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Frontiers in Clinical Drug
Research- Diabetes & Obesity
(Volume 7)
Edited by
Shazia Anjum
Institute of Chemistry
The Islamia University of Bahawalpur
Bahawalpur
Pakistan
)URQWLHUVLQ&OLQLFDO'UXJ5HVHDUFK±'LDEHWHVDQG2EHVLW\
Volume # 7
Editor: Shazia Anjum
ISSN (Online): 2352-3220
ISSN (Print): 2467-9607
ISBN (Online): 978-981-5123-58-6
ISBN (Print): 978-981-5123-59-3
ISBN (Paperback): 978-981-5123-60-9
©2023, Bentham Books imprint.
Published by Bentham Science Publishers Pte. Ltd. Singapore. All Rights Reserved.
First published in 2023.
BSP-EB-PRO-9789815123586-TP-215-TC-06-PD-20230320
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BSP-EB-PRO-9789815123586-TP-215-TC-06-PD-20230320
CONTENTS
PREFACE ................................................................................................................................................ i
LIST OF CONTRIBUTORS .................................................................................................................. ii
CHAPTER 1 CLINICAL AND DIAGNOSTIC IMPLICATIONS OF GLYCATED ALBUMIN
IN DIABETES MELLITUS: AN UPDATE .......................................................................................... 1
Km Neelofar, Jamshed Haneef and Farah Khan
INTRODUCTION .......................................................................................................................... 1
Non-enzymatic Glycation ....................................................................................................... 2
Non-enzymatic Glycation in Diabetes .................................................................................... 3
Human Serum Albumin .......................................................................................................... 4
Albumin Structure Upon Glycation ........................................................................................ 6
Biological Properties of Albumin Upon Glycation ................................................................ 7
Immunological Properties of Albumin Upon Glycation ......................................................... 8
Glycated Albumin as a Diagnosis Marker .............................................................................. 9
Glycated Albumin Measurements ........................................................................................... 11
CONCLUDING REMARKS ......................................................................................................... 13
CONSENT FOR PUBLICATION ................................................................................................ 13
CONFLICT OF INTEREST ......................................................................................................... 13
ACKNOWLEDGEMENTS ........................................................................................................... 13
REFERENCES ................................................................................................................................ 13
CHAPTER 2 CURRENT STRATEGIES OF NEW DRUGS FOR DIABETES MANAGEMENT 22
Maliha Sarfraz, Rahman M. Hafizur, Hayat Ullah, Sanaullah Sajid, Rana Waseem
Akhtar, Mamoona Noreen, Shazia Perveen and Misbah Ullah Khan
INTRODUCTION .......................................................................................................................... 23
CURRENT TREATMENTS FOR TYPE-2 DIABETES MELLITUS ...................................... 25
Thiazolidinediones .................................................................................................................. 25
Biguanide ................................................................................................................................ 26
Sulfonylureas .......................................................................................................................... 26
Meglitinides ............................................................................................................................ 27
SGLT2 Inhibitors .................................................................................................................... 28
Insulin ..................................................................................................................................... 28
Incretin Mimetics .................................................................................................................... 30
COMPLEMENTARY TREATMENTS FOR THE MANAGEMENT OF T2D ...................... 30
NATURAL PRODUCTS WITH ANTI-DIABETIC PROPERTIES ......................................... 31
CURRENT AND FUTURE THERAPIES FOR TYPE 1 DIABETES ...................................... 33
STEM CELL THERAPEUTIC APPROACH ............................................................................. 34
NANOTECHNOLOGY AND DIABETES ................................................................................... 36
EMERGING TECHNOLOGIES FOR DIABETES TREATMENT ......................................... 37
CONCLUSION ............................................................................................................................... 38
FUTURE PERSPECTIVES ........................................................................................................... 39
CONSENT FOR PUBLICATION ................................................................................................ 40
CONFLICT OF INTEREST ......................................................................................................... 40
ACKNOWLEDGEMENTS ........................................................................................................... 40
REFERENCES ............................................................................................................................... 40
CHAPTER 3 DIABETES TYPE II: SHOULD ASPARTAME BE A CONCERN? ....................... 48
Arbind Kumar Choudhary
BACKGROUND ............................................................................................................................. 48
Aspartame and Weight Management ...................................................................................... 50
Aspartame and Glucose Intolerance ....................................................................................... 50
Aspartame and Insulin Resistance .......................................................................................... 52
CONCLUSION ............................................................................................................................... 53
CONSENT FOR PUBLICATION ................................................................................................ 53
CONFLICT OF INTEREST ......................................................................................................... 53
ACKNOWLEDGEMENTS ........................................................................................................... 53
REFERENCES ............................................................................................................................... 54
CHAPTER 4 MENTAL HEALTH, ADHERENCE, AND SELF-MANAGEMENT AMONG
CHILDREN WITH DIABETES ............................................................................................................ 59
Beáta Erika Nagy, Brigitta Munkácsi and Karolina Eszter Kovács
INTRODUCTION .......................................................................................................................... 60
MENTAL HEALTH AND T1DM ................................................................................................. 60
Quality Of Health And Diabetes ............................................................................................. 60
Self-Rated Health In Diabetes ................................................................................................ 64
Illness Representations ............................................................................................................ 65
FACTORS INFLUENCING ADHERENCE ............................................................................... 66
Adherence In Adolescence ..................................................................................................... 67
Factors Influencing Diabetes-Specific Adherence .................................................................. 69
The Characteristics Of The Illness And The Related Factors ....................................... 70
Intrapersonal Factors ................................................................................................... 71
Interpersonal Factors .................................................................................................... 72
Environmental Factors .................................................................................................. 72
THE PURPOSE OF THE STUDY: THE CONNECTION BETWEEN MENTAL HEALTH,
ADHERENCE AND DIABETES .................................................................................................. 73
Sample Characteristics ............................................................................................................ 73
Experimental Group: Children Diagnosed With Type-1 Diabetes ............................... 74
Control Group ............................................................................................................... 77
Applied Tools .......................................................................................................................... 78
Demographic Questions .......................................................................................................... 78
The Creation of the Diabetes-Specific Adherence Questionnaire .......................................... 78
The Factor Analysis Of The Questionnaire .................................................................. 79
Children Depression Inventory (CDI) [133] ........................................................................... 81
World Health Organization Well-Being Index (WBI-5) [134] ............................................... 81
Self-rated Health (SRH) [135] ................................................................................................ 81
Psychological Mood and Somatic Symptoms [136] ............................................................... 81
Satisfaction with Life, SWL-present (SWL-p) SWL-future (SWL-f), Cantril-ladder [137];
Life Evalution Index [138] ...................................................................................................... 82
Pediatric Quality of Life Inventory, PedsQL Measurement Model [139, 140] ...................... 82
Satisfaction with Life Scale (SWLS) [141] ............................................................................ 83
Strengths and Difficulties Questionnaire (SDQ) [142] ........................................................... 83
Research Questions and Hypotheses ...................................................................................... 83
RESULTS ........................................................................................................................................ 84
The General Description of Adherence .................................................................................. 84
The Relationship Between Adherence and the Indexes of Mental Health ............................. 89
Psychological Factors Influencing Adherence ........................................................................ 93
SUMMARY ..................................................................................................................................... 100
Sociodemographic Factors Influencing Adherence ................................................................ 101
Psychological Factors Influencing Adherence ........................................................................ 102
CONCLUSION ............................................................................................................................... 103
CONSENT FOR PUBLICATION ................................................................................................ 105
CONFLICT OF INTEREST ......................................................................................................... 105
ACKNOWLEDGEMENTS ........................................................................................................... 105
REFERENCES ............................................................................................................................... 105
CHAPTER 5 RECENT TRIALS ON THE CARDIOPROTECTIVE EFFECTS OF NEW
GENERATION ANTI-DIABETIC AND LIPID-LOWERING AGENTS ........................................ 117
Omar M. Abdelfattah, Ahmed Sayed, Anas Al-Refaei, Jasmin Abdeldayem, Khaled
Moustafa, Nicholas Elias and Yehia Saleh
INTRODUCTION .......................................................................................................................... 118
SODIUM/GLUCOSE COTRANSPORTER-2 INHIBITORS (SGLT2I) .................................. 128
History, Mechanisms, and Pleiotropic Effects of SGLT2i ..................................................... 128
Pivotal Clinical Trials Involving SLGT2i ............................................................................... 129
Dual SGLT1/2 Inhibitors: The Next Step in the Evolution of SGLT2i? ................................ 131
INCRETINS .................................................................................................................................... 133
History of Incretins and their Mechanisms of Action ............................................................. 133
Safety and Efficacy of DDP-4i ............................................................................................... 134
Trials Evaluating the Safety and Efficacy of GLP-1ras .......................................................... 136
Summary and Synthesis of the Literature on Incretins ........................................................... 139
INSULIN .......................................................................................................................................... 142
A Historical Overview of the Discovery of Insulin ................................................................ 142
The Role of Glycemic Control In Outcome-optimization and a Discussion of Trials on
Recent Insulin Formulations ................................................................................................... 142
ALPHA-GLUCOSIDASE INHIBITORS ..................................................................................... 145
THIAZOLIDINEDIONES ............................................................................................................. 145
Comparison of the Different Novel Modalities and Critical Gaps in the Literature .............. 147
LIPID-LOWERING THERAPIES STATINS ............................................................................. 148
Historical Context and Foundational Trials (Pre-2010) .......................................................... 148
Contemporary Analyses and Trials (2010 and Onwards) ....................................................... 150
PCSK9 INHIBITORS .................................................................................................................... 151
Rationale and Initial Discoveries ............................................................................................ 151
Trials Demonstrating LDL-Lowering Efficacy ...................................................................... 152
Evidence of Clinical Efficacy and Reduction of Hard Outcomes .......................................... 153
OMEGA-3 FATTY ACIDS ........................................................................................................... 155
CONCLUSION ............................................................................................................................... 157
CONSENT FOR PUBLICATION ................................................................................................ 158
CONFLICT OF INTEREST ......................................................................................................... 158
ACKNOWLEDGEMENTS ........................................................................................................... 158
REFERENCES ............................................................................................................................... 158
CHAPTER 6 DIABESITY AND THE KIDNEY ............................................................................... 168
Mohamed E. Elrggal, Ahmed Elkeraie, Sol Carriazo, Hany Sawaf, Si Yuan Khor,
Yasmine Elkeraie, Issa Haddad, Khaled Moustafa and Mohamed Hassanein
INTRODUCTION .......................................................................................................................... 168
Epidemiology and Genetic Aspects Shared in Diabesity and Kidney Diseases ..................... 171
Pathophysiologic Mechanisms Cross-linking Diabesity and Kidney Diseases ...................... 173
Obesity ........................................................................................................................... 173
Diabetes ......................................................................................................................... 174
Diabesity ....................................................................................................................... 176
Non-Pharmacological Management ............................................................................. 178
A. Exercise .............................................................................................................................. 178
B. Dietary Therapy .................................................................................................................. 178
C. Behavioral Modifications ................................................................................................... 179
Pharmacological Treatment for the Management of Diabesity and Related Kidney
Disease .......................................................................................................................... 179
ANTI-DIABETIC MEDICATIONS ............................................................................................. 180
GLP-1 Receptor Agonists ....................................................................................................... 180
Liraglutide ..................................................................................................................... 181
Dulaglutide .................................................................................................................... 182
Semaglutide ................................................................................................................... 182
SGLT2 Inhibitors ........................................................................................................... 184
Metformin ...................................................................................................................... 184
ANTI-OBESITY MEDICATIONS ............................................................................................... 185
Orlistat ..................................................................................................................................... 185
Phentermine/topiramate .......................................................................................................... 185
Naltrexone/bupropion ............................................................................................................. 186
Surgical Options to Control Diabesity and Kidney Disease ......................................... 187
Future Pipeline Treatment ............................................................................................ 190
Tirzepatide ..................................................................................................................... 190
Cotadutide ..................................................................................................................... 192
Amylin Analogs ............................................................................................................. 192
Leucine/Metformin/Sildenafil Combination .................................................................. 193
CONCLUSION ............................................................................................................................... 193
CONSENT FOR PUBLICATION ................................................................................................ 193
CONFLICT OF INTEREST ......................................................................................................... 194
ACKNOWLEDGEMENTS ........................................................................................................... 194
REFERENCES ............................................................................................................................... 194
SUBJECT INDEX
....................................................................................................................................
20
PREFACE
Causes of diabetes are so complex but type II diabetes is directly linked with obesity at any
time of your age particularly if you have excessive fats around your tummy. Obesity triggers
your body’s metabolism which causes fat tissues to release fats into your blood that directly
affect insulin response and make you insulin sensitive- that’s why obesity causes prediabetes.
In order to understand this complex pathological disorder in our body and thereafter solutions
to surpass this challenge, volume 7 of our eBook series is dedicated to cutting-edge articles on
Diabetes or Obesity. The update can be found in the first chapter of this present volume that
non-enzymatic glycation of proteins, lipids, and fatty acids speeds up due to persistent
hyperglycemia and eventually causes associated secondary complications in diabetes.
The authors in the second chapter describe the current strategies of new drugs for diabetes
management. For example, the development of novel therapeutic groups such as amylin
analogs, incretin mimetics, GIP analogs, active peroxisome proliferator receptors, and
dipeptidyl peptidase-4 inhibitors and as well as bioactive compounds from herbs.
The third chapter of this series deals with the debatable topic of using aspartame for T2D
patients. More research is still needed to establish the pathological role of aspartame use in
T2D.
Chapter four of this volume covers the research to investigate the psychological
characteristics and adherence of children and adolescents with Type 2 diabetes. A joint
venture of the Faculty of Medicine and Faculty of Arts has developed that mapping mental
health and various therapeutic procedures, as well as their positive and negative effects, are of
paramount importance for both diabetes and obesity.
i
The fifth chapter of this volume is about the clinical trials of new-generation anti-diabetic and
lipid-lowering agents that also have simultaneously cardioprotective effects.
The sixth chapter of this volume describes that the kidneys are a vulnerable target of
diabesity. In this chapter, the epidemiology, pathophysiology, and treatment of
diabesity–induced kidney disease are discussed. The special focus on the therapeutic targets
and pharmacological management of diabesity-related kidney diseases is described herein.
I hope that the current volume of this series will provide updated information about the recent
developments in Diabetes & Obesity treatment for interested researchers and pharmaceutical
scientists. I would like to thank the editorial staff, particularly Mr. Mahmood Alam (Director
Publications) and Ms. Asma Ahmed (Senior Manager Publications) for their dedicated efforts
and the hard work.
Shazia Anjum
Institute of Chemistry
The Islamia University of Bahawalpur
Bahawalpur
Pakistan
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