Artificial Pancreas Gets Real

When Edward Damiano’s 11-month-old son, David, developed type 1 diabetes in 2000, he had to check his baby’s blood sugar 15 times a day. Now, 10 years later, Damiano’s research has led to the development of a quicker system for regulating blood glucose levels in those with the disease.

To maintain safe blood sugar levels, people with type 1 diabetes must submit to a demanding daily regimen that requires frequent monitoring of blood glucose (BG) and dosing of insulin by injection or infusion pump. Even with recently developed continuous glucose monitoring (CGM) technology, the diabetic or a caregiver must still double-check BG levels and administer insulin several times a day. Because the process is so labor-intensive, the type 1 diabetic community — nearly two million in the United States — has long sought an automated, “closed-loop” system that regulates BG with minimal human intervention.

Now investigators at Boston University and Massachusetts General Hospital have conducted the first clinical trial of a closed-loop system prototype developed by Damiano, a College of Engineering associate professor of biomedical engineering, and Firas H. El-Khatib, a senior research associate. The system uses decision-making software to pump insulin and glucagon (a blood sugar–raising hormone) beneath the skin based on BG readings every five minutes. The team — the first to complete a human trial of a closed-loop system using both insulin and glucagon — describes the system’s performance in the April 14 edition of Science Translational Medicine.

“Over time, our automated system would not only reduce the decision-making load on type 1 diabetes patients and their caregivers, but would also help keep patients’ blood glucose levels within a much healthier range than open-loop systems,” says Damiano. “As a result, they would experience far fewer low blood sugar episodes and avoid chronic high blood sugar levels associated with cardiovascular disease, kidney failure, retinal damage, and other long-term complications.”

Emulating the pancreas
Based on a series of experiments they have conducted on diabetic pigs since 2005, Damiano and El-Khatib’s closed-loop system uses a control algorithm to receive BG data from a standard, FDA-approved CGM sensor every five minutes and dose either lispro, a fast-acting insulin analog (for elevated BG), or glucagon (for low readings) with a standard, FDA-approved insulin infusion pump. In effect, the system works to emulate the endocrine pancreas, continually producing these two hormones to regulate blood sugar.

In the clinical trial, the research team studied 11 adults with type 1 diabetes at MGH, each hooked to an experimental version of the closed-loop system for 27 hours and supplied with three carbohydrate-rich meals. Consisting of an intravenous BG monitor, infusion pumps to deliver insulin and glucagon through abdominal tissue just beneath the skin, and a laptop containing the control software, the system compared each BG reading with a 100 milligrams per deciliter (mg/dL) “ideal” target, and computed insulin and glucagon doses aimed at minimizing the difference between the reading and the target.

Six of the subjects exhibited a near-normal aggregate mean BG of 140 mg/dL, which is significantly better than the 150-160 range recommended by the American Diabetes Association for people with type 1 diabetes. But the other five experienced episodes of hypoglycemia — low blood sugar caused by too much insulin — that had to be corrected by the subjects’ drinking orange juice.

The researchers determined that because these five subjects absorbed insulin at a much slower rate than modeled by the software, the system had administered excessive doses of insulin, thereby inducing hypoglycemia. By nearly doubling the expected absorption time in the software, they prevented hypoglycemia in repeat 27-hour experiments in these participants and achieved an aggregate mean BG of 166 mg/dL — still close to the ADA’s recommendation.

The seven-year goal
Damiano’s goal is to produce a practical artificial endocrine pancreas for outpatient use by the time his son is ready for college. “Two years ago,” he says, “I got him on to a CGM that allows me to put a receiver in my bedroom with alarms to wake me up to give him juice when his BG hits 75, or insulin when it reaches 140. In seven years David goes to college, and he won’t get the kind of control I can provide for him.”

In a follow-up study this spring, Damiano and his collaborators will test a standard portable infusion pump and standard CGM on 36 adult and pediatric subjects for about two days. The study will add exercise sessions and a small premeal “priming bolus” of insulin aimed at reducing overall mean BG. Eventually the software, currently stored on a laptop, will be condensed onto an integrated circuit on the pump.

The study was supported by grants from the Juvenile Diabetes Research Foundation, the Wallace Coulter Foundation, the Charlton Fund for Innovative Research in Diabetes, and the National Center for Research Resources.

This article originally appeared on the College of Engineering’s Web site.