Researchers have successfully tested a fully implantable glucose-monitoring device in pigs for nearly two years, according to new research published today in Science Translational Medicine. Scientists plan to file for approval from the U.S. Food and Drug Administration to begin human tests. Eventually, researchers aim to couple this kind of device with one that would automatically deliver insulin in response to changing blood-sugar levels.
The new device, about three centimeters in diameter and one centimeter thick, would be implanted into the chest in an outpatient procedure. It measures glucose levels in tissue and wirelessly transmits that information to an external receiver, such as a cell phone. Unlike existing continuous monitors, “there is nothing protruding from body,” says David Gough, a bioengineer at the University of California, San Diego, who developed the technology. Gough cofounded a company called GlySens to commercialize this and other technology his lab has developed.
Insulin-dependent diabetics are supposed to measure their blood sugar several times a day with a finger stick. This involves the glucose in a small drop of blood reacting with chemicals on a disposable test strip. In the last few years, a growing number of people have started to use continuous glucose monitors, which measure glucose levels every few minutes via a sensor embedded into the skin. The sensor is attached via a wire to a small processing unit taped to the abdomen, which sends the information to a receiver in a pocket or worn on the belt.
The advantage of these devices is that they can show trends in blood-sugar levels, helping patients to better tailor their next dose of insulin. However, with existing models, the sensor needs to be replaced every three to seven days and frequently recalibrated with traditional finger sticks. Scientists have been working for more than a decade to develop a fully implanted device that can accurately monitor glucose over months or years without replacement.
Like finger sticks, the new implanted monitor measures glucose levels using an enzyme called glucose oxidase. When glucose levels are high, the enzyme carries out a reaction that consumes oxygen, which is detected via a neighboring oxygen sensor. Gough says one of the major challenges in developing a sensor to work over the long-term was stabilizing the enzyme, which tends to degrade over days. To fix this problem, researchers added a second enzyme designed to eliminate one of the toxic byproducts of the reaction.
Gough’s team also had to deal with the formation of scar tissue around the device. Scar tissue reduces permeability of glucose and oxygen and can interfere with detection over time. Researchers solved this by adding a reference sensor–a platinum wire oxygen sensor without the enzyme. This sensor allows the device to correct for changes in permeability.
“I was impressed that the device operated continuously [in pig experiments] as long as it did–almost two years–and by the fact that it had fairly stable function,” says Steven Russell, a researcher and physician at Massachusetts General Hospital, who was not involved in the study. “One concern I had was accuracy. They reported it is as good as some subcutaneous sensors out there, which is true, but it’s not as good as the best of them.”
But commercializing the technology may prove difficult. “I think this is significant progress and an important proof of principle, but there are still substantial challenges to overcome,” says Roman Hovroka, a researcher at the University of Cambridge, who was not involved in the research. “It’s still a long journey to a commercial product.”
He points out that because the studies take a year or two, commercial development and clinical testing can be very expensive. Other companies developing continuous-sensing technologies have shifted efforts from long-term implanted devices to short-term technologies, says Hovroka, possibly because of these high development and testing costs.
Still, Hovroka and others say, a device capable of functioning over the long term is an important goal. Studies have shown that the frequency with which patients monitor their blood sugar affects how well they can control it, which in turn is tied to long-term health. “So presumably an implantable sensor would have a bigger impact on outcomes than a sensor that has to be replaced often,” says Hovroka. “But that needs to be offset with the need to perform local surgery on a yearly basis and the reliability of such devices.”