Discrete Blood Glucose Control in Diabetic Göttingen Minipigs

Abstract: Despite continuous research effort, patients with type 1 diabetes mellitus (T1D) experience difficulties in daily adjustments of their blood glucose concentrations. New technological developments in the form of implanted intravenous infusion pumps and continuous blood glucose sensors might alleviate obstacles for the automatic adjustment of blood glucose concentration. These obstacles consist, for example, of large time-delays and insulin storage effects for the subcutaneous/interstitial route. Towards the goal of an artificial pancreas, we present a novel feedback controller approach that combines classical loop-shaping techniques with gain-scheduling and modern H∞-robust control approaches. A disturbance rejection design is proposed in discrete frequency domain based on the detailed model of the diabetic Göttingen minipig. The model is trimmed and linearised over a large operating range of blood glucose concentrations and insulin sensitivity values. Controller parameters are determined for each of these operating points. A discrete H∞ loop-shaping compensator is designed to increase robustness of the artificial pancreas against general coprime factor uncertainty. The gain scheduled controller uses subcutaneous insulin injection as a control input and determines the controller input error from intravenous blood glucose concentration measurements, where parameter scheduling is achieved by an estimator of the insulin sensitivity parameter. Thus, only one controller stabilises a family of animal models. The controller is validated in silico with a total number of five Göttingen Minipig models, which were previously obtained by experimental identification procedures. Its performance is compared with an experimentally tested switching PI controller.