Minimally-Invasive and Efficient Method to Accurately Fit the Bergman Minimal Model to Diabetes Type 2.

Introduction: Diabetes mellitus is a global burden that is expected to grow 25 % by 2030. This will increase the need for prevention, diagnosis and treatment of diabetes. Animal and individualized in silico models will allow understanding and compensation for inter and intra-individual differences in treatment and management strategies for diabetic patients. The method presented here can advance the concept of personalized medicine. Methods: Twenty experiments were performed with Sprague-Dawley rats with streptozotocin induced experimental diabetes in which the insulin-glucose response curve was recorded over 60-100 min using only an insulin pump and a percutaneous glucose sensor. The information was used to fit the five-parameter Bergman Minimal Model to the experimental results using a genetic algorithm with a root-mean-squared optimization rule. Results: The Bergman Minimal Model parameters were estimated with high accuracy, low prediction bias, and low average root-mean-squared error of 15.27 mg/dl glucose. Conclusions: This study demonstrates a simple method to accurately parameterize the Bergman Minimal Model. We used Sprague-Dawley rats since their physiology is close to that of humans. The parameters can be used to objectively characterize the physiological severity of diabetes. In this way, planned treatments can compensate for natural variations of conditions both inter and intra patients. Changes in parameters indicate the patient's diabetic condition using values of glucose effectiveness ( S G = p 1 ) and insulin sensitivity ( S I = p 3 / p 2 ). Quantifying the diabetic patient's condition is consistent with the trend toward personalized medicine. Parameter values can also be used to explain atypical research results of other studies and increase understanding of diabetes.

Rapid automatic identification of parameters of the Bergman Minimal Model in Sprague-Dawley rats with experimental diabetes for adaptive insulin delivery.

Glucose-Insulin regulation models can be used to individualize insulin therapy. However, the experimental techniques currently used to identify the appropriate parameter sets of an individual are expensive, time consuming, and very unpleasant for the patient. Since there is a wide range of intrapersonal parameter variability, the identified parameters in a laboratory setting (at rest) are not optimal for dynamic conditions of daily activities. In this study we propose a methodology to identify three parameters of Bergman's Minimal Model in streptozotocin-induced diabetic rats from the experimental data of the glucose response to exogenous insulin doses, based on a genetic algorithm (GA). The algorithm requires glucose measurements from a continuous subcutaneous sensor once every 5 min and the amount of injected insulin. The model parameters of 20 in vivo experiments (from 19 rats) were identified with high accuracy and the average root-mean squared (RMS) error between predicted and measured glucose concentration was 17.6 mg/dl. Since the algorithm requires a relatively short (60-120 min) observation time it can be used for real-time parameter identification to optimize insulin infusion systems. Model parameter changes due to experimental settings like drug testing or in natural lifestyle changes should be calculable, on-the-fly, using data from only the glucose sensor and the amount of insulin delivered.

Black-box identification of a class of nonlinear systems by a recurrent neurofuzzy network.

This brief presents a structure for black-box identification based on continuous-time recurrent neurofuzzy networks for a class of dynamic nonlinear systems. The proposed network catches the dynamics of a system by generating its own states, using only input and output measurements of the system. The training algorithm is based on adaptive observer theory, the stability of the network, the convergence of the training algorithm, and the ultimate bound on the identification error as well as the parameter error are established. Experimental results are included to illustrate the effectiveness of the proposed method.

A discrete-time recurrent neurofuzzy network for black-box modeling of insulin dynamics in diabetic type-1 patients.

In this work we present a data-driven modeling of the insulin dynamics in different in silico patients using a recurrent neural network with output feedback. The inputs for the identification is the rate of insulin (microU/dl/min) applied to the patient, and blood glucose concentration. The output is insulin concentration (microU/ml) present in the blood stream. Once completed the off-line modeling, this model could be used for on-line monitoring of the insulin concentration for a better treatment. The learning law of the recurrent neural network is inspired by adaptive observer theory, and proven to be convergent in the parameters and stable in the Lyapunov sense, even with only 13 samples available. Simulation results are shown to validate the presented modeling.