For millions of people with diabetes worldwide, life is a series of fingersticks, injections, and surges and dips in blood sugar levels. But with its promise of automatically regulating a person's blood sugar, the artificial pancreas could change all that.
"The artificial pancreas will revolutionize the treatment of diabetes," says Eric Renard, MD, PhD, professor of endocrinology, diabetes and metabolism at Montpellier Medical School in Montpellier, France. "It will prevent diabetes complications, [which include blindness, kidney failure, amputations, heart disease, and death]. And quality of life will be tremendously improved as people won't have to be constantly pricking and monitoring themselves," says Renard, who is leading the first clinical trial of the device.
The man-made organ has three parts, all of which have to work perfectly in synch: a sensor that continually monitors blood or tissue sugar levels, an insulin infusion pump, and a computer algorithm that controls the delivery of insulin minute by minute based on measured blood sugar, says Jeffrey I. Joseph, DO, director of the Artificial Pancreas Center at Thomas Jefferson University in Philadelphia. The sensor relays information to the pump, which then dispenses just the right amount of insulin.
A fully automated and integrated device probably won't be ready for prime time for at least four years -- maybe more. But "we're getting there one step at a time," Joseph says, with researchers worldwide testing various components of the system alone or in combination.
Insulin Pump a Step Forward
Furthest along in development is the insulin pump, which is worn on a belt or totally implanted in the body. The external pump is already used by thousands of people with diabetes worldwide, and the implantable pump is approved in Europe and is in clinical trials in the U.S. Either can be used in an artificial pancreas.
The development of the implantable pump was a major step forward, Renard says, with studies showing significant advantages over multiple daily injections of insulin in controlling blood sugar levels and improving quality of life.
Made by Medtronic MiniMed of Northridge, Calif., the hockey puck-sized device is implanted under the skin of the abdomen, from where it delivers insulin to the body, "just like the real pancreas," he says.
Lori Hahn, a 41-year-old Californian who has had diabetes for more than a decade, says the implantable pump has changed her life. "Before the pump, my life was a roller coaster, both blood sugar-wise and emotionally," says Hahn, who is participating in a U.S. clinical trial. "I felt out of control and had to focus a lot of my time on controlling my blood sugar.
"With the implantable pump, I can forget I am a diabetic," says Hahn, a working wife and mother of three active youngsters.
The pump, which uses specially formulated insulin, is refilled every two to three months. It delivers insulin in short bursts throughout the day, similar to a pancreas. It is also programmed to deliver higher amounts of insulin for mealtimes. Before a meal or snack, a push of a button on a pager-sized personal pump communicator tells the pump to dispense a dose of insulin.
Smart System a Major Milestone
Other research is focusing on improving communication between the glucose sensor and the external insulin pump. According to Joseph, a major milestone was reached this summer when the FDA approved one of the first smart systems that allows the two systems to communicate via a wireless connection.
Such systems take a lot of the guesswork out of insulin dosing, he says.
Traditionally, patients had to prick their fingers and place the blood on a strip to get a blood sugar reading, estimate how many grams of carbohydrates they planned to eat, and mentally calculate how much insulin they needed. The system left much room for error, with the wrong calculation potentially leading to dangerously high or low blood sugar levels.
With the newly approved Paradigm system, which combines the Medtronic MiniMed insulin pump and a glucose monitor from Becton Dickinson, patients still prick their fingers to measure their blood sugar levels. But the pager-sized glucose monitor transmits the information straight to the insulin pump. The insulin pump then calculates the amount of insulin required for the current blood sugar. By having the pump calculate the dose required, you could prevent errors that sometimes result when patients input this data manually, he says.
"It's up to the patient to decide if the suggested amount is correct and push a button to deliver the recommended dose," Joseph says. "It's not an artificial pancreas as it's not fully automated. But it's a major advance of convenience and has the potential to improve blood sugar control in the clinical setting."
Measuring Blood Sugar Levels
About two dozen companies and academic labs are developing glucose sensors, Joseph says. Some are blood glucose sensors, others are tissue fluid glucose sensors; some are placed under the skin by the patient, others are implanted long-term in the body.
While glucose sensors have improved significantly over the past few years, they are still the limiting factor in making the artificial pancreas, he says.
Steve Lane, PhD, acting program leader of the Medical Technologies Program at the Department of Energy's Lawrence Livermore National Laboratory, agrees.
"Almost certainly the goal of production of an artificial pancreas will be achieved," says Lane, whose department worked on a prototype of the artificial pancreas in partnership with MiniMed. "But there are obstacles to be overcome, the major one being glucose sensing. To date, no one has developed a foolproof way of sensing glucose."
Animas Corp. is developing an implantable optical glucose sensor. In animal and preliminary human studies, the device accurately measured blood sugar levels in the blood using infrared optics.
"A miniature sensor head is placed around a blood vessel, and a light source is focused through the blood to a detector," says Joseph. "The absorption of light at specific infrared wavelengths determines the concentration of sugar in the blood."
Further along in development are Medtronic MiniMed's short-term and long-term implantable glucose sensors, designed to continually measure the level of sugar in the tissue fluid or blood.
First Artificial Pancreas Tested
In France, Renard is leading the first clinical trial of an artificial pancreas -- a fully automated system that combines Medtronic MiniMed's long-term glucose sensor and its implantable insulin pump.
In a minor surgical procedure, the implantable sensor is inserted into a neck vein leading to the heart. The sensor is connected, via an electrical-type wire under the skin, to the implantable insulin pump: As blood sugar levels fluctuate, a signal tells the pump how much insulin to deliver.
"The patient doesn't have to do anything," Renard says. "It's all automatic. Even if you're eating a high-carb meal, the sensor will give the appropriate signal to deliver more insulin."
Renard says data from the first five patients who used the device for at least six months show the sensor accurately measured glucose in 95% of cases when compared with values obtained by fingersticks.
"Our goal was to reach 90% accuracy, so this is very accurate," he says.
More importantly, blood sugar levels were maintained in the normal range more than 50% of the time in the patients using the pump connected to the sensor, compared with about 25% of the time for the patient using fingerstick values to tune insulin delivery from the implantable pump.
Also, the risk of blood sugar plummeting, known as hypoglycemia, to dangerously low levels -- a possibility whenever extra insulin is delivered -- dropped to less than 5%, Renard says.
Among the next steps, he says, is to make the sensor more durable so it only has to be changed every two or three years. While implantable insulin pumps work for an average of eight years before they have to be changed, the sensors stop working after an average of nine months, he says.
Nevertheless, Renard see this as an easy hurdle to overcome. "We will just use a different material and make it stronger," he says.
But Joseph says this may present a formidable challenge: "Many years of research [show that] sensors tend to fail within months rather than years due to the harsh environment of the body."
The mathematical programs that calculate just how much insulin should be delivered at different parts of the day also needs to be refined, Renard says. "Right now, the insulin pump allows a diabetic to spend about half of his day in normal glycemia, just like a non-diabetic. But that means that he is not in control the other 50%, which is a bit too high."
But again, he says, this is an easy problem to solve. "The major problem is to have the accurate sensor, and we have it now. Within two years we should have one that works longer and better, and after that, it will be clinically available."
Joseph agrees. "They have demonstrated the feasibility of having the glucose sensor talk to the insulin pump, which delivers insulin automatically -- and that is an artificial pancreas.
"Is it perfect? Absolutely not. But we are getting there."