The effects of aerobic and resistance exercise on inflammatory markers and metabolic control in ...

299 Pages·2014·3.35 MB·English

The effects of aerobic and resistance exercise on
inflammatory markers and metabolic control in
healthy individuals and type 1 diabetics using either
insulin pump or multiple dose injection

By

Mohamd Abdulrahman Alblihed

A thesis submitted to the De Montfort University for
the degree of Doctor of Philosophy in the Faculty of
Health and Life Sciences

2013
TABLE OF CONTENTS
TABLE OF CONTENTS .................................................................................................. 1
TABLE OF FIGURES ...................................................................................................... 8
LIST OF TABLES .......................................................................................................... 10
ABSTRACT .................................................................................................................... 12
ACKNOWLEDGEMENT .............................................................................................. 14
DECLARATION ............................................................................................................ 15
ABBREVIATION ........................................................................................................... 16
Chapter 1:Introduction .................................................................................................... 20
1. Diabetes Mellitus ................................................................................................. 20
1.1 Overview ....................................................................................................... 20
1.2 Diagnosing Diabetes ..................................................................................... 21
1.3 Impact of diabetes ......................................................................................... 23
1.3.1. Epidemiology and Complications of Diabetes ...................................... 23
1.3.2. Death Rates of Diabetes ........................................................................ 28
1.3.3. Finance and Economic Problem ............................................................ 29
1.4. Diabetes Mellitus Classification ................................................................... 30
1.4.1. Type 1 Diabetes (Insulin Dependent) .................................................... 30
1.5. Management, Lifestyle and Diet of diabetes patients ................................... 31
1.6. Diabetes and glucose .................................................................................... 33
1.6.1. Overview ............................................................................................... 33
1.6.2. Glucose transport pathways ................................................................... 34
1.6.3. Glucose control ...................................................................................... 35
1.6.4. Glycogen metabolism ............................................................................ 36
1.6.5. Effect of diabetes on glycogen stores .................................................... 37
1.7. Insulin ........................................................................................................... 38
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1.7.1. Definition .................................................................................................. 38
1.7.2. Synthesis and release of Insulin ................................................................ 38
1.7.3. Mechanism of action of insulin secretion ................................................. 39
1.7.4. Insulin resistance ....................................................................................... 42
1.7.5. Type of therapeutic insulin ....................................................................... 43
1.7.5.1. Injectable insulin ................................................................................ 43
1.7.5.2. Administering insulin by insulinpump .............................................. 44
1.7.5.2.1. World use of insulin pumps ............................................................ 45
1.7.5.2.2. How insulin pumps work ................................................................ 46
1.7.5.2.3. Insulin Pump versus Multi Daily Injection ..................................... 47
1.8. Exercise ......................................................................................................... 49
1.8.1. Resistance and aerobic exercise ................................................................ 50
1.8.2. Exercise and Immunity ............................................................................. 55
1.8.3. Effects of Acute exercise on the Immune System .................................... 56
1.8.4. Chronic Effects of Exercise on Immune System ...................................... 58
1.9. Overview on the Immune System ................................................................. 59
1.9.1. Autoimmunity ........................................................................................... 59
1.9.2. Immunology of Type 1 Diabetes............................................................... 60
1.9.3. Autoimmune Mechanisms Related to Type 1 Diabetes ............................ 62
1.9.4. Animal models of type 1 diabetes ............................................................. 63
1.9.5. Cytokines and Diabetes ............................................................................. 64
1.9.5.1. Interleukin-1 beta (IL-1β) ................................................................. 67
1.9.5.2. Interleukin-6 (IL-6) ............................................................................ 68
1.9.5.3. Interferon Gamma (IFN-γ) ................................................................. 69
1.9.5.4. Tumor Necrosis Factor Alpha (TNF-α) ............................................ 69
1.10. Study Objectives ....................................................................................... 70
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Chapter 2: Materials and Methods .................................................................................. 72
2.1. Exercise study, short-term (acute) and long-term (chronic) effects ............. 72
2.2. Insulin Pump Surveys ................................................................................... 72
2.2.1. Surveys Project Aims ............................................................................ 72
2.2.2. De Montfort University Insulin Pump Users Survey 2009 ................... 73
2.2.3. De Montfort University Insulin Pump and Exercise Survey 2011 ........ 73
2.2.4. Survey Distribution ............................................................................... 74
2.2.5. Analysis of survey responses ................................................................ 74
2.3. Practical study -Ethics Approval .................................................................. 75
2.3.1. Standard Operating Procedure (SOP) .................................................... 75
2.3.2. Volunteer Information Sheet (VIS) ....................................................... 75
2.3.3. Risk Assessment Form .......................................................................... 75
2.3.4. Consent Form ........................................................................................ 75
2.3.5. Volunteers Health Screen ...................................................................... 76
2.3.6. Confidentiality ....................................................................................... 76
2.3.7. Volunteer Record Sheet ......................................................................... 76
2.4. Volunteers ..................................................................................................... 77
2.4.1. Recruitment of Volunteers for Exercise Program ................................. 77
2.4.2. Volunteer Criteria .................................................................................. 78
2.5. Study design and Description of Exercise Sessions ..................................... 80
2.5.1. Exercise Physiology Lab ....................................................................... 80
2.5.2. Phlebotomy, First Aid, Defibrillation training and other courses ......... 80
2.5.3. Initial EPL Visit ..................................................................................... 81
2.5.4. Pre-exercise Visit and Familiarisation with exercise ............................ 81
2.5.5. Determination of intensity levels for aerobicexercise ........................... 82
2.5.6. Determination of One Repetition Maximum (1RM) for RE Exercise .. 82
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2.5.7. Warm-up ................................................................................................ 83
2.5.8. Resistance exercise (RE) ....................................................................... 85
2.5.9. Cycling .................................................................................................. 88
2.5.10. Warm-down ........................................................................................... 88
2.5.11. Long-term (chronic) exercise ................................................................ 89
2.5.12. Acute exercise ....................................................................................... 89
2.6. Visit measurements ....................................................................................... 89
2.6.1. Body fat percentage, weight, height, body mass index (BMI) .............. 90
2.6.2. Lipid profile ........................................................................................... 90
2.6.3. Blood glucose (BG) and hemoglobin A1c ............................................ 91
2.6.4. Venous blood sampling ......................................................................... 91
2.6.5. Assessment of caloric intake ................................................................. 92
2.7. Calibrating, filtering and sterilising the ADInstruments analyser ................ 92
2.8.2 Practical study ....................................................................................... 93
2.9 Cytokine detection ........................................................................................ 94
2.9.1 Enzyme-linked immunosorbent assay (ELISA) .................................... 94
2.9.1.1Capture antibody ................................................................................... 94
2.9.1.2 Detection antibody ............................................................................. 95
2.9.1.3 Standard Antibody ............................................................................. 95
2.9.1.4 Plate preparation for ELISA .............................................................. 96
2.9.1.4.1 Preparation ....................................................................................... 96
2.10 Materials ....................................................................................................... 97
Chapter 3: Insulin Pump Survey ..................................................................................... 99
3.1. Introduction ...................................................................................................... 99
3.2. Study Objectives ............................................................................................. 101
3.3. Materials and Methods ................................................................................... 102
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3.3.1. Survey Design, Layout and Measures ..................................................... 102
3.3.2. Target audience ....................................................................................... 103
3.3.3. Study population and sampling ............................................................... 104
3.3.4. Survey Distribution and response collection........................................... 104
3.3.5. Data collection ........................................................................................ 104
3.3.6. Statistical analyses (Analysis of responses) ............................................ 105
3.4. Results ............................................................................................................ 105
3.4.1. Background information Section ............................................................ 105
3.4.2. Diabetes section ...................................................................................... 109
3.4.3. Insulin Pump Section .............................................................................. 111
3.4.4. Exercise Section ...................................................................................... 113
3.4.5. Diet Section ............................................................................................. 116
3.4.6. Diabetes complications ........................................................................... 117
3.4.7. Bivariate Analysis (Crosstab Analysis) .................................................. 118
3.5. Discussion ...................................................................................................... 127
3.6. Conclusion ...................................................................................................... 135
CHAPTER 4:The Immunological Effect of Exercise ................................................... 137
4.1. Introduction ........................................................................................................ 137
4.2. Objectives of the Study ...................................................................................... 152
4.3. Materials and Methods ....................................................................................... 152
4.3.1. Study Volunteers.......................................................................................... 152
4.3.2. Screening and preliminary testing ............................................................... 153
4.3.3. Exercise Training ......................................................................................... 153
4.3.4. Blood collection ........................................................................................... 154
4.3.5. Statistical Analyses ...................................................................................... 156
4.3.6. Cytokine Measurements .............................................................................. 156
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4.4. Results ................................................................................................................ 157
4.4.1. Acute exercise (one session) ........................................................................ 157
4.4.2. Chronic exercise (12sessions) ...................................................................... 161
4.5. Discussion .......................................................................................................... 165
4.6. Conclusion .......................................................................................................... 180
CHAPTER 5: Effect of exercise onLipids Profiles and glycemic control .................... 182
5.1. Introduction .................................................................................................... 182
5.2. Effect of Exercise on Lipids and glycemia control ........................................ 183
5.3. Insulin pump compared to MDI ..................................................................... 184
5.4. Study Objectives ............................................................................................. 186
5.5. Subjects and Methods ..................................................................................... 186
5.5.1. Volunteers ............................................................................................... 186
5.5.2. Study Recruitment ................................................................................... 187
5.5.3. Six Weeks Exercise ................................................................................. 187
5.5.4. Parameters measured ............................................................................... 188
5.5.5. Statistical Analysis .................................................................................. 189
5.6. Results ............................................................................................................ 189
5.6.1. Characteristics ......................................................................................... 189
5.6.2. Exercise intensity .................................................................................... 190
5.6.3. Effect of exercise on Lipids .................................................................... 195
5.6.3.1. Low-density lipoprotein cholesterol (LDL) ..................................... 196
5.6.3.2. High-density lipoprotein cholesterol (HDL).................................... 197
5.6.3.3. Total Cholesterol (TC) ..................................................................... 198
5.6.3.4. Triglyceride (TG) ............................................................................. 199
5.6.4. Cholesterol ratio ...................................................................................... 200
5.6.4.1. TC/HDL ........................................................................................... 200
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5.6.4.2. HDL/LDL ........................................................................................ 201
5.6.4.3. TG/HDL ........................................................................................... 201
5.6.5. Effect of exercise on insulin doses .......................................................... 202
5.6.6. Blood glucose level ................................................................................. 203
5.7. Discussion ...................................................................................................... 206
5.8. Conclusion ...................................................................................................... 217
Chapter 6: Epilogue....................................................................................................... 219
6.1. General Discussion ............................................................................................. 219
6.2. Recommendations .............................................................................................. 221
6.4. Limitations .......................................................................................................... 222
6.5. Future work ........................................................................................................ 224
REFERENCES .............................................................................................................. 226
APPENDIX ................................................................................................................... 245

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TABLE OF FIGURES
Figures Titles Page
Figure 1.1:How insulin is delivered to cells (insulin signalling) 35
Figure 1.2: Insulin synthesis and secretion process 39
Figure 1.3: Molecular mechanism of glucose induced insulin secretion 40
Figure 1.4: Process of T1D initiation 66
Figure 2.1: Stretching left and right for lower and upper muscle groups 85
Figure 2.2: Five types of resistance exercise (3 sets, 10 repetitions each set) 87
Figure 3.1: Frequencies of BMI values in the survey 107
Figure 3.2: Survey respondents’ lipids levels 108
Figure 3.3: A1c level before and after insulin pump therapy 110
Figure 3.4: Insulin pumps selected by respondents or their providers 111
Figure 3.5:Types of insulin stated by respondents to be infused into their insulin 112
pumps
Figure 3.6:Intensity level during exercise sessions as reported by respondents 114
Figure 3.7A: The main types of exercise reported by respondents 115
Figure 3.7B: Subtypes of physical activity reported by respondents 115
Figure 3.8: Basal and Bolus delivery by insulin pump 119
Figure 4.1: Cytokine pathway and the blocking agents in T1D 145
Figure 4.2: Division of the exercise sessions throughout the study 154
Figure 4.3: Exercise protocol and blood sampling scheme for acute exercise 155
Figure 4.4: Blood sampling scheme for chronic exercise 155
Figure 4.5: Acute plasma levels of inflammatory cytokines IL-6 158
Figure 4.6: Acute plasma levels of inflammatory cytokines TNF-α 159
Figure 4.7: Acute plasma levels of inflammatory cytokines IL-1β 160
Figure 4.8: Acute plasma levels of inflammatory cytokines IFN-γ 161
Figure 4.9: Chronic plasma levels of inflammatory cytokines IL-6 162
Figure 4.10: Chronic plasma levels of inflammatory cytokines TNF-α 163
Figure 4.11: Chronic plasma levels of inflammatory cytokines IL-1β 164
Figure 4.12: Chronic plasma levels of inflammatory cytokines IFN-γ 165
Figure 4.13:Production of pro-inflammatory cytokines in immune cells 170
Figure 4.14:How regulatory T cells, that have lost forkhead box P3 (FOXP3) 173
expression
Figure 4.15: Contracting muscle fibres produce and release IL-6 177
Figure 5.1: Division of the exercise sessions throughout the study 188
Figure 5.2: LDL cholesterol before, during and after 12 sessions of exercise 197
Figure 5.3: HDL cholesterol before, during and after 12 sessions of exercise 198
Figure 5.4: Total cholesterol before, during and after 12 sessions of exercise 199
Figure 5.5: Triglyceride before, during and after 12 sessions of exercise 199
Figure 5.6: TC/HDL ratio 200
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Figure 5.7: HDL/LDL ratio 201
Figure 5.8: TG/HDL ratio 202
Figure 5.9: BG level for ND group 203
Figure 5.10: BG level for CSII group 204
Figure 5.11: BG level for MDI group 205
Figure 5.12: A1c for MDI and CSII group before and after 12 sessions 206

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