دانلود کتاب Diabetes and Cardiovascular Disease (Contemporary Cardiology)

فهرست مطالب :

Preface
Contents
Part I: Pathophysiology
Chapter 1: Introduction: Epidemiology, Definitions, and Pathophysiology
Introduction
The Diabetes Epidemic
A Heterogeneous Disease with Diverse Etiologies
The Twin Threat of Diabetes and Cardiovascular Disease
Diabetes Treatments and Emerging Applications
References
Chapter 2: Effects of Insulin on the Vascular System
Introduction
Technical Considerations
Physiology
Insulin’s Effects on Skeletal Muscle Blood Flow
Insulin’s Effects on the Heart
Insulin’s Effects on the Sympathetic/Parasympathetic Nervous System
Insulin’s Effects on the Kidneys
Insulin’s Effect on Blood Pressure and Vascular Resistance
Metabolic Implications of Insulin’s Vascular Effects
Interactions Between Insulin and Norepinephrine and Angiotensin II
Interactions Between Insulin and Adipocytokines
Pathophysiology: The Metabolic Syndrome
The Metabolic Syndrome and Insulin’s Effects on Skeletal Muscle Blood Flow
The Metabolic Syndrome and Insulin’s Effects on the Heart
The Metabolic Syndrome and Insulin’s Effects on the Sympathetic/Parasympathetic Nervous System
The Metabolic Syndrome and Insulin’s Effect on the Kidney
The Metabolic Syndrome and Insulin’s Effect on Blood Pressure
The Metabolic Syndrome and Interactions Between Insulin and Norepinephrine
Interventions to Ameliorate the Effects of the Metabolic Syndrome on the Vascular System
Conclusion
References
Chapter 3: Effects of Diabetes and Insulin Resistance on Endothelial Functions
Introduction
Insulin Resistance
Structure and Signaling of Insulin Receptors (IR) on the Vascular System
Physiologic Actions of Insulin on the Vascular System
Selective Insulin Resistance
Hyperglycemia
Advanced Glycation End-Products
Activation of the Polyol Pathway
Alteration in Oxidative Stress
Activation of the DAG–PKC Pathway
Dyslipidemia
Cellular and Functional Alterations in Vascular Endothelial Cells Induced By Diabetes
Vascular Contractility and Blood Flow
Vascular Permeability and Neovascularization
Na+-K+-ATPase
Basement Membrane Thickening and Extracellular Matrix Expansion
Thrombosis
Conclusion
References
Chapter 4: PPARs and Their Emerging Role in Vascular Biology, Inflammation and Atherosclerosis
Introduction
The Basic Science of Peroxisome Proliferator-Activated Receptor Biology
Peroxisome Proliferator-Activated Receptor-γ: Key Regulator of Adipogenesis and Insulin Sensitivity
Peroxisome Proliferator-Activated Receptor-α: Key Regulator of Fatty Acid Oxidation
Peroxisome Proliferator-Activated Receptor-β/δ: Widely Expressed, But Still Incompletely Understood
Peroxisome Proliferator-Activated Receptors in Vascular Biology and Atherosclerosis
Peroxisome Proliferator-Activated Receptor-γ in Inflammation, Vascular Biology and Atherosclerosis
Peroxisome Proliferator-Activated Receptors in Vascular Biology, Inflammation and Atherosclerosis
Endogenous Peroxisome Proliferator-Activated Receptor Activation: New Connections Between Fatty Acids, Lipid Metabolism and Peroxisome Proliferator-Activated Receptor Responses
Conclusion
References
Chapter 5: Diabetes and Thrombosis
Diabetes and Vascular Disease
Thrombosis and Atherosclerosis
Platelet Function in Subjects with Diabetes Mellitus
Evidence of Increased Platelet Reactivity
Mechanisms Responsible for Hyperreactivity of Platelets in People with Diabetes
Antiplatelet Therapy and Diabetes
The Coagulation System and Diabetes Mellitus
Mechanisms Responsible for a Prothrombotic State Associated with Diabetes
Diabetes and Fibrinolysis
Mechanisms Responsible for the Overexpression of PAI- in Diabetes
Fibrinolysis and Arterial Mural Proteolysis
Therapeutic Implications
References
Chapter 6: Genetics of Coronary Artery Disease in Diabetes Mellitus
Leveraging Genetics to Decrease the Cardiovascular Burden of Diabetes
Genetic Determinants of CAD in Diabetes
Genetic Variants Increasing CAD Risk in the General Population and in T2D
Genetic Variants Predisposing to Both T2D and CAD
The “Common Soil” Hypothesis and Insulin Resistance
Genetic Variants Increasing the Risk of CAD Specifically in the Presence of T2D
The 1q25 Locus
The HP Locus
Translating Genetic Findings to Clinical Practice
Improving CV Risk Assessment
Development of New Preventive Interventions
9p21 Locus
1q25 Locus
PCSK9
Personalization of Therapy
Genetics Determinants of Cardiovascular Response to Intensive Glycemic Control
Pharmacogenetic Studies on the Cardiovascular Effectiveness of Fenofibrate
Conclusions and Future Directions
References
Chapter 7: Nitric Oxide, Its Role in Diabetes Mellitus and Methods to Improve Endothelial Function
Introduction
Physiologic Effects of Nitric Oxide on the Vascular System
Nitric Oxide and the Development of Atherosclerosis
Endothelial Dysfunction and Diabetes Mellitus
Endothelium-Dependent Vasodilation in Animal Models
Human Studies of Endothelium-Dependent Vasodilation in Insulin-Dependent Diabetes Mellitus
Human Studies of Endothelium-Dependent Vasodilation in Non-insulin-Dependent Diabetes Mellitus
Possible Mechanisms of Impaired Endothelium-Dependent Vasodilation
Alterations in the Insulin Signaling Pathways and Endothelial Dysfunction
Impaired Nitric Oxide Synthesis and/or Sensitivity
Oxidative Stress and Role of NADPH Oxidases
Oxidized LDL (ox-LDL)
Decreased l-arginine Availability
Decreased Availability of Cofactors of NO Synthesis
S-glutathionylation of eNOS
Increased Concentration of Endogenous Inhibitors of eNOS, ADMA, and Caveolin-1
Increased Nitric Oxide Inactivation (Decreased Bioavailability) and/or Breakdown of Nitric Oxide
Free Fatty Acids and Nitric Oxide
Other Risk Factors in Diabetic Endothelial Dysfunction
Dyslipidemia
Hypertension
Lipotoxicity
Potential Preventive and Therapeutic Options
Protein Kinase C Inhibitors
Inhibitors of AGE Production
Vitamins C and E
Tetrahydrobiopterin
l-Arginine
Estrogen
Angiotensin-converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers
Lipid Lowering Medications
Insulin Sensitizers
DPP-4 Inhibitors and GLP-1 Receptor Agonists
SGLT-2 Inhibitors
Conclusions
References
Chapter 8: Adiponectin, Diabetes, and the Cardiovascular System
Introduction
The Role of Healthy White Adipose Tissue: An Active Endocrine Organ
Adipose Tissue Dysfunction and Its Role in the Development of Cardio-metabolic Disorders
Adiponectin Biosynthesis and Structural Properties
Adiponectin Receptors
The Role of Adiponectin in Physiology and Pathophysiology
Regulation of Adiponectin
Adiponectin and Cardiometabolic Risk Factors
Insulin Resistance and Type 2 Diabetes Mellitus
Hypertension
Dyslipidemia
Cigarette Smoking
The Role of Adiponectin in Cardiovascular Disease
Adiponectin’s Direct Vascular and Atheroprotective Effects
Adiponectin’s Direct Cardioprotective Effects
Cardiac Metabolism and Function
Myocardial Ischemia–Reperfusion Injury and Cell Survival
Cardiac Hypertrophy
Adiponectin and Cardiovascular-Related Outcomes and Mortality
Therapeutic Modulation of Adiponectin and Its Receptors
Adiponectin
Adiponectin Receptors
Proglucagon Family of Molecules and Gut-Derived Peptide Physiology
Ghrelin
PYY
GLP-1
OXM
Glicentin
PP
CCK
Amylin
GIP
Glucagon
GLP-2
SGLT2/SGLT2i Physiology
Conclusion
References
Chapter 9: Diabetes and Atherosclerosis
Introduction
Endothelial Dysfunction
Nitric Oxide
Prostacyclin
Endothelin 1
Thromboxane
Inflammation
Oxidative Stress
Adhesion Molecules
Influence of Altered Hemodynamics on Endothelial Dysfunction
Epigenetic Modifications and Micro RNAs
Mechanisms of Foam Cell Formation
Quantitative/Qualitative Abnormalities of Lipoproteins
Lipoprotein Modification
Lipoprotein Glycation
Lipoprotein Oxidation and Glycoxidation
Phospholipid Oxidation
Modified LDL Antibodies and LDL-Containing Immunocomplexes
Sphingolipids
Pathogenesis of Diabetic Vasculopathy
Macrophage Activation by Modified Lipoproteins and LDL-Immune Complexes
Expression of Metalloproteinases Induced by Modified Lipoproteins and Modified LDL-Immune Complexes: Role in Plaque Rupture
Thrombus Formation
Abnormalities in Platelet Function
Abnormalities in Coagulation
Abnormalities in the Fibrinolytic System
References
Chapter 10: The Effects and Treatment of Inflammation on Diabetes Mellitus and Cardiovascular Disease
Introduction
A Basic Review of the Immune System and Inflammation
An Intertwining Relationship Between Diabetes and Inflammation
Inflammation as a Risk Factor for Type II DM
Type II DM Causing an Inflammatory Response
The Role of Diabetes-Related Inflammation with Cardiovascular Disease and Atherosclerosis
Current Treatments, Novel Therapies, and Future Potential
The Effect of Oral Hypoglycemic Medications on Inflammation (Table 10.1)
The Effect of Anti-inflammatory Drugs on Type 2 Diabetes Mellitus and Cardiovascular Disease
Trials on Type 2 DM: (Table 10.2)
Trials on Targeting the Inflammatory Process Cardiovascular Disease as the End-Point
References
Part II: Associated Conditions of Type 2 Diabetes Mellitus
Chapter 11: The Role of Sleep Apnea in Diabetes Mellitus and Cardiovascular Disease
Introduction
Definitions
Prevalence and Risk Factors
Pathophysiology
Obstructive Sleep Apnea
Central Sleep Apnea
SDB evaluation, Screening, and Diagnosis
Treatment for SDB in General
Sleep Apnea and Heart Failure
Treatment of SDB in HF
Sleep-Disordered Breathing and Arrhythmias
Sleep Apnea and Atrial Fibrillation
OSA, Bradycardia, and Sick Sinus Syndrome
OSA and Ventricular Arrhythmias
SDB and Stroke
OSA and Hypertension
OSA and CAD
OSA and Sudden Cardiac Death
Sleep Apnea and Diabetes
Pathophysiology in Relation to T2DM
Screening for OSA in Patients with T2DM
Treatment
Sleep-Disordered Breathing and High-risk Pregnancy Conditions
Summary and Future Directions
References
Chapter 12: The Metabolic Syndrome and Vascular Disease
Introduction
Defining the Metabolic Syndrome
Epidemiology
Cardiovascular Risk
Insulin Resistance
Pancreatic β-Cell Dysfunction
Prandial Glucose
Adipokines
Oxidative Stress
Systemic Inflammation
Endothelial Dysfunction
Advanced Glycosylation End Products
Renal Glucose Metabolism
Microbiota
Addressing Patients with MetS
Intensive Lifestyle
Low-Fat/Low-Calorie Dietary Patterns
The Mediterranean Diet
The DASH Diet
The Ornish Diet
Dietary Supplements
Pharmacologic Therapies
Hypertension
Cholesterol
Insulin Resistance
Metformin
Acarbose
PPARγ Agonists
GLP1 Receptor Agonists
SGLT2 Inhibitors
Medications for Weight Loss
Surgical Treatment
Conclusion
References
Chapter 13: Diabetes and Hypertension
Introduction
Epidemiological Aspects of Hypertension in Diabetes and the Metabolic Syndrome
Hemodynamic and Metabolic Characteristics of Hypertension in Diabetics
Loss of Nocturnal Decline of BP (Non-dipping)
Volume Expansion and Salt Sensitivity
Microalbuminuria
Isolated Systolic Hypertension
Orthostatic Hypotension
Pathophysiology of Hypertension in Diabetics
Cardiovascular Effects of Insulin and Insulin-like Growth Factor 1 in the Normal and in the Insulin-Resistant State
Treatment Goals and Pharmacological Therapy
Lifestyle Modifications in Management of Hypertension (Table 13.3)
Pharmacological Therapy for Hypertension in Patients with Diabetes
Thiazide Diuretics
ACE Inhibitors, ARBS, ARNI
β-Blockers
Calcium Channel Blockers
Other Pharmacological Interventions to Treat Coronary Heart Disease
Risk Factors
Conclusions
References
Chapter 14: Diabetes and Dyslipidemia
Introduction
Role of Risk Factors in ASCVD
Role of Lipids in ASCVD
Lipid Abnormalities in Patients with Diabetes
Effect of Glucose-Lowering Drugs on Lipids
Pathophysiology of the Dyslipidemia of Diabetes
Increase in Triglycerides
Overproduction of VLDL by the Liver
Decreased Degradation of Triglyceride-Rich Lipoproteins
Effects of Hypertriglyceridemia on HDL and LDL
Role of Poor Glycemic Control
Role of Obesity and Inflammation
Role of Adipokines
Effect of Lipid-Lowering on Atherosclerotic Cardiovascular Events in Diabetes
Life Style Studies
Monotherapy Drug Studies
Statins
Fibrates
Niacin
Ezetimibe
Other Drugs
Combination Drug Therapy
Statins + Fibrates
Statin + Niacin
Statin + Ezetimibe
Statin + PCSK9 Inhibitors
Statins + Low-Dose Omega-3-Fatty Acids
Statins + High-Dose Omega-3-Fatty Acids
Current Guidelines for Serum Lipids
American Diabetes Association
American College of Cardiology and American Heart Association
National Lipid Association
American Association of Clinical Endocrinologists/American College of Endocrinology
European Society of Cardiology and European Atherosclerosis Society
Our Recommendations for Guidelines
Treatment of Lipid Abnormalities in Patient with Diabetes
Life Style Changes
Drug Therapy
Statins
Ezetimibe
Fibrates
Bile Acid Sequestrants
Niacin
Omega-3-Fatty Acids
PCSK9 Inhibitors
Bempedoic Acid
Therapeutic Approach
First Priority: LDL-C
Second Priority: Non-HDL-C and Triglycerides
Very High Triglycerides
Low HDL-C
Conclusion
References
Part III: Diabetic Microvascular Disease
Chapter 15: Diabetic Retinopathy
Introduction
Pathophysiology of Diabetic Retinopathy
Early Studies
Present Understanding
Genetic Risk Factors
Natural History and Clinical Features of Diabetic Retinopathy
Epidemiology
Clinical Findings in Diabetic Retinopathy
Classification of Diabetic Retinopathy
Treatment of Diabetic Retinopathy
Overview
Proliferative Diabetic Retinopathy
Panretinal Photocoagulation
Anti-VEGF Therapy
Diabetic Macular Edema
Focal Laser Photocoagulation
Steroid Therapy
Anti-VEGF Therapy
Vitrectomy for Advanced PDR
Novel Treatments
Fenofibrate
Plasma Kallikrein Inhibitors (PKI)
Ang-Tie2 Targeting Drugs
Photobiomodulation
Conclusions/Summary
References
Chapter 16: Microcirculation of the Diabetic Foot
Introduction
Anatomy of Skin Morphology and Microcirculation
Regulation of Skin Blood Flow
The Concept of “Small Vessel Disease”
Structural Changes of the Foot Microcirculation
Functional Changes of the Microcirculation
Methods of Evaluating the Microcirculation of the Feet
Measurements of Capillary Blood Flow Using Laser Doppler Flowmetry
Measurements of Transcutaneous Oxygen Tension (TcPO2)
Capillaroscopy
Measurements and Quantifying Tissue Oxygenation Using Hyperspectral Imaging
Photoacoustic Imaging
Changes in Vascular Reactivity
Functional Changes
The Role of the Nerve Axon Reflex in Vasodilation
Differences Between Forearm and Foot Microcirculation
Microvascular Changes in Diabetic Foot with Charcot Arthropathy
Conclusions
References
Chapter 17: Diabetic Nephropathy
Introduction
Pathogenesis
Tubuloglomerular Feedback [10, 11]
Advanced Glycation End-Products (AGE) [12]
AGE–RAGE Interaction [13]
Mitochondrial Dysfunction [14]
Genetic Predisposition [15, 16]
Nephropathy Staging (Fig. 17.2 and Table 17.1)
Treatment to Prevent or Delay Progression of DKD
Glycemic Control
Metformin
Sulfonylureas
Thiazolidinediones (TZDs)
Incretins
Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs)
Sodium–Glucose Cotransporter-2 (SGLT-2) Inhibitors
Advanced Kidney Disease
Hypertension
Proteinuria
Non-proteinuria
RAAS
Mineralocorticoid Receptor (MR) Antagonists
Endothelin Receptor Antagonists
Lifestyle Modifications
Conclusion
References
Chapter 18: Diabetes and Cerebrovascular Disease
Introduction
Diabetes as a Risk Factor for Stroke and Cognitive Impairment, Pathophysiologic Mechanisms, and Preventive Strategies
Epidemiologic Considerations: Insulin Resistance, Diabetes, and the Risk of Stroke
Diabetes, Subclinical Brain Injury, and Vascular Cognitive Impairment
Pathophysiology of Cerebral Vascular Injury
Glycemic Control and Mitigation of Stroke Risk: Evidence from Clinical Trials
Insulin Resistance
Hyperglycemia and Intensive Glycemic Control
Glycemic Control and its Effect on Brain Atrophy and Cognitive Impairment
Management of Cardiovascular Risk Factors for Stroke Prevention in Diabetic Patients
Hypertension
Hypercholesterolemia
Diabetes and Hyperglycemia in Acute Stroke: Pathophysiology, Outcomes, Glycemic Variability, and Management of Glycemia in the Acute Phase of Stroke
Incidence and Mechanisms of Post-Stroke Hyperglycemia
Mechanisms of Exacerbation of Acute Ischemic Injury by Hyperglycemia
Oxidative Stress, Lactic Acidosis, and Cellular Energy Failure
Reduced Collateral Blood Flow and Penumbra Salvage
Blood–Brain Barrier Dysfunction
Post-stroke Inflammatory Response
Hyperglycemia and Clinical Stroke Outcomes
Mortality and Functional Outcome after Ischemic and Hemorrhagic Stroke
Impact of Diabetes and Hyperglycemia on Intravenous Thrombolysis and Mechanical Thrombectomy Outcomes
Additional Components of Dysglycemia in Acute Stroke: Hypoglycemia and Glycemic Variability
Hypoglycemia
Glycemic Variability
Glycemic Management in the Acute Phase of Stroke
Overview
Optimal Timing of Treatment Initiation and Treatment Duration
Glucose Threshold for Hypoglycemic Treatment Initiation
Optimal Regimen for Glucose Control
Optimal Target Glucose Range
Current Guidelines and Standard of Practice for Glycemic Control in Acute Stroke
References
Chapter 19: Diabetes and the Autonomic Nervous Systems
The Autonomic Nervous System
Central Autonomic Dysfunction
Peripheral Autonomic Nervous System
Sympathetic Division
Parasympathetic Division
Neurotransmitters of the Autonomic Nervous System
Evaluation of the Autonomic Nervous System
Clinical History
Autonomic Questionnaires
Physical Exam
Autonomic Testing
Tilt Table Testing
Cardiovagal Testing
Sudomotor Function Testing
Skin Biopsy for Immunohistochemistry
Other Clinically Appropriate Testing
Clinical Manifestations of Autonomic Dysfunction in DM
Peripheral Neuropathy
Orthostatic Hypotension
Gastroparesis
Temperature and Sweat Changes
Pathophysiology of Diabetic Autonomic Neuropathic Changes
Oxidative Stress
Tumor Necrosis Factor-Alpha
Mitochondrial Dysfunction and Diabetes
Interventions for Autonomic Dysfunction
Conservative Therapies for Orthostatic Hypotension
Pharmacological Management for Orthostatic Hypotension
Fludrocortisone
Midodrine
Droxidopa
Pyridostigmine (Mestinon)
Treatment of Neuropathic Pain
Tricyclic Antidepressants
Serotonin and Norepinephrine Reuptake Inhibitors
Gabapentinoids Include Gabapentin and Pregabalin
Combination Therapy
Future Research: GLP1
References
Chapter 20: Diabetes and Erectile Dysfunction
Introduction
Epidemiology
Physiology of Erectile Function
Basic Anatomy
Mechanism of Erectile Function
Clinical Evaluation of Erectile Function
Erectile Dysfunction and Diabetes Mellitus
Molecular Mechanisms of ED in T2DM
Erectile Dysfunction and Hypertension
Structural Changes Caused by HTN Leading to ED
Erectile Dysfunction as a Marker of Cardiovascular Disease
Treatment of Hypertension
Thiazide Diuretics
Beta-Blockers
Calcium Channel Blockers
ACE Inhibitors
ARBs
Treatment of Diabetes Mellitus
Insulin
Biguanides
Sulfonylureas
Thiazolidinediones
Dipeptidyl Peptidase-4 Inhibitors (Gliptins)
Glucagon-Like Peptide 1 Receptor Agonists
Sodium-Glucose Co-Transporter-2 Inhibitors (Gliflozins)
Treatment of Erectile Dysfunction
Oral Agents
Intracavernosal Injections
Intraurethral Suppositories and Gels
Mechanical Devices
Penile Prosthesis Surgery
Conclusion
References
Part IV: Peripheral Vascular Disease
Chapter 21: Peripheral Vascular Disease in Patients with Diabetes Mellitus
Introduction
Pathogenesis of Atherosclerosis in Diabetes Mellitus
Clinical Presentation
Principles of Evaluation
Principles of Therapy
Medical Treatment for PAD
Exercise Therapy
Antiplatelet Therapy
Statins
Cilostazol
Pentoxifylline
ACE Inhibitors
Surgical Treatment for PAD
Summary
References
Chapter 22: Epidemiology of Peripheral Vascular Disease
Introduction
Epidemiologic Principles Relevant to the Study of Arterial Diseases
The Prevalence and Incidence of Peripheral Artery Disease
Risk Factors for Peripheral Artery Disease
Conditions Associated with Peripheral Artery Disease
Mortality Associated with Peripheral Artery Disease
Conclusions
References
Part V: Cardiovascular Disease
Chapter 23: Managing Stable Coronary Artery Disease in Diabetes
Background
Stable Coronary Artery Disease
Antiplatelets
Aspirin and/or Clopidogrel
Aspirin and Ticagrelor
Aspirin and Rivaroxaban
Blood Pressure
Blood Pressure Target
Choice of Antihypertensive Agents
Hyperlipidemia
Statins
Non-statin LDL-C–Lowering Treatments
Non-LDL Target Therapies
Lifestyle Modifications
Smoking
Diet
Psychosocial Factors and Sleep
Physical Activity
Weight
Stable Angina
Evaluation
Medical Therapy
Revascularization
References
Chapter 24: The Management of Hyperglycemia and DM in Patients with an Acute Coronary Syndrome
Introduction
Hyperglycemia Defined in Relation to Acute Coronary Syndrome
Prevalence of Elevated Glucose Levels in Acute Coronary Syndrome
Relationship Between Glucose Levels and Mortality in Acute Coronary Syndrome
Dynamic Changes in Glucose Levels in Acute Coronary Syndrome
Clinical Trials of Glucose Control in Patients with Acute Coronary Syndrome
Relationship Between Glucose Variability and Patient Outcomes During Acute Coronary Syndrome
The Prognostic Importance of Hypoglycemia in Patients with Acute Coronary Syndrome
Current Patterns of Glucose Control in Acute Coronary Syndromes
Summary and Recommendations
References
Chapter 25: Diabetes and Percutaneous Interventional Therapy
Section A: Coronary Interventions in the Diabetic Population
Introduction
Diabetes Mellitus and Atherosclerosis
Impact of Diabetes Mellitus on Ischemic Vascular Disease
Management of Diabetic Coronary Artery Disease
Left Main Disease
Section B: Peripheral Arterial Interventions in the Diabetic Population
Introduction
Lower Extremity PAD
Revascularization Approach: Surgery Versus Endovascular Intervention
Endovascular Therapies in the Diabetic Patient
Drug-Coated Balloons and Drug-Coated Stents
Debulking Therapies
Renal Interventions
Carotid Interventions
References
Chapter 26: Cardiac Surgery and Diabetes Mellitus
Introduction
Operative Risks of Cardiac Surgery in Diabetic Patients
Strategies for Myocardial Revascularization in Diabetic Patients
CABG Versus Percutaneous Angioplasty
CABG Versus Stenting
Surgical Outcomes in Diabetic Patients
Surgical Considerations in Diabetic Patients
Operative Considerations
Postoperative Care
Molecular Mechanisms of Pathogenesis in Diabetes During Cardiac Surgery
Endothelin-1 and Oxidative Stress
Gene Expression Profiles of Diabetic Patients After Cardiac Surgery with Cardiopulmonary Bypass and Cardioplegia
Conclusions
References
Chapter 27: Heart Failure and Cardiac Dysfunction in Diabetes
Introduction
Epidemiology of Diabetes and Heart Failure
Diabetes in Heart Failure
Heart Failure in Diabetes
Prognosis of Patients with Heart Failure and Diabetes
Causes of Heart Failure
Clinical Presentation of Diabetic Cardiomyopathy
Cellular and Molecular Mechanisms
Evaluation of Heart Failure in Patients with Diabetes
Treatment of Heart Failure in Diabetes
Management of Diabetes in Patients with Heart Failure
Intensity of Blood Glucose Levels
Pharmacologic Management of Diabetes in Patients with Heart Failure
Older Oral Agents
Insulin
Cardiac-specific Diabetes Medications
Glucagon-like Peptide-1 Receptor Agonists
Sodium–Glucose Co-transporter 2 Inhibitors
SGLT2 Inhibitors in Heart Failure with Preserved Ejection Fraction
SGLT2 Inhibitors in Chronic Kidney Disease
Management of Heart Failure in Patients with Diabetes
General Management
Pharmacologic Therapy
Diuretics
Renin–Angiotensin–Aldosterone System Inhibitors
Beta-Blockers
Adjunctive Pharmacologic Therapy
Heart Failure with Preserved Ejection Fraction
Device Therapy
Revascularization
Advanced Therapies
Conclusion and Future Directions
References
Part VI: Treatment–Weight Loss Strategies
Chapter 28: Lifestyle and Nutrition Therapy
Background/Introduction
Lifestyle Intervention and Diabetes Self-management Education and Support in Patients with Diabetes
Diabetes Prevention
Diabetes Self-management Education and Support
Lifestyle Intervention Programs for Diabetes
Physical Exercise
Mechanisms of Improved Glycemic Control
Cardiovascular Risk Factor Reduction
Recommendations
Weight Management and Behavior modification
Prevalence
Definition
Treatment of Obesity
Behavior Modification
Medical Nutrition Therapy Guidelines for the Management of Type 2 Diabetes Mellitus and Cardiovascular Risk Factors
Evidence for Medical Nutrition Therapy
Healthy Eating Patterns for Management of DM, ASVD, and Obesity
Evidence-Based Medical Nutrition Therapy Recommendations
Goals of MNT for DM and ASVD Risk
Personalized Nutrition Interventions
Carbohydrates
Dietary Fat
Diabetes Technology
Smoking Avoidance and Cessation of Smoking
References
Chapter 29: Treatment: Lifestyle and Medication
Introduction
Weight Management in Patients with Type 2 Diabetes and Obesity
Weight Management: A Clinical Approach
Multidisciplinary Approach to Weight Management
Components of Multidisciplinary Approach
Medication Adjustment
Nutrition Therapy
Exercise Therapy
Cognitive Behavioral Support
Use of Digital Health for Scalable Application of Lifestyle Intervention in Patients with Diabetes
Bariatric Surgery
Weight Management in Patients with Type 1 Diabetes and Obesity
Introduction
Mechanisms of Weight Gain
Insulin Therapy
Intensity of Insulin Therapy
Double Diabetes
Physical Inactivity
Weight Management in Type 1 Diabetes
Nutrition Therapy
Increased Physical Activity and Exercise
Medications
Insulin
Metformin
Glucagon-Like Peptide-1 (GLP-1) Analogs
Amylin Analog
Sodium–Glucose Transporter-2 (SGLT-2) Inhibitors
Anti-obesity Medications
Bariatric Surgery
Further Reading
Chapter 30: Surgical Treatment for Obesity and Diabetes Mellitus
American Statistics
Obesity
History of Bariatric Surgery
Indications for Surgery
Comorbidity Resolution
Metabolic Syndrome
Hypertension
Insulin Resistance/Type 2 Diabetes Mellitus
Heart Failure
LV Structure and Function
Angina Pectoris
Summary
References
Part VII: Medical Therapy of Type 2 Diabetes Mellitus
Chapter 31: Renin-Angiotensin-Aldosterone System in Diabetic Cardiovascular Complications
Effect of Diabetes on the Renin Angiotensin Aldosterone System (RAAS)
Overview of the RAAS: Angiotensinases, Peptides, and Receptors
Activation and Imbalance of the RAAS in Diabetes
Ang II Sensitivity in Diabetes
Role of the RAAS in Cardiovascular Disease in Diabetes
Role of the RAAS in Atherogenesis in Diabetic Animal Models
Effects of RAAS Inhibition on CVD Outcomes in Diabetic Patients
Effects of ACE Inhibition Following Acute Myocardial Infarction on Cardiovascular Outcomes in Diabetes
Effects of RAAS Inhibition in Heart Failure
Role of Mineralocorticoid Receptor Antagonists in Heart Failure
Mechanisms of RAAS-Induced Cardiovascular Diseases
Pressure and Hemodynamic Effects
Intravascular Actions of the RAS
Endothelium-Dependent Vasodilatation
Effects on Cardiovascular Progenitor Cells
Role of the RAAS on Glycemic Control, Insulin Sensitivity, and Diabetes Onset
Effect of RAAS Inhibition on Glycemic Control and Insulin Sensitivity
RAAS Inhibition and New-Onset Diabetes
RAAS and Coronavirus 2019 (COVID-19) Disease
Effect of RAAS Blockade on ACE2 Expression
Effects of RAAS Blockade on COVID-19: The Clinical Context
Conclusions and Future Directions
References
Chapter 32: Metformin, Sulfonylureas, DPP-4 Inhibitors and Cardiovascular Outcomes in Type 2 DM
Introduction
Metformin
Underlying Mechanisms
United Kingdom Prospective Study (UKPDS)
Meta-Analysis of Clinical Trials and Observational Studies
Potential Modulation of CV Outcomes by Metformin
Perspectives
Sulfonylureas
Underlying Mechanisms
From UGDP to UKPDS
More Recent Randomized Clinical Trials
Meta-Analysis of Clinical Trials
Observational Studies
SUs Versus Metformin
SUs Versus DPP-4is
Are All Sulfonylureas Similar Regarding CV Risk?
Glinides, as an Alternative to Sulfonylureas
DPP-4 Inhibitors
Underlying Mechanisms
CV Outcomes in Meta-Analyses of Phase 2–3 Trials
Results of Dedicated CV Outcome Trials
Observational Studies
DPP-4is Versus Metformin
DPP-4is Versus SUs
DPP-4is Versus SGLT2is
DPP-4is Versus Different Comparators
Concern About a Higher Risk of Heart Failure
Clinical Implications
Place of Classical Glucose-Lowering Agents
Special Focus on Antidiabetic Agents in the COVID-19 Era
Conclusion
References
Chapter 33: SGLT2 Inhibitors and GLP1 Antagonists on Diabetes and Cardiovascular Disease
Introduction
Sodium–Glucose Cotransporter 2 Inhibitors (SGLT2i)
Pharmacological Effects of SGLT2 Inhibitors
Cardiovascular Safety Trials of SGLT2 Inhibitors
EMPA REG Outcome [22]
CANVAS [14]
DECLARE [16]
VERTIS [25]
CVD Safety Trials Conclusions
Outcomes in Patients with and Without Established ASCVD (Figs. 33.3, 33.4, and 33.5)
SGLT2 Inhibitor Trials in Patients with Chronic Kidney Disease
CREDENCE [15, 29]
DAPA CKD [29]
SGLT2 Inhibitors in Patients with Heart Failure
Heart Failure with Reduced Ejection Fraction (HFrEF)
DAPA HF [31]
EMPEROR Reduced [33]
SOLOIST WHF [30]
EMPULSE (Presented at the American Heart Association Virtual Annual Session on 14 November 2021 and Accepted for Publication in Nature Medicine)
Heart Failure and Preserved Ejection Fraction (HFpEF)
EMPEROR Preserved Trial [35] ClinicalTrials.gov Identifier NCT01297257
DELIVER (Dapagliflozin to Improve the LIVEs of Patients with Preserved Ejection Fraction Heart Failure): ClinicalTrials.gov Identifier—NCT03619213
Heart Failure Guidelines
Adverse Effects of SGLT2 Inhibitors and Recommendations for Their Prevention
Acute Kidney Injury
Off-Target Adverse Effects
Amputation
Cancer
Fractures
Mode of Action of SGLT2 inhibitors
Future Cardiovascular Trials with Sglt2 Inhibitors
Conclusions
Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA)
Cardiovascular Outcome Trials for GLP 1A Agonists
ELIXA [84, 85]
LEADER [17]
SUSTAIN-6 [19]
EXSCEL [86]
HARMONY Outcomes [87]
REWIND [85]
PIONEER-6 [88]
Impact of GLP-1 RA on Kidney Outcomes
GLP-1 RA and Heart Failure
Safety of GLP-1 Agonists
Mechanisms of CV Benefit of GLP-1 Agonists
Summary of Outcomes with GLP-1 RA
Application of SGLT2 Inhibitors and GLP-1 Receptor Agonists in Patients with Diabetes
References
Chapter 34: Insulin Treatment of Diabetes Mellitus-Tight vs. Conventional Control
Introduction
Diabetes Control and Complications Trial (DCCT)
Interventional Phase
Observational Follow-Up Phase
The United Kingdom Prospective Diabetes Study (UKPDS)
Interventional Phase
The Metformin Subgroup
Follow-Up Phase
Action in Diabetes and Vascular Disease: Preterax and Diamicron—MR-Controlled Evaluation (ADVANCE)
Interventional Phase
Follow-Up Phase
Action to Control Cardiovascular Risk in Diabetes (ACCORD)
Interventional Phase
Follow-Up Phase
VA Diabetes Trial (VADT)
Interventional Phase
VADT Follow-Up Phase
Placing Glucose-Lowering CVD Trials in Context
Additional Explanations for Distinct Differences in Outcomes among Glucose-Lowering Studies
A New Paradigm: Nonglycemic Lowering Drugs with Additional Benefits
Clinical Implications
References
Part VIII: Treatment in Special Populations and Conditions
Chapter 35: Differences of Diabetes Treatment and Care in Various Ethnic Minorities
Introduction
Description of Diverse Populations in the U.S.
Health Care Disparities
Prevalence and Incidence of Diabetes by Race/Ethnicity
Prevalence and Incidence of Complications of Diabetes by Race/Ethnicity
Microvascular Complications
Nephropathy
Retinopathy
Neuropathy
Macrovascular Complications
Heart Disease
Cerebrovascular Disease
Peripheral Artery Disease and Amputations
Mortality
Race/Ethnicity Differences in Cardiovascular Risk Factors
Obesity
Hypertension
Dyslipidemia
Race/Ethnicity Differences in Management of CVD Risk Factors
Glycemic Control
CVD Target Achievement
Data on Diabetes and CVD by Gender
Data on Diabetes and CVD by Sexual Orientation Group
Data on Diabetes and CVD in Immigrants in the U.S.
Biological Factors That Impact the Difference in Risk and Disease
Body Mass Index and Fat Distribution
Glucose Metabolism
Genetics
Social, Psychological, and Cultural Factors in Diabetes and CV Care
Social Determinants of Health
Psychological Factors
Culture Aspects
Conclusions and Recommendations
References
Chapter 36: Diabetes and COVID
Introduction
Risk Factors
Potential Interplay of Diabetes in the Pathophysiology of COVID-19
Multiorgan Failure in Patients with Diabetes and COVID-19
Endothelial Dysfunction
Management of Diabetes in Patients with COVID-19
Conclusion
References
Chapter 37: Tailoring the Treatment of Type 2 Diabetes Mellitus to the Individual
The Impact of Cardiovascular Disease in Patients with Diabetes
Setting a Glycemic Target
Cardiovascular Implications of Glucose-Lowering Drug Classes
Sodium–Glucose Cotransporter 2 Inhibitors
GLP-1 Receptor Agonists
Thiazolidinediones
Dipeptidyl Peptidase-4 Inhibitors
Older Agents: Metformin, Sulfonylureas, and Insulin
Implementing a Personalized Treatment Strategy in Patients with CVD
References
Index