Obesity and Diabetes: Scientific Advances and Best Practice

Foreword
Preface
Contents
Part I: Epidemiology, Inheritance, Environment and Pathways
Chapter 1: Introduction to Obesity and Diabetes: The Windows of Opportunity
The Problem
The Solution
Pediatric and Adult Obesity
Obesity-Induced Prediabetes or Diabetes
State of the Art
The Three (or Five) Trillion Dollar Question
Market Stratification
Ongoing Initiatives
Final Considerations
References
Chapter 2: Nutrition Transition and Obesity Trends in Argentina Within the Latin American Context
Understanding the Path to the Obesity Epidemic
The Population Context
Worldwide Changes in Recent Decades
The Burden of Obesity Worldwide
General Dietary Patterns
Findings in Latin America
Focus on Argentina
Highly Processed Foods
Physical Activity Patterns
Disease Burden
Public Health Interventions and Future Perspectives
Childhood Undernutrition and Adult Obesity
References
Chapter 3: Challenges and Economic Burden of Diabetes in Africa
Introduction
Social and Financial Burden
Challenges to Diabetes Management in Africa
Epidemiological transitions:
Access to Health Care
Knowledge, Beliefs, and Health Seeking Behaviors in Africa
Lack of Political Will
Under-Allocation of Resources
Complications and Mortality Attributable to Diabetes
Prevalence and Incidence of Diabetes Complications
Disability and Mortality
Economic Burden of Diabetes Mellitus
Costs Attributable to Diabetes Mellitus in Africa
Purchasing Power Parity Calculations
Direct Cost
Profile of African Countries
Indirect Cost
Intangible Cost
Cost of Diabetes Complications
Comparative Health Care Expenditures in Africa
Perspectives
National Diabetes Programs (NDPs)
Sustainable Development Goals
Universal Health Coverage (UHC)
References
Chapter 4: Brown Adipose Tissue in Obesity and Diabetes
Adipose Tissue Classification: Types, Location, and Function
Clinical Measurement of Brown Adipose Tissue
Positron Emission Tomography (PET) Imaging
Magnetic Resonance (MR)
Preclinical Imaging Techniques (Thermometry, Ultrasound, and Near-Infrared Spectroscopy)
Ultrasonography
Near-Infrared Spectroscopy (NIRTRS)
Secretory Activity of Brown Adipose Tissue
Brown Adipokines or ``Batokines´´
Batokines and Transplantation
Brown Adipose Tissue Signaling to Other Tissues
Neuroendocrine Regulation of Brown Adipose Tissue
Sympathetic BAT Innervation
Experimental Denervation
Sensory Innervation of BAT
Adipose Tissue Dysfunction in Obesity and Diabetes
Sick Fat
The WAT Expandability Hypothesis
Brown Adipose Tissue in Obesity and Diabetes
BAT Dysfunction During Obesity
Therapeutic Perspectives for Brown and White Adipose Tissue Manipulation
Chemical Activation of BAT
Bat Transplantation
Direct BAT Grafting
Promises and Pitfalls of Human BAT Transplantation
References
Chapter 5: White and Brown Adipose Tissue in Obesity and Diabetes
Distribution and Functions of Human Adipose Tissue
White Adipose Tissue
Brown Adipose Tissue
Anatomical Sites
Beige Adipose Tissue
White Adipose Tissue and Insulin Resistance
Glucose Homeostasis Crosstalk
Inflammatory Adiposopathy
Ectopic Fat Depots
Activation of Human Brown Adipose Tissue
Cold Exposure Techniques
Exercise Activation
Food Intake and Thermoregulation
Role of Brown Fat in Human Metabolism in Healthy, Obese, and Diabetic Individuals
BAT Hormone-Like Secretions
Correlations with Obesity and Diabetes
Methods for Detecting Human Brown Adipose Tissue
Monitoring of Skin Temperature
Radiolabeled Glucose Analog
Tracer and Imaging Alternatives
Immunohistochemical or Gene-Expression Confirmation
Future Investigations into Human Brown Adipose Tissue Physiology
Dietary Components
Pharmaceutical Compounds
Gut Microbiota as a New Target to Combat T2D
Future Perspectives
References
Chapter 6: microRNAs in Obesity and Metabolic Diseases
Obesity: The Worldwide Epidemic
White Adipose Tissue: An Overview
Adipose Tissue Proliferation
miRNAs: Small RNAs with a Big Role in Gene Regulation
Epigenetic Control Mechanisms
miRNAs in Multicellular Organisms
Transcriptome Sculpting
miRNA Biogenesis and Action Mechanisms
Detection of miRNAs
miRNAs Target Prediction
miRNA in Obesity and Obesity-Associated Comorbidities
Role of miRNAs in Adipose Tissue
Adipogenesis Pathways
Let-7 miRNA and Diabetes Prevention
Other Tissue-Specific miRNAs and Metabolic Diseases
Adipose Tissue Cross Talk and miRNAs
Intercellular Message Signaling
Role of miRNAs in the Pancreas
Additional Pancreatic Activities of miRNAs
Role of miRNAs in the Muscle
Insulin Resistance
Myocardial Metabolism
Role of miRNAs in the Liver
Additional miRNAs
Circulating miRNAs
Anti Nuclease Protection
Circulating miRNA in Obesity, Diabetes and Associated Conditions
Blood Glucose, Blood Pressure and Metabolic Syndrome
Bariatric Surgery
Pediatric Protocols
Translational Considerations
References
Chapter 7: From Adipogenic Viruses to Antidiabetic Drug: A Translational Journey
Introduction
Infectobesity
SMAM-1 Adenovirus
Human Adipogenic Virus: Adenovirus 36
Ad36 Improves Glycemic Control
Mechanism of Ad36 Action
Virus-Induced Obesity: A Causative Role in Humans
Exploiting the Antidiabetic Property of Ad36
Possibilities for Therapeutic Administration
Summary
References
Chapter 8: Genetic Profiles in the Obese Population
Introduction
Monogenic Obesity
Homeostatic Pathways Involved in the Regulation of Appetite and Satiety
Non-syndromic Form of Obesity
Leptin Gene Aberrations
Leptin Receptor Disorders
Clinical Profile
The Melanocortin Pathway
Syndromic Form of Obesity
Prader Willi Syndrome
Bardet-Biedl Syndrome
Alstrom and Cohen Syndrome
Polygenic or Common Obesity
Relevant Candidates
Ongoing Studies and Future Perspectives
References
Chapter 9: The Upstream Environment for the Obesity Epidemic
Introduction: The Obesity Epidemic
Comorbidities of Obesity
Environment and Obesity
Sprawl
Food Access
Exercise Access and Physical Activity
Neighbourhood Social Environment
Environment and Diabetes
Spatio-Temporal Aspects of Obesity
Conclusion: Unresolved Issues and Future Perspectives
References
Chapter 10: Inflammation and Its Role in Obesity-Related Complications
Introduction
Inflammation and Innate Immunity
Intertwined Relation of Obesity and Inflammation
Intestinal Dysbiosis and Obesity
High-Calorie Diet and Inflammation
Nonbacterial Dietetic Immunogens and Inflammation
Factors Responsible for Inflammation in Obesity
Genetic and Epigenetic Factors
MicroRNAs
Cellular Links Between Obesity and Inflammation
Adipocytes
Treg Cells
γδ T Cells
B Lymphocytes
Myeloid Cells
Molecular Mediators of Obesity and Inflammation
TNF-α
IL-1β
Adiponectin and Leptin
Secreted Frizzled-Related Protein 5
Obesity, Inflammation and Cancer
Liver Cancer
Pancreatic Cancer
Colorectal Cancer
Therapeutic Approaches for Obesity and Inflammation
Probiotics and Phytochemicals
Cell-based Therapy
References
Chapter 11: Crosstalk Between Adipose Tissue, Macrophages, and Other Immune Cells: Development of Obesity and Inflammation-ind...
Introduction
Adipose Tissue as a Source of Inflammation
Tumor Necrosis Factor α
Interleukin-6
Monocyte Chemoattractant Protein-1 (MCP-1)
Adipocytokines: A Linking Mediator Between Adipose Tissue, Inflammation, and Immunity
Normal vs. Sick Fat
Orchestration of Inflammatory Responses
Immune Cell Recruitment
Macrophages
Dendritic Cells (DCs)
Lymphocytes
Regulatory T (Treg) Cells
Unconventional Lymphocytes
iNKT Cells
gammadelta T Cells
Innate Lymphoid Cells (ILCs)
Metabolic Regulation of Adipose Tissue-residing Immune Cellsin Different Disease Conditions
Arterial Hypertension
Atherosclerosis
Insulin Resistance and Diabetes
References
Chapter 12: Diabetes Forecasts and Statistics for the Coming Decades
Introduction
Global Profile of the Diabetes Epidemic
Decreased Diabetes Incidence in the USA
The Elderly Population
Gender and Social/economic Profiles
Demographic Patterns
Worldwide Estimations for 2040
Public Health Challenges
Diabetes Complications
Direct and Indirect Costs
Outlook for the Next 30 Years
Improved Screening, Diagnosis, and Prognosis
References
Chapter 13: Pancreatic Islets of Langerhans: Adapting Cell and Molecular Biology to Changes of Metabolism
The Pancreatic Islet
Cytoarchitecture, Vascularization, Innervation, and Paracrine Interactions
Postnatal Pancreas
Role of Nonbeta Islet Cells
Beta-cell Proliferation
Insulin Synthesis
Insulin Output Modulation
Signaling Pathways Related to Insulin
Glucose Transporters
Islet Transplantation and Stem-cell Differentiation
Stem Cell Sources
Alpha-cell Plasticity
Regenerative Medicine
The Beta-cells Mass
Beta Cell Mass Increase
Pancreatic Islets in Obesity and Intermittent Fasting
Fasting and Glucotoxicity
Cellular Effects
Fasting and Refeeding Sequence
References
Chapter 14: Targeting Advanced Glycation End Products (esRAGE and sRAGE) for Obesity, Diabetes, and its Associated Complicatio...
Introduction
Concept of Obesity
Type 2 Diabetes Mellitus
Hypertension, Dyslipidemia, and Cardiovascular Disease
Atherosclerotic Cardiac Disease
Cancer
Other Comorbidities
Lifestyle, Pharmacotherapy, and Surgery
The Advanced Glycation End Products (AGEs)-Receptor for Advanced Glycation End Products (RAGE) System
Oxidative Damage
Dietary Imbalance
The RAGE Family
esRAGE and sRAGE Signaling
Correlation with Comorbidities
Obesity and Diabetes
Therapeutic Interventions
References
Chapter 15: Anti-incretin Effect: A Missing Link between Obesity, Diabetes, and Metabolic Surgery
Introduction
The Anti-incretin Theory
Early Response to Dysglycemia after Bariatric Surgery
Post-bariatric Hypoglycemia
Potential Pathways and Molecules
Dopamine
Ghrelin
Other Molecules
Correlation with Diabetes and Obesity Remission Following Metabolic Surgery
Enhancement of Pancreatic Beta-cell Mass
Future Perspectives
References
Part II: Genomics, Metabolomics and Other Omics
Chapter 16: An Update on Mendelian Forms of Obesity and their Personalized Treatments
Introduction
Leptin Deficiency
Leptin Receptor Deficiency
Proopiomelanocortin Deficiency (POMC)
Proprotein Convertase 1 Deficiency (PC1)
Melanocortin 3 Receptor Deficiency (MC3R)
Melanocortin 4 Receptor Deficiency (MC4R)
Kinase Suppressor of Ras 2 Deficiency (KSR2)
Melanocortin 2 Receptor Accessory Protein 2 (MRAP2) Deficiency
Adenylate Cyclase 3 (ADCY3) Deficiency
Steroid Receptor Coactivator-1 (SRC-1) Deficiency
Semaphorin 3 Signaling Deficiency
An Overview of Current Treatments of Obesity in Child and Adult Populations
Lifestyle Modifications
Behavioral Modifications
Pharmaceuticals
Bariatric Surgery
Diagnosis and Treatments of Mendelian Forms of Obesity
Diagnosis of Nonsyndromic Monogenic Obesity
Personalized Management of Nonsyndromic Monogenic Forms of Obesity
Bariatric Surgery in Monogenic Obesity
References
Chapter 17: The Genetic Basis of Diabetic Kidney Disease
Introduction
Pathophysiology of DKD in T1D and T2D
Nondiabetic Kidney Deterioration
Disease Trajectory
The Genetic Architecture of DKD through GWASs
Combined Databases
Coding vs Noncoding Variants
Ethnic Patterns
Contributions of Low Frequency and Rare Variations in DKD Patients
Statistical Challenges
From Genetic Causes of DKD to Personalized Therapies
Angiotensin Modulators
Future Directions
Epigenomics
References
Chapter 18: Epigenetics and Chronic Inflammation: Role in Early Detection of Type 2 Diabetes
Introduction
Metabolic Memory
Adipose Tissue Changes and Cytokine Expression
Chronic Inflammation and Insulin Resistance
Epigenetics of T2D
Hyperglycemia and Epigenetics
Investigations in Twins
Epigenetic Wide Association Studies
Noncoding RNA
MicroRNAs in Type 2 Diabetes and Inflammation
Long Noncoding RNA in Type 2 Diabetes
Noncoding RNAs as Therapeutics Targets
High Fat Diet and Polyphenols
Beta Cell Dysfunction
Early Detection/Relative Risk Tests
Ongoing Clinical Trials
References
Chapter 19: Salivary and Urinary Metabolome in Pediatric Obesity and Metabolic Syndrome
Introduction
Metabolic Features of Pediatric Obesity and MetS
Urine and Salivary Pathways and Biomolecules
Saliva Production
Urine Production
Salivary and Urinary Metabolome
Salivary Metabolome
Urinary Metabolome
Small Intestinal Bacterial Overgrowth
Potential Targets for New Drug Development
Phytotherapeutic Agents
Gut Microbiota Interventions
Ongoing Studies
References
Chapter 20: `State-of-the-Art´ Metabolomics Investigations of Type 2 Diabetes
The Role of Metabolomics
The Normal and Pathological Metabolome
Targeted vs. Untargeted Approach
Biomarkers of Type 2 Diabetes
Serum and Plasma Biomarkers
Amino Acids and Phospholipids
Prognostic Metabolites
Saliva
Acetone and Lactate
Other Biomolecules
Oral Diseases and Other Confounding Factors
Sample Contamination
Urine
Disturbed Metabolic Pathways Involved in T2D Pathogenicity
Personal Experience: Retrospective Network Pathway Analysis of Published Data
Prognostic Fingerprints
Short vs. Long-term Glycemic Homeostasis
Kidney Dysfunction and Ketosis
Potential Bedside/´Point-of-Care´ Metabolomics
Future Developments
Bedside Devices
Metabolomic Panels
Portable Oral Prosthesis and Breath Volatolomic Analysis
Artificial Pancreas and Wearable Technology
References
Chapter 21: The Gut Microbiome and Type 2 Diabetes Mellitus
Introduction
The Disruptive Role of Antibiotics
Lipopolysaccharide (LPS)-associated Endotoxemia
Metformin and Gut Ecology
Metabolic Syndrome and Obesity
Inflammation
Composition of Gut Microbiota
Factors Involved in T2D Pathogenesis
Incretins
Short Chain Fatty Acids (SCFAs)
AMP-activated Protein Kinase (AMPK)
Metabolic Functions
Epithelial Barrier Impairment and Pro-Inflammatory Cytokines
Bile Acid Transformation
Gut Microbiome in Pathogenesis of T2D
Current Therapeutics
Bariatric Surgery
Prebiotics, Probiotics, and Synbiotics
Supplementation Meta-analyses
Other Perspectives
Fecal Microbiota Transplant (FMT)
Personalized Nutrient/Diet
Plant Extract-based Therapy
References
Chapter 22: Immunotherapeutic Approach to the Treatment and Prevention of Obesity
Introduction
Lifestyle Interventions
Pharmacological Management
The Role of Vaccines
Features of Therapeutic Vaccines
Ghrelin Vaccines
Vaccine Against Synthetic Ghrelin Peptides
Virus Like Particles (VLPs)
Nanogel-based vaccine
Glucose-dependent Insulinotropic Polypeptide (GIP) Vaccines
Adipocyte Vaccines
Somatostatin Vaccine
Adenovirus 36 (Ad36) Vaccine
Future Possibilities
References
Part III: Associated Disorders and Obesity Paradoxes
Chapter 23: Metabolic Syndrome Update
Introduction
Diagnosis: Conflicts and Regional Criteria
Worldwide Growth of Metabolic Syndrome
Involved Organs and Pathways
Mechanism of Insulin Action
Insulin Resistance and Molecular Events
Insulin Resistance and Cardiovascular Disease
Skeletal Muscle IR
Hepatic IR
Adipose Tissue IR
Lipotoxicity and Glucotoxicity
Role of Inflammation in Met S
Proinflammatory Cytokines
Thrombotic Mediators and Prooxidants Associated with Metabolic Syndrome
Is the Gut Microbiome Involved?
Microbe and Host Cell Cross Talk
Immune Activation in Dysbiosis
Genetic Links Determine Susceptibility to IR and Met S
Nutritional Genomics and Epigenetics in Met S
Possibilities of Prevention and Therapy
Ongoing Studies and Future Perspectives
References
Chapter 24: Non-alcoholic Fatty Liver Disease: A Global Public Health Issue
Worldwide Growth of Non-alcoholic Fatty Liver Disease
Correlations with Obesity, Diabetes, and Metabolic Syndrome
Obese and Nonobese NAFLD
NAFLD and Diabetes
The Natural Course of NAFLD
Coffee and Alcohol
Noninvasive Diagnostic Methods vs. Liver Biopsy
Single vs. Multiple Criteria
Imaging Tools
First-line Liver Fibrosis Assessment
Pathophysiology
Subsequent Steps
The Liver Damage Cascade
The Microbiota and the Gut Barrier Function
Disease-specific Variants
Lifestyle and Pharmacological Interventions
Bariatric Interventions
Drug Therapy
References
Chapter 25: Nonalcoholic Fatty Pancreatic Disease (NAFPD)
Introduction
The Spectrum of Metabolic Syndrome
Historical Notes
Nomenclature
Epidemiology
Pathogenesis of NAFPD-Obesity
Age
Metabolic Syndrome
beta-Cell Function
Other Possible Etiologies
Diagnosis
Confounding Variables
Transabdominal Ultrasound
Endoscopic Ultrasound (EUS)
CT Scan
MRI and MRS
Histology
Possible Complications-Metabolic Syndrome
Acute and Chronic Pancreatitis
Pancreatic Insufficiency
Pancreatic Fibrosis
Pancreatic Cancer
Surgical Risk
Treatment
Weight Loss
Oral Hypoglycemic Agents
References
Chapter 26: Normal-weight Obesity: A Hidden Pandemic
Introduction
Healthy Versus Unhealthy Lean and Obese Subjects
Prevalence of Normal-weight Obesity
Diagnostic Criteria for Normal weight obesity
Possible Contribution of Free Fatty Acids (FFAs)
Pathogenesis and Cardiometabolic Risk of Normal-weight Obesity
Metabolic Consequencesof Normal-weight Obesity
Liver Fat Accumulation
Fatty Pancreas
Normal-weight Central Obesity (NWCO)- A Similar Entity as Normal Weight Obesity
Abdominal Obesity
Epicardial Adipose Tissue (EAT)
Involved Pathways
Diagnostic Tools: Body Composition Analysis
Other Asian Populations
Metabolomic Research in Normal-weight Obesity
Genomic Sequencing
Therapeutics and Prevention of Normal-weight Obesity
Conclusion
References
Chapter 27: Obesity in Children/Adolescents and Obesity-Related Comorbidities
Pediatric Obesity: A Worldwide Concern
Definitions of Obesity
Epidemiologic Trends
Risk Factors
Primary vs. Secondary Causes of Obesity
Drug-induced Secondary Obesity
Genetic Risk Scores and Epigenetics
Clinical Evaluation
Lifestyle Interventions
Pharmacotherapy
Metabolic and Bariatric Surgery
Comorbidities and Long-term Follow-up
Cardiovascular Risk
Natural History of Atherosclerosis
Dyslipidemia
Management of Dyslipidemia
Hypertension
Salty Foods
Semi-vegetarian Diets
Insulin Resistance/Type 2 Diabetes
Severity of Adolescent T2D
Pediatric Prediabetes
Metabolic Syndrome
Polycystic Ovarian Syndrome
Nonalcoholic Fatty Liver Disease (NAFLD)
NAFLD Management
Non-cardiometabolic Comorbidities
Obstructive Sleep Apnea (OSA)
Musculoskeletal (MSK) issues
Vitamin D (VitD) deficiency
Psychological Impact and Considerations
Ongoing Studies and Future Perspective
References
Chapter 28: Obesity and Cancer: Linked Molecular Mechanisms
Introduction
Comorbidities
Biological Mechanisms Linking Obesity to Cancer
Hyperinsulinemia/Insulin Resistance
Sex Hormones
Adipokines and Cancer
Adiponectin and Cancer
Hypoadiponectinemia
Breast Cancer
Gastrointestinal Malignancies
Colorectal Cancer
Ovarian Cancer
Endometrial Cancer
Prostate Cancer
Low Chronic Inflammation
The Obesity Paradox in Cancer
Obesity and Therapy
Drug Dosage
Specific Cancer Therapies for Obese and Diabetic Patients?
Metformin
Thiazolidinediones (TZDs) and Other Agents
Therapies Targeting APN
Oral Adiponectin Receptor Agonist
Statins and Assorted Drugs
References
Chapter 29: Cognitive Impairment in Obesity and Diabetes
Introduction
Obesity, Cognitive Decline and Dementia
Type 2 Diabetes, Cognitive Decline and Dementia
Insulin Alterations, Inflammation and Oxidative Stress in Obesity/T2D
Additional Pathways
The Intestinal Microbiota and the Gut-brain Axis
Metabolic Endotoxemia
Neurotransmitters
Vascular Alterations in Obesity and/or T2D: More than an Oxygen Issue
Obesity and/or T2D are Associated with AD
Can Anti-obesity and Anti-T2D Therapy be Repurposed for AD?
Non Pharmacological Approaches
Pharmacological Approaches
References
Chapter 30: Metabolic Pathways Underlying Neuropsychiatric Disorders and Obesity
Introduction
Neuropsychiatric Disease and Obesity
Neuropsychiatric Disease and Obesity
Mood Disorders and Obesity
Schizophrenia and Obesity
Dementia and Obesity
Biological Mechanisms
Inflammation
Obesity-associated Insulin Resistance
Depression and Type 2 Diabetes
Alzheimer´s Disease, Insulin Resistance and Type 2 Diabetes
Hypercortisolaemia
Leptin / Leptin Receptor
Leptin and Dementia
Intestinal Microbiota
Microbiota Fingerprints in Metabolic and Psychiatric Disorders
Probiotics in Psychiatric Diseases
References
Chapter 31: Heart Failure and the Obesity Paradox
Current Status of Chronic Heart Failure
Heart Failure and Obesity
Prognosis in Decompensated Patients
Outcomes in Obese Patients
Possible Involved Pathways and Biomolecules
Anthropometric Measurements
Other Heart Chambers
Biohumoral and Neurohormonal Changes
Obesity Paradox
Cardiovascular Mortality
Risks of Bias in the Interpretation of the Paradox
Recommended Lines for Further Investigation
References
Chapter 32: Inflammatory Mechanisms in Diabetic Kidney Disease
Introduction
The Inflammatory Pathogenesis of Diabetic Kidney Disease
Conventional Therapeutic Interventions for the Treatment of Diabetic Kidney Disease
Arterial Hypertension
Healthy Lifestyle
New Therapeutic Approaches: Glucagon-Like Peptide-1 Receptor Agonists
Glucagon-Like Peptide-1 Receptor Agonist Trials
Dulaglutide
Liraglutide
Semaglutide
Lixisenatide
Exenatide
Glucagon-Like Peptide-1 Receptor Agonist Trials: Ongoing Kidney-Outcome Studies
Putative Mechanism of Observed Kidney Outcomes
Future Perspectives
References
Chapter 33: The Epidemiology of the Diabetes: Depression Comorbidity in Brazil-Inequality and Interaction
Introduction: Why Diabetes and Depression?
Box 33.1 Analysis of the Brazilian National Health Survey (PNS 2013)
Diabetes: Increasingly a Disorder of Poverty
Box 33.2 The Brazilian Context
The Social Patterning of Diabetes, Obesity and Depression in Brazil
Mechanisms of Health Inequalities
Differential Consequences
Interacting Comorbidity
Clustering
Differential Exposure
Obesity Patterns in Brazil
Gene Expression and Miscellaneous Mechanisms
Differential Vulnerability
The Impact of Obesity
Summarizing
References
Chapter 34: Contribution of Hyperglycemia and Unhealthy Diet to Cardiovascular Mortality
Obesity, a Risk Factor for Cardiovascular Disease
Chronic Inflammation
Dietary Pattern and Its Impact
The Mediterranean Paradigm
Metabolic Disease and Dysglycemia
Predisposing Factors tor Type 2 Diabetes
The Impact of Dyslipidemia
Endothelial Damage
General Biomarkers and Novel Technologies
New Biomarkers
Big Data and the Gut Microbiome
The Precision Medicine Approach
References
Chapter 35: Gestational Diabetes Mellitus
Gestational Diabetes: A Growing Problem
Other Metabolic Features of Pregnancy
Screening and Diagnosis
Managing Gestational Diabetes
Glucose Management
Dietary Interventions
Exercise Programmes
Contraindications to Exercise
Glucose-Lowering Medication and Supplements
Oral Therapy
Vitamins and Other Supplements
Future Prognosis for Mother and Child
Short-Term Outcomes
Long-Term Outcomes
Cardiovascular, Metabolic and Other Complications
Complications of the Newborn
Post-partum Screening and Care
Diet, Exercise and Metformin
Other Oral Drugs
The Multiple Advantages of Breastfeeding
Progression to Type 2 Diabetes
The Challenges of Effective Screening
E-Health and Postpartum Follow-Up
Summary
References
Chapter 36: Update on Gestational Diabetes
The Growing Prevalence of Gestational Diabetes
Additional Influences
Screening and Risk Evaluation
Classification of Gestational Diabetes
Obstetric and Pharmacologic Management
Dietary Guidance
Pharmacotherapy
Oral Glucose-Lowering Prescriptions: Metformin
Glyburide
Antenatal Fetal Testing
Indications for Ultrasonographic Monitoring
Optimal Delivery Time
Intrapartum Glucose Homeostasis
Complications and Follow Up
Additional Neonatal Aberrations
Long-Term Complications
Maternal Complications
Diagnostic Work Up and Long-Term Care
Ongoing Studies and Future Directions
References
Chapter 37: Vascular Complications in Type 2 Diabetes
Introduction
High-Risk Groups
Hypertension
Dyslipidemia
Diabetic Cardiomyopathy
Platelet Dysfunction
Clinical Features of Vascular Disease in Patients with Diabetes Mellitus
Atherosclerotic Disease
Coronary Artery Disease
Cerebrovascular Disease
Peripheral Artery Disease
Treatment
Lifestyle Modification
Hypertension
State of Art
Dyslipidemia
Fibrate Combination
Omega 3 Fatty Acids
State of the Art
Antiplatelet Therapies
Glucose-Lowering Therapies and Cardiovascular Disease
Glucose Lowering and Cardiovascular Disease
Hypoglycemia
Glucose-Lowering Agents and Cardiovascular Disease
Other Antidiabetic Molecules
Insulin Effects
Multifactorial Intervention
Bariatric and Metabolic Surgery
References
Part IV: General Therapy and Prevention
Chapter 38: What We Know and Don´t About High-Intensity Sweeteners
Introduction
High-Intensity Sweeteners
HIS: Beyond Calorie Restriction
Interactions with Sweet Taste Digestive Receptors and Insulin Secretion
HIS on Sweet Taste Receptors in the GI Tract
HIS and Insulin Response
Discrepancies in Obese Subjects
Impact on Appetite
Glucose Homeostasis
Energy Intake
Impact on Body Weight Management
Impact on Blood Glucose Management
Other Diseases or Abnormalities
Carcinogenesis
Disruption of Gut Microbiota
Cardiovascular and Kidney Disease
Total and Cardiovascular Mortality
Ongoing Studies and Future Perspectives
References
Chapter 39: Personalised Molecular Feedback for Weight Loss
Importance of Quantitative Biomarkers of Weight Loss
Advantages and Limitations of Internet and Mobile Resources
Dietary Tracking
Biomarkers for BMI and Adiposity
Metabolomic Markers
Biomarkers for Foods and Drinks
Phytotherapeutic Interventions
Appetite Regulation
Molecular Biomarkers in the Real World
Angiotensin-Converting Enzyme
Lactate and Insulin
Ongoing Investigations and Future Perspectives
Personalised Nutrition
References
Chapter 40: Diabetes and Obesity in the Child and Adolescent: Guidelines and Challenges
Background
Overview of Existing Guidelines and Recommendations
The Maternal and Child Health Bureau, Health Resources and Services Administration: 1998 Obesity Evaluation and Treatment-Expe...
AAP Guidance: 2007 Expert Panel and 2015 Algorithm for the Assessment and Management of Childhood Obesity in Patients 2Years a...
AAP Clinical Practice Guideline on the Management of Newly Diagnosed Type 2 Diabetes Mellitus (T2DM) in Children and Adolescen...
The Children´s Hospital Association Consensus Statement: 2014
Endocrine Society Clinical Practice Guideline: 2017 Pediatric Obesity-Assessment, Treatment, and Prevention: An Endocrine Soci...
The Obesity Medical Association: 2018 Pediatric Obesity Algorithm
American Diabetes Association (ADA): Evaluation and Management of Youth-Onset Type 2 Diabetes-A Position Statement: 2018
AAP Policy Statement: 2019 Pediatric Metabolic and Bariatric Surgery-Evidence, Barriers, and Best Practices
Issues with the Guidelines/Recommendations
Media Use
Failure to Address the Dramatic Increase in Youth Onset Type 2 Diabetes
The Lack of Pharmacotherapeutic Options for Children and Adolescents
Obstacles to Bariatric Surgery in the Adolescent with Obesity
Few Programs Providing Multidisciplinary Treatment for Youth with Obesity
Recognition of Rare Variants of Obesity
Failure to Recognize the Burden of Risk Factors as Children with Obesity Become Young Adults
Conclusions
References
Chapter 41: Type 2 Diabetes: An Unresolved Disease
Diabetes: A Historical Disease
Diabetes: A Disease of Many Faces
Type 1 Diabetes Mellitus
Neonatal Diabetes
Latent Autoimmune Diabetes of Adults (LADA)
Maturity-Onset Diabetes of the Youth
Gestational Diabetes Mellitus
Type 2 Diabetes Mellitus
Type 2 Diabetes Mellitus: A Spectrum of Dysglycaemic Profiles
Impaired Glucose Regulation
Type 2 Diabetes Mellitus Profile
Early Life Genetics and Epigenetics
Genetic Element
Diagnostic and Screening Testing
Obesity
Diabetes: From Historical Curiosity to a Serious Epidemic
Preventive Screening
References
Chapter 42: Glucose Control in the Intensive Care Unit
Introduction
Hyperglycemia and Outcome: A Causal Relationship or Not?
Harm by Iatrogenic Hypoglycemia?
How to Explain the Discrepant RCT Results?
Differences in Blood Glucose Targets
Different Protocols to Monitor Glucose and Administer Insulin
Different Feeding Protocols
Toward Precision Medicine?
Do Diabetes Patients Benefit from More Loose Blood Glucose Control?
An Individualized Target?
Strategies to Optimize Glucose Control
Decision-Support Software
Continuous Glucose Monitoring
Closed-Loop Glucose Control: The Artificial Pancreas
Conclusion
References
Chapter 43: Continuous Glucose Monitors as Wearable Lifestyle Behavior Change Tools in Obesity and Diabetes
Barriers to HbA1c Reductions
Continuous Glucose Monitoring
CGM Use in Type 1 Diabetes
Continuous Glucose Monitoring in Type 2 Diabetes
Continuous Glucose Monitoring in Nondiabetic Populations
Variability of Glucose Concentrations in Nondiabetic Populations
Acceptability of CGM in Nondiabetic Populations
Continuous Glucose Monitors as Lifestyle Behavior Change Tools
Dietary Modification
Food Diaries and Glucose Monitoring Feedback
Smartphone Apps
The Contribution of CGM Devices
Periodical Guided Analysis of CGM Records
Physical Activity Behavior
Weight Control
Hunger Training
Restored Glucose Homeostasis
Theory-Based Insights on Using CGM as Biological Feedback to Motivate Lifestyle Behavior Change
Future Opportunities for Continuous Glucose Monitorings
References
Part V: Innovative Endoscopic, Cell Therapy and Other Interventions
Chapter 44: Endoscopic Techniques for Obesity and Diabetes
Introduction
Gastric Aspiration: Aspire Assist
Space-Occupying Devices: Intragastric Balloon (IGB)
Type 2 Diabetes
Transpyloric Shuttle (TPS)
Gastric Reduction: Endoscopic Sleeve Gastroplasty (ESG)
POSE (Primary Obesity Surgery Endoluminal)
Endomina Method
Metabolic Procedures: Duodenal Mucosal Resurfacing (Fractyl)
Duodenal Jejunal Bypass Liner/DJBL (EndoBarrier)
Endoscopic Magnetic Partial Jejunal Diversion/EMPJD
References
Chapter 45: Bariatric Embolization: A Possible Non-surgical Option for Weight Reduction
Introduction
Current Techniques
Role of Interventional Radiology
Basis of Bariatric Embolization for Weight Loss
Appetite and Ghrelin Production
Stomach as an Endocrine Organ
Anatomy of the Gastric Fundus
Ghrelin Suppression After Gastric Bypass Surgery
Bariatric Embolization
Patient Selection
Vascular Access
Embolic Agents
Radiation Dose
Post-procedure Immediate Care
Long-Term Metabolic Effects
Combination Therapy with Clinical and Surgical Maneuvers
Ongoing Human Trials and Other Lines of Investigation
References
Chapter 46: Progress in Noninvasive Beta-Cell Mass Imaging
Introduction
Main Chronic Disorders Related to Beta-Cells
Glucotoxicity
Lipotoxicity
beta-Cell Mass in Human Obesity
Beta Cell Mass in T2D
Rodent Versus Human beta Cells
Cell Types
Beta-Cell Imaging
Histological Estimations
Noninvasive Imaging of Pancreatic beta Cells
Single Diagnostic Tools
Optical Imaging
Magnetic Resonance Imaging (MRI)
Radiopharmaceutical Imaging
Single Photon Emission Computed Tomography (SPECT)
Combined Diagnostic Tools
PET/MRI
SPECT/CT
Clinical Trials
References
Chapter 47: Cancer Staging with 18F-FDG PET/CT in Hyperglycemic Patients
Clinical Importance of 18F FDG PET/CT in Cancer Staging
Indications in Lymphomas
Carcinoma and Adenocarcinoma
Tumor Uptake and Hyperglycemia
Mechanism of [18F]FDG Uptake
Intracellular Pathways of Glucose and Labelled Glucose
Cancer Cell Pathways
Effects of Hyperglycemia on [18F]FDG Distribution and PET/CT Scan Interpretation
Diagnostic Strategies in Normal and Disglycemic Patients
Conclusions
References
Chapter 48: Pancreatic Islet Transplantation: A Surgical Approach to Type 1 Diabetes Treatment
Cost and Prevalence of Diabetes
Diabetes Pathophysiology
Exogenous Insulin Treatment
Islet Transplantation
Intrahepatic Duct Site
Clinical Autologous Islet Engraftment
Clinical Islet Allogenic Engraftment
Islet Graft Assessment
Clinical Islet Xenogeneic Engraftment
Long-term Challenges
Regulatory Issues
Acceptance by Hospital Personnel
Advances in Immunosuppression Regimes
Advances in Immunomodulatory Drugs
Enhancing Immunoisolation Technology
Microencapsulation of Islet Graft
Macroencapsulation
References
Chapter 49: Pancreatic Transplantation in Diabetes: Indications, Contraindications and Perspectives
Introduction
Indication
Type 1 Diabetes
Type 2 Diabetes (T2DM)
Simultaneous Pancreas Kidney (SPK)
Pancreas After Kidney (PAK)
Pancreas Transplantation Alone (PTA)
Contraindications
Cardiac and Pelvic Vascular Assessment
Surgical Complications
Cohort Study
Age
Obesity
Donors
Perspectives
Robotic Pancreas Transplantation
β Cell Replacement
Pancreas Islet Transplantation
Stem Cell-Derived Beta Cells
3D Bioprinting
References
Part VI: Pharmacological Therapy and Cost Containment
Chapter 50: Pharmacotherapy of Type 2 Diabetes
Introduction
Major Antidiabetic Drug Families
Sulfonylureas
Mechanism of Action
Extra-Pancreatic Actions
Efficacy
Effect on Body Weight
Contraindications
Adverse Effects
Glinides (Meglitinides/D-Phenylalanine Analogs)
Mechanism of Action
Efficacy
Effect on Body Weight
Contraindications
Adverse Effects
Biguanides
Mechanism of Action
Efficacy
Effect on Body Weight
Contraindications
Adverse Effects
Thiazolidinediones (TZDs)
Mechanism of Action
Efficacy
Effect on Body Weight
Contraindications
Adverse Effects
GLP-1 Receptor Agonists (Injectable Drugs)
Mechanism of Action
Effect on Weight
Contraindications
Adverse Effects
DPP-4 Inhibitors
Mechanism of Action
Efficacy
Effect on Weight
Contraindications
Adverse Effects
Alpha-Glucosidase Inhibitors
Mechanism of Action
Efficacy of Alpha-Glucosidase Inhibitor
Contraindications
Adverse Effects
Sodium-Glucose Co-transporter-2 Inhibitors/Gliflozins (SGLT-2 Inhibitors)
Mechanism of Action
Efficacy of SGLT-2 Inhibitors
Effect on Body Weight
Contraindications
Adverse Effects
Oral/Nasal Insulin
Box 50.1 Pharmacotherapical Recommendations for Type 2 Diabetes (Modified from American Diabetes Association) (American Diabet...
Pharmacological Approaches of the American Diabetes Association (ADA)
General Features of Available and Pipeline Drugs
References
Chapter 51: GLP1-Receptor Agonists in Diabetes: Drugs, General Effects, and Cardiovascular Impact
Cardiovascular Risk of Obesity and Diabetes
GLP-1RA Drugs
General Effects
Pancreas
Gastrointestinal Tract
Renal
Liver
Adipose Tissue and Energetic Control
Neurodegenerative Diseases
Cardiovascular: Arteries
Myocardium
Blood Pressure and Heart Rate
Cardiovascular Impact of GLP-1RA Drugs
Thiazolidinediones
Sodium Glucose Co-transporter 2
GLP-1RA
International Endorsements
Future Perspective
References
Chapter 52: Diabetes and Treatments
Introduction
History
Etiology and Pathophysiology of DMT1 and DMT2
Type 1 Diabetes
Type 2 Diabetes
Delivery of Insulin, Islet Transplantation, and Stem Cells
Noninvasive Insulin Administration
The Artificial Pancreas
Drugs
Pharmacotherapy of DMT1
Non-insulin Pharmacological Agents
Pharmacotherapy of DMT2
Therapeutic Aims
Monotherapy of DMT2
Combination Therapy for DMT2
Insulin Introduction
Exenatide, Liraglutide, Lixisenatide and Semaglutide
Sitagliptin, Vildagliptin, Saxagliptin, Linagliptin, and Alogliptin
Acarbose, Miglitol, and Voglibose
Pioglitazone
Sulphonylureas and Glinides (Gliclazide, Glipizide, Glimepiride, Repaglinide)
Dapagliflozin, Canagliflozin, and Empagliflozin
References
Chapter 53: Treatment of Diabetes and Heart Failure
Introduction
Cardiovascular Disease Profiles
Guidelines for Primary and Secondary Prevention of Cardiovascular Disease in Diabetes
Physical Activity
Weight Loss
Smoking Cessation
Blood Pressure
Antiplatelet Therapy
Lipid-Lowering Therapy
Glucose-Lowering Drugs and Cardiovascular Disease
Insulin
Prevention of Hypoglycemia
Metformin
Sulfonylureas
Thiazolidinediones
Dipeptidyl Peptidase-4 Inhibitors
Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors
Lower Limb Amputation
Involved Pathways
GLP-1 Agonists
Multiple Cardiovascular Effects
Can Renal Complications Be Mitigated?
Do Guidelines Exist for Pre-Diabetes?
Pharmacotherapy
Statins and Pre-diabetes
Ongoing Studies and Future Perspectives
Antidiabetic Agents in Normoglycemic Patients
Non-insulin Glucose-Lowering Agents in Type 1 Diabetes
References
Chapter 54: Cardiovascular Impact of Newer Diabetes Medications
Introduction
Elevated Morbidity and Mortality
Heavy Financial and Social Burden
Better Therapeutic Screening
Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RAs) and Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors
Cardiovascular Impact of Glucagon-like Peptide-1 Receptor Agonists (GLP1-RA)
Oral GLP1-RA
Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors
Ethnic and Clinical Considerations
Renal Protection
Official Guidelines
Therapeutic Recommendations for DM Patients with High CV Risk
Primary Approach
Obesity and Renal Comorbidities
Contraindications
Diabetes End Points and Pharmacologic Alternatives
References
Chapter 55: Pathogenesis and Molecular Targets in Treatment of Diabetic Wounds
Introduction
Normal Wound Healing
Diabetic Wounds
Etiology and Pathogenesis
Diabetic Foot Ulcer
Classification of Diabetic Foot Ulcer
Wagner-Meggit
Depth Ischemic
University of Texas
International Working Group (2019 Guidelines)
SAD
PEDIS
Other Classifications
Major Factors and Key Molecular Pathways of Diabetic Wounds
Mitochondrial Overproduction of Reactive Oxygen Species
Alteration of Growth Factors
Platelet-Derived Growth Factor
Vascular Endothelial Growth Factor
Transforming Growth Factor Beta
Matrix Metalloproteinase 9
Defective Cytokine Production
Abnormal Cellular Activity
Neuropathy
Nitric Oxide Interventions
Vascular Disease
Preventive Care
Therapeutic Approaches: Standard Care Versus Cells, Biomaterials, and Growth Factors
References
Chapter 56: Efficiency in Public Health Through the Promotion of Diabetes Day Hospitals: A Regional Proposal
Efficiency in Public Health
Day Hospital Concept
Social Impact of Diabetes
Diabetes Day Hospital
Final Remarks
References
Part VII: Bariatric and Metabolic Surgery
Chapter 57: Surgical Options in Obesity and Diabetes
Introduction
Classification of Bariatric Operations
Metabolic Operations
Laparoscopic Adjustable Gastric Band (LAGB)
Clinical Results
Laparoscopic Sleeve Gastrectomy (LSG)
Clinical Results
Roux-en-Y Gastric Bypass (RYGB)
Clinical Results
One Anastomosis Gastric Bypass
Clinical Results
The Biliopancreatic Diversion (BPD)
Clinical Results
Conclusion
References
Chapter 58: One Anastomosis Gastric Bypass in the Treatment of Obesity: Effects on Body Weight and the Metabolome
Introduction
Metabolic Abnormalities Associated with Obesity
Obesity Treatment and the Role of Bariatric Surgery
One Anastomosis Gastric Bypass
Surgical Technique, Weight Loss, and Complications
Surgical Complications
Standardized Interventions
Metabolic Effects
Fasting Lipid Profile and Postprandial Lipemia
Plasma Fatty Acid Profile
Excessive Free Fatty Acids
Plasma Amino Acid Profile
Bile Acids
Conclusions
References
Chapter 59: Robotic Bariatric Surgery
Introduction
History and Evolution of Robotic Minimally Invasive Surgery
The da Vinci Surgical System
Introduction of New Technology
Training Pathway for the da Vinci Robot
The Advantages and Disadvantages of Robotic Surgery
Monetary Costs
Learning Curve/Operating Theater Time
Unique Hazards
Driving Forces Behind the Improvements in Bariatric Surgery
Enhanced Recovery After Surgery (ERAS) Programs
Databases
Robotic Bariatric Procedures
Robotic Sleeve Gastrectomy: The Evolution of Technique from Laparoscopic, Hybrid Procedures to Totally Robotic
Outcomes of Robotic Sleeve Gastrectomy
Robotic Roux-en-Y Gastric Bypass: The Evolution of Technique: From Laparoscopic, to Hybrid Laparoscopic/Robotic, to Totally Ro...
Outcomes of Robotic RYGB
Robotic Adjustable Gastric Band
Robotic Biliopancreatic Diversion with Duodenal Switch (BPD-DS)
Revisional Bariatric Procedures
Future Directions of Robotic Technology in Bariatric Procedures
Augmented Reality
Autonomous Surgery
New Robotic Platforms and Manufacturers
Senhance (Transenterix Inc., Morrisville, NC, USA)
Versius (Cambridge Medical Research, Cambridge, UK)
References
Chapter 60: The Role of Obesity and Bariatric Surgery in the Management of Knee and Hip Osteoarthritis
Introduction
Impact of Obesity on Lower Limb Osteoarthritis
Weight-Bearing Forces
Mechanical Factors
Gait Changes
Inflammatory Factors
Association of Inflammation with Mechanical Stress
Leptin
Adiponectin
Resistin
Other Adipocytokines
Impact of Obesity on Arthroplasty
Late Postoperative Abnormalities
Functional Outcome
Impact of Weight Loss and Bariatric Surgery on Osteoarthritis
Impact of Bariatric Surgery on Arthroplasty
Bariatric Surgery and Total Arthroplasty: Which Comes First, the Chicken or the Egg?
Mobility and Access to Care
Financial Issues
Ongoing Trials and Future Perspectives
Future Directions
References
Chapter 61: Relapse of Diabetes After Metabolic/Bariatric Surgery
Introduction
Pathogenesis of T2D
How to Predict Metabolic/Bariatric Surgery Outcomes
Predictive Scores
Revisional Bariatric and Metabolic Surgery
References
Chapter 62: Malnutrition in Obesity
Introduction
Deficiencies Across All Classes
Definition of Obesity and Its Types
Metabolic Obesity
Obesity and Muscle Wasting
Types of Bariatric Surgery
Nutritional Deficiencies
Deficiencies Post-Bariatric Surgery
Nutritional Deficiencies Before and After Bariatric Management
Protein
Essential Fatty Acids
Vitamin D
Vitamin B1 (Thiamine)
Vitamin B12 and Folate
Vitamins A, C, E, K
Iron
Zinc
Copper
References
Part VIII: New Apps, Drugs, Artificial Intelligence and Public Health Initiatives
Chapter 63: Sugar-Sweetened Beverage Taxes: Origins, Mechanisms, and Current Worldwide Status
Introduction
Drink Composition
Tax Strategies
The Demand for Sugar-Sweetened Beverages (SSBs)
Affordability and Risk Exposure
Practical Example
Consumption Scenarios
Tax and Soda Sales
Multi-pronged Strategy
Taxing Sugar-Sweetened Beverages (SSBs): Rationale
The Pitfalls of Wrong Perceptions
Taxing Sugar-Sweetened Beverages (SSBs): Mechanisms
A Comprehensive and Enlightened Approach
Sugar Tax in the Real World
Price Elasticity of Demand
Cross Price Elasticity of Demand
The General Economy
Behavior of the Industry and the Government
Current Worldwide Status
Sugared Drinks in Mexico
Other Consequences in Mexico
Unjust and Regressive Taxes?
The Broader Context
Conclusions
References
Chapter 64: Mobile Health Interventions for Weight Management in Overweight and Obese Populations
Introduction
mHealth Overview
Usage and Trends
mHealth for Weight Loss in General Populations
Special Populations
Pregnancy
Adolescents
Quality Assessment
Consideration of Publication Bias
Integration of Behaviour Change Techniques
Use of Theory
Emerging Research in Other Populations
Commercial Weight Loss Apps
App Quality
Mindfulness and Weight Loss
Top-Ranked Apps
Evidence for Effectiveness
Privacy Issues
Consumer Preferences for mHealth
User-Friendly Features
Barriers
Challenges with mHealth
New Areas of mHealth Research
Preliminary Student Analysis
Randomized Trial of a Mindfulness App
Protocol Inclusion Criteria and Methods
Perspectives for Future Improvement
Relevance of the e-Diary
Conclusion
References
Chapter 65: Biomarkers and Machine Learning Applications in Obesity
Introduction
Background Knowledge
Knowledge Discovery in Databases (KDD) and Data Mining
Machine Learning
Biomarkers
Anthropometric Predictive Indices
Genetics
Epigenetics
Biochemical Markers and Proteins
The Gut Microbiome
Metabolomics
Machine Learning Tools: Obesity
Predictive Tools in Obesity
Feature Extraction and Closely Related Factor Evaluation
Diet and Food-Driven Applications
Bariatric Surgery
Childhood Obesity
References
Chapter 66: Current Approaches in Diabetes Mellitus Prediction: Applications of Machine Learning and Emerging Biomarkers
Introduction
Diabetes Etiology and Biochemistry
Biomarkers of Diabetes
Genetics of Diabetes
Epigenetic Biomarkers of Diabetes
Statistical Methods (Logistic Regression)
Machine Learning
Deep Learning
Personal Experience
Biomarkers and Their Derivatives
Dataset Preparation and Experimental Design
Computational Methods and Software
Study Participants and Experimental Groups
Training and Testing Subset Size Selection
Classification Performance and Model Comparison
Calibration Plots and Cut-Off Threshold Selection
Probability of T2DM Development
Comments
Conclusions
References
Chapter 67: Lifestyle Interventions for Sarcopenic Obesity in Polycystic Ovary Syndrome
General Features of Polycystic Ovary Syndrome
Sarcopenic Obesity
Mechanisms for Sarcopenic Obesity
Lipid Metabolism
Myokines
Dietary Interventions: Vitamin D
Omega-3 Fatty Acids
Antioxidant Supplementation
Selenium Supplementation
Chromium Picolinate
Carnitine
Combinations of Nutritional Supplements
Dietary Approaches
DASH Diet
Low-Glycemic Index Diets
Low Carbohydrate Diets
The Mediterranean Diet and the Portfolio Diet
Exercise
Aerobic Training
High-Intensity Interval Training (HIIT)
Resistance Training
Summary/Overall Recommendations
References
Chapter 68: Drug Pipeline for Obesity Therapy
Introduction
Current Drugs
Drugs in Pipeline
Centrally Acting Drugs
Melanocortin Receptor Agonist
Setmelanotide
Gut Hormones and Incretin Targets
Glucagon-Like Peptide-1 (GLP-1) Analogs: Semaglutide (Ozempic)
Dual Action GLP-1/Glucagon Receptor Agonists
Oxyntomodulin
Peptide YY
PYY Analogs
Novel Targets
Methionine Aminopeptidase 2 (MetAP2) Inhibitors: ZGN-1061
Lipase Inhibitor: Cetilistat
Triple Monoamine Reuptake Inhibitor: Tesofensine
Fibroblast Growth: Factor 21
Anti-obesity Vaccines
Ghrelin
Somatostatin
Adenovirus 36
Conclusion
References
Chapter 69: MC4R as a Target for Pharmacotherapeutic Treatment of Obesity and Type 2 Diabetes
Incidence and Societal Burden of Obesity
Challenges in Pharmacological Management of Obesity
Melanocortin Receptors (MCRs)
Melanocortins and Feeding Behavior
Hormones and Biomolecules
Signaling Pathways
Agonists with Potential Therapeutic Interest and Clinical Trials
Diabetes as a Consequence of Obesity
Perspectives
References
Chapter 70: Nanotechnology: Can It Be a Crusader in Diabesity?
Introduction
Limitations of Current Pharmacological Therapies
Diabetes Overview
Nanotechnology Promise
Pharmacological Applications
Defining `Nanoscale´
Origins of Nanotechnology
Nanotechnology Advances for the Treatment of Diabetes
Artificial Pancreas
Biological Nanosensors and Diabetes Monitoring
Smart Tattoos
Pancreatic Beta Cell Mass
Nanotechnology Targeted Treatment for Obesity
Lipid Nanoparticles
Conclusion
References
Part IX: Obesity Devices and Supplemental Material
Chapter 71: Old and New Anti-obesity Devices for Medical, Surgical, and Endoscopical Use
Introduction
Dental Wiring and Oral Intake Restriction
SMARTByte Palate Prosthesis Device
Intragastric Balloon
Gastric Aspiration
Nonsurgical Bypass of the Upper Gut
Plenity Capsule
Final Considerations
References
Chapter 72: Electroceutical Approaches for Gastroparesis
Introduction
Electrophysiology
ICC Regulation of Slow Waves
Measurement of Slow Waves In Vivo
Gastroparesis
Diagnostic Scintigraphy
Pathophysiology
Differential Diagnosis
Low-frequency Pacing and High-Frequency Stimulation
Pacing
Gastric Pacing for Obesity Treatment
High Frequency Stimulation
Human Trials
Clinical Protocols
Future Outlook
References
Chapter 73: Useful Online Resources Hosting Information on Obesity and Diabetes
Glossary