| Publications by Biophoenix' Principals |
| Opportunities in Obesity, Anorexia, and Bulimia | |
|---|---|
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| Publisher: | PJB Publications Ltd |
| Year of publication: | 1992 |
| Type of publication: | Management report |
| Publisher's reference (if any): | CBS 397 |
| Author(s): | Sreten Bogdanovic |
| Approximate page count: | 160 |
| Price when published: | £300 |
Remarks:
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OPPORTUNITIES IN OBESITY, ANOREXIA, AND BULIMIA
A Report for
Scrip World Pharmaceutical News
(November 1991)
TABLE OF CONTENTS
TABLE OF CONTENTS i
CHAPTER 1 INTRODUCTION
1.1 The Importance of Obesity 1
1.2 The Importance of Other
Eating Disorders 2
1.3 Potential Targets for
Intervention in Obesity 2
1.4 Current Treatments for Obesity 3
1.5 Newer Anti-Obesity Treatments 3
1.6 Scope of this Report 4
1.7 Definitions and Diagnosis of Obesity 5
1.7.1 Introduction 5
1.7.2 The Metropolitan Tables 5
1.7.3 The Fogarty Tables 6
1.7.4 The Body Mass Index (BMI) 6
1.8 Body Composition 7
1.8.1 Introduction 7
1.8.2 Importance of Body Fat Content 7
1.8.3 Measurement of Body Fat Content 8
1.8.3.1 Direct Carcass Analysis 8
1.8.3.2 Visual Inspection
and Somatotyping 8
1.8.3.3 Anthropometry 8
1.8.3.3.1 The Android-Gynoid
Ratio (AGR or WHR) 8
1.8.3.3.2 Measurement of Skinfold
Thicknesses 9
1.8.3.4 Gravimetry 9
1.8.3.5 Dilutional Techniques 10
1.8.3.6 Miscellaneous
Physical Techniques 11
1.8.4 Conclusions 11
1.9 Grading Obesity 11
1.10 Prevalence of Overweight
and Obesity 12
CHAPTER 2 RISKS AND CONSEQUENCES OF OBESITY
2.1 Introduction 14
2.2 Total Mortality 14
2.3 Prospective Studies of Mortality 14
2.3.1 `Pooling Project' 14
2.3.2 Framingham Study 15
2.3.3 American Cancer Society Survey 15
2.3.4 G”teborg Study 16
2.3.5 Norwegian Study 16
2.3.6 Honolulu Heart Program Study 16
2.4 Effects of Age and Obesity on Mortality 17
2.5 Obesity and Morbidity 17
2.5.1 Cardiovascular Morbidity 17
2.5.2 Pulmonary Dysfunction 18
2.5.3 Gallbladder and Digestive Disease 18
2.5.4 Diabetes Mellitus 19
2.5.5 Reproductive Dysfunction 20
2.5.6 Other Medical Problems 21
2.6 Socioeconomic Consequences of Obesity: 21
2.6.1 At School 21
2.6.2 At Work 22
2.6.3 At Play 22
2.6.4 In Developing Countries 23
CHAPTER 3 CAUSES OF OBESITY
3.1 Introduction 24
3.2 Genetics 24
3.2.1 Twin Studies 24
3.2.2 Parental Influence 25
3.2.3 Genetic Obesity Syndromes 25
3.2.3.1 Introduction 25
3.2.3.2 Genetic Obesity Syndromes in Man 25
3.2.3.2.1 Prader-Willi Syndrome 25
3.2.3.2.2 Other Syndromes 27
3.2.3.3 Genetic Obesity Syndromes in Animals 28
3.2.3.3.1 Introduction 28
3.2.3.3.2 Monogenic and Polygenic
Obesities 28
3.2.3.3.3 The obese (ob/ob) mouse 29
3.2.3.3.4 The diabetes (db/db) Mouse 31
3.2.3.3.5 The fatty (fa/fa) Rat 32
3.2.3.3.6 Polygenic Models 32
3.2.4 Molecular Genetics of Obesity 32
3.2.4.1 Apolipoprotein B RFLPs 32
3.2.4.2 Mapping Obesity Genes in the Mouse 33
3.2.4.3 A Human Homologue of the obese Gene? 33
3.2.4.4 Quantitative Molecular Genetics
and Obesity 35
3.3 Energy Intake and Expenditure 36
3.3.1 Introduction 36
3.3.2 The Measurement of Food Intake and
Energy Expenditure 36
3.3.2.1 Units of Measurement 36
3.3.2.2 Nutrient and Whole-body Calorimetry 36
3.3.2.3 Metabolic Respirometry 37
3.3.3 Food Intake in Obesity 38
3.3.3.1 Introduction 38
3.3.3.2 Regulation of Food Intake
by the Brain 38
3.3.3.3 Thermostatic Theory 39
3.3.3.4 Lipostatic Theory 40
3.3.3.5 Glucostatic Theory 41
3.3.4 Contribution of Overeating to
Human Obesity 43
3.3.4.1 Food Intake in Relation
to Age Group 43
3.3.4.2 Food Intake and Energy Expenditure
by Individuals 43
3.3.4.3 The Vermont Prison Study 44
3.3.4.4 Conclusions 45
3.3.5 Obesity and Energy Expenditure 46
3.3.5.1 Categories of Energy Expenditure 46
3.3.5.2 Voluntary Energy Expenditure 47
3.3.5.3 Resting Energy Expenditure 48
3.3.5.4 Diet-Induced Thermogenesis 49
3.3.5.5 Thermic Effect of
Cigarette Smoking 50
3.3.6 Altered Thermogenesis in
Non-obese States 52
3.3.6.1 Introduction 52
3.3.6.2 Cancer 52
3.3.6.3 Severe Infectious Disease 53
3.3.6.4 Cystic Fibrosis 53
3.3.6.5 Severe Trauma 54
3.3.6.6 Extra Post-exercise Oxygen
Consumption 54
3.3.7 Effects of Food Intake Pattern
and Composition 55
3.3.7.1 Force-Feeding and Weight Gain 55
3.3.7.2 The Effects of Dietary Composition 55
3.3.7.2.1 High Fat Diets 55
3.3.7.2.2 High Sucrose Diets 56
3.3.7.2.3 Highly Palatable Diets
and the `Cafeteria' Model 57
3.3.7.2.4 Caloric Dilution and
Dietary Composition 58
3.3.8 Summary of Animal Models of Obesity
Caused by Diet, Chemicals, and Surgery 58
3.4 Psychological Factors in Obesity 59
3.4.1 Introduction 59
3.4.2 Incidence of Psycho-
pathology in the Obese 60
3.4.3 Psychological Effects of Weight Loss 61
3.4.4 Seasonal Affective Disorder (SAD) 61
3.4.4.1 Seasonal Rhythms
of Food Intake 61
3.4.4.2 Clinical Features of SAD 62
3.4.4.3 Phototherapy in SAD 62
3.4.4.4 Mechanism of Carbohydrate Craving 64
3.5 Endocrinological Factors in Obesity 65
3.5.1 Introduction 65
3.5.2 Thyroid 66
3.5.3 Adrenals 66
3.5.4 Ovaries and Testes 67
3.5.5 Hypothalamus and Pituitary 68
3.5.6 Endocrine Pancreas 68
3.5.6.1 Insulin Resistance 68
3.5.6.2 Non Insulin-Dependent
Diabetes Mellitus 70
CHAPTER 4 ANOREXIA AND BULIMIA
4.1 Anorexia Nervosa 71
4.1.1 Introduction 71
4.1.2 History 71
4.1.3 Prevalence 71
4.1.4 Clinical Features 72
4.1.5 Biochemical Features 73
4.1.6 Endocrine Features
of Anorexia Nervosa 73
4.1.7 Aetiology 75
4.1.8 Treatment of Anorexia Nervosa 76
4.1.8.1 Psychiatric Therapies 76
4.1.8.2 Drug Therapies 77
4.1.9 Prognosis 78
4.2 Bulimia Nervosa 78
4.2.1 Introduction 78
4.2.2 Prevalence 78
4.2.3 Clinical Features 79
4.2.4 Aetiology 80
4.2.5 Endocrine Features of
Bulimia Nervosa 81
4.2.6 Treatment of Bulimia Nervosa 81
4.2.6.1 Psychiatric Therapies 81
4.2.6.2 Drug Therapies 82
4.2.7 Prognosis 82
CHAPTER 5 NONPHARMACOLOGICAL THERAPIES FOR OBESITY
5.1 Introduction 83
5.2 Approaches to the Treatment of Obesity 83
5.3 Risk/Benefit Estimations for
Obesity Therapies 83
5.4 Dietary Treatments for Obesity 84
5.4.1 Introduction 84
5.4.2 Estimating Weight Loss on a
Reducing Diet 84
5.4.2.1 Determination of Daily
Energy Requirements 85
5.4.2.2 The Calorific Value of
Adipose Tissue 86
5.4.2.3 How Much Weight Needs
to be Lost? 86
5.4.3 Conventional Diets 87
5.4.4 Very Low Calorie Diets (VLCDs) 89
5.4.5 Starvation Diets 90
5.4.6 How Well do Reducing Diets Work? 90
5.5 Behaviour Modification 91
5.5.1 Introduction 91
5.5.2 Nature of Behaviour Therapy 91
5.5.3 Outcome of Behaviour Therapy 92
5.5.4 Self-Help Groups 92
5.5.5 Psychoanalysis 93
5.6 Exercise and Weight Loss 93
5.6.1 Types of Exercise Regime 93
5.6.2 Results of Exercise Treatment 93
5.6.2.1 Exercise Alone 93
5.6.2.2 Exercise and Diet 94
5.6.2.3 Long Term Results of
Exercise Treatment 94
5.7 Jaw-Wiring 95
5.8 Treatments Affecting the Stomach 95
5.8.1 Introduction 95
5.8.2 Gastric Bubbles 96
5.8.3 Surgical Interventions 96
5.8.3.1 Overview 96
5.8.3.2 Gastric Bypass Operations 97
5.8.3.2.1 Procedure 97
5.8.3.2.2 Results 97
5.8.3.3 Gastroplasty 98
5.8.3.3.1 Horizontal Gastroplasty 98
5.8.3.3.2 Vertical Banded
Gastroplasty (VBG) 98
5.8.3.3.3 Comparison of Gastric
Bypass and Gastroplasty 98
5.8.3.4 Vagotomy 99
5.9 Jejunoileal Bypass Surgery 99
5.9.1 Overview 99
5.9.2 Standard Procedures 99
5.9.3 Modified Procedures 100
5.9.4 Therapeutic Efficacy 100
5.9.5 Long-Term Complications 101
5.10 Regional Fat Removal 102
5.10.1 Surgical Removel 102
5.10.2 Liposuction 102
5.10.3 Local Use of Lipolytic Agents 102
5.11 Caloric Dilution 103
5.11.1 Overview 103
5.11.2 High Fibre Diets 103
5.11.3 Fat Substitutes 104
5.11.3.1 Sucrose Polyesters (Olestra) 104
5.11.3.2 Phenylmethylpolysiloxane (PS) 104
5.11.3.3 Stellar, Simplesse, and
Related Products 105
5.11.4 Artificial Sweeteners 105
5.11.4.1 Saccharin 105
5.11.4.2 Aspartame 106
5.11.4.3 Acesulphame 106
5.11.4.4 Clinical Efficacy of
Sweeteners in Obesity 106
CHAPTER 6 APPETITE SUPPRESSANTS AND STIMULANTS
6.1 Introduction 108
6.2 Measuring Appetite, Hunger, and Satiety 108
6.3 Neuropharmacology - A Primer 110
6.3.1 Overview of the Nervous System 110
6.3.2 Neurotransmitters 110
6.3.3 Sympathetic System 110
6.3.4 Parasympathetic System 111
6.3.5 Serotoninergic System 111
6.3.6 Central Nervous System 111
6.3.7 Opioidergic System 112
6.3.8 Actions of Drugs on Neurotransmitters 113
6.4 Anorexigenic Drugs Acting on
Catecholamine Neurotransmitters 113
6.4.1 Introduction 113
6.4.2 Dopaminergic Effects 114
6.4.2.1 Amphetamine 114
6.4.2.2 Neuroleptics/Antipsychotics 114
6.4.3 Adrenergic Effects 115
6.4.3.1 Amphetamine 115
6.4.3.2 Mazindol and Diethylpropion 115
6.4.3.3 Ciclazindol and other Agents 116
6.5 Anorexigenic Drugs Acting on
Serotoninergic Neurotransmission 116
6.5.1 Fenfluramine Congeners 116
6.5.2 Peripheral Effects of Fenfluramine 117
6.5.3 Serotonin and Satiety 118
6.6 Anorexigenic Drugs Acting
on Opioidergic Systems 118
6.7 Clinical Effects of Obesity-Related Drugs Acting
on Catecholamine or Serotonin Neurotransmission 119
6.7.1 Overview 119
6.7.2 Efficacy and Safety 119
6.7.3 Newer Adrenergic Agents 121
6.7.4 Newer Dopaminergic Agents 121
6.7.5 Newer Serotoninergic Agents 121
6.7.6 L-DOPA 123
6.7.7 Adrenergic/serotoninergic
Combination Therapies 123
6.8 GABA-ergic Anorexigenic Agents 124
6.9 Anorexigenics Acting at
Benzodiazepine Receptors 124
6.10 Opioidergic Anorexigenics 124
6.11 Local Anaesthetics 125
6.12 Prostaglandins 126
6.13 Anticonvulsants and Muscle Relaxants 126
6.14 Miscellanous Non-peptide Anorexigenics 126
6.15 Peptide Anorexigenic Agents 127
6.15.1 Introduction 127
6.15.2 Human Chorionic Gonadotrophin (hCG) 128
6.15.3 Cholecystokinin (CCK) 128
6.15.4 Bombesin 129
6.15.5 Pancreatic Polypeptide (PP) 130
6.15.6 Glucagon and Insulin 130
6.16.7 Amylin 131
6.15.8 Neurotensin 132
6.15.9 Somatostatin 132
6.15.10 Peptide Releasing Factors 132
6.15.11 Satietins 133
6.15.12 Adipsin 134
6.15.13 Cytokines 136
6.15.14 Calcitonin 137
6.15.15 Miscellaneous Peptides 138
CHAPTER 7 AGENTS WHICH AFFECT NUTRIENT HANDLING
7.1 Introduction 139
7.2 Agents Affecting Food Absorption 139
7.2.1 Introduction 139
7.2.2 Perfluorooctyl Bromide 139
7.2.3 Acarbose 139
7.2.4 Other ŕ-glucosidase Inhibitors 140
7.2.5 Lipase Inhibitors 140
7.3 Agents Affecting Peripheral
Energy Storage 141
7.3.1 Introduction 141
7.3.2 ŕ-Adrenergic Antagonists 141
7.3.3 Inhibitors of Insulin Secretion 141
7.3.4 Oral Hypoglycaemic Agents 142
7.3.5 Inhibitors of Lipogenesis
and Fat Accumulation 142
7.4 Thermogenic Drugs 143
7.4.1 Introduction 143
7.4.2 Relationship of Metabolic
Rate to Weight Gain 143
7.4.3 Review of Oxidative
Phosphorylation 144
7.4.4 Uncoupling Agents 145
7.4.5 Brown Adipose Tissue (BAT)
and Thermogenin 145
7.4.6 Overfeeding and Thermogenesis 146
7.4.7 Is BAT Relevant in Human Beings? 147
7.4.8 Other Forms of Thermogenesis 147
7.4.9 Survey of Thermogenic Agents 147
7.4.9.1 Thyroid Hormones 147
7.4.9.2 Ephedrine, Methyl-
xanthines, and Aspirin 150
7.4.9.3 Dehydroepiandrosterone (DHEA) 151
7.4.9.4 New Thermogenic
á-adrenergic Agonists 153
7.4.9.4.1 Overview 153
7.4.9.4.2 Efficacy in Animal and
Clinical Studies 153
7.4.9.4.3 Site and Mechanism
of Thermogenesis 154
7.4.9.4.4 Thermoselectivity 155
7.4.9.4.5 Nutrient Repartitioning Effect 155
7.4.9.5 Other Thermogenic Agents 156
CHAPTER 8 MARKETS AND COMPANIES
8.1 Introduction 157
8.2 Market Potential of
Anti-obesity Drugs 157
8.3 Market Potential in Anorexic
States and Bulimia 158
8.4 Market Summary 159
8.5 How Much is the Market Worth? 160
8.6 Which Anti-obesity Products
will Succeed? 161
8.7 Company Profiles 162
8.7.1 Abbott Laboratories Incorporated 162
8.7.2 American Home Products Corporation 163
8.7.3 Bayer Aktiengesellschaft 164
8.7.4 California Biotechnology Incorprated 165
8.7.5 Ciba-Geigy Aktiengesellschaft 166
8.7.6 Genentech Incorporated 167
8.7.7 Eli Lilly & Company Incorporated 169
8.7.8 Merck & Company Incorporated 170
8.7.9 Novo-Nordisk AS 170
8.7.10 Pfizer Incorporated 171
8.7.11 Roche Limited 172
8.7.12 Sandoz Limited 174
8.7.13 G.D Searle & Company Incorporated 175
8.7.14 SmithKline Beecham PLC 176
FURTHER READING 179
APPENDIX 1: COMPOUNDS REFERRED TO BY ALPHANUMERIC CODES A1
APPENDIX 2: COMPOUNDS REFERRED TO BY GENERIC/CHEMICAL NAMES A4
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