A New Approach for Viewing Non-Steady State Dynamics

Abstract

Non-steady state plasma glucose dynamics are examined using a non-linear three compartment catenary structure. The glucose model is primarily used to test the hypothesis that insulin reduces endogenous glucose production rate and increases the number of glucose transporters. The performance of the model is compared to the one compartment model approximation (Steele equation). The approach adopted here is fundamentally different to that of current approaches in that the tracer dynamic is used not as an integral part of the model but rather to validate the non-linear model and its controllers. The performance of the model is tested in uncontrolled diabetic patients (following 2A hour insulin withdrawal) undergoing low dose (2.6 U/hour) and high dose (10.6 U/hour) insulin infusion.It is shown that following low and high dose insulin infusion the reductions in hepatic glucose production are similar and the increase in number of glucose transporters is higher in high dose than low dose. The different estimates of the metabolic clearance rate in the non-steady state are compared. It is shown that the MCR estimates derived from division of tracer infusion rate and plasma tracer concentration in the non-steady state closely resemble that of one compartment approximation with Michaelis-Menten loss, calculated at the measured plasma glucose concentration.