Last May, 15-year-old Jacob Conte was scaling a rock wall at City Climb Gym in New Haven. Under the skin on his abdomen and concealed underneath his clothing, he wore a small sensor that transmitted his blood glucose level readings every five minutes to a smartphone device in his backpack. Jacob has type 1 diabetes and requires regular infusions of insulin. The smartphone told an insulin pump affixed to his belt when and how much insulin to deliver. The pump, in turn, injected insulin under the skin of his abdomen through a short thin tube.
Maintaining Jacob’s blood sugar control can be tricky, requiring constant vigilance and dozens of decisions each day. When he plays football or snowboards, he has to avoid drops in blood sugar that could make him dizzy or pass out. Before eating, he tests his blood sugar and takes insulin, but if food is delayed, the insulin might kick in too soon, causing his blood sugar to drop. Nighttime—when more than half of hypoglycemic (low blood sugar) emergencies occur—is especially perilous. Patients sometimes pass out without waking up. If Jacob wakes up in the middle of the night with symptoms of hypoglycemia, he tests his blood sugar and eats a snack. “It’s kind of a burden,” he said. “Everything in my life revolves around it.”
Marrying sensor and pump
For Jacob Conte and others, managing diabetes is about to change. The climbing session was part of a four-day clinical trial in which he and four other teenagers with type 1 diabetes took an “artificial pancreas” for a test run. Rather than a biomedically engineered organ made of tissue, the artificial pancreas is the marriage of a sensor that monitors glucose levels, a dosing algorithm and a pump that sends insulin into the bloodstream as needed. Wearing the sensor and pump doesn’t interfere with Jacob’s normal activities—including climbing the rock wall, playing football or sleeping—and the devices are hidden under his clothing, so nobody knows they’re there.
Yale researchers have been studying the artificial pancreas for the last decade, but last spring was the first time it was tested in pediatric patients outside the hospital—here and at two other centers. The device, developed by Medtronic, is now being tested at 10 centers (of which Yale is one) in a large clinical trial that is expected to lead to Food and Drug Administration approval in 2017. It could revolutionize how patients manage their diabetes.
Most of the 35 million people around the world who have type 1 diabetes inject themselves with insulin several times a day or use an insulin pump. Smaller than a smartphone, the pump is programmed to deliver tiny doses of insulin. Patients also sometimes use a continuous glucose monitor that has a sensor like the one Jacob Conte wore. The two devices work independently of each other. The artificial pancreas is different in that it closes the loop between them, allowing the pump to adjust insulin delivery every five minutes in response to the body’s glucose levels.
“The ability of the system to self-adjust automatically while patients go about their daily lives would really be transformative in the lives of people with diabetes,” said pediatric endocrinologist Stuart Weinzimer, MD, who led the trial at City Climb Gym.
A quest that began in the 1970s
The path to the artificial pancreas has spanned decades. It began in the late 1970s, when researchers found better ways to monitor and control blood glucose levels. With the advent in 1977 of the hemoglobin A1C test, known simply as A1C, doctors could analyze blood sugar control over a period of two to three months, providing a longer view than isolated blood glucose readings taken during clinic visits. The insulin pump—first tested in a clinical trial by pediatric endocrinologist Dr. William Tamborlane at Yale in 1979—more closely resembled the way the pancreas produces insulin by delivering small doses throughout the day with larger doses at meals.
But in 1979 diabetes remained difficult to manage. “In those days, when we started to be able to measure more accurately how well controlled our patients were, most of the numbers would have been viewed today as totally unacceptable,” said Robert Sherwin, MD, director of the Yale Center for Clinical Investigation, who was on the team that first tested the insulin pump.
The ability of the system to self-adjust automatically while patients go about their daily lives would really be transformative in the lives of people with diabetes.
Stuart Weinzimer, MD
The pump, which gave patients better control over their blood sugar, gained traction in the early 1990s when research showed that controlling blood sugar levels reduced such diabetes-related complications as blindness, kidney failure and neuropathy. The next step was to replace the finger stick patients needed to perform every few hours with a sensor that would measure glucose continuously. Dr. Tamborlane worked with Medtronic to test a continuous glucose monitoring device that received FDA approval in 1999. In 2002, he and Dr. Weinzimer began to explore the possibility of combining the sensor with a pump to develop an artificial pancreas.
Compared to today’s artificial pancreas systems—several are in development, but Medtronic’s is furthest along—the early systems were cumbersome. The sensors were much larger, and a radio transmitter had to be taped to the body and connected to a receiver plugged into a laptop. Today, the components are compact and the systems use wireless technology to transmit sensor readings.
There is a pressing need to improve diabetes treatment despite the advances over the last 25 years. The current recommended target hemoglobin A1C level is less than 7 percent for adults, and less than 7.5 percent for those under 19, according to the American Diabetes Association. Yet the average adult A1C is 8.4 percent, and only about 25 percent of adolescents and young adults met the recommended blood sugar targets, with adolescents averaging 9 percent.
More control—and a chance to let go of the reins
In clinical trials, the artificial pancreas has helped patients manage their blood sugar better with less effort. “He had the best control while he was on this closed-loop system than he’s had in the past nine months,” said Nicole Liedke, whose 15-year-old son was part of last spring’s clinical trial.
When the first iteration of the artificial pancreas hits the market, the device won’t be totally automatic. Patients will still have to instruct the pump to provide a dose of insulin before meals to maintain optimal blood sugar control, and the sensor has to be recalibrated regularly. But for patients like Jacob Conte, letting go of the reins a bit, especially at night, will be life-changing.
Jacob’s mother, who also has diabetes, was with him during the clinical trial. “He’s making history,” she said, as tears welled up in her eyes. “For him and for our family, this was an unexpected opportunity of a lifetime.”