Bayesian Optimization Assisted Meal Bolus Decision Based on Gaussian Processes Learning and Risk-Sensitive Control

Effective postprandial glucose control is important to glucose management for subjects with diabetes mellitus. In this work, a data-driven meal bolus decision method is proposed without the need of subject-specific glucose management parameters. The postprandial glucose dynamics is learnt using Gaussian process regression. Considering the asymmetric risks of hyperand hypoglycemia and the uncertainties in the predicted glucose trajectories, an asymmetric risk-sensitive cost function is designed. Bayesian optimization is utilized to solve the optimization problem, since the gradient of the cost function is unavailable. The proposed approach is evaluated using the 10-adult cohort of the FDA-accepted UVA/Padova T1DM simulator and compared with the standard insulin bolus calculator. For the case of announced meals, the proposed method achieves satisfactory and similar performance in terms of mean glucose and percentage time in [70, 180] mg/dL without increasing the risk of hypoglycemia. Similar results are observed for the case without the meal information (assuming that the patient follows a consistent diet) and the case of basal rate mismatches. In addition, advisory-mode analysis is performed based on clinical data, which indicates that the method can determine safe and reasonable meal boluses in real clinical settings. The results verify the effectiveness and robustness of the proposed method and indicate the feasibility of achieving improved postprandial glucose regulation through a data-driven optimal control method.

[1]  Claudio Cobelli,et al.  Insulin Sensitivity Index-Based Optimization of Insulin to Carbohydrate Ratio: In Silico Study Shows Efficacious Protection Against Hypoglycemic Events Caused by Suboptimal Therapy. , 2018, Diabetes technology & therapeutics.

[2]  P. Whittle,et al.  A hamiltonian formulation of risk-sensitive Linear/quadratic/gaussian control , 1986 .

[3]  S. Genuth,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. , 1993, The New England journal of medicine.

[4]  Xiaoke Yang,et al.  Risk-Sensitive Model Predictive Control with Gaussian Process Models* , 2015 .

[5]  R. Hovorka,et al.  Nonlinear model predictive control of glucose concentration in subjects with type 1 diabetes. , 2004, Physiological measurement.

[6]  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..

[7]  A. Schiffrin,et al.  Multiple daily self-glucose monitoring: its essential role in long-term glucose control in insulin-dependent diabetic patients treated with pump and multiple subcutaneous injections. , 1982, Diabetes care.

[8]  Ali Cinar,et al.  Online Glucose Prediction Using Computationally Efficient Sparse Kernel Filtering Algorithms in Type-1 Diabetes , 2020, IEEE Transactions on Control Systems Technology.

[9]  K. Obermayer,et al.  Multiple-step ahead prediction for non linear dynamic systems: A Gaussian Process treatment with propagation of the uncertainty , 2003, NIPS 2003.

[10]  Hsiao-Ping Huang,et al.  Fuzzy-Logic-Based Supervisor of Insulin Bolus Delivery for Patients with Type 1 Diabetes Mellitus , 2013 .

[11]  Beatriz López,et al.  Personalized Adaptive CBR Bolus Recommender System for Type 1 Diabetes , 2019, IEEE Journal of Biomedical and Health Informatics.

[12]  Eyal Dassau,et al.  Enhanced Model Predictive Control (eMPC) Strategy for Automated Glucose Control. , 2016, Industrial & engineering chemistry research.

[13]  Ali Cinar,et al.  Real-time insulin bolusing for unannounced meals with artificial pancreas , 2017 .

[14]  Ali Cinar,et al.  Artificial Pancreas Systems: An Introduction to the Special Issue , 2018 .

[15]  Lena Mamykina,et al.  Data-driven modeling and prediction of blood glucose dynamics: Machine learning applications in type 1 diabetes , 2019, Artif. Intell. Medicine.

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

[17]  Ahmad Haidar,et al.  The Artificial Pancreas and Meal Control: An Overview of Postprandial Glucose Regulation in Type 1 Diabetes , 2018, IEEE Control Systems.

[18]  Gian Paolo Incremona,et al.  Model predictive control with integral action for artificial pancreas , 2018, Control Engineering Practice.

[19]  C. Cobelli,et al.  The UVA/PADOVA Type 1 Diabetes Simulator , 2014, Journal of diabetes science and technology.

[20]  Francis J. Doyle,et al.  Run-to-run control of blood glucose concentrations for people with type 1 diabetes mellitus , 2006, IEEE Transactions on Biomedical Engineering.

[21]  Francis J. Doyle,et al.  Multivariate learning framework for long‐term adaptation in the artificial pancreas , 2018, Bioengineering & translational medicine.

[22]  Howard Zisser,et al.  Glucose Estimation and Prediction through Meal Responses Using Ambulatory Subject Data for Advisory Mode Model Predictive Control , 2007, Journal of diabetes science and technology.

[23]  Niels Kjølstad Poulsen,et al.  Adaptive control in an artificial pancreas for people with type 1 diabetes , 2017 .

[24]  Yunpeng Pan,et al.  Efficient Reinforcement Learning via Probabilistic Trajectory Optimization , 2018, IEEE Transactions on Neural Networks and Learning Systems.

[25]  B Shashaj,et al.  Benefits of a bolus calculator in pre‐ and postprandial glycaemic control and meal flexibility of paediatric patients using continuous subcutaneous insulin infusion (CSII) , 2008, Diabetic medicine : a journal of the British Diabetic Association.

[26]  David C Klonoff,et al.  The current status of bolus calculator decision-support software. , 2012, Journal of diabetes science and technology.

[27]  Marko V. Jankovic,et al.  A Dual Mode Adaptive Basal-Bolus Advisor Based on Reinforcement Learning , 2019, IEEE Journal of Biomedical and Health Informatics.

[28]  Christofer Toumazou,et al.  Advanced Insulin Bolus Advisor Based on Run-To-Run Control and Case-Based Reasoning , 2015, IEEE Journal of Biomedical and Health Informatics.

[29]  Ali Cinar,et al.  Seasonal Local Models for Glucose Prediction in Type 1 Diabetes , 2020, IEEE Journal of Biomedical and Health Informatics.

[30]  Nando de Freitas,et al.  Taking the Human Out of the Loop: A Review of Bayesian Optimization , 2016, Proceedings of the IEEE.

[31]  Donald R. Jones,et al.  Efficient Global Optimization of Expensive Black-Box Functions , 1998, J. Glob. Optim..

[32]  Chengyuan Liu,et al.  GluNet: A Deep Learning Framework for Accurate Glucose Forecasting , 2020, IEEE Journal of Biomedical and Health Informatics.

[33]  Ali Cinar,et al.  Model-Fusion-Based Online Glucose Concentration Predictions in People with Type 1 Diabetes. , 2018, Control engineering practice.

[34]  Ali Cinar,et al.  Plasma-Insulin-Cognizant Adaptive Model Predictive Control for Artificial Pancreas Systems. , 2019, Journal of process control.

[35]  S Roberts,et al.  Gaussian processes for time-series modelling , 2013, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[36]  Dimitrios I. Fotiadis,et al.  Evaluation of short-term predictors of glucose concentration in type 1 diabetes combining feature ranking with regression models , 2015, Medical & Biological Engineering & Computing.

[37]  Carl E. Rasmussen,et al.  Gaussian Processes for Data-Efficient Learning in Robotics and Control , 2015, IEEE Transactions on Pattern Analysis and Machine Intelligence.

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

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

[40]  Manfred Morari,et al.  Learning and Control Using Gaussian Processes , 2018, 2018 ACM/IEEE 9th International Conference on Cyber-Physical Systems (ICCPS).

[41]  R. Bergman,et al.  Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. , 1981, The Journal of clinical investigation.

[42]  Claudio Cobelli,et al.  Meal Simulation Model of the Glucose-Insulin System , 2007, IEEE Transactions on Biomedical Engineering.

[43]  Carl E. Rasmussen,et al.  Gaussian processes for machine learning , 2005, Adaptive computation and machine learning.

[44]  G. Charpentier,et al.  ARX model for interstitial glucose prediction during and after physical activities , 2019, Control Engineering Practice.