Linear Model Identification for Personalized Prediction and Control in Diabetes.

OBJECTIVE Type-1 diabetes (T1D) is a metabolic disease, characterized by impaired blood glucose (BG) regulation, which forces patients to multiple daily therapeutic actions, the most critical of which is exogenous insulin administration. T1D management can considerably benefit of mathematical models enabling accurate BG predictions and effective/safe automated insulin delivery. In building these models, dealing with large inter- and intra-patient variability in glucose-insulin dynamics represents a major challenge. The aim of the present work is to assess linear black-box methods, including a novel non-parametric methodology, for learning individualized models of glucose response to insulin and meal, suitable for model-based prediction and control. METHODS We focus on data-driven techniques for linear model-learning and compare the state-of-art parametric pipeline, exploring all its degrees of freedom (including population vs. individualized parameter identification, model class chosen among ARX/ARMAX/ARIMAX/Box-Jenkins, model order selection criteria, etc.), with a novel non-parametric approach based on Gaussian regression and stable spline kernel. By using data collected in 11 T1D individuals, we evaluate effectiveness of the different models by measuring root mean squared error (RMSE), coefficient of determination (COD), and time gain of the associated BG predictors. RESULTS Among the tested approaches, the non-parametric technique results in the best prediction performance: median RMSE=29.8mg/dL, and median COD=57.4%, for a prediction horizon (PH) of 60 min. With respect to the state-of-the-art parametric techniques, the non-parametric approach grants a COD improvement of about 2%, 7%, 21%, and 41% for PH = 30, 60, 90, and 120 min (paired-sample t-test p 0.001, p=0.003, p=0.03, and p=0.07 respectively). CONCLUSION Non-parametric linear model-learning grants statistically significant improvement with respect to the state-of-art parametric approach. The higher PH, the more pronounced the improvement. SIGNIFICANCE The use of a linear non-parametric model-learning approach for model-based prediction and control could bring to a more prompt, safe and effective T1D management.