Multilevel model based glucose control for type-1 diabetes patients

Diabetes is a disease that involves alterations at multiple biological levels, ranging from intracellular signalling to organ processes. Since glucose homeostasis is the consequence of complex interactions that involve a number of factors, the control of diabetes should be based on a multilevel analysis. In this paper, a novel approach to design of closed-loop glucose controllers based on multilevel models is presented. A control scheme is proposed based on combining a pharmacokinetic/pharmacodynamic model with an insulin signal transduction model for type 1 diabetes mellitus patients. Based on this, an insulin feedback control schemes is designed. Two main advantages of explicitly utilizing information at the intracellular level were obtained. First, significant reduction of hypoglycaemic risk by reducing the undershoot in glucose levels in response to added insulin. Second, robust performance for inter-patient changes, demonstrated through application of the multilevel control strategy to a well established in silico population of diabetic patients.