SIMULATION OF THE HUMAN ENERGY SYSTEM
C P Botha
Thesis presented in partial fulfilment of the requirements for the degree
PHILOSOPIDAE DOCTOR
in the. faculty of Engineering
Department of Mechanic.al Engineering
Potchefstroomse Universiteit vir Christelike Hoer Onderwys
Title: Author: Promoter: Department: Faculty: Degree: Key terms: Preface
ABSTRACT
Simulation of the human energy system
CorBotha
Prof. E. H. Mathews
Mechanical Engineering
Engineering
Philosophiae Doctor
Simulation; Human energy system; CHO counting; GI; ets; Equivalent teaspoons sugar; Blood sugar response prediction; Insulin response prediction; Exercise energy requirement; Insulin requirement calculation; Stress and illness quantification; Dynamic integrated simulation; Energy pathways; Human energy system control; Blood glucose simulation
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 need 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 fooq.
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 measurabie 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.
Titel: Outeur: Studieleier: Departement: Fakulteit: Graad: Sleutelterme: Inleiding
SAMEVATTING
Simulation of the human energy system
CorBotha
Prof. E. H. Mathews
Meganiese ingenieurswese
Ingenieurswese
Philosophiae Doctor
Simulasie; Menslike energiestelsel; Koolhidraattelling; Glisemiese index; ets; Ekwivalente teelepels suiker; Bloedsuiker-responsvoorspelling; Insulien-responsvoorspelling; Oefening-energiebehoefte; Energiebane; lnsulien-behoefteberekening; Stress- en siektekwantifisering; Dinamiese. geintegreerde simulasie; Menslike energiestelsel-beheer; Bloedglukose-simulasie
Daar word algemeen aanvaar dat biotegnologie die volgende ekonomiese golf sal wees. Om al die voordele van hierdie groeiende industrie te benut sal suksesvolle implementering van simulasietegnieke nodig wees. Die simulasie van die menslike energiestelsel is een van die simulasies wat benodig word.
Farmaseutiese maatskappye is tans besig om groot bedrae geld te bele in navorsing wat die simulasie van liggaamsprosesse behels. Hulle doel is om genesing, behadeling, medikasie, ens. te vind vir belangrike siektes. Hierdie siektes sluit epidemies soos diabetes, kanker, hartsiektes, vetsug, stress, bloeddrukprobleme, ens. in. Een van die belangrikste oorsake van hierdie siektes is swak beheer van bloedsuikervlakke.
Die bloedglukosestelsel is een van die hoof substelsels van die totale menslike energiestelsel. In
hierdie studie word 'n simulasiemodel en -prosedure vir die simulasie van bloedglukoserespons as gevolg van eksteme invloede op die menslike energiestelsel voorgestel.
Die · studie word aangebied in twee dele. Die eerste deel behels die ontwikkeling van 'n nuwe konsep vir die kwantifisering van energie wat na binne, binnein en vanaf die menslike energiestelsel vloei. Die miwe kwantifiseringseenheid word "ets" genoem. Die tweede deel van die studie behels die implementasie van die ets-konsep ten einde die simulasiemodel te ontwikkel.
Onwikkeling van die ets-konsep
In die eerste deel van · die studie word die ets-konsep, wat gebruik word vir glukose-responsvoorspelling, ontwikkel en aangebied.
Die twee huidige metodes vir die bogenoemde voorspellings, naamlik koolhidraattelling en die glisemiese index, word bespreek. V erder word daar aangedui dat dit huidiglik verkeerdelik aanvaar word dat 100% van die chemiese energie wat in kos opgesluit is beskikbaar gestel word vir die menslike energiestelsel. Dit word gewys dat die ets-konsep 'n beter metode is om die beskikbare energy van kos te meet.
Om die ets-konsep te verifieer word twee skakels met ets. bestudeer. Hierdie skakels is die met insulien-responsvoorspelling asook met voortdurige energiebenutting. Daar word aangewys dat vir beide skakels daar liniere verwantskappe bestaan met goeie korrolasies teen empiriese data. Dit word ook aangetoon dat faktore vir persoonlike karakteriserings vir verskillinde mense slegs afhang van een meetbare veranderlike vir elke skakel.
Uiteindelik word twee nuwe toepassings van die ets-konsep ondersoek. Die eerste is 'n nuwe metode om ets:-waardes vir kos en oefening te gebruik ten einde beide kort- en lang-werkende insulienbehoeftes vir Tipe 1 diabete te bepaal. Die tweede toepassing behels 'n nuwe kwantifiseringsmetode om die effek van stress en siekte in terme van ets te beskryf.
Ontwikkeling van die bloedglukose-simulasiemodel
Die tweede deel van die studie behels 'n literatuurstudie wat handel oor die menslike fisiologie, die ontwikkeling van die bloedsuiker-simulasiemodel asook 'n verifieringstudie met betrekking tot die bloesuiker-simulsiemodel.
Eerstens word 'n kort oorsig gegee ten opsigte van die motivering en die noodsaaklikheid agter die simulasies. 'n Bespreking oor die implementering van die tegnieke vir die modelkonstruksie word dan aangewys waarna die prosedure vir oplossing van die model ook aangetoon word.
Gedurende die literatuurstudie wat handel oor die menslike fisiologie behels twee detail skematiese uitlegte voorgestel en bespreek. Die eerste uitleg dui die ingewikkelde energiebane van die energiestelsel aan. Die tweede uitleg hied 'n gedetaileerde hespreking oor die beheerstelsel wat met die energiebaan van glukose verband hou.
Gevolglik word die literatuurstudie van die model vir die voorspelling van glisemiese respons voorgele. Die ontwerp van komponentmodelle, wat benodig word vir die interne prosesse, word ontwikkel asook die beheerstrategie wat op die beheerstelsel van die simulasiemodel van toepassing is.
Laastens word die simulasiemodel vir bloedglukose aangewend tot werklike toetsgevalle en die kwaliteit van die voorspellings word beoordeel. Die verifiering van die model en die simulasie-prosedure behels 'n vergely.king tussen gesimuleerde en gemete data. Twee verifieringstudies was gedoen, naamlik lang- en korttermyn toetse. Die kwaliteit van beide is bepaal deur sekere beoordelingskriteria. Daar is gevind dat die model meer as 70% akkuraat vir die langtermyn toetse is en meer as 80% akkuraat vir die korttermyn toetse is.
Gevolgtrekking
Ten einde word· daar gewys dat simulasie van 'n vereenvoudigde menslike energiestelsel nie slegs moontlik is nie, maar ook relatief akkuraat is. Hierdie simulasies word moontlik gemaak deur 'n eenvoudige kwantifiseringsmetode. Die metode word voorsien deur die ets-konsep wat in die eerste deel van die studie ontwikkel is. Sekere voorstelle word ook gemaak vir toekomstige navorsing aangaande beide die ets-konsep en die simuiasiemodel.
Ter afsluiting kan hierdie eerste en nuwe poging van die simulasiemodel en ets-konsep wat in hierdie studie voorgele word ook gebruik word as 'n nodige voorsprong vir nuwe biotegnologiese ontdek.kings.
ACKNOW~EDGEMENTS
I would like to express my gratitude to Prof. E. H. Mathews for the opportunity to perform this study. I greatly appreciate the opportunity to use the ets concept as well as his literature reviews and basis reports used for Chapters 2 to 4. His guidance, motivation and knowledge throughout this project were invaluable.
A special thanks to Human-Sim (Pty) Ltd. and Dr A. van Dyk for providing financial support to conduct this study.
Many thanks also to all my colleagues at Human-Sim (Pty) Ltd. for their continued support and inputs. Especially to Mr. J. van Rensburg for the literature reviews and .the basis reports used for Chapter 6. Also to Dr. D. C. Arndt for his insight as well as
Mr.
R.Pelz~rand Mr.
F. Keet for the mountains of collected literature.Lastly, I would like to thank my parents as well as my family and friends. Without your ongoing support and encouragement this study would not have been possible.
TABLE OF CONTENTS
ABST.RACT •••••••••••••••••...•••.•••••••••••••••••••.••••••••••••••••••••••••••••.••••••••••••••••••••••••.••••••••••••.•••.•.••••••••••• 1
SAMEV ATTIN'G •••.••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••.••
IV
A
CKN" 0 WLEDGEMENTS •••.•••••••••••..•••...••••••••....•••••.•••••••.••••.•.••••.••••••••.•.•••••••••...••.••••.••..•.•••••VII
TABLE OF CONTENTS •••..••••••...•.••••••••.•.•...•••••.•..••••.•...•.•..••••••••....•••.•.•....•••••.••••••..•••••••••••..•VIII
NOMENCLATURE ••.••••••.••••••••••••••••••.•••••••••••••••.•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••XIII
LIST OF FIGURES AN'D TABLES ••••••....•••.•••...•.•••••••••..•..•.••••••••....•.•••.•.••••••.••••...•••••••••••...XIX
CHAPTER 1 INTRODUCTION •••••••••••••••.•••••••••••••••.•.•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••.•• 1 1.1 PREAMBLE ... 21.2 BACKGROUND ... 2
1.2.1 THE HUMAN ENERGY SYSTEM ... 3
1.2.2 DIABETES MELLITUS ... 4 1.2.3 1.2.4 1.2.5 1.2.6 1.2.7 OBESITY ... ; ... 5
ENDURANCE ENERGY EXPENDITURE (EXERCISE) ... ; ... 6
STRESS ... : ... 7
OTHER BLOOD GLUCOSE CONNECTIONS ... : ... ; ... 7
SIMULATION OF THE HUMAN ENERGY SYSTEM ... : ... 8
1.3 1.4 1.5 1.6 1.7 MISSION STATEMENT AND OBJECTIVES ... 11
BENEFICIARIES OF THE STUDY ... 11
CONTRIBUTIONS OF THIS STUDY ... 13
OUTLINE OF THE STUDY ... 14
REFERENCES ... 16
CHAPTER 2
LINKING ENERGY FLOW IN THE BODY ...23
2.1 INTRODUCTION ... 24
2.2 CARBOHYDRATE COUNTING ... 25
2.2.1 BACKGROUND ... 25
2.2.2 LIMITATIONS CONCERNING CARBOHYDRATE COUNTING ... 26
2.3 GLYCAEMIC INDEX ... 27
2.3.1 BACKGROUND ... 27
2.3.2 LIMITATIONS CONCERNING GI ... : ... 30
2.3 .3 GLYCAEMIC LOAD ... 31
2.4 NEW CONCEPT: EQUIVALENT TEASPOONS SUGAR (ETS) ... 32
2.4.1 ENERGY EXTRACTED FROM INGESTED CARBOHYDRATES ... 32
2.4.2 .2.4.3 2.5 . DERIVATION OF THE ETS FORMULA ... : ... 36
DISCUSSION ... 37
CONCLUSION ... 39
2.6 REFERENCES ... : ... 40
CHAPTER 3 VERIFICATION OF THE ETS LINKS ... 43
3.1 INTRODUCTION ... 44
3.2 INSULIN RESPONSE TO INGESTED CARBOHYDRATES ... 44
3 .2.1 DERIVATION OF THE LINK BETWEEN INSULIN RESPONSE AND ETS ... 45
3.2.2 VERIFICATION OF THE EQUATIONS ... 49
3.2.3 DISCUSSION OF THE RESULTS ... 53
3.3 EXERCISE ENERGY EXPENDITURE ... 55
3.3.1 CURRENT METHODS ... · ... ; ... 56
3.3 .2 DERIVATION OF THE LINK BETWEEN EXERCISE AND ETS ... 57
3.3 .3 . MEASUREMENT OF THE VARIABLES ... 62
3.3.4 APPLICATIONOFTHEEQUATIONS ... 63
3.3.5 VERIFICATIONOFTHEEQUATIONS ... 64
' 3.4 CONCLUSION ... 67
3.5 REFERENCES ... :· ... 68
CHAPTER 4 NEW LINKS WITH THE ETS CONCEPT ... 72
4.1 INTRODUCTION ... 73
4.2 DIABETIC INSULIN REQUIREMENT ... 73
4.2.1 SHORT-ACTING INSULIN REQUIREMENT ... 74
4.2.2 TYPICAL VALUES OF
f
1 ... 784.2.3 LONG-ACTING INSULIN REQUIREMENT ... 79
4.2.4 VALIDATION OF THE METHOD ... ; ... 81
4.3 QUANTIFICATION OF STRESS AND ILLNESS ... 82
4.3.1 BACKGROUND ... 82
4.3.2 ANEW QUANTIFICATION METHOD ... 84
4.3 .3 VALIDATION OF THE QUANTIFICATION METHOD ... 85
4.3 .4 APPLICATION OF THE DISCOVERY ... 87
4.4 CONCLUSION ... 89
4.5 REFERENCES ... ~ ... 89
CHAPTER 5 INTEGRATED SIMULATION BACKGROUND~ ... 93
5.1 INTRODUCTION ... : ... 94
5.2 DYNAMIC INTEGRATED SIMULATION ... 94
5.3 MODEL DESIGN ... 95
5.4 SOLVING THE SIMULATION MODEL ... 97
5.4.1 ENERGY FLOW BETWEEN MODEL COMPONENTS ... 97
5.4.2 ENERGY FLOW TO AND FROM THE COMPONENTS ... 98
5.5 COMPUTER IMPLEMENTATION ... 99
5.6 CONCLUSION ... 100
5.7 REFERENCES ... 101
CHAPTER 6 HUMAN ENERGY SYSTEM BACKGROUND ••••••••••••••••••••••••••••••••••••••••••••••••••• 103 6.1 INTRODUCTION ... ; ... 104
6.2 THE HUMAN ENERGY SYSTEM ... 104
6.2.1 FUEL SOURCE TYPES ... 105
6.2.2 6.2.3 6.2.4 6.3 6.3.1 6.3.2 6.3.3 FACTORS AFFECTING AVAILABILITY OF FUEL ... 106
ENERGY UTILISATION ... 107
ENERGY STORAGE .. . ... ... ... . .. . .. . .. ... ... ... .... .. . . . ... ... . . . ... . .. ... ... ... . . . .... .. ... . . .. ... 111
THE MAJOR ENERGY PATHWAYS ... 113
THE CARBOHYDRATE PATHWAY ... 115
THEAMINOACIDPATHWAY ... 116
THE FAT PATHWAY ... ~ ... 117
6.4 THE BLOOD SUGAR CONTROL SYSTEM ... 118
6.4.1 CONTROL ORGANS AND TISSUES ... 119
6.4.2 ENDOCRINE CONTROL GLANDS ... 122
6.4.3 MAIN CONTROL HORMONES ... 124
6.4.4 ADDITIONAL CONTROL HORMONES ... 126
6.5 THE BLOOD SUGAR CONTROL PROCESSES ... 129
6.5.1 STORAGE HORMONES ... 132 6.5.2 6.5.3 6.6 6.7 RETRIEVALHORMONES ... 132 UTILISATION... 134 CONCLUSION ... 135 REFERENCES... 136
CHAPTER 7 HUMAN ENERGY SYSTEM SIMULATION ... 143
7.1 INTRODUCTION ... : ... ; ... 144
7.2 INTEGRATED GLUCOSE ENERGY FLOW ... 144
7.3 COMPONENT MODELS ... 146
7.3.1 DIGESTION SYSTEM MODEL ... ; ... 147
7.3.2 BLOODSTREAM MODEL ... 154
7.3.3 ENERGY EXPENDITURE MODEL ... 157
7.3.4 PRIMARY STORAGE MODEL ... 162
7.3.5 SECONDARY STORAGE MODEL ... 165
7.4 GLUCOSE ENERGY CONTROL SYSTEM ... 166
7.4.1 RELEASE OR TIME DELAY FUNCTION ... ; ... 168
7 .4.2 REGULATION HORMONE CONTROLLER MODEL. ... 170
7 .4.3 COUNTER REGULATION HORMONE CONTROLLER MODEL ... 173
7.4.4 STORAGE CONTROLLER MODEL ... 175
7.5 CONCLUSION ... ; ... 178
7.6 REFERENCES ... 178
CHAPTER 8 SIMULATION MODEL VERIFICATION ... 182
8.1 'INTRODUCTION ... 183
8.2 REFERENCE DATA ACQUISITION ... 183
8.2.1 TEST SUBJECTS··· 184
8.2.2 LONG-TERMTRIALS ... 185
8.2.3 SHORT-TERM TRIALS ... 188
8.3 VERIFICATION STUDY ... ; ... 191
8.3.1 WHOLE-DAY SIMULATIONS ... ; ... 191
8.3.2 ISOLATED DISTURBANCE SIMULATIONS ... 194
8.4 INTERPRETATION OF THE RESULTS ... :. 197
8.5 REFERENCES ... 198
CHAPTER 9 CLOSURE ••••••.••••••••••••••••••..•..••••••••••.••••••••••••••••••••••••.•••••••••••.•••••••••••••••••••••••. 200
9.1 INTRODUCTION ... 201
9.2 SUMMARY OF THE CONTRIBUTIONS ... 201
9 .2.1 NEW CONCEPT: EQUIVALENT TEASPOONS SUGAR (ETS) ... 201
9.2.2 SIMULATION OF THE HUMAN ENERGY SYSTEM ... 204
9.3 RECOMMENDATIONS FOR FURTHER WORK ... 206
9.4 CLOSURE ... 207
9.5 REFERENCES ... 208
APPENDIX A DETAILS OF THE TEST SUBJECTS ... 209
APPENDIX B MEASURED AND SIMULATED DATA ... 211
ABBREVIATIONS
ACSL ACTH ADH ARSC AUC BMI CHO CVD DARPA ets FSH GI GIP GL IBM IGF-1 II ISB LH MSC PIDRDA
RQ TSHAdvanced Continuous Systems Language Adrenocorticotropic Hormone
Antidiuretic Hormone
Arctic Region Supercomputing Centre Area Under the Curve
Body Mass Index Carbohydrate( s)
Cardiovascular Disease
Defence Advanced Research Projects Agency Equivalent Teaspoons Sugar
Follicle Stimulating Hormone Glycaemic Index
Glucose Dependent Insulinotropic Peptide Glycaemic Load
International Business Machines Insulin-like Growth Factor- I Insulin Index
Institute for Systems Biology Luteinising Hormone
Materials and Process Simulation Centre Proportional Integral Differential
Recommended Daily Allowance Respiratory Quotient
Thyroid Stimulating Hormone
XIII
USA United States of America
XML Extended Mark-up Language
SYMBOLS
AUC88 AUCFood AUC1 AUG Ingested AUG Injected AUG Reftrence I:!J3S Rise !lBS Fall Bl(t) BS(t) BS Blood(t) CControl (;Control C Control(!) C Control(t-1)C
Control-Min CFDose CFE/apsed CFExercise CFStorageArea under the curve of blood sugar response. Area under the curve ofthe food being tested. Area under the curve of insulin response.
Area of the blood glucose response curve of ingested glucose. Area of the blood glucose response curve of injected glucose. Area under the curve of the reference food in the test.
Absolute rise in blood sugar concentration due to an ingested meal.
Absolute drop in blood sugar concentration due to injected (or secreted) insulin. Blood insulin response.
Blood sugar response.
Blood sugar concentration at a specific time.
Amount of counter regulation hormone in the system.
Change in the amount of counter regulation hormone in the system.
Amount of counter regulation hormone in the system at a specific time step. Amount of counter regulation hormone in the system at the previous time step. Minimum amount of counter regulation hormone that is released.
Correction factor for the ets dose of a meal.
Correction factor for the elapsed time from a previous meal.
Relationship between energy expended and insulin consumed for exercise. Correction factor for the glycaemic index of a previous meal.
Second meal correction factor.
Relationship between glucose change and hormones consumed during change. Energy flow.
EAbsorb ECHO Eels EExpended E Expended(RDA) Ein Elngested Euver Eout Ere/eased ERDA EStored Estored Eteaspoon sugar Eused ets etS Actual efS Effective etsMax etsRDA etsstress etSTotal fAUC! fc-Control fcHO /Expended
Total amount of energy absorbed into the bloodstream. Converted carbohydrate energy potential.
Total amount of blood glucose energy available from ingested ets. Total amount of energy expended by the body.
Total recommended amount of energy to be expended daily. Energy flowing into a component.
Energy extracted from ingested food. Energy extracted from the liver store. Energy flowing QUt of a component. Energy released by a storage component. Total amount of daily energy required. Energy retrieved from glucose energy stores. Energy stored in a storage component. Energy available from a teaspoon of sugar. Energy utilised by a system component. Equivalent teaspoons sugar.
Actual amount of ets consumed in a meal. Effective amount of ets consumed in a meal. Maximum ets dose available from a meal.
Recommended daily allowance of equivalent teaspoons sugar. Maximum amount of ets secreted due to stress or illness.
Total amount of ets for which long-acting insulin has to be injected. Insulin response area I ets relationship efficiency factor.
Gradient of the PID counter regulation control strategy for regulation hormones. Efficiency factor for converting ingested carbohydrates into blood sugar energy. Efficiency factor for converting ingested ets into expendable blood glucose energy.
!FAT Efficiency factor for converting ingested fat into blood sugar energy.
!Fat Efficiency factor for retrieving blood glucose energy from fat stores.
/ 1 Insulin response I ets relationship efficiency factor.
/ 1Bs Insulin I blood sugar relationship efficiency factor.
f
1_control Gradient of the PIDregulation control strategy for regulation hormones.ftngest Efficiency factor for extracting energy from ingested food.
!Liver Efficiency factor for retrieving blood glucose energy from the liver store.
f
Muscles Efficiency factor for retrieving blood glucose energy from muscle stores. !PROTEIN Efficiency factor for converting ingested protein into blood sugar energy.!store Efficiency factor for retrieving energy from glucose energy stores.
!stress Ability factor to secrete ets due to stress or illness.
G
Glucose energy flow.G
Basal Glucose energy required for everyday living. GBasal Amount ofbasal energy required.G Blood Blood glucose concentration.
G Blood(t> . Blood glucose concentration at a specific time step.
G Blood(t-l) Blood glucose concentration at the previous time step.
G81aod-c-setpoint Blood glucose energy setpoint for counter regulation hormones.
G Blood-J-Setpoint Blood glucose energy setpoint for regulation hormones.
G
Digest Glucose energy flow from the digestion system to the bloodstream.G
Exercise Glucose energy flow from the bloods~eam to the energy expenditure.G
Exercise-Min Minimum value ofG
Exercise.G Liver Capacity of an average person's liver storage.
GMavement Glucose energy required for,movements.
GMovement Total amount of glucose energy required for movements.
G
RDA<t> Glucose energy required per day at a specific time step.(;Storage G Storage( I) G Storage( I-I)
G
Storage-Min (;Store-IN (;Store-OUT GicHo Gisugar Icomrol j Control I Control(t) I Control(t-1) j Control-Min I Exercise I Injected( Long) I SecreJed K Lm
teaspoon sugarGlucose energy flow between the primary storage and secondary storage. Glucose energy storage flow at a specific time step.
Glucose energy storage flow at the previous time step.
Maximum glucose energy flow rate between storage components. Minimum glucose energy flow rate between storage components. Glucose energy flow from the bloodstream to the primary storage. Glucose energy flow from the primary storage to the bloodstream.
Conversion potential of energy from ingested food (approximated with GI). Glycaemic index of a previous meal.
Conversion potential of energy from sugar. Basal insulin level.
Amount of regulation hormone in the system.
Change in the amount of regulation hormone in the system.
Amount of regulation hormone in the system at a specific time step. Amount of regulation hormone in the system at the previous time step. Minimum amount of regulation hormone that is released.
Insulin consumed from the blood when exercising. Short-acting insulin requirement.
Long-acting insulin requirement. Amount of insulin secreted.
Blood sugar I ets conversion factor.
Maximum amount of energy available from carbohydrates. Length.
Mass of carbohydrates contained in the food.
Mass of carbohydrates contained in a teaspoon of sugar.
Time elapsed between consumption and restoration ofbasallevel.
t tCurre111 f Digest f Elapsed (Event (Exercise t Exhaustion (Meal
UNITS
ets g h kCal kg m min mmol unit(s)w
Time.Current time in the simulation process. Total digestion time of the specific meaL Time elapsed up to current time.
Duration of an exercise. Duration of the exercise.
Duration of exercise until exhausted. Elapsed time of digestion of pure glucose. Time of day a meal is taken.
Time of day an exercise is performed. Duration of the release function. Volume ofblood of a person.
Amount of oxygen consumed by the body.
Maximum amount of oxygen the body can consume. Weight.
Equivalent Teaspoons Sugar Grams Hours Kilocalories Kilograms Litre Meters Minutes Milli-mol Insulin units Watt XVIII
LIST OF FIGURES AND TABLES
FIGURES
FIGURE 1.1-SCHEMATICREPRESENTATIONOFTHELAYOUTOFTHISSTUDY . ... 15
FIGURE 2.1 -MEASUREMENT OF AUC OF THE GLUCOSE RESPONSE DUE TO INGESTED CHO IN
ORDER TO DETERMINE THE Gl OF THE TEST FOOD . ... 29 FIGURE 2.2 - SCHEMATIC REPRESENTATION OF MEASUREMENTS OF BLOOD SUGAR RESPONSE WHEN
A TYPE] DIABETIC EATS EQUAL AMOUNTS OF CHO CONTAINED IN GLUCOSE AND
FRUCTOSE . ... 33
FIGURE 2.3 -SCHEMATIC REPRESENTATION OF EXPECTED BLOOD GLUCOSE RESPONSE IF THE CORRECT DEFINITION OF Gl IS "RATE OF DIGESTION": TYPE 1 DIABETIC INGESTING
THE SAME MASS OF CHO THROUGH GLUCOSE AND FRUCTOSE . ... ~ ... 34
FIGURE 3.1 -LINEAR BEST FIT TREND LINE AND CORRESPONDING R2-VALUE FOR NORMALISED
AUC1 VALUESAGAINSTCHO INGESTION(ONE TEST SUBJECT} ... 50
FIGURE 3.2- LINEAR BEST FIT TREND LINE AND CORRESPONDING R2-V ALUE FOR NORMALISED
A UC1 VALUES AGAINST Gl VALUES OF INGESTED FOOD (ONE TEST SUBJECT} . ... 51 FIGURE 3.3- LINEAR BEST FIT TREND LINE AND CORRESPONDING R2-V ALUE FOR NORMALISED
AUC1 VALUES AGAINST ETS VALUES OF INGESTED FOOD (ONE TEST SUBJECT} ... 52
FIGURE 4.1- SCHEMATIC REPRESENTATION OF THE DEFINITIONS OF llBS Rise AND llBS Fall' ... 77 FIGURE 6.1- THE "CROSSOVER CONCEPT" OF BROOKS SHOWING INCREASING IMPORTANCE OF
CARBOHYDRATE OXIDATION AT HIGH EXERCISE INTENSITIES . ... ] 08
FIGURE 6.2 -SIMPLIFIED SCHEMATIC LAYOUT OF THE MAJOR ENERGY PATHWAYS IN THE HUMAN
ENERGY SYSTEM. ... 114
FIGURE 6.3 -SIMPLIFIED SCHEMATIC LAYOUT OF THE BLOOD SUGAR CONTROL SYSTEM IN THE
HUMAN ENERGY SYSTEM ... 130
FIGURE 7.1- SCHEMATIC LAYOUT OF THE INTEGRATED HUMAN ENERGY SIMULATION MODEL ... 145
FIGURE 7.2- LINEAR SCALING FOR THE CALCULATION OF CFEiapsed ... 149
FIGURE 7.3-LINEAR SCALING FOR THE CALCULATION OF CF01 ... 150 FIGURE 7.4- CF SM VALUES FOR DIFFERENT VALUES OF CFEiapsed AND CFGI . ... 151
FIGURE 7.5-DEFINED RANGE OF VALUES FOR t Digest ... 154
FIGURE 7.6-SCHEMATIC REPRESENTATION OF THE ENERGY FLOW THROUGH THE LINEAR STORAGE TANK MODEL OF THE BLOODSTREAM COMPONENT. ... 155 FIGURE 7. 7-SCHEMATIC REPRESENTATION OF THE ENERGY FLOW THROUGH THE LINEAR STORAGE
TANK MODEL OF THE PRIMARY STORAGE COMPONENT . ... 163
FIGURE 7.8-SCHEMATIC LAYOUT OF THE CONTROUER COMPONENT CONNECTIONS • ... 167 FIGURE 7.9- A GRAPHICAL REPRESENTATION OF THE RELEASE FUNCTION: THE SUM OF THE TWO
SINE CURVES, NAMELY (
J;
ANDJ;) . ...
169FIGURE 7.10-P!D CONTROL STRATEGY FOR THE REGULATION HORMONE (INSULIN) CONTROUER
COMPONENT. ... ; ... 172 FIGURE 7.11 - PJD CONTROL STRATEGY FOR THE COUNTER REGULATION HORMONE CONTROLLER
COMPONENT. ... 174
FIGURE 7.12-STEP CONTROL STRATEGY FOR THE STORAGE SYSTEM CONTROLLER COMPONENT. ... 176
FIGURE 8.1 -COMPARISON BETWEEN MEASURED AND SIMULATED DATA FOR THE WHOLE-DAY
SIMULATIONS ... 192
FIGURE 8.2-EXAMPLE OF A WHOLE-DAY SIMULATION PERFORMED FOR A DIABETIC SUBJECT. ... : ... 193
FIGURE 8.3-COMPARISON BETWEEN MEASURED AND SIMULATED DATA FOR THE ISOLATED FOOD
SIMULATIONS ... 195
FIGURE 8.4-COMPARISON BETWEEN MEASURED AND SIMULATED DATA FOR THE ISOLATED
EXERCISE SIMULATIONS ... ; ... 195 FIGURE 8.5-COMPA/USON BETWEEN MEASURED AND SIMULATED DATA FOR THE ISOLATED INSULIN
SIMULATIONS ... 196
TABLES
TABLE 2.1-TYPICAL VALUES FOR ECH0 /mcHo IN ACCORDANCE TO CORRESPONDING Gl VALUES ... 35 TABLE 3.1 -PEARSON'S R2
-VALVES FOR CORRELATIONS BETWEEN NORMALISED INSULIN RESPONSE
INTEGRALS ( AUC1 ) AND CHO, GlAND ETS VALUES ... 53 TABLE 4.1-CALCULATIONS OF
iJ
FOR THREE TYPE 1 DIABETIC TEST SUBJECTS ... 78 TABLE 4.2-CALCULATIONS OFf
1 FROM THE 450 RULE BY WALSH ET AL ... 79 TABLE 4.3-AMOUNT OF VIRTUAL ETS ADJUSTED IN THE SIMULATION MODEL OF A 65 KG PERSON TOMIMIC THE MAXIMUM BLOOD GLUCOSE RESPONSE FOR STRESS . ... 85
TABLE 6.1 -CONTROL SETPOINTS FOR COUNTER REGULATION (RETRIEVAL) HORMONE RELEASE ... 133 TABLE 8.1 -SUMMARY OF THE GROUP OF HEALTHY SUBJECTS USED FOR THE CLINICAL TRIALS . ... 185 TABLE 8.2-SUMMARY OF THE GROUP OF DIABETIC SUBJECTS USED FOR THE CLINICAL TRIALS ...
J
85 TABLE 8.3 -ACCURACY OF THE WHOLE-DAY SIMULATIONS . ... 193TABLE 8.4 -ACCURACY OF THE ISOLATED SIMULATIONS . ... 197
