Automatic blood glucose control for type 1 diabetes: A trade-off between postprandial hyperglycemia and hypoglycemia

Abstract Artificial pancreas (AP) systems perform automated insulin delivery to subjects with type 1 diabetes mellitus (T1DM). In this paper, a nonlinear suboptimal controller is designed to make a trade-off between the elimination of hypoglycemia events and the limitation of postprandial hyperglycemia. All the in silico simulations are performed using the distribution version of the UVA/Padova type 1 diabetes (T1D) simulator. The proposed nonlinear AP system is based on an individualized control law which is designed in three steps. At first, a nonlinear model of the glucose–insulin regulatory system is identified based on the data collected from some safe experiments. Then, using the personalized models for all the patients of the simulator and a nonlinear technique called state-dependent Riccati equation (SDRE), suboptimal controllers are designed in which a trade-off between the abilities to correct hyperglycemia and to minimize hypoglycemia is made by considering variable weighting matrices for the controller. Since the SDRE controller has a state-feedback structure, unscented Kalman filter (UKF) is employed to generate estimations for unmeasured state variables from the measured subcutaneous blood glucose level. To assess the performance of the proposed AP system, several scenarios are considered for 33 in silico patients (11 adults, 11 adolescents, and 11 children). The obtained results are analyzed and compared with two other AP systems. Patients’ blood glucose concentrations are maintained in safe levels in all the simulated scenarios and very limited hyperglycemia and no hypoglycemia are observed even in a challenging scenario. The promising results are so encouraging and the proposed AP system is worthy to be tested in vivo.

[1]  Claudio Cobelli,et al.  Artificial Pancreas: Model Predictive Control Design from Clinical Experience , 2013, Journal of diabetes science and technology.

[2]  Josep Vehí,et al.  A New Blood Glucose Control Scheme for Unannounced Exercise in Type 1 Diabetic Subjects , 2020, IEEE Transactions on Control Systems Technology.

[3]  Giovanni Sparacino,et al.  Diabetes: Models, Signals, and Control , 2009 .

[4]  C. Cobelli,et al.  In Silico Preclinical Trials: A Proof of Concept in Closed-Loop Control of Type 1 Diabetes , 2009, Journal of diabetes science and technology.

[5]  Anirban Roy,et al.  The effect of insulin feedback on closed loop glucose control. , 2011, The Journal of clinical endocrinology and metabolism.

[6]  Patricio Colmegna,et al.  Automatic regulatory control in type 1 diabetes without carbohydrate counting , 2018 .

[7]  Pierdomenico Pepe,et al.  Recent Results on Glucose–Insulin Predictions by Means of a State Observer for Time Delay Systems , 2016 .

[8]  Y. Batmani Blood glucose concentration control for type 1 diabetic patients: a non-linear suboptimal approach. , 2017, IET systems biology.

[9]  Richard N Bergman,et al.  The minimal model of glucose regulation: a biography. , 2003, Advances in experimental medicine and biology.

[10]  Beatriz Ricarte,et al.  Insulin Estimation and Prediction: A Review of the Estimation and Prediction of Subcutaneous Insulin Pharmacokinetics in Closed-Loop Glucose Control , 2018, IEEE Control Systems.

[11]  Rudolph van der Merwe,et al.  The unscented Kalman filter for nonlinear estimation , 2000, Proceedings of the IEEE 2000 Adaptive Systems for Signal Processing, Communications, and Control Symposium (Cat. No.00EX373).

[12]  Daniel Howsmon,et al.  Closed-Loop Control Without Meal Announcement in Type 1 Diabetes. , 2017, Diabetes technology & therapeutics.

[13]  Cesar C. Palerm,et al.  Physiologic insulin delivery with insulin feedback: A control systems perspective , 2011, Comput. Methods Programs Biomed..

[14]  G. Steil,et al.  Feasibility of Automating Insulin Delivery for the Treatment of Type 1 Diabetes , 2006, Diabetes.

[15]  B. Wayne Bequette,et al.  Challenges and recent progress in the development of a closed-loop artificial pancreas , 2012, Annu. Rev. Control..

[16]  Eyal Dassau,et al.  Periodic-Zone Model Predictive Control for Diurnal Closed-Loop Operation of an Artificial Pancreas , 2013, Journal of diabetes science and technology.

[17]  R. Bergman Toward Physiological Understanding of Glucose Tolerance: Minimal-Model Approach , 1989, Diabetes.

[18]  Claudio Cobelli,et al.  Toward a Run-to-Run Adaptive Artificial Pancreas: In Silico Results , 2018, IEEE Transactions on Biomedical Engineering.

[19]  Niels Kjølstad Poulsen,et al.  Adaptive model predictive control for a dual-hormone artificial pancreas , 2018, Journal of Process Control.

[20]  Niels Kjølstad Poulsen,et al.  Overnight glucose control in people with type 1 diabetes , 2018, Biomed. Signal Process. Control..

[21]  Patricio Colmegna,et al.  Reducing Risks in Type 1 Diabetes Using ${\cal H}_\infty$ Control , 2014, IEEE Transactions on Biomedical Engineering.

[22]  Stuart A Weinzimer,et al.  Effect of Insulin Feedback on Closed-Loop Glucose Control: A Crossover Study , 2012, Journal of diabetes science and technology.

[23]  Dale E. Seborg,et al.  Control-Relevant Models for Glucose Control Using A Priori Patient Characteristics , 2012, IEEE Transactions on Biomedical Engineering.

[24]  Patricio Colmegna,et al.  Linear parameter-varying model to design control laws for an artificial pancreas , 2018, Biomed. Signal Process. Control..

[25]  K. Kuehl,et al.  Randomized trial of a dual‐hormone artificial pancreas with dosing adjustment during exercise compared with no adjustment and sensor‐augmented pump therapy , 2016, Diabetes, obesity & metabolism.

[26]  Nader Meskin,et al.  Nonlinear Suboptimal Tracking Controller Design Using State-Dependent Riccati Equation Technique , 2017, IEEE Transactions on Control Systems Technology.

[27]  Eyal Dassau,et al.  Velocity-weighting & velocity-penalty MPC of an artificial pancreas: Improved safety & performance , 2018, Autom..

[28]  Tayfun Çimen,et al.  Systematic and effective design of nonlinear feedback controllers via the state-dependent Riccati equation (SDRE) method , 2010, Annu. Rev. Control..

[29]  Claude H. Moog,et al.  Model Free iPID Control for Glycemia Regulation of Type-1 Diabetes , 2018, IEEE Transactions on Biomedical Engineering.

[30]  Amjad Abu-Rmileh,et al.  A Gain-Scheduling Model Predictive Controller for Blood Glucose Control in Type 1 Diabetes , 2010, IEEE Transactions on Biomedical Engineering.

[31]  Lauren M. Huyett,et al.  Closed-Loop Artificial Pancreas Systems: Engineering the Algorithms , 2014, Diabetes Care.

[32]  Eyal Dassau,et al.  Periodic zone-MPC with asymmetric costs for outpatient-ready safety of an artificial pancreas to treat type 1 diabetes , 2016, Autom..

[33]  Darine Zambrano,et al.  Internal model sliding mode control approach for glucose regulation in type 1 diabetes , 2010, Biomed. Signal Process. Control..

[34]  Hervé Cormerais,et al.  Artificial pancreas for type 1 diabetes: Closed-loop algorithm based on Error Dynamics Shaping , 2012 .