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

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 Hypoglycemia
Severe Hypoglycemia
Glucagon
Glucagon Emergency Kits
Nasal Glucagon
Liquid Glucagon Rescue Pen
Emerging Rescue Therapies for Severe Hypoglycemia
BioChaperone Glucagon
Dasiglucagon
Intravenous Glucose
Treatment of Hypoglycemia After Exercise
Strategies to Reduce or Prevent Hypoglycemia
Prevention
Strategies to Reduce Hypoglycemia
Technology in the Reduction and Prevention of Hypoglycemia
Continuous Glucose Monitoring
Continuous Subcutaneous Insulin Infusion (CSII)
Sensor-Augmented Pumps (SAP)
Sensor-Augmented Pumps with Low Glucose Suspension (Suspend on Low)
Sensor-Augmented Pump Therapy with Predictive Low Glucose Management (Suspend Before Low)
Closed Loop Systems
Beta Cell Replacement
References
Further Reading
Books
T1D and Hypoglycemia
Physiology and Pathophysiology of Hypoglycemia
Insulins and Hypoglycemia
Pancreas Transplantation
HRS: Hypoglycemia Risk Score
Hypoglycemia in ACCORD, ADVANCE, and VADT
46: Inpatient Management of Diabetes and Hyperglycemia
Introduction
Recognition and Diagnosis of Hyperglycemia and Diabetes on Admission
Therapeutic Agents and Regimens for Inpatient Glycemic Control
Glycemic Control of the Non-critically Ill Patient
Glycemic Monitoring
Glycemic Target Values
Approach to Management
Glycemic Control of the Critically Ill Patient
Glycemic Monitoring
Glycemic Target Values
Approach to Management
Glycemic Control of the Perioperative Patient
Glycemic Monitoring
Glycemic Target Values
Approach to Preoperative Management
Special Considerations
Enteral and Parenteral Nutrition
Glucocorticoid Therapy
Insulin Pumps
Hypoglycemia
Transitioning from Hospital to Home
Conclusion
References
47: Diabetes and Infection
Introduction
Magnitude of Risk
Pathogenesis
The Immune Response
Diabetes and Viral Infections
The Coronavirus Pandemic and Diabetes
Pathophysiology of COVID-19 Infection in Hyperglycemia and Diabetes
Management of Patients with COVID-19 and Diabetes
Diabetes Parasitic Diseases and “The Hygiene Hypothesis”
Categories of Infections in Patients with Diabetes
Principles of Management
Awareness of Diabetes-Associated Diseases
Adequate Choice of Antibiotics
Glycemic Control
Source Control
When to Refer
Conclusion
References
48: COVID-19, Diabetes, and Cardiovascular Disease
Pathogenesis
Epidemiology
Management of Diabetes, COVID-19, and Cardiovascular Disease
Cardiovascular Complications of COVID-19 Infection
Conclusion
References
Part IX: Chronic Complications
49: Biochemical Mechanisms of Vascular Complications in Diabetes
Diabetes and Vascular Complications
Metabolic Stress
Polyol Pathway
Hexosamine Biosynthesis Pathway and O-GlcNAcylation of Proteins (Fig. 49.3)
Synthesis of Diacylglycerols and Protein Kinase C Activation
Glycation and Advanced Glycation End Products
Nuclear Factor Kappa B (NFκB)
Dicarbonyl Stress, Methylglyoxal, and Endogenous Glycation
NADH Overproduction or Reductive Stress
Oxidative Stress
Altered Lipid Metabolism, Dyslipidemia, and Accumulation of Cytotoxic Lipids
Inflammatory Stress
TGFβ and Epithelial Mesenchymal Transition in Diabetic Nephropathy (Fig. 49.4)
Endothelial Dysfunction and Nitric Oxide Deficiency
Anaerobic Metabolism and Neuropathic Pain
Suggested/Further Reading
References
Glossary
50: Diabetes and Cardiovascular Disease
Introduction
Ischemic Heart Disease in Diabetic Patients
Epidemiology
Pathophysiology of Atherosclerosis (Fig. 50.2) and Endothelial Dysfunction: Metabolic Syndrome
Treatment of Risk Factors and Its Impact on Primary Prevention
Cardiovascular Risk Evaluation in Diabetic Patients
Stable Ischemic Heart Disease
Acute Coronary Syndromes
Heart Failure in Diabetic Patients
Introduction and Epidemiology
Pathophysiology
Prevention and Treatment of HF and DM
Diseases of the Aorta in Diabetic Patients
Diabetes and Aortic Dissection/Aneurysm
Diabetes and Aortic Stenosis
Arrhythmias in Diabetic Patients
Special Features of Arrhythmias and Atrioventricular Blocks in Diabetic Patients
References
51: Diabetes and Stroke: The Role of Glucose Regulation
Stroke as a Long-Term Complication of Uncontrolled Diabetes Mellitus
Introduction
Epidemiological Overview of Diabetes and Stroke
Microvascular Complications of Diabetes
Macrovascular Complications of Diabetes
DM and Hyperglycemia in Acute Ischemic Stroke
Diabetes and Primary Stroke Prevention
Influence of Antidiabetic Drug Classes for Primary Stroke Prevention
Optimization of Diabetic Control and Additional Stroke Risk Factors
Diabetes and Secondary Stroke Prevention
Management of Additional Risk Factors and Secondary Stroke Prevention in DM
References
52: Peripheral Arterial Disease and Diabetes Mellitus
Epidemiology
Diagnostic Challenge
Pathophysiology, Natural History, and Outcomes
Management
Risk Factor Modification
Diabetes
Smoking
Hypertension
Dyslipidemia
Obesity
Exercise
Antiplatelets
Pharmacologic Treatment of Claudication
Revascularization
Indications
Interventional Challenges
Endovascular Versus Open
Percutaneous Therapy
Open Surgery
Areas of Current Interest
References
53: Ophthalmic Disease in Diabetes
Introduction
Epidemiology of Diabetes and Diabetic Retinopathy
Variability in the Results of Epidemiological Studies
Incidence and Progression of DR
The Impact of the Nordic (European) Diabetic Classification on Screening of Diabetic Retinopathy
OCT as a Current Screening Tool and AI as an Adjunct to Screen Activity
OCTA and OCTA as Part of Multimodal Imaging in Diabetic Retinopathy
Diabetic Retinopathy Physiopathology
Classification of Diabetic Retinopathy and Diabetic Macular Edema
ESASO Classification of Diabetic Maculopathy
Current Treatment of Diabetic Retinopathy
Ocular Manifestations of DM Other Than DR
Vitreoretinal Manifestations
Non-Retinal Manifestations
Eyelids
Cornea
Crystalline Lens
Refractive Error
Cataract
Glaucoma
Neuro-Ophthalmic Disorders
Pupillary Abnormalities
Oculomotor Nerve Palsy
Non-Arteritic Ischemic Optic Neuropathy
Conclusion
References
54: Diabetes and Oral Health
Introduction
Oral Health and Quality of Life
Periodontal Disease and Systemic Interaction Models
Periodontal Disease and Systemic Interaction Models
Periodontal Diagnosis and Treatment
Dental Caries in Diabetics
Hyposalivation and Xerostomia
Frequent Mucosal Lesions in Diabetics
Candidiasis
Wound Healing and Changes in the Mucosa
Healthcare Protocol of Diabetics in the Dental Office, Dental Management, Clinical History, and Patient’s Level of Control
Clinical Management of Diabetic Patients in the Dental Office
Antibiotics and Antimicrobial Prophylaxis
Antibiotics and Antimicrobial Prophylaxis
Guidelines the Physician Should be Aware of to Suspect an Oral Disease
Conclusions
Concluding Remarks
References
55: Renal Disease in Diabetes
History
Epidemiology of Diabetic Nephropathy
Pathophysiology
Hemodynamic Pathway
Metabolic Pathway
Polyol Path
Hexosamine Pathway
Advanced Glycation End Product (AGE) Pathway
Protein Kinase C Pathway
Inflammatory Pathway
Autophagy
SGLT-2
Albuminuria
Natural History of Diabetic Nephropathy: The Clinical Picture
Early Hypertrophy and Hyperfunction (Hyperfiltration)
Silent Nephropathy (Glomerular Lesion Without Clinical Disease)
Incipient Diabetic Nephropathy
Overt Diabetic Nephropathy
End-Stage Renal Failure
New Findings in the Natural History of Diabetic Nephropathy
Natural History and KDIGO Classification
Nephropathology
Biopsy Adequacy
Histology
Prevention of Diabetic Nephropathy
Treatment of Diabetic Nephropathy
Non-pharmacologic Intervention
Salt Intake
Protein Restriction
Pharmacologic Interventions
Renin-Angiotensin-Aldosterone System (RAS)
Novel Therapies
Sodium Glucose Transporters
GLP1 Receptor Agonists (GLP1AR)
Finerenone
Conclusions
References
56: Peripheral Diabetic Neuropathies
Introduction
Epidemiology
Pathophysiology
‘Chronic Pain Hurts the Brain’
Diagnosis
Forms of Diabetic Neuropathy
Sensorimotor Neuropathy
Diabetes-Associated Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Treatment of Diabetic Neuropathy
Preventive Treatment
Symptomatic Treatment: Painful Diabetic Neuropathy
References
57: Diabetic Cardiac Autonomic Neuropathy
Introduction
Definition of CAN
Epidemiology of CAN
Risk Factors for the Diabetic Cardiac Autonomic Neuropathy
Pathogenesis of CAN
Classification of Diabetic Cardiaс Autonomic Neuropathy [25]
Clinical Impact of CAN
Clinical Manifestations of CAN
Morbidity and Mortality in Cardiac Autonomic Neuropathy
CAN Assessment
Assessment of Symptoms
Assessment of Signs
Cardiovascular Autonomic Reflex Tests
Heart Rate Variability
Recommendations [50]
During 24-h Recordings
Heart Rate Turbulence
Baroreflex Sensitivity
Muscle Sympathetic Nerve Activity
Catecholamine Assessment and Cardiovascular Sympathetic Tests
Heart Sympathetic Imaging and Heart Function Tests
Recommendations [50]
Diagnostic Criteria for CAN
Staging of CAN
Conclusions [38]
Recommendations [38]
Management of CAN
Intensive Glycemic Control and Multifactorial Risk Intervention
Lifestyle Modification
Treatment of Dyslipoproteinemia
Correction of Metabolic Abnormalities in the Myocardium
Thrombosis Prevention and Treatment
Aldose Reductase Inhibitors
Replacement Therapy with the Help of Myoinositol
Aminoguanidine
Neurotrophic Therapy
Antineural Autoimmunity Human Immunoglobulin for Intravenous Use
Endoneural Perfusion Inhibition with the Development of Hypoxia
Activation of Free Radical Stress
Vitamins with Antioxidant Properties [a Liposoluble Vitamin B1 (Benfotiamine)], Combined Medications
Fatty Acids Metabolism Disorders (γ-Linolenic Acid, Acetyl L-Carnitine)
ω-3 PUFAs Medications
Symptomatic Treatment of Orthostatic Hypotension
New Glucose-Lowering Medications and Autonomic Nervous System
Sodium Glucose Transporter 2 Inhibitors (SGLT2i)
Glucagon-like Peptide 1 Receptor Agonists (GLP1-RA)
References
Glossary
58: Autonomic Visceral Neuropathy and Gastrointestinal Disorders
Introduction
Neuropathy in Diabetes Mellitus
The Hyperglycaemia Hypothesis
The Influence of Severe Hypoglycaemia
Gastrointestinal Disorders in Patients with Diabetes
Gastrointestinal Reflux Disease
Gastroparesis
Diarrhoea
Constipation
Diagnosis of Diabetic Autonomous Neuropathy
Further Reading
References
59: Urologic Complications in Patients with Diabetes
Introduction
Bladder Dysfunction (BD) and Cystopathy
Pathophysiology
Clinical Manifestations
Diagnosis
Treatment
Benign Prostatic Hyperplasia (BPH) and Urethral Obstruction
Pathophysiology
Clinical Manifestations
Diagnosis
Treatment
Sexual Dysfunction
Erectile Dysfunction (ED)
Pathophysiology
Diagnosis
Treatment
Urinary Tract Infections
Pathophysiology
Clinical Manifestations
Diagnosis
Treatment
Conclusions
References
60: Musculoskeletal Complications of Diabetes Mellitus
Introduction
Bone Effects of Diabetes: Bone Density and Fracture Risk
Muscle Effects of Diabetes
Diabetic Myonecrosis
Diabetic Amyotrophy
Joint and Connective Tissue Effects of Diabetes
Adhesive Capsulitis of the Shoulder (Frozen Shoulder Syndrome, Shoulder Periarthritis) Enter Box 60.1
Limited Joint Mobility (Diabetic Cheiro-Arthropathy) Enter Box 60.2
Dupuytren Contracture (DD)
Calciphylaxis
Stenosing Flexor Tenosynovitis (Trigger Finger)
Calcific Shoulder Periarthritis (Tendinitis)
Carpal Tunnel Syndrome (CTS)
Reflex Sympathetic Dystrophy
Diffuse Idiopathic Skeletal Hyperostosis (DISH), Forestier’s Disease
Crystal-Induced Arthritis and Gout
Osteoarthritis
Charcot Arthritis
Diabetic Foot
Conclusion
References
61: Diabetes and the Skin
Introduction
Pathogenesis
Skin Manifestations of Diabetes Mellitus
Acanthosis Nigricans
Acrochordon
Acquired Perforating Dermatosis
Bullosis Diabeticorum
Diabetic Cheiroarthropathy (Diabetic Stiff Hand or Limited Joint Mobility Syndrome)
Diabetic Dermopathy
Disseminated Granuloma Annulare
Eruptive Xanthomas
Infections
Lichen Planus
Necrobiosis Lipoidica
Psoriasis Vulgaris
Pruritus, Xerosis Cutis, and Keratosis Pilaris
Rubeosis Faciei—Palmar Erythema and Periungual Telangiectasia
Skin Thickening and Scleredema Diabeticorum
Ulcers
Vitiligo
Yellow Skin
Mucormycosis
Necrotising Fasciitis
COVID-19, the Skin, and Diabetes
Side Effects of Medication
Side Effects of Insulin
Insulin Lipodystrophy.
Oral Hypoglycemic Medication
Concluding Remarks
Glossary
References
Further Reading
62: Foot Complications
Introduction
Charcot Neuroarthropathy
Foot Amputation
Digital Amputation (Fig. 62.11)
Ray Amputation
Transmetatarsal Amputation
Isolated and Panmetatarsal Head Resection
Tarsometatarsal (Lisfranc) Midtarsal (Chopart) Amputations (Figs. 62.17 and 62.18)
Conclusion
References
63: Diabetes and Cancer
Introduction
Historical Facts
Epidemiology
Types of Diabetes Mellitus
Diabetes Mellitus and Oncogenesis—The Main Correlation
Biological Linking Factors
Role of Hyperinsulinaemia in Cancer Biology
Indirect Effects of Hyperinsulinaemia on Cancer Biology
The Role of Hyperglycaemia in Cancer Biology
Mechanisms Leading to Proliferative Activity of Hyperglycaemia [21, 44, 45]
Mechanisms Leading to Anti-apoptotic Activity of Hyperglycaemia [44]
Mechanisms Leading to Hyperglycaemia-Mediated Metastasis [44–47]
Role of Obesity and Fat-Induced Chronic Inflammation in Cancer Biology
Diabetes and the Correlation with Oncogenesis in Particular Organs
Pancreatic Cancer
Laryngeal Cancer
Pharyngeal Cancer
Oral Cancer
Anti-diabetic Medications and Their Influence on Neoplastic Transformation
Metformin: Mechanism of Action and Its Influence on Carcinogenesis
Indirect Impact of Metformin on Neoplastic Transformation [6, 105, 113–120]
Direct Impact of metformin on Neoplastic Transformation
Effects of Metformin on Neoplasms of the Digestive System
Effects of Metformin on Neoplasms of the Genitourinary System
Effects of Metformin on Lung Cancer
Effects of Metformin on Head and Neck Cancers
Sulfonylureas: Mechanism of Action and Influence on Carcinogenesis
Exogenous Insulin: Influence on Carcinogenesis
Thiazolidinediones: Mechanism of Action and Influence on Carcinogenesis
Incretin-Based Medications: Mechanisms of Action and Influence on Carcinogenesis
Alpha-Glucosidase Inhibitors (AGIs)
Sodium-Glucose Co-transporter 2 Inhibitors (SGLT2 Inhibitors)
Summary
Concluding Remarks
References
Further Reading
Glossary
Part X: Diabetes in Special Populations
64: Diabetes in Children and Adolescents
Introduction
Definition and Diagnostic Tests for Diabetes in Children
Diagnostic Tests for Diabetes
Diagnostic Tests for Increased Risk of Diabetes (Prediabetes)
Etiological Classification
Type 1 Diabetes Mellitus
Epidemiology
Pathogenesis of Type 1 Diabetes Mellitus
Genetic Risk Factors of Type 1 Diabetes Mellitus
Environmental Risk Factors of Type 1 Diabetes Mellitus
Clinical Presentation
Management of Type 1 Diabetes Mellitus
Diabetes Self-Management Education and Support
Diabetes Education
Glycemic Control
Blood Glucose Monitoring
Insulin Therapy
Nutritional Management
Exercise Management in Type 1 Diabetes
Effect of Treatment on the Honeymoon Period of Type 1 Diabetes
Glucagon
Islet Transplantations and Stem Cell Therapy
Addition of Metformin for Children with Type 1 Diabetes Mellitus
Management of Hypoglycemia in Children and Adolescents with Diabetes
Sickness
Surgery
Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State
Autoimmune Conditions
Psychosocial Issues
Vaccination
Pregnancy Prevention
Management of Cardiovascular Risk Factors
Hypertension
Dyslipidemia
Nephropathy
Retinopathy
Neuropathy
Smoking
Quality of Life
Type 2 Diabetes
Pathophysiology of T2D Mellitus
Treatment
Nutritional and Exercise Management
Smoking and Tobacco Use
Glycemic Monitoring
Glycemic Targets
Pharmacological Treatment
Metformin
Glucagon-like peptide-1 analogs
Insulin
Bariatric Surgery
Comorbidities
Obesity
Hypertension
Nephropathy
Dyslipidemia
Polycystic Ovarian Syndrome
Non-alcoholic Fatty Liver Disease
Obstructive Sleep Apnea
Depression
Additional Health Problems Related to Obesity and T2D
Transition from Pediatric to Adult Care
References
Suggested Reading
65: Pregnancy: Pregestational and Gestational Management
Introduction
Classification and Diagnosis
Recommendations for the Diagnosis of Diabetes in the Pregnant Woman (American Diabetes Association, 2016)
Changes in Carbohydrate Metabolism in the Pregnant Woman
Treatment
Insulin
The Use of Oral Hypoglycemic Drugs in Pregnancy
Glyburide
Metformin
Management of Pregnancy
Conclusions
References
Further Reading
Glossary
66: The Elderly with Diabetes
Diabetes in Older Adults
Geriatric Considerations in the Management of Diabetes in the Older Adult
Geriatric Syndromes and Assessments for Older Patients with Diabetes
Medical Domain
Malnutrition
Functional Domain
Impaired Mobility
Self-Care Deficit and Functional Decline
Falls
Urinary Incontinence
Psychological Domain
Dementia
Depression
Poor Quality of Life
Social Domain
Food Insecurity
Special Consideration for Diabetes Management in Older Adults
Hypoglycemia in Older Adults: Primary and Secondary Prevention
Secondary Prevention
Primary Prevention
Pharmacotherapy
References
Further Reading
Part XI: Novel Therapeutic Approaches: Evidence-Based and Others
67: The Artificial Pancreas
Introduction
History
Technology
Components of an Artificial Pancreas
Insulin Pump
Continuous Glucose Monitoring
Computer
Algorithms
PID
Model Predictive Controller
Fuzzy Logic
Clinical Testing
Evaluating an Artificial Pancreas
Clinical Trial Structure
Safety
Effectiveness
Clinical Trials of Artificial Pancreas Devices
Available Devices
Future Devices
Cyber-Security
Concluding Remarks
References
68: Unproven Therapies for Diabetes
Introduction
Prevalence and History of Diabetes
Complementary and Alternative Medicine
Definition and Epidemiology
Possible Reasons Towards CAM Popularity
CAM Therapies for Diabetes Management
Many Anti-diabetic Medications Have a Natural Origin
Prevalence and Patterns of CAM Use Among Diabetes Patients
Concerns with CAM Therapies
Compromised Quality of CAM Products
Complications from Drug Interactions
Underdeveloped Research and Poor Quality of Clinical Trials
False Claims and Fake Publicity
Lack of Proper Regulations and Policies
Absence of Proper Communication with Health Practitioners
Concerns with Other CAM Therapies
Impact of CAM on Diabetes Treatment Outcomes
Recommendations for a Prospective CAM Use
Proper Patient–Physician Fit and Judicious Choice of Therapies
Proper Regulations and Well-Conducted Research
Integrating CAM into Conventional Care
CAM Therapy and COVID-19
Conclusion
References
69: Insulin Delivery: An Evolution in the Technology
Introduction
Insulin Delivery Devices
Insulin Vial and Syringe
Insulin Pen
First Generation Insulin Pens
Next-Generation Insulin Pens
Connected Pens
InPen Smart Insulin Pen
Injection Aids: I-Port Advance Injection Port
Insulin Pumps
Continuous Subcutaneous Insulin Infusion (CSII)
Patch Pumps
Continuous Intraperitoneal Insulin Infusion (CIPII)
Sensor-Augmented Pump Therapy (SAP)
Automation of Insulin Pump
Artificial Pancreas (Closed Loop)
Alternate Controller-Enabled Infusion (ACE) Pumps
Do-It-Yourself Artificial Pancreas (DIY-APS)
OpenAPS
AndroidAPS
Loop
Bionic Pancreas (BP)
D-Dads
Bolus Calculator Apps
Implanted Pancreas
Insulin Inhalers
Jet Injectors
Oral Insulin
Colonic Insulin Delivery
Nasal Insulin
Buccal Insulin
Transdermal
Other Non-conventional Routes
Ocular Route
Rectal Route
Intra-Tracheal
Conclusion
References
Index