Intermittent closed-loop blood glucose control for people with type 1 diabetes on multiple daily injections

Background and objectives: Recent advances in Automated Insulin Delivery systems have been shown to dramatically improve glycaemic control and reduce the risk of hypoglycemia in people with type 1 dia-betes. However, they are complex systems that require specific training and are not affordable for most. Attempts to reduce the gap with closed-loop therapies using advanced dosing advisors have so far failed, mainly because they require too much human intervention. With the advent of smart insulin pens, one of the main constraints (having reliable bolus and meal information) disappears and new strategies can be employed. This is our starting hypothesis, which we have validated in a very demanding simulator. In this paper, we propose an intermittent closed-loop control system specifically intended for multiple daily injection therapy to bring the benefits of artificial pancreas to the application of multiple daily injections.Methods: The proposed control algorithm is based on model predictive control and integrates two patient-driven control actions. Correction insulin boluses are automatically computed and recommended to the patient to minimize the duration of hyperglycemia. Rescue carbohydrates are also triggered to avoid hy-poglycemia episodes. The algorithm can adapt to different patient lifestyles with customizable triggering conditions, closing the gap between practicality and performance. The proposed algorithm is compared with conventional open-loop therapy, and its superiority is demonstrated through extensive in silico eval-uations using realistic cohorts and scenarios. The evaluations were conducted in a cohort of 47 virtual patients. We also provide detailed explanations of the implementation, imposed constraints, triggering conditions, cost functions, and penalties for the algorithm.Results: The in-silico outcomes combining the proposed closed-loop strategy with slow-acting insulin ana-log injections at 09:00 h resulted in percentages of time in range (TIR) (70-180 mg/dL) of 69.5%, 70.6%, and 70.4% for glargine-100, glargine-300, and degludec-100, respectively, and injections at 20:00 h re-sulted in percentages of TIR of 70.5%, 70.3%, and 71.6%, respectively. In all the cases, the percentages of TIR were considerably higher than those obtained from the open-loop strategy, being only 50.7%, 53.9%, and 52.2% for daytime injection and 55.5%, 54.1%, and 56.9% for nighttime injection. Overall, the occur-rence of hypoglycemia and hyperglycemia was notably reduced using our approach.Conclusions: Event-triggering model predictive control in the proposed algorithm is feasible and may meet clinical targets for people with type 1 diabetes. (c) 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Automated summary

This study proposes an intermittent closed-loop control system for multiple daily injection therapy in people with type 1 diabetes. The control algorithm is based on model predictive control and incorporates correction insulin boluses and rescue carbohydrates to optimize glycaemic control. In-silico evaluations demonstrate the superiority of the proposed algorithm over conventional open-loop therapy.