Preface - Biotechnology is generally accepted to be the next economical wave of the future. In order to attain the many benefits associated with this growing industry simulation modelling techniques have to be implemented successfully. One of the simulations that ne' ed to be performed is that of the human energy system. Pharmaceutical companies are currently pouring vast amounts of capital into research regarding simulation of bodily processes. Their aim is to develop cures, treatments, medication, etc. for major diseases. These diseases include epidemics like diabetes, cancer, cardiovascular diseases, obesity, stress, hypertension, etc. One of the most important driving forces behind these diseases is poor blood sugar control. The blood glucose system is one of the major subsystems of the complete human energy system. In this study a simulation model and procedure for simulating blood glucose response due to various external influences on the human body is presented. The study is presented in two parts. The first is the development of a novel concept for quantifying glucose energy flow into, within and out of the human energy system. The new quantification unit is called ets (equivalent teaspoons sugar). The second part of the study is the implementation of the ets concept in order to develop the simulation model. Development of the ets concept - In the first part of the study the ets concept, used for predicting glycaemic response, is developed and presented. The two current methods for predicting glycaemic response due to ingestion of food are discussed, namely carbohydrate counting and the glycaemic index. Furthermore, it is shown that it is currently incorrectly assumed that 100% of the chemical energy contained in food is available to the human energy system after consumption. The ets concept is derived to provide a better measure of available energy from food. In order to verify the ets concept, two links with ets are investigated. These are the links with insulin response prediction as well as with endurance energy expenditure. It is shown that with both these links linear relationships provide a good approximation of empirical data. It is also shown that individualised characterisation of different people is only dependent on a single measurable variable for each link. Lastly, two novel applications of the ets concept are considered. The first is a new method to use the ets values associated with food and energy expenditure in order to calculate both short-acting and long-acting insulin dosages for Type 1 diabetics. The second application entails a new quantification method for describing the effects of stress and illness in terms of ets. Development of the blood glucose simulation model - The second part of the study presents a literature study regarding human physiology, the development for the blood glucose simulation model as well as a verification study of the simulation model. Firstly, a brief overview is given for the need and motivation behind simulation is given. A discussion on the implementation of the techniques for construction of the model is also shown. The procedure for solving the model is then outlined. During the literature study regarding human physiology two detailed schematic layouts are presented and discussed. The first layout involves the complex flow pathways of energy through the human energy system. The second layout presents a detailed discussion on the control system involved with the glucose energy pathway. Following the literature review the model for predicting glycaemic response is proposed. The design of the component models used for the simulations of the internal processes are developed in detail as well as the control strategies implemented for the control system of the simulation model. Lastly, the simulation model is applied for glycaemic response prediction of actual test subjects and the quality of the predictions are evaluated. The verification of the model and the procedure is performed by comparing simulated results to measured data. Two evaluations were considered, namely long-term and short-term trials. The quality of both are determined according to certain evaluation criteria and it is found that the model is more than 70% accurate for long-term simulations and more than 80% accurate for short-term simulations. Conclusion - In conclusion, it is shown that simplified simulation of the human energy system is not only possible but also relatively accurate. However, in order to accomplish the simulations a simple quantification method is required and this is provided by the ets concept developed in the first part of this study. Some recommendations are also made for future research regarding both the ets concept and the simulation model. Finally, as an initial endeavour the simulation model and the ets concept proposed in this study may provide the necessary edge for groundbreaking biotechnological discoveries. / PhD (Mechanical Engineering) North-West University, Potchefstroom Campus, 2003

Preface - Biotechnology is generally accepted to be the next economical wave of the future. In order to attain the many benefits associated with this growing industry simulation modelling techniques have to be implemented successfully. One of the simulations that ne' ed to be performed is that of the human energy system. Pharmaceutical companies are currently pouring vast amounts of capital into research regarding simulation of bodily processes. Their aim is to develop cures, treatments, medication, etc. for major diseases. These diseases include epidemics like diabetes, cancer, cardiovascular diseases, obesity, stress, hypertension, etc. One of the most important driving forces behind these diseases is poor blood sugar control. The blood glucose system is one of the major subsystems of the complete human energy system. In this study a simulation model and procedure for simulating blood glucose response due to various external influences on the human body is presented. The study is presented in two parts. The first is the development of a novel concept for quantifying glucose energy flow into, within and out of the human energy system. The new quantification unit is called ets (equivalent teaspoons sugar). The second part of the study is the implementation of the ets concept in order to develop the simulation model. Development of the ets concept - In the first part of the study the ets concept, used for predicting glycaemic response, is developed and presented. The two current methods for predicting glycaemic response due to ingestion of food are discussed, namely carbohydrate counting and the glycaemic index. Furthermore, it is shown that it is currently incorrectly assumed that 100% of the chemical energy contained in food is available to the human energy system after consumption. The ets concept is derived to provide a better measure of available energy from food. In order to verify the ets concept, two links with ets are investigated. These are the links with insulin response prediction as well as with endurance energy expenditure. It is shown that with both these links linear relationships provide a good approximation of empirical data. It is also shown that individualised characterisation of different people is only dependent on a single measurable variable for each link. Lastly, two novel applications of the ets concept are considered. The first is a new method to use the ets values associated with food and energy expenditure in order to calculate both short-acting and long-acting insulin dosages for Type 1 diabetics. The second application entails a new quantification method for describing the effects of stress and illness in terms of ets. Development of the blood glucose simulation model - The second part of the study presents a literature study regarding human physiology, the development for the blood glucose simulation model as well as a verification study of the simulation model. Firstly, a brief overview is given for the need and motivation behind simulation is given. A discussion on the implementation of the techniques for construction of the model is also shown. The procedure for solving the model is then outlined. During the literature study regarding human physiology two detailed schematic layouts are presented and discussed. The first layout involves the complex flow pathways of energy through the human energy system. The second layout presents a detailed discussion on the control system involved with the glucose energy pathway. Following the literature review the model for predicting glycaemic response is proposed. The design of the component models used for the simulations of the internal processes are developed in detail as well as the control strategies implemented for the control system of the simulation model. Lastly, the simulation model is applied for glycaemic response prediction of actual test subjects and the quality of the predictions are evaluated. The verification of the model and the procedure is performed by comparing simulated results to measured data. Two evaluations were considered, namely long-term and short-term trials. The quality of both are determined according to certain evaluation criteria and it is found that the model is more than 70% accurate for long-term simulations and more than 80% accurate for short-term simulations. Conclusion - In conclusion, it is shown that simplified simulation of the human energy system is not only possible but also relatively accurate. However, in order to accomplish the simulations a simple quantification method is required and this is provided by the ets concept developed in the first part of this study. Some recommendations are also made for future research regarding both the ets concept and the simulation model. Finally, as an initial endeavour the simulation model and the ets concept proposed in this study may provide the necessary edge for groundbreaking biotechnological discoveries. / PhD (Mechanical Engineering) North-West University, Potchefstroom Campus, 2003