Surgeons have performed whole-pancreas transplants for years as a treatment for uncontrollable diabetes. But islet cell transplants are less invasive and, since only the islet cells have to be harvested, there's a greater supply of donor organs. A pancreas that's not suitable for a whole-organ transplant could still supply islet cells.

        Dr. Woodle won't call the procedure a “cure” for diabetes. Patients who undergo islet cell transplants have to take immunosuppressant drugs for the rest of their lives to prevent rejection of the cells. But most hopeful patients don't make the distinction Dr. Woodle does.

Not for everyone

        Mr. Clark and his wife, Linda Freeman, a pharmacist, researched the drug issue “vigorously,” he says, and were relieved to learn the regimen is steroid-free. Steroids are toxic to islet cells and tend to raise blood sugar levels. He had to take prednisone for a previous illness and, “I had to use twice as much insulin” to keep his blood sugar under control.

        “That was one of the issues for me,” he said.

        The transplant study isn't open to just anyone with diabetes. To qualify, candidates have to have blood sugar levels that can't be controlled with medication and be unable to sense when their blood sugar reaches very low levels, a condition called hypoglycemia.

        Mr. Clark has used an insulin pump, a device that constantly infuses insulin without the need for injections, since 1997, and he teaches other people with diabetes how to use the devices.

        The pump has been “almost liberating” in terms of controlling how high his blood sugar gets, but he still has a problem with hypoglycemia.

        “My sugar can dip into the 30s (normal is about 100 to 125) and I can't tell, where other people would be passing out,” he says.

        Hypoglycemia can cause fatigue, loss of consciousness and coma, as well as severe mood swings. It's sometimes fatal.

        Like many diabetics, he's especially prone to hypoglycemia when he's asleep — a scary proposition for his wife, who often can't rouse him.

A success story

        Lois Vicars underwent islet cell transplant on April 8. Three days after the surgery, she no longer needed insulin to keep her blood sugar under control.

        Mrs. Vicars, who lives in Loveland, is a rarity: She required a single donor to achieve insulin independence.

        She was 24 when she was diagnosed (13 years ago) and was the fourth patient in Cincinnati to get the surgery.

        The transplant has been the only thing that has kept Mrs. Vicars's diabetes under control. Neither injected insulin nor an insulin pump kept her blood sugar levels from swinging wildly.

        “It was a total nightmare. That really sums it up,” she says.

        She counted carbohydrates to make sure she was eating properly and tested her blood sugar several times a day, but her blood sugar levels were still on a roller coaster ride. “Sometimes my sugar would be as low as 30. Sometimes it would be 250. And sometimes that would happen in the same day,” she says.

        Some days she couldn't drive because her blood sugar was too low and she couldn't risk passing out at the wheel, so she'd be late for work or have to stay home. Some days her blood sugar was too high and she couldn't even push a grocery cart through the supermarket.

        “It limits you,” she says.

Blocking the way

        Islet cell transplant is still an experimental procedure. The results of the study now under way will determine whether it becomes standard treatment for uncontrollable diabetes, experts say.

        “There's a tremendous amount of interest” in the procedure's future, Dr. Woodle says.

        There are two limiting factors now against the procedure. One, as with all organ transplants, is a short supply of donor pancreases.

        Researchers are looking for alternative sources of alternative cells. Stem cells, immature cells that researchers believe can be “tweaked” into developing a variety of cells, offer great promise, if researchers can find a way to “grow” them into islet cells. Some researchers are also studying whether pigs can provide islet cells for humans.

        The second limitation is money. Few insurers will cover the procedure while it's still considered experimental, and hospitals can't require patients to pay for experimental procedures. That means the hospital itself has to foot the bill — anywhere from $60,000 to $120,000 — or secure a grant to cover the costs. Doctors who are qualified to perform the procedure are also in short supply.

        Few people realize how labor-intensive a disease like diabetes is. Patients have to count calories and carbs, watch their weight, try to exercise and check their blood sugar three or four times a day.

        Mr. Clark checks his “six to 12 times a day, depending on what's going on.” He's always on the alert for signs that his blood sugar is dropping or climbing too high.

        “The first thing I do when I get up in the morning is wash my hands and check my blood sugar. If I get up in the night to go to the bathroom, I check my blood sugar and before each meal I check my blood sugar. And three hours after each meal, I check my blood sugar,” he says. “Outside of living my life, what I'm doing is managing my diabetes.”

        If his blood sugar is too low, he needs to eat a few pieces of hard candy or swallow a couple of glucose tablets. If it's dangerously low, he might need an injection of glucogagon, a hormone that raises blood sugar. He might need to go to the emergency room.

        If his blood sugar's too high, he might need to inject insulin or cut down on the amount he eats.

        Giving all that up “is almost like a fantasy,” Mr. Clark says.

        Living with diabetes means living with preventive maintenance: Exercise, when possible, balanced meals, calorie counts, glucose checks and keeping hard candy or orange juice handy when glucose levels are too low or too high. Mr. Clark is aware of what could happen if he allows his diabetes to run rampant — heart disease, blindness, loss of limbs and kidney failure are all possibilities. He's determined not to let that happen.

        If Mr. Clark gets the islet cell transplant and it's successful, Mrs. Vicars can tell him exactly what the consequences are:

        Freedom.

        “It means being able to do what I want when I want to, not because I have to. Being able to eat when you're hungry, not because your blood sugar's high. Not having to eat when you're not hungry,” she says. “All the books say, don't let it control your life. But if you have uncontrollable diabetes, I don't see where that's possible. Not and stay sane.”

        Without his diabetes to worry about, Mr. Clark says, “I'll have to rethink my entire day.”

        It's not the needles and the diet and the exercise that he looks forward to giving up. “The issue is that diabetes monitors your life while you monitor diabetes. To not have to do that, I'd have to rethink everything. Right now, it would be difficult for me to know that I don't have to do that. It's so habitual, it's so ingrained, it's ridiculous.”

        He's willing to find new hobbies, he jokes.

        “I don't think I"ll have any difficulty filling up my day.”

       



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