Davide Martino Raimondo

Model Predictive Control of Type 1 Diabetes: An in Silico Trial:

Background: The development of artificial pancreas has received a new impulse from recent technological advancements in subcutaneous continuous glucose monitoring and subcutaneous insulin pump delivery systems. However, the availability of innovative sensors and actuators, although essential, does not guarantee optimal glycemic regulation. Closed-loop control of blood glucose levels still poses technological challenges to the automatic control expert, most notable of which are the inevitable time delays between glucose sensing and insulin actuation. Methods: A new in silico model is exploited for both design and validation of a linear model predictive control (MPC) glucose control system. The starting point is a recently developed meal glucose-insulin model in health, which is modified to describe the metabolic dynamics of a person with type 1 diabetes mellitus. The population distribution of the model parameters originally obtained in healthy 204 patients is modified to describe diabetic patients. Individual models of virtual patients are extracted from this distribution. A discrete-time MPC is designed for all the virtual patients from a unique input-output-linearized approximation of the full model based on the average population values of the parameters. The in silico trial simulates 4 consecutive days, during which the patient receives breakfast, lunch, and dinner each day. Results: Provided that the regulator undergoes some individual tuning, satisfactory results are obtained even if the control design relies solely on the average patient model. Only the weight on the glucose concentration error needs to be tuned in a quite straightforward and intuitive way. The ability of the MPC to take advantage of meal announcement information is demonstrated. Imperfect knowledge of the amount of ingested glucose causes only marginal deterioration of performance. In general, MPC results in better regulation than proportional integral derivative, limiting significantly the oscillation of glucose levels. Conclusions: The proposed in silico trial shows the potential of MPC for artificial pancreas design. The main features are a capability to consider meal announcement information, delay compensation, and simplicity of tuning and implementation.

GIM, Simulation Software of Meal Glucose—Insulin Model

Background: A simulation model of the glucose—insulin system in normal life conditions can be very useful in diabetes research, e.g., testing insulin infusion algorithms and decision support systems and assessing glucose sensor performance and patient and student training. A new meal simulation model has been proposed that incorporates state-of-the-art quantitative knowledge on glucose metabolism and its control by insulin at both organ/tissue and whole-body levels. This article presents the interactive simulation software GIM (glucose insulin model), which implements this model. Methods: The model is implemented in MATLAB, version 7.0.1, and is designed with a windows interface that allows the user to easily simulate a 24-hour daily life of a normal, type 2, or type 1 diabetic subject. A Simulink version is also available. Three meals a day are considered. Both open- and closed-loop controls are available for simulating a type 1 diabetic subject. Results: Software options are described in detail. Case studies are presented to illustrate the potential of the software, e.g., compare a normal subject vs an insulin-resistant subject or open-loop vs closed-loop insulin infusion in type 1 diabetes treatment. Conclusions: User-friendly software that implements a state-of-the-art physiological model of the glucose-insulin system during a meal has been presented. The GIM graphical interface makes its use extremely easy for investigators without specific expertise in modeling.

Cooperative Constrained Control of Distributed Agents With Nonlinear Dynamics and Delayed Information Exchange: A Stabilizing Receding-Horizon Approach

This paper addresses the problem of cooperative control of a team of distributed agents with decoupled nonlinear discrete-time dynamics, which operate in a common environment and exchange-delayed information between them. Each agent is assumed to evolve in discrete-time, based on locally computed control laws, which are computed by exchanging delayed state information with a subset of neighboring agents. The cooperative control problem is formulated in a receding-horizon framework, where the control laws depend on the local state variables (feedback action) and on delayed information gathered from cooperating neighboring agents (feedforward action). A rigorous stability analysis exploiting the input-to-state stability properties of the receding-horizon local control laws is carried out. The stability of the team of agents is then proved by utilizing small-gain theorem results.

Evaluating the Efficacy of Closed-Loop Glucose Regulation via Control-Variability Grid Analysis

Background: Advancements in subcutaneous continuous glucose monitoring and subcutaneous insulin delivery are stimulating the development of a minimally invasive artificial pancreas that facilitates optimal glycemic regulation in diabetes. The key component of such a system is the blood glucose controller for which different design strategies have been investigated in the literature. In order to evaluate and compare the efficacy of the various algorithms, several performance indices have been proposed. Methods: A new tool—control-variability grid analysis (CVGA)—for measuring the quality of closed-loop glucose control on a group of subjects is introduced. It is a method for visualization of the extreme glucose excursions caused by a control algorithm in a group of subjects, with each subject presented by one data point for any given observation period. A numeric assessment of the overall level of glucose regulation in the population is given by the summary outcome of the CVGA. Results: It has been shown that CVGA has multiple uses: Comparison of different patients over a given time period, of the same patient over different time periods, of different control laws, and of different tuning of the same controller on the same population. Conclusions: Control-variability grid analysis provides a summary of the quality of glycemic regulation for a population of subjects and is complementary to measures such as area under the curve or low/high blood glucose indices, which characterize a single glucose trajectory for a single subject.

Input-to-State Stability: A Unifying Framework for Robust Model Predictive Control

This paper deals with the robustness of Model Predictive Controllers for constrained uncertain nonlinear systems. The uncertainty is assumed to be modeled by a state and input dependent signal and a disturbance signal. The framework used for the analysis of the robust stability of the systems controlled by MPC is the wellknown Input-to-State Stability. It is shown how this notion is suitable in spite of the presence of constraints on the system and of the possible discontinuity of the control law.

Model predictive control of glucose concentration in type I diabetic patients: An in silico trial

Abstract In this paper, the feedback control of glucose concentration in type I diabetic patients using subcutaneous insulin delivery and subcutaneous continuous glucose monitoring is considered. A recently developed in silico model of glucose metabolism is employed to generate virtual patients on which control algorithms can be validated against interindividual variability. An in silico trial consisting of 100 patients is used to assess the performances of a linear output feedback and a nonlinear state-feedback model predictive controller, designed on the basis of the in silico model. More than satisfactory results are obtained in the great majority of virtual patients. The experiments highlight the crucial role of the anticipative feedforward action driven by the meal announcement information. Preliminary results indicate that further improvements may be achieved by means of a nonlinear model predictive control scheme.

Regional Input-to-State Stability for Nonlinear Model Predictive Control

In this note, regional input-to-state stability (ISS) is introduced and studied in order to analyze the domain of attraction of nonlinear constrained systems with disturbances. ISS is derived by means of a non smooth ISS-Lyapunov function with an upper bound guaranteed only in a sub-region of the domain of attraction. These results are used to study the ISS properties of nonlinear model predictive control (MPC) algorithms

Robust Model Predictive Control With Integral Sliding Mode in Continuous-Time Sampled-Data Nonlinear Systems

This paper proposes a control strategy for nonlinear constrained continuous-time uncertain systems which combines robust model predictive control (MPC) with sliding mode control (SMC). In particular, the so-called Integral SMC approach is used to produce a control action aimed to reduce the difference between the nominal predicted dynamics of the closed-loop system and the actual one. In this way, the MPC strategy can be designed on a system with a reduced uncertainty. In order to prove the stability of the overall control scheme, some general regional input-to-state practical stability results for continuous-time systems are proved.

Robust Model Predictive Control of Nonlinear Systems With Bounded and State-Dependent Uncertainties

In this note, a robust model predictive control scheme for constrained discrete-time nonlinear systems affected by bounded disturbances and state-dependent uncertainties is presented. In order to guarantee the robust satisfaction of the state constraints, restricted constraint sets are introduced in the optimization problem, by exploiting the state-dependent nature of the considered class of uncertainties. Moreover, unlike the nominal model predictive control algorithm, a stabilizing state constraint is imposed at the end of the control horizon in place of the usual terminal constraint posed at the end of the prediction horizon. The regional input-to-state stability of the closed-loop system is analyzed. A simulation example shows the effectiveness of the proposed approach.

Input design for guaranteed fault diagnosis using zonotopes

a b s t r a c t An input design method is presented for guaranteeing the diagnosability of faults from the outputs of a system. Faults are modeled by discrete switches between linear models with bounded disturbances and measurement errors. Zonotopes are used to efficiently characterize the set of inputs that are guaranteed to lead to outputs that are consistent with at most one fault scenario. Provided that this set is nonempty, an element is then chosen that is minimally harmful with respect to other control objectives. This approach leads to a nonconvex optimization problem, but is shown to be equivalent to a mixed-integer quadratic program that can be solved efficiently. Methods are given for reducing the complexity of this program, including an observer-based method that drastically reduces the number of binary variables when many sampling times are required for diagnosis.