A Survey of Insulin-Dependent Diabetes—Part II: Control Methods

We survey blood glucose control schemes for insulin-dependent diabetes therapies and systems. These schemes largely rely on mathematical models of the insulin-glucose relations, and these models are typically derived in an empirical or fundamental way. In an empirical way, the experimental insulin inputs and resulting blood-glucose outputs are used to generate a mathematical model, which includes a couple of equations approximating a very complex system. On the other hand, the insulin-glucose relation is also explained from the well-known facts of other biological mechanisms. Since these mechanisms are more or less related with each other, a mathematical model of the insulin-glucose system can be derived from these surrounding relations. This kind of method of the mathematical model derivation is called a fundamental method. Along with several mathematical models, researchers develop autonomous systems whether they involve medical devices or not to compensate metabolic disorders and these autonomous systems employ their own control methods. Basically, in insulin-dependent diabetes therapies, control methods are classified into three categories: open-loop, closed-loop, and partially closed-loop controls. The main difference among these methods is how much the systems are open to the outside people

Modeling and Prediction in Diabetes Physiology

Diabetes is a group of metabolic diseases characterized by the inability of the organism to autonomously regulate the blood glucose levels. It requires continuing medical care to prevent acute complications and to reduce the risk of long-term complications. Inadequate glucose control is associated with damage, dysfunction and failure of various organs. The management of the disease is non trivial and demanding. With today’s standards of current diabetes care, good glucose regulation needs constant attention and decision-making by the individuals with diabetes. Empowering the patients with a decision support system would, therefore, improve their quality of life without additional burdens nor replacing human expertise. This thesis investigates the use of data-driven techniques to the purpose of glucose metabolism modeling and short-term blood-glucose predictions in Type I Diabetes Mellitus (T1DM). The goal was to use models and predictors in an advisory tool able to produce personalized short-term blood glucose predictions and on-the-spot decision making concerning the most adequate choice of insulin delivery, meal intake and exercise, to help diabetic subjects maintaining glycemia as close to normal as possible. The approaches taken to describe the glucose metabolism were discrete-time and continuous-time models on input-output form and statespace form, while the blood glucose short-term predictors, i.e., up to 120 minutes ahead, used ARX-, ARMAX- and subspace-based prediction

Diabetes Mellitus Glucose Prediction by Linear and Bayesian Ensemble Modeling

Diabetes Mellitus is a chronic disease of impaired blood glucose control due to degraded or absent bodily-specific insulin production, or utilization. To the affected, this in many cases implies relying on insulin injections and blood glucose measurements, in order to keep the blood glucose level within acceptable limits. Risks of developing short- and long-term complications, due to both too high and too low blood glucose concentrations are severalfold, and, generally, the glucose dynamics are not easy too fully comprehend for the affected individual—resulting in poor glucose control. To reduce the burden this implies to the patient and society, in terms of physiological and monetary costs, different technical solutions, based on closed or semi-closed loop blood glucose control, have been suggested. To this end, this thesis investigates simplified linear and merged models of glucose dynamics for the purpose of short-term prediction, developed within the EU FP7 DIAdvisor project. These models could, e.g., be used, in a decision support system, to alert the user of future low and high glucose levels, and, when implemented in a control framework, to suggest proactive actions. The simplified models were evaluated on 47 patient data records from the first DIAdvisor trial. Qualitatively physiological correct responses were imposed, and model-based prediction, up to two hours ahead, and specifically for low blood glucose detection, was evaluated. The glucose raising, and lowering effect of meals and insulin were estimated, together with the clinically relevant carbohydrate-to-insulin ratio. The model was further expanded to include the blood-to-interstitial lag, and tested for one patient data set. Finally, a novel algorithm for merging of multiple prediction models was developed and validated on both artificial data and 12 datasets from the second DIAdvisor trial

Model Fusion to Enhance the Clinical Acceptability of Long-Term Glucose Predictions

This paper presents the Derivatives Combination Predictor (DCP), a novel model fusion algorithm for making long-term glucose predictions for diabetic people. First, using the history of glucose predictions made by several models, the future glucose variation at a given horizon is predicted. Then, by accumulating the past predicted variations starting from a known glucose value, the fused glucose prediction is computed. A new loss function is introduced to make the DCP model learn to react faster to changes in glucose variations. The algorithm has been tested on 10 \textit{in-silico} type-1 diabetic children from the T1DMS software. Three initial predictors have been used: a Gaussian process regressor, a feed-forward neural network and an extreme learning machine model. The DCP and two other fusion algorithms have been evaluated at a prediction horizon of 120 minutes with the root-mean-squared error of the prediction, the root-mean-squared error of the predicted variation, and the continuous glucose-error grid analysis. By making a successful trade-off between prediction accuracy and predicted-variation accuracy, the DCP, alongside with its specifically designed loss function, improves the clinical acceptability of the predictions, and therefore the safety of the model for diabetic people

TRATAMIENTO DE PACIENTES T1DM UTILIZANDO UN ALGORITMO NEURO-DIFUSO DE CONTROL ÓPTIMO INVERSO: UN ENFOQUE DE PROTOTIPADO RÁPIDO

Resumen: La condición de Diabetes Mellitus Tipo 1 (DMT1) ocurre cuando el páncreas se comporta de manera anormal e impide la producción de insulina parcialmente o totalmente. Por lo tanto, la glucosa no es metabolizada para convertirse en una fuente natural de energía y permanece en el torrente sanguíneo. Esta enfermedad causa miles de muertes alrededor del mundo. Los sectores de salud, así como la comunidad científica, han fortalecido los esfuerzos para proporcionar tratamientos más efectivos. En este trabajo, se expone un novedoso enfoque de control neuro-difuso para la regulación de la glucosa en sangre en pacientes virtuales con DMT1. La estrategia es diseñada tal que las funciones de membresía están definidas para determinar la tasa de infusión de insulina para evitar eventos de hiperglucemia e hipoglucemia. Adicionalmente, se lleva a cabo un prototipado rápido programando la ley de control óptimo inverso en la tarjeta de desarrollo LAUNCHXL-F28069M de Texas Instruments Inc. El análisis de la variabilidad de control (Siglas en inglés CVGA) obtenido a través del simulador Uva/Padova muestra claramente un desempeño satisfactorio para la reducción de hiperglucemia e hipoglucemia en una población de 10 adultos virtuales. De esta manera, el trabajo tiene como objetivo expandir la investigación de la diabetes hacia el Páncreas Artificial (PA) como un dispositivo programable

The development of a glucose prediction model in critically ill patients

Purpose: The aim of the current study is to develop a prediction model for glucose levels applicable for all patients admitted to the ICU with an expected ICU stay of at least 24 h. This model will be incorporated in a closed-loop glucose system to continuously and automatically control glucose values. Methods: Data from a previous single-center randomized controlled study was used. All patients received a FreeStyle Navigator II subcutaneous CGM system from Abbott during their ICU stay. The total dataset was randomly divided into a training set and a validation set. A glucose prediction model was developed based on historical glucose data. Accuracy of the prediction model was determined using the Mean Squared Difference (MSD), the Mean Absolute Difference (MAD) and a Clarke Error Grid (CEG). Results: The dataset included 94 ICU patients with a total of 134,673 glucose measurements points that were used for modelling. MSD was 0.410 +/- 0.495 for the model, the MAD was 5.19 +/- 2.63 and in the CEG 99.8% of the data points were in the clinically acceptable regions. Conclusion: In this study a glucose prediction model for ICU patients is developed. This study shows that it is possible to accurately predict a patient's glucose 30 min ahead based on historical glucose data. This is the first step in the development of a closed-loop glucose system. (C) 2021 Elsevier B.V. All rights reserved

Continuous glucose monitoring sensors: Past, present and future algorithmic challenges

Continuous glucose monitoring (CGM) sensors are portable devices that allow measuring and visualizing the glucose concentration in real time almost continuously for several days and are provided with hypo/hyperglycemic alerts and glucose trend information. CGM sensors have revolutionized Type 1 diabetes (T1D) management, improving glucose control when used adjunctively to self-monitoring blood glucose systems. Furthermore, CGM devices have stimulated the development of applications that were impossible to create without a continuous-time glucose signal, e.g., real-time predictive alerts of hypo/hyperglycemic episodes based on the prediction of future glucose concentration, automatic basal insulin attenuation methods for hypoglycemia prevention, and the artificial pancreas. However, CGM sensors’ lack of accuracy and reliability limited their usability in the clinical practice, calling upon the academic community for the development of suitable signal processing methods to improve CGM performance. The aim of this paper is to review the past and present algorithmic challenges of CGM sensors, to show how they have been tackled by our research group, and to identify the possible future ones