Fully Automated Artificial Pancreas for Adults With Type 1 Diabetes Using Multiple Hormones: Exploratory Experiments.

ABSTRACT

OBJECTIVES: A fully automated insulin-pramlintide-glucagon artificial pancreas that alleviates the burden of carbohydrate counting without degrading glycemic control was iteratively enhanced until convergence through pilot experiments on adults with type 1 diabetes. METHODS: Nine participants (age, 37±13 years; glycated hemoglobin, 7.7±0.7%) completed two 27-hour interventions: a fully automated multihormone artificial pancreas and a comparator insulin-alone artificial pancreas with carbohydrate counting. The baseline algorithm was a model-predictive controller that administered insulin and pramlintide in a fixed ratio, with boluses triggered by a glucose threshold, and administered glucagon in response to low glucose levels. RESULTS: The baseline multihormone dosing algorithm resulted in noninferior time in target range (3.9 to 10.0 mmol/L) (71%) compared with the insulin-alone arm (70%) in 2 participants, with minimal glucagon delivery. The algorithm was modified to deliver insulin and pramlintide more aggressively to increase time in range and maximize the benefits of glucagon. The modified algorithm displayed a similar time in range for the multihormone arm (79%) compared with the insulin-alone arm (83%) in 2 participants, but with undesired glycemic fluctuations. Subsequently, we reduced the glucose threshold that triggers glucagon boluses. This resulted in inferior glycemic control for the multihormone arm (81% vs 91%) in 2 participants. Thereafter, a model-based meal-detection algorithm to deliver insulin and pramlintide boluses closer to mealtimes was added and glucagon was removed. The final dual-hormone system had comparable time in range (81% vs 83%) in the last 3 participants. CONCLUSION: The final version of the fully automated system that delivered insulin and pramlintide warrants a randomized controlled trial.