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Type 2 diabetes (T2D) is a chronic metabolic disorder requiring effective management to avoid complications. Metformin is a first-line drug agent and is routinely prescribed for the control of glycemia, but its underlying dynamics are complicated and not fully quantified. This paper formulates a control-oriented and interpretable mathematical model that integrates metformin dynamics into a classic beta-cell–insulin–glucose (BIG) regulation system. The paper’s applicability to theoretical and clinical settings is enhanced by rigorous mathematical analysis, which guarantees the model is globally bounded, well-posed, and biologically meaningful. One of the key features of the study is its global stability analysis using Lyapunov functions, which demonstrates the asymptotic stability of critical equilibrium points under realistic physiological constraints. These findings support the predictive reliability of the model in explaining long-term glycemic regulation. Bifurcation analysis also clarifies the dynamic interplay between glucose production and utilization by identifying parameter thresholds that signify transitions between homeostasis and pathological states. Residual analysis, which detects Gaussian-distributed errors, underlines the robustness of the fitting process and suggests possible refinements by including temporal effects. Sensitivity analysis highlights the predominant effect of the initial dose of metformin on long-term glucose regulation and provides practical guidance for optimizing individual treatment. Furthermore, changing the two considered metformin parameters from their optimal values—altering the dose by ±50% and the decay rate by ±20%—demonstrates the flexibility of the model in simulating glycemic responses, confirming its adaptability and its potential for optimizing personalized treatment strategies. Full article

Type 1 diabetes mellitus is a disease that affects millions of people around the world. Recent progress in embedded devices has allowed the development of artificial pancreas that can pump insulin subcutaneously to automatically regulate blood glucose levels in diabetic patients. In this work, a Lyapunov-based intelligent controller using artificial neural networks is proposed for application in automated insulin delivery systems. The adoption of an adaptive radial basis function network within the control scheme allows regulation of blood glucose levels without the need for a dynamic model of the system. The proposed model-free approach does not require the patient to inform when they are going to have a meal and is able to deal with inter- and intrapatient variability. To ensure safe operating conditions, the stability of the control law is rigorously addressed through a Lyapunov-like analysis. In silico analysis using virtual patients are provided to demonstrate the effectiveness of the proposed control scheme, showing its ability to maintain normoglycemia in patients with type 1 diabetes mellitus. Three different scenarios were considered: one long- and two short-term simulation studies. In the short-term analyses, 20 virtual patients were simulated for a period of 7 days, with and without prior basal therapy, while in the long-term simulation, 1 virtual patient was assessed over 63 days. The results show that the proposed approach was able to guarantee a time in the range above 95% for the target glycemia in all scenarios studied, which is in fact well above the desirable 70%. Even in the long-term analysis, the intelligent control scheme was able to keep blood glucose metrics within clinical care standards: mean blood glucose of 119.59 mg/dL with standard deviation of 32.02 mg/dL and coefficient of variation of 26.78%, all below the respective reference values. Full article

The metabolic disease Type 1 Diabetes Mellitus (DM1) is caused by a reduction in the production of pancreatic insulin, which causes chronic hyperglycemia. Patients with DM1 are required to perform multiple blood glucose measurements on a daily basis to monitor their blood glucose dynamics through the use of capillary glucometers. In more recent times, technological developments have led to the development of cutting-edge biosensors and Continuous Glucose Monitoring (CGM) systems that can monitor patients’ blood glucose levels on a real-time basis. This offers medical providers access to glucose oscillations modeling interventions that can enhance DM1 treatment and management approaches through the use of novel disruptive technologies, such as Cloud Computing (CC), big data, Intelligent Data Analysis (IDA) and the Internet of Things (IoT). This work applies some advanced modeling techniques to a complete data set of glycemia-related biomedical features—obtained through an extensive, passive monitoring campaign undertaken with 25 DM1 patients under real-world conditions—in order to model glucose level dynamics through the proper identification of patterns. Hereby, four methods, which are run through CC due to the high volume of data collected, are applied and compared within an IoT context. The results show that Bayesian Regularized Neural Networks (BRNN) offer the best performance (0.83 R²) with a reduced Root Median Squared Error (RMSE) of 14.03 mg/dL. Full article