Linear parameter-varying model to design control laws for an artificial pancreas

The contribution of this work is the generation of a control-oriented model for insulin-glucose dynamic regulation in type 1 diabetes mellitus (T1DM). The novelty of this model is that it includes the time-varying nature, and the inter-patient variability of the glucose-control problem. In addition, the model is well suited for well-known and standard controller synthesis procedures. The outcome is an average linear parameter-varying (LPV) model that captures the dynamics from the insulin delivery input to the glucose concentration output constructed based on the UVA/Padova metabolic simulator. Finally, a system-oriented reinterpretation of the classical ad-hoc 1800 rule is applied to adapt the model's gain. The effectiveness of this approach is quantified both in open- and closed-loop. The first one by computing the root mean square error (RMSE) between the glucose deviation predicted by the proposed model and the UVA/Padova one. The second measure is determined by using the ν-gap as a metric to determine distance, in terms of closed-loop performance, between both models. For comparison purposes, both open- (RMSE) and closed-loop (ν-gap metric) quality indicators are also computed for other control-oriented models previously presented. This model allows the design of LPV controllers in a straightforward way, considering its affine dependence on the time-varying parameter, which can be computed in real-time. Illustrative simulations are included. In addition, the presented modeling strategy was employed in the design of an artificial pancreas (AP) control law that successfully withstood rigorous testing using the UVA/Padova simulator, and that was subsequently deployed in a clinical trial campaign where five adults remained in closed-loop for 36 h. This was the first ever fully closed-loop clinical AP trial in Argentina, and the modeling strategy presented here is considered instrumental in resulting in a very successful clinical outcome.Fil: Colmegna, Patricio Hernán. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sánchez Peña, Ricardo S.. Instituto Tecnológico de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gondhalekar, R.. Harvard University; Estados Unido

Automatic Glucose Control during Meals and Exercise in Type 1 Diabetes: Proof-of-Concept in Silico Tests Using a Switched LPV Approach

Keeping the blood glucose levels within the safe range during meals and exercise still represents a major hurdle not only for patients with type 1 diabetes (T1D), but also for Artificial Pancreas (AP) systems. One of the reasons a fully (autonomous) closed-loop solution has not been released onto the market yet is the slow action of current insulin analogs. To partially overcome this limitation, the authors have previously designed a switched control strategy equipped with an insulin-on-board (IOB) safety loop that mitigates meal-related glucose excursions without carbohydrate counting. In this letter, a similar strategy based on a Linear Parameter-Varying (LPV) control law has been adapted to safely handle also exercise challenges with minimum user intervention. In silico results using the UVA/Padova simulator evidence that the proposed closed-loop scheme is feasible under moderate-intense exercise bouts by effectively and safely reducing the risk of hypoglycemia.Fil: Colmegna, Patricio Hernán. University of Virginia; Estados Unidos. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bianchi, Fernando Daniel. Instituto Tecnológico de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sanchez Peña, Ricardo Salvador. Instituto Tecnológico de Buenos Aires. Departamento de Matemática. Centro de Sistemas y Control; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Control-Oriented Model with Intra-Patient Variations for an Artificial Pancreas

In this work, a low-order model designed for glucose regulation in Type 1 Diabetes Mellitus (T1DM) is obtained from the UVA/Padova metabolic simulator. It captures not only the nonlinear behavior of the glucose-insulin system, but also intrapatient variations related to daily insulin sensitivity (SI) changes. To overcome the large inter-subject variability, the model can also be personalized based on a priori patient information. The structure is amenable for linear parameter varying (LPV) controller design, and represents the dynamics from the subcutaneous insulin input to the subcutaneous glucose output. The efficacy of this model is evaluated in comparison with a previous control-oriented model which in turn is an improvement of previous models. Both models are compared in terms of their open- and closed-loop differences with respect to the UVA/Padova model. The proposed model outperforms previous T1DM controloriented models, which could potentially lead to more robust and reliable controllers for glycemia regulation.Fil: Moscoso Vásquez, Hilda Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Tecnológico de Buenos Aires. Departamento de Matemática. Centro de Sistemas y Control; ArgentinaFil: Colmegna, Patricio Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Virginia; Estados Unidos. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Rosales, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Garelli, Fabricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Sanchez Peña, Ricardo Salvador. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Tecnológico de Buenos Aires. Departamento de Matemática. Centro de Sistemas y Control; Argentin

Artificial Pancreas System With Unannounced Meals Based on a Disturbance Observer and Feedforward Compensation

© 2021 IEEE. Personal use of this material is permitted. Permissíon from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertisíng or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.[EN] This brief is focused on the closed-loop control of postprandial glucose levels of patients with type 1 diabetes mellitus after unannounced meals, which is still a major challenge toward a fully autonomous artificial pancreas. The main limitations are the delays introduced by the subcutaneous insulin pharmacokinetics and the glucose sensor, which typically leads to insulin overdelivery. Current solutions reported in the literature typically resort to meal announcement, which requires patient intervention. In this brief, a disturbance observer (DOB) is used to estimate the effect of unannounced meals, and the insulin pharmacokinetics is taken into account by means of a feedforward compensator. The proposed strategy is validated in silico with the UVa/Padova metabolic simulator. It is demonstrated how the DOB successfully estimates and counteracts not only the effect of meals but also the sudden drops in the glucose levels that may lead to hypoglycemia. For unannounced meals, results show a median time-in-range of 80% in a 30-day scenario with high carbohydrate content and large intrasubject variability. Optionally, users may decide to announce meals. In this case, considering severe bolus mismatch due to carbohydrate counting errors, the median time-in-range is increased up to 88%. In every case, hypoglycemia is avoided.This work was supported in part by the Ministerio de Economia y Competitividad under Grant DPI2016-78831-C2-1-R and in part by the European Union through FEDER Funds.Sanz Diaz, R.; García Gil, PJ.; Diez, J.; Bondía Company, J. (2021). Artificial Pancreas System With Unannounced Meals Based on a Disturbance Observer and Feedforward Compensation. IEEE Transactions on Control Systems Technology. 29(1):454-460. https://doi.org/10.1109/TCST.2020.2975147S45446029

Receding Horizon Control of Type 1 Diabetes Mellitus by Using Nonlinear Programming

Receding Horizon Controllers are one of the mostly used advanced control solutions in the industry. By utilizing their possibilities we are able to predict the possible future behavior of our system; moreover, we are able to intervene in its operation as well. In this paper we have investigated the possibilities of the design of a Receding Horizon Controller by using Nonlinear Programming. We have applied the developed solution in order to control Type 1 Diabetes Mellitus. The nonlinear optimization task was solved by the Generalized Reduced Gradient method. In order to investigate the performance of our solution two scenarios were examined. In the first scenario, we applied “soft” disturbance—namely, smaller amount of external carbohydrate—in order to be sure that the proposed method operates well and the solution that appeared through optimization is acceptable. In the second scenario, we have used “unfavorable” disturbance signal—a highly oscillating external excitation with cyclic peaks. We have found that the performance of the realized controller was satisfactory and it was able to keep the blood glucose level in the desired healthy range—by considering the restrictions for the usable control action

Identifiability of Control-Oriented Glucose-Insulin Linear Models: Review and Analysis

One of the main challenges of glucose control in patients with type 1 diabetes is identifying a control-oriented model that reliably predicts the behavior of glycemia. Here, a review is provided emphasizing the structural identifiability and observability properties, which surprisingly reveals that few of them are globally identifiable and observable at the same time. Thus, a general proposal was developed to encompass four linear models according to suitable assumptions and transformations. After the corresponding structural properties analysis, two minimal model structures are generated, which are globally identifiable and observable. Then, the practical identifiability is analyzed for this application showing that the standard collected data in many cases do not have the necessary quality to ensure a unique solution in the identification process even when a considerable amount of data is collected. The two minimal control-oriented models were identified using a standard identification procedure using data from 30 virtual patients of the UVA/Padova simulator and 77 diabetes care data from adult patients of a diabetes center. The identification was performed in two stages: calibration and validation. In the first stage, the average length was taken as two days (dictated by the practical identifiability). For both structures, the mean absolute error was 16.8 mg/dl and 9.9 mg/dl for virtual patients and 21.6 mg/dl and 21.5 mg/dl for real patients. For the second stage, a one-day validation window was considered long enough for future artificial pancreas applications. The mean absolute error was 23.9 mg/dl and 12.3 mg/dl for virtual patients and 39.2 mg/dl and 36.6 mg/dl for virtual and real patients. These results confirm that linear models can be used as prediction models in model-based control strategies as predictive control.Fil: Hoyos, J. D.. Universidad Nacional de Colombia. Sede Medellín; ColombiaFil: Villa Tamayo, M. F.. Universidad Nacional de Colombia. Sede Medellín; ColombiaFil: Builes Montano, C. E.. Universidad de Antioquia; ColombiaFil: Ramirez Rincon, A.. Universidad Pontificia Bolivariana; ColombiaFil: Godoy, José Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Garcia Tirado, J.. University of Virginia; Estados UnidosFil: Rivadeneira Paz, Pablo Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentin

LPV-based quality interpretations on modeling and control of diabetes

In this study we introduce different novel interpretations in the case of Linear Parameter Varying (LPV) methodology, which are directly usable in modeling and control design in diabetes research. These novel interpretations are based on the parameter vectors of the LPV parameter space. The theoretical solutions are demonstrated on a simple, known Type 1 Diabetes Model used in intensive care

Data-Driven Robust Reinforcement Learning Control of Uncertain Nonlinear Systems: Towards a Fully-Automated, Insulin-Based Artificial Pancreas

In this paper, a novel robust tracking control scheme for a general class of discrete-time nonlinear systems affected by unknown bounded uncertainty is presented. By solving a parameterized optimal tracking control problem subject to the unknown nominal system and a suitable cost function, the resulting optimal tracking control policy can ensure closed-loop stability by achieving a sufficiently small tracking error for the original uncertain nonlinear system. The computation of the optimal tracking controller is accomplished through the derivation of a novel Q-function-based $\lambda$-Policy Iteration algorithm. The proposed algorithm not only enjoys rigorous theoretical guarantees, but also avoids technical weaknesses of conventional reinforcement learning methods. By employing a data-driven, critic-only least squares implementation, the performance of the proposed algorithm is evaluated to the problem of fully-automated, insulin-based, closed-loop glucose control for patients diagnosed with Type 1 and Type 2 Diabetes Mellitus. The U.S. FDA-accepted DMMS.R simulator from the Epsilon Group is used to conduct a comprehensive in silico clinical campaign on a rich set of virtual subjects under completely unannounced meal and exercise settings. Simulation results underline the superior glycaemic behavior achieved by the derived approach, as well as its overall maturity for the design of highly-effective, closed-loop drug delivery systems for personalized medicine