Cramp, DG; (1975) The Measurement and Modelling of Blood Glucose Dynamics in Man. Doctoral thesis , University of London.

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Abstract

The aim of the work presented in this thesis is to establish a mathematical model for use in the study of blood glucose dynamics and their disorders in man. A large number of models have been developed that represent various aspects of blood glucose dynamics and of these the majority have been attempts to provide a mathematical description of glucose tolerance test curves. Most of these models have no immediate clinical application and have also failed to provide any real insight into the system that controls the flow of glucose into and from the blood glucose compartment. To do this a mathematical model must be formulated that approximates to an isomorphic description of the glucose regulatory system. Such a model must be based on sound biochemical and physiological knowledge. However, the complexity of the glucose system is such that complete simulation is not possible. In this study, a model has been developed and is described that places particular emphasis upon the role of the liver in controlling blood glucose dynamics. Compartments are provided for glucose, glucose-6-phosphate, and glycogen which are the dominant metabolic substrates. Mass balance equations have been written in terms of the enzymatic reactions that are involved in glucose transport and substrate kinetics. Insulin and glucagon hormonal controllers have also been incorporated. The model has been tested by inputs representing intravenous glucose infusion, intravenous glucose, insulin and glucagon injection. The model appears to simulate in general terms experimental data, and has yielded information about both the system structure and the enzyme dynamics involved. Of particular importance is the evidence that fine control of the glucose system is an intrinsic function of the enzyMe systems and that only coarse control of the system is provided by the hormonal environment.Little work has been done in this field, but the present model is unlike any previous model in that the inherent non-linearities of the metabolic system are developed from known enzymological data. The approach illustrates the possible value of using kinetic data obtained from -in -vitro, experiments in predicting physiological changes within the in vivo system. It is considered that mathematical models of this type can provide the biomedical scientist with insight into the functioning of metabolic systems and highlight areas of weak knowledge.

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