Device Could Give Diabetics Normal Life
While all the other youngsters furiously scribbled away on their high school entrance tests, Daniela Melgar, a 14-year-old diabetic, felt dizzy and put down her pencil.
Though reluctant to miss precious minutes of the test, Daniela pulled out her blood glucose monitor, pricked her skin and waited for the results. Then she popped a sugar pill that brought her glucose level up to normal.
Daniela, a San Diego resident, had no choice--if she hadn’t tested herself, she might have fainted.
For her and many others, the inconvenience of diabetes is not the daily insulin injections but the cumbersome process of monitoring their blood glucose levels, crucial and potentially life-saving action that must take precedence over every activity.
But a new implanted glucose sensor, now under review by the U.S. Food and Drug Administration, could one day dramatically simplify and maybe even extend Daniela’s life. With this device constantly monitoring the body’s blood sugar level, she could simply glance at a wristwatch-like gadget on her arm or at a beeper and instantly get an up-to-the-minute reading. And better monitoring, some experts say, could allow diabetics to live longer.
For more than a decade, UC San Diego professor of bioengineering David Gough has worked on the glucose sensor--a quest that has frustrated numerous scientists. But Gough has persisted, and his device has now been successfully tested on dogs. Pending approval from the FDA, he hopes to begin clinical trials this year in which the device will be implanted in people.
It is a device, experts say, that could one day revolutionize the lives of diabetics.
It is, however, a tool of the future. Medical devices take about five years to clear regulatory hurdles and reach the marketplace, assuming there are no major glitches, FDA spokeswoman Sharon Snider said. But in the field of diabetes, where few new developments have reached consumers, it could mean a major breakthrough.
“This could significantly improve the lifestyle of many diabetics,” Gough said. “It may lead to extending their lifetime and improving the quality of their lives.”
But many questions must be answered before the device is readily available, including: Will it be simple and convenient enough to be widely used? How long will it work? (In dogs, the device used batteries that allowed it to operate for three months at a time.)
“There’s not much question that it will work in human bodies--it’s worked so well in animals,” Gough said. “But the longer it can work, the more convenient it will be for patients.”
Other scientists say they eagerly await Gough’s glucose sensor, one of two research approaches that have shown promise.
“Gough is a respected scientist and has clearly made strides,” said Robert E. Silverman, head of the diabetes branch at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md. “Nobody has really cracked the mechanical sensor, but Gough has made some progress.”
Silverman and other experts agree that, if Gough can prove the safety of the glucose sensor in people, it would be very easy to connect such a device to existing implantable insulin pumps--using the two devices to mimic what the body normally does.
Diabetes is a chronic disorder affecting the body’s ability to produce and use insulin, an essential hormone. In a normal body, the pancreas releases insulin when the level of sugar in the bloodstream rises after eating. The insulin allows the body’s cells to use the sugars for energy.
In a diabetic, the body’s immune system wipes out the insulin-secreting cells, called islets. When the body does not obtain insulin, it uses stored carbohydrates, a potentially harmful process that can lead to coma or even death.
Today, diabetes is treated with daily insulin injections. But some researchers believe that these periodic injections cause varying concentrations of insulin that in turn may result in the possible long-term side effects of diabetes, including nerve, eye and kidney damage.
About 14 million Americans have diabetes, of which there are two types: juvenile- and maturity-onset, according to the Juvenile Diabetes Foundation. Juvenile diabetes, or Type 1, is most commonly diagnosed anywhere from infancy to the 30s. About 1.5 million Type 1 diabetics in the United States depend on insulin injections to stay alive.
The glucose sensor being developed by Gough is designed primarily for use by these Type 1 diabetics because they must carefully monitor their glucose levels, sometimes four or more times a day.
“Having a sensor and a pump would make it totally automatic, and the person could return to a normal lifestyle,” said Gough, who is also vice chairman of UCSD’s department of applied mechanics and engineering sciences.
Gough estimates that the sensor and pump combination could be available to the public within five years. Although many researchers have attempted to devise such a sensor, Gough says his is the first to be reviewed by the FDA. In the United States, it is also the device that has been implanted for the longest time in animals, he says.
In its current form for use in dogs, the device is just a little larger than a credit card and is fitted under the skin in the back of the neck. But Gough figures that for use in people, the device will resemble a pacemaker. It will be honed down to the size of a quarter with a foot-long trailing wire. And, like a pacemaker, it may be placed in the upper torso with its wire going into the bloodstream. At the end of the wire, two enzyme sensors measure the level of oxygen and glucose in the blood.
Gough is experimenting with implanting the sensors in tissue sites in dogs, along their backs. If this work is successful, scientists will try implants in tissue sites in humans, just below the skin in the forearm or abdomen, for instance. A tissue site has the advantage of allowing a patient to insert the device himself, Gough said.
For now, researchers plan to use the sensor in the bloodstream when they launch clinical trials, he said.
The demands on such a sensor would be numerous, Silverman said.
“It’s got to measure the same today as a month from now. It’s got to last weeks. It’s got to be fast, measure and get the answer quickly--it can’t take half an hour to take a measurement,” he said.
“If one could snap one’s fingers and have that, then yes, it becomes a simple engineering task to interface with a pump and set up a closed loop system,” Silverman said. “I don’t think that’s a problem; the big problem is the glucose sensor.”
One potential problem with the implanted glucose sensor, Silverman cautioned, is the body’s tendency to reject foreign objects. “The body does a wonderful job of trying to get rid of those things,” he said.
Gough, however, believes this is a hurdle that can be vaulted. He pointed out that pacemakers and other implanted devices have been used for almost 30 years.
“This is one of our biggest problems, and this is one thing we have to look at,” he said. “But pacemakers work, and they work very well.”
Gough and Jon Armour, a UCSD graduate student, hope to complete their research before the National Institutes of Health next year announces the results of its decade-long trial on the long-term symptoms of diabetes.
This trial, involving 1,440 diabetics, is meant to answer a much-debated question: Does better monitoring and controlling of insulin levels prevent or slow the number of complications suffered by diabetics?
About 30% of diabetics suffer kidney damage as a result of the disease, Silverman said. And about half of those who have had diabetes for 20 years begin to experience damage to their vision, he said. (Scientists are still unable to understand why only some diabetics suffer these symptoms; nor can they predict which diabetics are most vulnerable.)
Many experts believe that diabetics would avoid these symptoms if they could maintain steady insulin levels and constant monitoring--rather than the inevitable swings that now occur.
Blood sugar can abruptly increase or drop within 15 minutes. So, if a diabetic monitors his glucose level four times a day, he may well miss some of these variations.
“We hope to be able to prove once and for all that the effort it takes to control insulin is worth it,” said Silverman, who declined to comment on the preliminary results of the trial.
If the trial determines that better control does, indeed, prolong the lives of diabetics, the cry for a better glucose sensor will be even louder.
Gough’s implanted sensor is one of several promising avenues of research being pursued. Other scientists are experimenting with islet transplants, or transplantation of the insulin-producing cells.
Last year, scientists devised a method that enabled them to transplant pancreas cells from cows, dogs or pigs into rats.
Scientists hope that eventually humans will receive these transplanted islet cells, encased in protective fibers to prevent rejection from the immune system. They hope the transplanted cells will continue to function and release insulin.
Doctors have tried to use human pancreatic tissue, but their efforts have been hampered by what they can harvest from a small number of cadavers. Should the animal cell transplants prove successful, scientists would have an ample supply, said Clark Colton, a professor of chemical engineering at Massachusetts Institute of Technology, who has conducted islet transplant research.
“There are too many obstacles that remain to be solved and much research to be done,” Colton said.
Asked to predict which might prove more successful, islet transplants or Gough’s glucose sensor, Silverman said, “I think we probably are going to have a close race.”
