The Diabetes Textbook : Clinical Principles, Patient Management and Public Health Issues

The Diabetes Textbook: Clinical Principles, Patient Management and Public Health Issues (2 nd Edition) addresses diabetes from a comprehensive, multidisciplinary perspective. Its purpose is to integrate state-of-the-art information on diabetes from specialists in various disciplines, including epidemiology, public health, pathophysiology, non-pharmacologic and pharmacologic treatment, patient support, acute and chronic complications, new and unproven therapies, and prevention. The main benefit of “The Diabetes Textbook” is its integrative approach. The book is therefore intended for three main types of readers: 1) physicians and health professionals seeking a comprehensive approach to diabetes; 2) those with previous expertise in a specific professional area who want to expand their knowledge; and 3) those interested in learning about topics not previously covered, who will find the contents of “The Diabetes Textbook” both enriching and innovative. The Diabetes Textbook is intended for a broad readership, including professors of medicine and related disciplines (nursing, nutrition, psychology); general physicians; internists and specialists, e.g. in ophthalmology, endocrinology, cardiology, obstetrics and gynecology, pediatrics, geriatrics, epidemiology and public health. To address these readers’ needs, the second edition is divided into the following eleven sections: 1) Magnitude of the Problem from an Individual and Social Context, 2) Diagnosis, Classification and Mechanisms of Disease, 3) Global Experiences in Diabetes Care, 4) Basic Components of Management: Patient-Centeredness, Evidence-Based Medicine, and Outcomes, 5) Resources of Support for Persons with Diabetes, 6) Drug Therapy, 7) Cardiovascular Risk Factors, 8) Acute Complications, 9) Chronic Complications, 10) Diabetes in Special Populations, and 11) Novel Therapeutic Approaches: Evidence-Based and Non-Proven, and Diabetes Prevention. Preface to the Second Edition References Contents 1: Preface: A New Disease? References Further Reading Part I: Magnitude of the Problem from an Individual and Social Context 2: The Dynamics of Diabetes Prevalence, Morbidity, and Mortality Introduction Current Burden of Prevalence and Incidence Prevalence Undiagnosed Diabetes Incidence Prediabetes Trends and Trajectories in the Epidemic Prevalence and Incidence Impact on Lifetime Risk and Years of Life A Turn of the Tide? The Burden and Trends in Diabetes Complications Prevalence and Incidence Trends in Complications Diabetes and Mortality A Diversification of Long-Term Diabetes Associated with Diabetes Primary Conclusions and Implications References 3: The Economic Costs of Diabetes Paradigms of Medical Care Introduction Economics in Health Care: The Basics Types of Economic Analysis Efficiency Measures The Economic Burden of the Disease on Persons with Diabetes and Their Families References Further Reading Glossary 4: The Ecological Approach to Self-Management in Diabetes Broad Patterns of Social and Ecological Relationships with Health Articulating a Broad View of Experience and Environment: Ecological Perspectives Relationships Among Influences: The Example of Genetic Expression and the Environment The Illusion of the Fundamental. Genetics as a Model for Analyzing Social and Ecological Influences Ecological Analysis and Diabetes Sustaining Health Behaviors: Follow-Up and Support Community Resources Access to Healthy Food The Ecology of Professionals A Social Strategy: Peer Support Strategic Advantages of Peer Support A Community Strategy: Community Action North Karelia: CVD Risk Reduction in Finland Integrating Community and Peer Support in Shanghai Cigarette Smoking Community Organization for Diabetes Prevention in India A Policy Strategy: Health in All Policies Healthy Cities Globalization Globalization and Health Income Distribution and Other Effects of Globalization Supranational Policy Interactions Among Determinants and Sectors Examples: Housing and Urban Life Examples: Urban Environmental Impacts, Planning and Development Neighborhood Design and Social Isolation HiAP and Community Organization A Key Change in Perspective Extension to Diabetes Concluding Thoughts References 5: Social Determinants of Health and Diabetes Outcomes Social Disparity in the Diabetes Burden Supposed Mechanism of Social Disparity in Diabetes Social Determinants of Diabetes Interventions to Close the Social Gap in Diabetes Outcomes Conclusion References Part II: Diagnosis, Classification and Mechanisms of Disease 6: Definition, Diagnostic Criteria, Screening, Diagnosis, and Classification of Diabetes and Categories of Glucose Intolerance: An Update Definition Diagnostic Criteria ADA Criteria for Diagnosis of Prediabetes Criteria for Screening for Diabetes or Prediabetes in Asymptomatic Adults Screening for Prediabetes and Diabetes Diagnostic Methods Glycated Hemoglobin Standardization of HbA1c Classification of Diabetes Mellitus Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus Gestational Diabetes Mellitus One-Step Strategy Two-Step Strategy Step 1 Step 2 Screening for GDM Screening for Persistent Diabetes After Pregnancy Specific Types of Diabetes Due to Other Causes Monogenic Diabetes Syndromes Neonatal Diabetes Diabetes Mellitus Secondary to Pancreatic Disorders Acute and Chronic Pancreatitis Fibrocalculous Pancreatitis Pancreatic Ductal Adenocarcinoma Endocrinopathies Acromegaly Cushing’s Syndrome Other Endocrine Disorders Glucagonoma Somatostatinoma Drug-Induced Diabetes Mellitus Thiazide Diuretics Statins Beta-Blockers Antipsychotic Medications Antiretroviral Therapy Posttransplantation Diabetes Mellitus References Further Reading Glossary 7: Homeostasis of Glucose and Intermediate Metabolism: From the Lens of a Clinician Introduction Phases of Glucose Homeostasis Glucose Pathways in Health and Disease (Figs. 7.1 and 7.2) Glycolysis (Embden-Meyerhof-Parnas Pathway) Clinical Relevance Gluconeogenesis Glycogen Metabolism Glycogenesis Glycogenolysis Pentose Phosphate Pathway (PPP), Phosphogluconate Pathway or Hexose Monophosphate (HMP) Shunt Glucose Transporters or SWEET Proteins Organ Systems That Help Regulate Glucose Metabolism Pancreas Insulin Glucagon Somatostatin Amylin Pancreatic Polypeptide Liver Kidney Role of the Hypothalamic Pituitary Axis Gut Regulation of Glucose: Role of Incretin Hormones Gall Bladder: The New Metabolic Orchestrator References 8: Pathophysiology of Type 1 Diabetes Introduction Etiopathogenesis of Type 1 Diabetes Genetic Factors Immunological Factors Environmental Factors Microbiota COVID-19 Infection The Role of NKT Cells in the Physiopathology of Type 1 Diabetes References 9: Pathophysiology of Type 2 Diabetes Glucose Homeostasis Pathophysiology of Type 2 Diabetes The Ominous Octet β-Cell Dysfunction Insulin Resistance Hepatic Insulin Resistance Muscle Insulin Resistance Adipose Tissue Insulin Resistance Alpha Cells (Increased Glucagon Secretion) Incretin Defect Kidneys (Increased Glucose Reabsorption) Brain (Neurotransmitter Dysfunction and Central Appetite Dysregulation) The “Dirty Dozen,” the “Unlucky Thirteen,” and Much More Dopamine Vitamin D Renin-Angiotensin System Testosterone Gut and Gut Microbiota Gut Gut Microbiota Iron Overload Covid-19 and Type 2 diabetes Conclusion References 10: Genetic Determinants of Type 2 Diabetes Definition of Genetic Polymorphisms The Importance of Studying Genetic-Environmental Variant Interaction and Its Perspective in Clinical Application Genome-Wide Association Studies (GWAS) The Importance of Ancestry in Association Studies Genes Associated to T2D TCF7L2 Variants Gene Variants of Genes ABCC8 and KCNJ11 Variants of Gene CAPN10 Variants of PPARγ Gene (Peroxisome Proliferator-Activated Receptor Gamma) Variants of the CDKN2A/B Gene Variants of the FTO Gene Variants of the IRS-1 Gene Variant of the Gene Hepatocyte Nuclear Factor 1-Alpha (HNF1A) Variant of the Gene Solute Carrier Family 30 Member 8 (SLC30A8) Other Variants Associated to Insulin Resistance and Dyslipidemias Biological Validation Studies Conclusions References Glossary 11: Gene Expression Modifications in Type 2 Diabetes Introduction Adipose Tissue Pancreas Skeletal Muscle Carbohydrate Metabolism Lipid Metabolism Mitochondrial Function The Role of Insulin in Gene Expression Liver Whole-Blood Gene Expression in DT2 Whole-Blood Gene Expression as a Possible Tool for Early Detection of T2D miRNAs in Blood Samples References Glossary 12: The Immune System and Inflammation in Type 2 Diabetes Introduction Types of Adipose Tissue Ectopic Fat Accumulation Epicardial Adipose Tissue Perivascular Fat Obesity and Acute and Chronic Inflammation Type 2 Diabetes and Immune Cells Macrophages Mast Cells Eosinophils Lymphocytes B Cells Natural Killer T Cells Invariant Natural Killer T Dendritic Cells Markers of Inflammation TNF-α IL-1β IL-6 IL-18 TGF-β1 Resistin Leptin IL-1Ra IL-4 IL-10 Adiponectin Perspectives onT2D Immunotherapy References Further Reading Glossary 13: Dysfunction and Death of Pancreatic Beta-Cells in Type 2 Diabetes Introduction The Origin of β-Cells Embryonic Development and Differentiation Postnatal Development of the Pancreas β-Cell Dysfunction and the Loss of Pancreatic Β-Cell Mass β-Cell Apoptosis Glucolipotoxicity Oxidative Stress Mitochondrial Alterations Endoplasmic Reticulum Stress Obesity and Inflammation B-Islet Amyloid Polypeptide (IAPP) β-Cell Apoptosis and p53 p53 Phosphorylation p53 O-N-Acetylglucosamination p53 Poly(ADP-Ribosylation) p53 Regulation by Mdm2 Cell Cycle Alterations Cell Proliferation Rate β-Cell Dedifferentiation Adaptative β-Cell Proliferation MicroRNAs in Pancreatic β-Cells Function and Dysfunction Susceptibility of Pancreatic β-Cells to Infection by the SARS-CoV-2 Virus Conclusions References Further Reading Glossary 14: Obesity in the Pathophysiology of Diabetes Introduction: Obesity as a Public Health Problem Obesity: Measurements and Assessment Adipocyte and Adiposity Development Types of Adipocytes and Differentiation Effects of Hormones and Adipokines on Adipogenesis and Glucose Metabolism Hormones and Growth Factors Major Adipokines Other Adipokines Inflammatory Adipokines Fatty Acid Metabolism Effects on Adipogenesis and Glucose Metabolism Obesity Effects on the Pathogenesis of Type 2 Diabetes Effects of Fetal Develop on Adult Glucose Metabolism The Effect of Adult Obesity on Glucose Metabolism Obesity and the Lipotoxicity Syndrome Pathogenesis of Obese Type 2 Diabetes Underlining Factors of Obesity-Induced Insulin-Resistance Inflammation and Insulin Resistance Mitochondrial Dysfunction and Obesity-Induced Insulin Resistance Oxidative Stress and Obesity-Induced Insulin Resistance Endoplasmic Reticulum Stress and Obesity-Induced Insulin Resistance Skeletal Muscle Glucose and Lipid Metabolism Liver Insulin Resistance and Hyperglycemia β-Cell Dysfunction in Obese T2D Subjects Underlying Mechanisms Implicated in β-Cell Failure in T2D References 15: Pathogenesis of Gestational Diabetes Mellitus Introduction Insulin Sensitivity Introduction Placental Hormones Maternal Hormones Maternal Vitamin D Maternal Adipokines Immunological Changes and Low-Grade Inflammation Oxidative Stress Maternal Gut Microbiome β-Cell Function and Insulin Secretion Introduction Maternal Hormones Placental Hormones Low-Grade Inflammation Oxidative Stress Glucotoxicity and Lipotoxicity Maternal Vitamin D Autoimmunity Genetic Causes Conclusions References 16: Nonalcoholic Fatty Liver in the Pathogenesis of Diabetes Introduction Definition of NAFLD Epidemiology Clinical Manifestations Diagnosis Liver Biopsy and Noninvasive Markers of Fibrosis NAFLD and T2DM Interplay Pathogenetic Mechanisms Metabolic Mechanisms Involved in NAFLD Adipose Expansion and Inflammation Insulin Resistance and Hyperinsulinemia Metabolic Consequences of NAFLD Hepatic Lipogenesis and Hypertriglyceridemia Hepatic Insulin Resistance and Hyperglycemia Other Mechanisms Involved in NAFLD Pathogenesis Genetics Factors Diet and Gut Microbiome Mechanisms Involved in NAFLD Progression References Part III: Examples of Global Experiences in Diabetes Care 17: Diabetes Management in Asia Diabetes Burdens in Asia: Morbidity and Mortality Prevalence and Incidence of Diabetes and Related Complications Socioeconomic Burden Special Types of Diabetes in Asia Fibrocalculous Pancreatic Diabetes (FCPD) Disparities in Diabetes Care in Asia Management of Diabetes in Asia Non-pharmacological Approaches Lifestyle Modification Medical Nutrition Therapy (MNT) Physical Activity Pharmacological Approaches Oral Antidiabetic Drugs (OADs) Insulin Therapy Non-insulin Injectable Therapy (Glucagon-Like Peptide 1) Management of Special Types of Diabetes (Monogenic Forms and FCPD) Newer Approaches to Diabetes Management in Asian Context Impact of COVID-19 Pandemic on Diabetes Care and Potential Role of Digital Health Technologies Conclusions References Further Reading 18: Diabetes Management in Latin America Epidemiology of Type 1 Diabetes Mellitus in Latin America and the Caribbean Temporal Trends Determinants and Drivers of Incidence of Type 1 Diabetes in Latin America Age at Diagnosis Delivery and Quality of Care Access to Care and Insulin Complications Epidemiology of Type 2 Diabetes Mellitus in Latin America and the Caribbean Prevalence Incidence Mortality Local Quantification of Risk Factors Chronic Diabetes-Related Complications Epidemiology: Microvascular Epidemiology: Macrovascular Final Remarks Diabetes Interventions in Latin America and the Caribbean Interventions in Type 1 Diabetes Mellitus Interventions in Type 2 Diabetes Mellitus Primary Prevention Secondary and Tertiary Prevention Final Remarks Implementation Science for Type 2 Diabetes Mellitus in Latin America and the Caribbean Examples of Successful Experiences Case 1: The VIDA Project Case 2: The Meta Salud Diabetes Implementation Study Case 3: Combined Diabetes Prevention and Disease Self-Management Intervention for Nicaraguan Ethnic Minorities: A Pilot Study Know-Do-Gaps for Type 1 Diabetes Mellitus Access to Treatment Hypoglycaemic Medication Insulin Cardiovascular Treatment in People with Diabetes Prediction Tools Diagnostic and Prognostic Diabetes-Related Complications New Research Trends Population Health Novel Analytic Approaches References 19: Diabetes Management in the United States Introduction Prevalence and Cost Burdens Health Impacts National Trends Screening Management of Cardio-Metabolic Risks Screening for Diabetes Complications Incidence of Complications Gaps in Care Outpatient Settings in the United States The Patient The Provider The System Disparities in Diabetes Prevention and Management Demographic Disparities Socioeconomic Disparities Disparities in Care Delivery Diabetes Medical Management Updates Medical Management of Diabetes Most Recent Changes in Guidelines SGLT2-Inhibitors DPP-4 Inhibitor and GLP-1 Agonists Advancements in Diabetes Technologies Challenges and Barriers to Medical Management Quality Improvement Initiatives in Outpatient Diabetes Care Clinical Care Models and Practice Redesign Conceptual Basis Application of Care Models for Diabetes Evidence Lessons Learned Policies and Incentives to Address Accountability and Quality in Diabetes Care Pay-for-Performance Policies COVID-19 and Telehealth Research Gaps Concluding Remarks References 20: Diabetes Management in Africa Introduction Health Beliefs and Perceptions Relating to Diabetes in Africa Health-Seeking Behaviors of People with Diabetes in Africa Impact of These Beliefs on the Prevention and Control of Diabetes in Africa Management of Hyperglycemia Screening and Diagnosis Lifestyle Modification Medical Nutrition Therapy Physical Activity and Other Lifestyle Measures Pharmacologic Therapy Oral Antidiabetic Medications (OAD)/Oral Hypoglycemic Agents (OHA) Insulin Therapy Combination Therapy with Oral Antidiabetic Medications and Insulin Specificities of the Management of Ketosis-Prone Type 2 Diabetes Prevention and Management of Acute and Chronic Complications of Diabetes Prevention and Management of Chronic Complications Management of Acute Complications of Diabetes Management of Comorbidities Follow-Up of Patients Current Challenges to Diabetes Management in Africa Newer Approaches to Diabetes Management in Africa References Further Reading Part IV: Basic Components of Management: Patient Centeredness, Evidence-Based Medicine and Outcomes—Challenges for Implementation 21: The Patient-Centered Medical Home, Primary Care, and Diabetes Introduction Milestones of Patient-Centered Care Primary Care as the Site of the Medical Home Roots and Milestones of Patient-Centered Care The Link Between Primary Care and Patient-Centered Care The Paradox Challenges to Implement the Patient-Centered Medical Home Transitioning from Primary Care to the PCMH Patient-Centered Care Defined Attributes of Patient-Centered Care Effectiveness of the Patient-Centered Medical Home The Patient-Centered Medical Home and Diabetes Conclusion References 22: Outpatient Diabetes Management and the Chronic Care Model Introduction Lessons Learned and Lessons Still Unlearned Transforming Diabetes Care Effectiveness of Diabetes Outpatient Management: The Evidence Outpatient Management of Type 1 Diabetes Comorbidity and Multi-morbidity in Diabetes Management Comorbidity and Multi-morbidity in Diabetes Linking Multi-morbidity in Diabetes Comorbidity in Clinical Practice Multi-morbidity in Diabetes Management Diabetes and the Chronic Care Model The CCM in Diabetes Diabetes as a Complex Disease Conclusions References 23: Clinical Practice Guidelines, Evidence-Based Medicine and Diabetes The Unwarranted Variation in Health Care and Its Consequences The Ascent of Clinical Practice Guidelines Defining Clinical Guidelines Rationale and Evolution Development of CPG Challenges of Implementation CPG and Implementation Science Crossing the Professional Abyss Evidence-Based Medicine and CPG Changing Approaches of Diabetes Guidelines Evidence-Based Medicine and Diabetes Guidelines Evolution of Diabetes Guidelines Patient-Centeredness and CPG The Evidence Behind Diabetes Guidelines Quality of Evidence of Diabetes Guidelines Conflict of Interest, Magnitude, and Consequences The Quest for Quality in Diabetes Guidelines Diabetes Guidelines and the Real World Beyond Glycemic Targets and the Role of Patients The Role of Comorbidities Conclusions References 24: Measuring Diabetes Quality of Care: Clinical Outcomes, Cost-Effectiveness, and Patient Experience of Care Introduction Measuring Clinical Quality of Care: Accountability Versus Improvement Measures Measuring Patient Experience of Care Shared Decision-Making and Treatment Burden Measuring Affordability and Cost-Effectiveness of Diabetes Care Summary References Further Reading 25: Challenges to Diabetes Care Innovation. The Case of a Major Public Institution in Mexico Introduction Diabetes Care Coverage Bottlenecks Internal Facilitators and Barriers to Innovation Implementation Process Facilitators and Barriers Facilitators and Barriers in the External Context of Innovation Costs of Scaling-Up Innovations and Budgetary Impact Discussion Recommendations References 26: Clinical Inertia and Diabetes Outcomes Introduction Clinical Inertia Definitions and Evolution Origins and Definition The Impact of Clinical Inertia in Diabetes Management Factors Associated with Clinical Inertia Clinical Inertia in Defense of Patients Contribution of Clinical Guidelines to Clinical Inertia Addressing Clinical Inertia Conclusion References 27: Patient Adherence: Challenges, Myths, and Realities Introduction An Evolving Concept Defining Adherence Addressing Nonadherence A Brief Story of Adherence Compliance, Concordance, or Adherence? Measuring Adherence Early Interventions to Improve Adherence Interventions to Improve Adherence: The Evidence The Role of System Deficiencies on Adherence Measuring Adherence in Hypertension and Beyond Adherence and the Complexities of Diabetes Self-Management Nonadherence in Diabetes Methods for Measuring Adherence in Diabetes Adherence to Antidiabetics Behavioral Aspects Psychological Issues and Adherence in Diabetes Behavioral Strategies to Improve Adherence Motivational Interviewing Diabetes Empowerment Addressing Adherence Conclusions References Part V: Resources of Support for Persons with Diabetes 28: Challenges and Opportunities in Diabetes Education Definition of Diabetes Self-Management Education and Support Evidence Supporting the Effectiveness of Diabetes Education Recommendations for Diabetes Education Standards for Diabetes Education Challenges in Meeting Diabetes Education Needs: Addressing the Problem Identify Education and Support Needs Employ Qualified Staff Ensure Ongoing Access Who Are the Diabetes Educators? Developing a Diabetes Education Program Strategies for Successful Diabetes Education Collaborate with Patients Ask Rather than Tell Recognize that Words Matter Gather Educational Resources Provide a Written Care Plan Identify Resources Use the Teach Back Technique Mentor Others Examples of Diabetes Education Initiatives Around the Globe Increasing the Role of the Pharmacist in Community Education in Saudi Arabia Using Conversation Maps® to Facilitate Education in Pakistan Using Community Health Workers in Diabetes Education and Prevention in Rural India Engaging Group Activities for Support in Japan Online Diabetes Educator Preparation: Certificate and Degree Programs Additional Roles for the Diabetes Educator Appendix References 29: Diabetes and Mental Health: From Distress to Depression Introduction Definitions Epidemiology of Comorbid Depression–Diabetes Mechanisms Underlying the Association Diabetes–Distress–Depression (Fig. 29.1) Adherence to Treatment, Hygienic, and Dietetic Measures The Hypothalamic-Pituitary Adrenal (HPA) Axis Dysfunction Abnormalities of the Sympathetic Nervous System (SNS) Inflammation and Innate Immunity Depression Diabetes Depression–Diabetes–Inflammation Circadian Rhythms Antidepressant Stage of Development Childhood Adolescence Impact on Clinical Evolution and Quality of Life of Comorbid Diabetes–Depression Implications for Research References 30: Continuous Glucose Monitoring in Clinical Practice: Ambulatory Glucose Profile and the Application of Advanced Glucose Sensing Technologies to Clinical Decision-Making Introduction AGP in Clinical Care Conclusion Multiple Choice Questions References 31: Healthy Lifestyles for the Self- Management of Type 2 Diabetes Lifestyle Behaviors Among People with Type 2 Diabetes Healthy Lifestyle as a Component of Type 2 Diabetes Management Barriers to Healthy Lifestyles for Diabetes Self-Management Individual-Level Barriers Interpersonal-Level Barriers Community-Level Barriers System-Level Barriers Supporting Healthy Lifestyles for Diabetes Self-Management Diabetes Self-Management Education and Support Social Support Healthcare-Community Linkages Technology and Telehealth Financing Lifestyle Diabetes Management Conclusion References 32: Evidence and Implementation of Medical Nutrition Therapy in Persons with Diabetes Introduction Diabetes Nutrition Therapy: The Evidence Effective Nutrition Therapy Recommendations: Eating Patterns, Macronutrients, Weight Management, Fiber, Alcohol, Micronutrients/Herbal Supplements, and Weight Management Individualization of the Nutrition Prescription and Eating Patterns Conclusion Multiple Choice Questions References 33: Evidence and Implementation of Physical Activity and Exercise in Diabetes Mellitus Introduction Key Concepts About Physical Activity and Exercise Human Movement Physical Activity Exercise Physical Fitness Sedentary Behavior Physical Inactivity Evidence of Benefits of Physical Activity and Exercise on Diabetes Mellitus The Importance of the Intensity Levels of Activities/Exercise in Patients with Diabetes Mellitus Low Intensity Moderated Intensity Vigorous Intensity Physical Activity Recommendations for People with Diabetes Counseling, the Five A’s, and Motivational Interviewing Exercise in the Presence of Specific Long-Term Complications of Diabetes Summary References Part VI: Drug Therapy 34: The “Old” Oral Antidiabetics Introduction Methods Results Metformin Sulfonylureas Thiazolidinediones Alpha Glucosidase Inhibitors and Meglitinides Conclusion Shared Decision-Making References 35: Incretin Therapies: Current Use and Emerging Possibilities History of Incretins Discovery of the Incretin Effect First Clinical Usage Mechanisms of Physiologic Action of Endogenous GLP-1 Stimulation of GLP-1 Secretion Effects on the Pancreas Effects on Intestinal Motility Effects on the Central Nervous System Mechanism of Action of GIP Pharmacological Substances Exenatide Liraglutide Exenatide LAR Dulaglutide Lixisenatide Semaglutide Efpeglenatide Tirzepatide Comparisons of Clinical Data from Available Trials and Discussion of Clinical Effects Pipeline of Incretin-Based Substances for Diabetes and Obesity Treatment Side Effects of the GLP-1 Analog Class DPP-4 Inhibitors Concluding Remarks References Glossary 36: Sodium-Glucose Cotransporter 2 Inhibitors Introduction The Emergence of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) Mechanism of Action Individual Profiles Comparative Efficacy and Safety of Canagliflozin with Oral Antidiabetics Comparative Efficacy of Canagliflozin with Insulin Cardiovascular Benefits of SGLT2 Inhibitors Renal Effects Other Metabolic Effects: Increased Ketogenesis a “Superfuel?” Safety and Tolerability Genitourinary Infections Ketoacidosis Conclusion References 37: Use of Insulin in Outpatient Diabetes Management Introduction Patient Selection Clinical Guidelines Insulin Types and Time of Action (Table 37.2 and Fig. 37.2) Inhaled Insulin [19–22] Insulin Management Regimens (Figs. 37.1 and 37.3 and Appendix) Basal Insulin Regimen [1] Intensive Regimens (Figs. 37.1 and 37.3) Conventional Insulin Regimen Premixed Insulin Basal Plus Basal-Plus GLP-1ra Basal Bolus Fixed Basal Bolus Flexible Basal Bolus (Figs. 37.4, 37.5, and 37.6, Appendix) Basal Bolus with Sliding Scale Insulin Pumps Insulin Adverse Effects Storage and Insulin Application Techniques Conclusions Appendix: Initial Doses for Each Regimen References Further Reading Untitled 38: Insulin Pump Therapy How It Works: The Basics Insulin Pump Candidates Patient Requirements Advantages of CSII Therapy Disadvantages of CSII Therapy Types of Insulin Pump Initial Settings Initial Total and Basal Insulin Dose Initial Bolus Calculation Adjustments Step by Step Special Situations Exercise Sick Days Fasting Hospitalizations Surgery [1, 2, 15] Menstruation [15] Pregnancy [1, 15] Alcohol [15] Travel [15] Insulin Adjustments When Travelling Insulin Pump Therapy on Vacation [15] Going Off the Pump Going Back on the Pump CGM Integrated Systems Conclusions Suggested Additional Reading References Part VII: Cardiovascular Risk Factors 39: Diabetes and Hypertension Introduction Pathophysiology Large-Scale Trials Assessing HTN Review of the Evidence Guidelines and BP Targets Lifestyle Modification DM Medications Antihypertensive Medications Other Monitoring Modalities COVID-19 and Antihypertensive Therapy in Individuals with Diabetes Future Considerations Conclusion References Further Reading 40: Diabetes and Atherogenic Dyslipidemia Introduction Prevalence of Dyslipidemia in Diabetes Pathophysiology of Dyslipidemia in Diabetes Atherogenicity of Dyslipidemia in Diabetes Management of Dyslipidemia in Diabetes Mellitus Medical Nutrition Therapy Effects of Exercise Pharmacologic Interventions A Rational Approach to Drug Therapy Conclusions References 41: Obesity and Diabetes: Clinical Aspects Introduction Assessment of Obesity Body Mass Index (BMI) Body Circumference(s) Waist Circumference Waist-to-Hip Ratio Body Fat Skinfold Thickness Bioelectrical Impedance Analysis (BIA) Dual Energy X-Ray Absorptiometry (DEXA) The Four-Compartmental Model Causes of Obesity Hereditable Factors Environmental Factors Diet Physical Activity Type 2 Diabetes (T2D) Treatment for Obesity and T2D Lifestyle Intervention Pharmacological Interventions Surgical Intervention Conclusion References Further Reading Glossary 42: Metabolic and Bariatric Surgery in Diabetes Management Introduction Types of Bariatric Surgery Laparoscopic Adjustable Gastric Band (LAGB) Sleeve Gastrectomy (SG) Roux-en-Y Gastric Bypass (RYGB) Biliopancreatic Diversion with Duodenal Switch (BPD-DS) One Anastomosis Gastric Bypass (OAGB) Single Anastomosis Duodeno-ileal Bypass with Sleeve Gastrectomy (SADI-S) Mechanisms of Action of Bariatric Surgery Gastric Volume Restriction Malabsorption Enteroendocrine Modifications Ghrelin Incretins Adipokines Gut Microbiota Bile Acids Histological and Anatomical Changes Outcomes After Metabolic Surgery Weight Loss After Metabolic Surgery Diabetes Remission and Main Diabetes-Associated Abnormalities Following Metabolic Surgery Evidence from Randomized Controlled Trials Renal Changes and Micro-/Macrovascular Complications Outcomes of Other Comorbidities Associated with Obesity and Metabolic Syndrome Following Metabolic Surgery Hypertension Obstructive Sleep Apnea Dyslipidemia Cardiovascular Disease Special Topics The Use of Metabolic Surgery in Type 2 Diabetes Patients with a BMI < 35 kg/m2 Metabolic Surgery in Type 1 Diabetics Diabetes Remission and Relapse Using Different Types of Metabolic Surgery Long-Term Outcomes of Metabolic Surgery Complications After Bariatric/Metabolic Surgery Evolving Technologies for Metabolic Treatment Endoscopic Magnetic Compression Anastomotic Devices Duodenal Mucosal Resurfacing Endoluminal Bypass Liners Duodenal-Jejunal Bypass Liner Gastro-duodenal Bypass Liner References Glossary Untitled Untitled 43: Diabetes and Smoking: The Burden of Evidence Introduction Smoking and Diabetes: Incidence and Mechanism Smoking and Non-microvascular or Non-macrovascular Complications Smoking and Microvascular Complications of Diabetes Smoking and Diabetic Nephropathy Smoking and Diabetic Retinopathy (DR) Smoking and Diabetic Neuropathy Smoking and Macrovascular Complications of Diabetes Coronary Artery Disease Smoking and Cerebrovascular Accident/Stroke Smoking and Peripheral Artery Disease Smoking Cessation, Diabetes, and Technology References Part VIII: Acute Complications 44: Hyperglycemic Crises: Diabetic Ketoacidosis Pathogenesis Precipitating Causes Ketosis-Prone Diabetes COVID-19 and DKA Diagnosis Symptoms and Signs Laboratory Findings Treatment Fluid Therapy Insulin Therapy Potassium Bicarbonate Phosphate Transition to Subcutaneous Insulin Prevention References 45: Hypoglycemia: Diagnosis, Management, and Prevention Introduction Hypoglycemia Definition and Classification Physiology of Hypoglycemia Normal Glucose Counterregulation First Defense Secondary Defense Third Defense Late Defense Glycemic Thresholds Glycemic Mechanisms Pathophysiology of Glucose Counterregulation in Diabetes T1D T2D Hypoglycemia Unawareness Hypoglycemia: Associated Autonomic Failure Epidemiology T1D T2D Oral and Injectable Agents Metformin Alpha-Glucosidase Inhibitors Sulfonylureas Amylin Dipeptidyl Peptidase-4 (DPP-4) Inhibitors Sodium-Glucose Co-transporter 2 (SGLT2) Inhibitors Insulin Glargine Detemir Degludec Glargine U300 Fast-Acting Insulin Analogues Clinical Manifestations Diagnosis and Detection Causes Risk Factors and Determinants Physical Activity and Exercise Alcohol Medications Beta-Blockers Renal Failure Congestive Heart Failure Sepsis, Trauma, and Burns Glucose Variability Nocturnal Hypoglycemia Pregnancy Elderly Children and Adolescents Hypoglycemia Impact Hypoglycemia and Cardiovascular Disease Hypoglycemia in ACCORD, ADVANCE, and VADT Cardiac Arrhythmias Cognitive Function and Dementia Dead-in-Bed Syndrome and Sudden Death Quality of Life Fear of Hypoglycemia Critical Illness and Hospitalization Treatment of Hypoglycemia Mild Hypoglycemia Moderate Hypoglycem The Diabetes Textbook: Clinical Principles, Patient Management and Public Health Issues (2nd Edition) addresses diabetes from a comprehensive, multidisciplinary perspective. Its purpose is to integrate state-of-the-art information on diabetes from specialists in various disciplines, including epidemiology, public health, pathophysiology, non-pharmacologic and pharmacologic treatment, patient support, acute and chronic complications, new and unproven therapies, and prevention. The main benefit of The Diabetes Textbook is its integrative approach. The book is therefore intended for three main types of readers: 1) physicians and health professionals seeking a comprehensive approach to diabetes; 2) those with previous expertise in a specific professional area who want to expand their knowledge; and 3) those interested in learning about topics not previously covered, who will find the contents of The Diabetes Textbook both enriching and innovative. The Diabetes Textbook is intended for a broad readership, including professors of medicine and related disciplines (nursing, nutrition, psychology); general physicians; internists and specialists, e.g. in ophthalmology, endocrinology, cardiology, obstetrics and gynecology, pediatrics, geriatrics, epidemiology and public health. To address these readers needs, the second edition is divided into the following eleven sections: 1) Magnitude of the Problem from an Individual and Social Context, 2) Diagnosis, Classification and Mechanisms of Disease, 3) Examples of Global Experiences in Diabetes Care, 4) Basic Components of Management: Patient-Centeredness, Evidence-Based Medicine, and Outcomes, 5) Resources of Support for Persons with Diabetes, 6) Drug Therapy, 7) Cardiovascular Risk Factors, 8) Acute Complications, 9) Chronic Complications, 10) Diabetes in Special Populations, and 11) Novel Therapeutic Approaches: Evidence-Based and Others