Impact of Accelerating Insulin on an Artificial Pancreas System Without Meal Announcement: An In Silico Examination

Abstract

Background: Controlling postprandial blood glucose without the benefit of an appropriately sized premeal insulin bolus has been challenging given the delays in absorption and action of subcutaneously injected insulin during conventional and artificial pancreas (AP) system diabetes treatment. We aim to understand the impact of accelerating insulin and increasing aggressiveness of the AP controller as potential solutions to address the postprandial hyperglycemia challenge posed by unannounced meals through a simulation study. Methods: Accelerated rapid-acting insulin analogue is modeled within the UVA/Padova simulation platform by uniformly reducing its pharmacokinetic time constants (α multiplier) and used with a model predictive control, where the controller’s aggressiveness depends on α. Two sets of single-meal simulations were performed: (1) where we only tune the controller’s aggressiveness and (2) where we also accelerate insulin absorption and action to assess postprandial glycemic control during each intervention. Results: Mean percent of time spent within the 70 to 180 mg/dL postprandial glycemic range is significantly higher in set (2) than in set (1): 79.9, 95% confidence interval [77.0, 82.7] vs 88.8 [86.8, 90.9] ([Note to typesetter: Set all unnecessary math in text format and insert appropriate spaces between operators.] P < .05) for α = 2, and 81.4 [78.6, 84.3] vs 94.1 [92.6, 95.6] ( P < .05) for α = 3. A decrease in percent of time below 70 mg/dL is also detected: 0.9 [0.4, 2.2] vs 0.6 [0.2, 1.4] ( P = .23) for α = 2 and 1.4 [0.7, 2.8] vs 0.4 [0.1, 1.4] ( P < .05) for α = 3. Conclusion: These proof-of-concept simulations suggest that an AP without prandial insulin boluses combined with significantly faster insulin analogues could match the glycemic performance obtained with an optimal hybrid AP.