A switching hybrid control method for automatic blood glucose regulation in diabetic Göttingen minipigs

• Presentation of a new hybrid switching control method for blood glucose control in diabetic Göttingen minipigs.
• Explanation of animal trials: Göttingen minipigs, diabetes induction, protocol for controller-based and manual insulin therapy.
• Introduction of a switching control method and controller design by means of two mathematical models of the porcine glucose metabolism.
• Experimental evaluation of control method by animal trials taking into account control performance and technical limitations.
• Results: controller-based insulin therapy is superior to manual insulin treatment.

A new hybrid control method for blood glucose concentration is developed which switches between two operation modes. The effects of meal-induced disturbances on blood glucose concentrations are expected to be more serious than the time-varying behaviour of glucose metabolism during nocturnal phases. Thus, the control method determines insulin impulses (boli) as a manipulated variable during the day and calculates continuous insulin infusion (basal rates) at night. To test the controller-based insulin therapy in vivo, animal trials with diabetic Göttingen minipigs are used as a proxy for human studies. The controller parameters are selected by in silico studies based on mathematical minipig models, and the resulting individualised controllers are experimentally verified. For this, two control performance requirements must be taken into account: blood glucose concentrations below the critical threshold of 50 mg/dl have to be avoided, and blood glucose peaks caused by ingestion of minipig diet have to be quickly counteracted. Results from these animal experiments show that the closed-loop system satisfies both control requirements and improves insulin therapy compared with a standard therapeutic protocol.