A bionic insulin-glucagon pancreas achieved significantly better glycemic control than insulin pump therapy in adults and adolescents with type 1 diabetes, researchers reported at the annual scientific sessions of the American Diabetes Association.
The testing conditions in the two 5-day random-order crossover studies "simulated real-world outpatient settings with close monitoring for safety in adults and adolescents. Meals and physical activity were not regulated, in contrast with previous studies," wrote Dr. Stephen Russell at Massachusetts General Hospital and Harvard Medical School in Boston and his associates in a report published simultaneously with the presentation (N. Engl. J. Med. 2014 June 15 [doi: 10.1056/NEJMoa1314474]).
Adults achieved significantly lower mean plasma glucose levels during the bionic-pancreas period compared with the control period (7.4 vs. 8.8 mg/dL), as did adolescents (7.7 vs. 8.7 mg/dL), the investigators said. And differences were significant even though about 75% of patients had better baseline glycemic control than national averages, they said.
The studies included 20 adults from the Beacon Hill Study and 32 adolescents from the Summer Camp Study, said investigators. The bionic pancreas device included an Apple iPhone 4S, whose control algorithm received continuous glucose monitoring data and triggered dosing every 5 minutes, and a G4 Platinum continuous glucose monitor from Dexcom connected to the iPhone by a hardware interface. The device’s user interface showed continuous glucose readings and insulin and glucagon doses, and enabled the wearer to record meal sizes as typical, more than usual, less than usual, or a "small bite." Based on meal size, the device adapted the insulin dose to meet 75% of the estimated 4-hour postprandial need. If the glucose sensor failed, the device automatically delivered insulin based on the estimated amount calculated from that time on previous days, and also gave correction doses of insulin or glucagon based on manually entered fingerstick plasma glucose data.
During the control period, adults lived at home as usual, managing their diabetes with their own insulin pump, the investigators said. They wore the G4 Platinum monitor with alarms deactivated and the blood glucose level masked, kept diaries of exercise, hypoglycemic episodes, and carbohydrate interventions, received a food allowance, and were encouraged to eat at restaurants. Adolescents lived at the diabetes summer camp alongside teenagers who were not part of the study, and also wore the masked device during the control period, said Dr. Russell and his associates.
In addition to the difference in mean glucose levels, adults had 67% less time with low glucose readings on the bionic pancreas than on the insulin pump (4.1% vs. 7.3% of the time), the researchers said. Adolescents had a 50% decrease in the amount of carbohydrates given to treat hypoglycemia, but no significant difference in amount of time with low glucose readings, which the researcher said might be because the summer camp rapidly responded to hypoglycemic episodes.
Adults had no severe hypoglycemic events, but during the bionic pancreas period, two had nausea and one vomited within 2 hours after a glucagon dose, and four had infusion sets removed because of pain or swelling, said the investigators. Adolescents had no severe hypoglycemia during the bionic pancreas period, they said, but during the control period, one patient became confused and hypoglycemic.
The slow absorption of available rapid-acting subcutaneous insulin analogues and the poor stability of current glucagon formulations are challenges in designing these devices, according to Dr. Russell and associates. "Since a single device that integrates all the components of a bionic pancreas is not yet available, we had to rely on wireless connectivity to the insulin and glucagon pumps, which was not completely reliable," they wrote, adding that the device could overestimate blood glucose level if patients take acetaminophen. "The balance of risks and benefits associated with delivering more insulin to achieve more physiologic glycemic control will require further study," they added, noting that the long-term safety of small peripheral doses of glucagon also is unknown.
The National Institute of Diabetes and Digestive and Kidney Diseases, the Leona M. and Harry B. Helmsley Charitable Trust, the Earle Charlton Fund for Innovative Research in Diabetes, the Frederick Banting Foundation, and Ralph Faber and John Whitlock funded the study. Three authors have patents or pending patents for blood glucose control systems. Dr. Russell and one co-author reported receiving fees from Medtronic, Tandem Diabetes, Sanofi Aventis, Eli Lilly, Abbott Diabetes Care, Biodel, and Dexcom.