Blood glucose control in diabetic Göttingen minipigs

Diabetes mellitus is a widespread disease which is characterized by an unphysiologically high steady-state level of the blood glucose concentration. Currently, this metabolic disease requires manual treatment with insulin. Despite large research efforts, no closed-loop blood glucose control system has been presented yet which can be applied under real-life conditions due to several technical constraints and control performance requirements. This thesis uses animal trials to test closed-loop methods for accelerating the technological progress. The animal trials serve as proxy for human studies and can be regarded as an intermediate step between in silico and in vivo control performance evaluation. The focus of this thesis is on control-based insulin therapy for type 1 diabetes patients. A new control strategy for blood glucose stabilization is developed and experimentally evaluated with diabetic Göttingen Minipigs. To this aim, a new mathematical nonlinear model of the glucose metabolism in diabetic Göttingen Minipigs is introduced and the model parameters are identified. A new hybrid switching controller structure is developed which distinguishes between day and night application. The individualized controller is experimentally evaluated with diabetic minipigs. It prevents critical drops in blood glucose in unphysiological ranges and reduces unacceptable high blood glucose levels rapidly. Additionally, the controller shows robust behavior with respect to intraindividual metabolic variations.