Proefschrift Universiteit van Amsterdam. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Preface - Biotechnology is generally considered to be the wave of the future. To facilitate accurate and rapid development of medication and treatments, it is critical that we are able to simulate the human body. One section of this complex model would be the human energy system. Pharmaceutical companies are currently pouring vast amounts of capital into research regarding general simulation of cellular structures, protein structures and bodily processes. Their aim is to develop treatments and medication for major diseases. Some of these diseases are epidemics like cancer, cardiovascular diseases, stress, obesity, etc. One of the most important causes of these diseases is poor blood glucose control. Current management methods for insulin dependent diabetes are limited to trial and error systems: clearly ineffective and prone to errors. It is critical that better management systems be developed, to ease the diabetic epidemic. The blood glucose control system is one of the major systems in the body, as we are in constant need of energy to facilitate the optimum functioning of the human body. This study makes use of a developed simulation model for the human energy system to ease the management of Diabetes mellitus, which is a malfunction of the human energy system. This dissertation is presented in two parts: The first part discusses the human energy simulation model, and the verification thereof, while the second presents possible applications of this model to ease the management of Diabetes. The human energy system simulation model - This section discusses the development and verification of the model. It also touches on the causes, and current methods, of managing diabetes, as well as the functioning of the human energy system. The human energy model is approached with the conservation of energy in mind. A top down model is developed, using data from independent studies to verify the model. Application of human energy simulation model - The human energy simulation model is of little use if the intended audience cannot use it: people suffering from malfunctioning energy systems. These include people having trouble with obesity, diabetes, cardiovascular disease, etc. To facilitate this, we need to provide a variety of products useable by this group of people. We propose a variety of ways in which the model can be used: Cellular phone applications, Personal digital assistants (PDAs) applications, as well as computer software. By making use of current technology, we generate a basic proof-of-concept application to demonstrate the intended functionality. / MIng (Mechanical Engineering) North-West University, Potchefstroom Campus, 2004

Preface - Biotechnology is generally considered to be the wave of the future. To facilitate accurate and rapid development of medication and treatments, it is critical that we are able to simulate the human body. One section of this complex model would be the human energy system. Pharmaceutical companies are currently pouring vast amounts of capital into research regarding general simulation of cellular structures, protein structures and bodily processes. Their aim is to develop treatments and medication for major diseases. Some of these diseases are epidemics like cancer, cardiovascular diseases, stress, obesity, etc. One of the most important causes of these diseases is poor blood glucose control. Current management methods for insulin dependent diabetes are limited to trial and error systems: clearly ineffective and prone to errors. It is critical that better management systems be developed, to ease the diabetic epidemic. The blood glucose control system is one of the major systems in the body, as we are in constant need of energy to facilitate the optimum functioning of the human body. This study makes use of a developed simulation model for the human energy system to ease the management of Diabetes mellitus, which is a malfunction of the human energy system. This dissertation is presented in two parts: The first part discusses the human energy simulation model, and the verification thereof, while the second presents possible applications of this model to ease the management of Diabetes. The human energy system simulation model - This section discusses the development and verification of the model. It also touches on the causes, and current methods, of managing diabetes, as well as the functioning of the human energy system. The human energy model is approached with the conservation of energy in mind. A top down model is developed, using data from independent studies to verify the model. Application of human energy simulation model - The human energy simulation model is of little use if the intended audience cannot use it: people suffering from malfunctioning energy systems. These include people having trouble with obesity, diabetes, cardiovascular disease, etc. To facilitate this, we need to provide a variety of products useable by this group of people. We propose a variety of ways in which the model can be used: Cellular phone applications, Personal digital assistants (PDAs) applications, as well as computer software. By making use of current technology, we generate a basic proof-of-concept application to demonstrate the intended functionality. / MIng (Mechanical Engineering) North-West University, Potchefstroom Campus, 2004

This study examined the energy dependence of cancer cells. Glucose was found to be their main energy source. It seems possible to use this dependence to advantage in the fight against cancer. A novel experiment to reduce the blood glucose supply and utilisation was proposed. It entailed caloric restriction, suppression of glucose secretion by the liver as well as suppression of stress hormones (which elevates glucose levels). This minimises the blood glucose value. As a last step, anti-insulin is provided to inhibit cancer cells to utilise the glucose. The cancer cells are thus deprived of their main energy source. This should lead to a reduction or elimination of tumours and will aid in preventing their development. Although feasible, this method turned out to be too expensive to perform the necessary clinical trials to prove the hypothesis. Next, the focus shifted to cancer prevention. The human energy system was analysed with the goal to reduce the circulating glucose level. The main focus here was metabolised CHO energy consumption. A previously proposed unit – the Equivalent Teaspoon Sugar, or ets , was used to quantify energy with. It was shown that cancer risk increases significantly when the recommended ets consumption per day is exceeded. Furthermore, it was shown that including fibre in a meal reduces the ets value of the meal. One gram of fibre leads to a reduction of around 0.6 ets . The link between exercise, stress, fibre, their resulting blood glucose levels and cancer were quantified in terms of ets . Exercise expends ets , while stress causes the liver to secrete more ets . Experimental data was analysed to confirm the relationships. In conclusion an equation was formulated to describe the combined effect of all these elements on the energy system. One’s total daily ets consumption can be obtained from the equation, and it was linked to one’s cancer risk. Adapting a lifestyle that ensures the correct daily ets intake will lead to a significant reduction in cancer risk. This study proved that cancer cells are very dependent on sugar and a restriction of this energy source forces them into regression. Using this knowledge to advantage may help in the combat one of the biggest killers of our time – cancer. / Thesis (Ph.D. (Electrical and Electronic Engineering))--North-West University, Potchefstroom Campus, 2012

This study examined the energy dependence of cancer cells. Glucose was found to be their main energy source. It seems possible to use this dependence to advantage in the fight against cancer. A novel experiment to reduce the blood glucose supply and utilisation was proposed. It entailed caloric restriction, suppression of glucose secretion by the liver as well as suppression of stress hormones (which elevates glucose levels). This minimises the blood glucose value. As a last step, anti-insulin is provided to inhibit cancer cells to utilise the glucose. The cancer cells are thus deprived of their main energy source. This should lead to a reduction or elimination of tumours and will aid in preventing their development. Although feasible, this method turned out to be too expensive to perform the necessary clinical trials to prove the hypothesis. Next, the focus shifted to cancer prevention. The human energy system was analysed with the goal to reduce the circulating glucose level. The main focus here was metabolised CHO energy consumption. A previously proposed unit – the Equivalent Teaspoon Sugar, or ets , was used to quantify energy with. It was shown that cancer risk increases significantly when the recommended ets consumption per day is exceeded. Furthermore, it was shown that including fibre in a meal reduces the ets value of the meal. One gram of fibre leads to a reduction of around 0.6 ets . The link between exercise, stress, fibre, their resulting blood glucose levels and cancer were quantified in terms of ets . Exercise expends ets , while stress causes the liver to secrete more ets . Experimental data was analysed to confirm the relationships. In conclusion an equation was formulated to describe the combined effect of all these elements on the energy system. One’s total daily ets consumption can be obtained from the equation, and it was linked to one’s cancer risk. Adapting a lifestyle that ensures the correct daily ets intake will lead to a significant reduction in cancer risk. This study proved that cancer cells are very dependent on sugar and a restriction of this energy source forces them into regression. Using this knowledge to advantage may help in the combat one of the biggest killers of our time – cancer. / Thesis (Ph.D. (Electrical and Electronic Engineering))--North-West University, Potchefstroom Campus, 2012

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