Microvascular Disease in Diabetes

ISBN-13: 9781119309604 / Angielski / Twarda / 2020 / 280 str.

Francesco Tecilazich

Spis treści

Foreword to: Microvascular Disease in Diabetes xvEditor Biography xviiList of Contributors xix1 Introduction 1Andrea Giustina and Stefano FraraReferences 32 Pathophysiology 5Francesco TecilazichIntroduction 5Anatomo-Physiology of Microvessels 5Regulation of Microvascular Tone 6Endothelial-Dependent Vasodilation 6Endothelial-Independent Vasodilation 6Nerve Axon Reflex (NARV) 7Myogenic Response 7Functional Hyperemia 7Venoarteriolar Response (VAR) 8Structural Changes in the Microcirculation 8Functional Changes in the Microcirculation 8Endothelial Dysfunction 8VSMC Dysfunction 9NARV Impairment 9Defective Myogenic Response 10Reduced Functional Hyperemia 10Endothelial Dysfunction 11Role of the Immune System and Leukostasis 11Role of Hyperglycemia 12AGEs 12Polyol Pathway 12Oxidative Stress 13PKC 13Transforming Growth Factor (TGF)-ß 14Hexosamine Pathway 14PARP 14ET-1 14Vasoconstrictor Prostanoid Synthesis 15Role of Insulin Resistance 15Role of Inflammation 15References 163 Genetics of Diabetic Microvascular Disease 23Niina Sandholm and Carol ForsblomIntroduction 23Genetics of DKD 23Heritability of DKD 23Candidate Genes for DKD 24Linkage Studies for DKD 25Genome-Wide Association Studies on DKD 25Sequencing Efforts for DKD 29Genetics of Diabetic Retinopathy 30Heritability of Diabetic Retinopathy 30Candidate Genes for Diabetic Retinopathy 30Linkage Studies for Diabetic Retinopathy 31GWAS on Diabetic Retinopathy 31Sequencing Efforts for Diabetic Retinopathy 33Genetics of Diabetic Neuropathy 33Heritability of Diabetic Neuropathy 33Candidate Genes for Diabetic Neuropathy 33GWASs on Diabetic Neuropathy 34Future Directions 34Larger Studies are Needed 34How to Define the Phenotype? 35Variability in the Phenotypic Definitions 35Criteria for Controls 36Do Genetics of Microvascular Complications in T1D and T2D Differ? 36Low-Frequency and Rare Variants May Affect Diabetic Complications 36Sequencing of Rare and Low-Frequency Variants 36Linkage Analysis with GWAS Data 37Genetics May Reveal Biology and Infer Causality 37Conclusions 37References 374 Epigenetics of Diabetic Microvascular Disease 45Luciano PirolaDiabetic Complications Include Microvascular and Macrovascular Injury 45The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study in Type 1 Diabetic Patients, and the UKPDS Study in Type 2 Diabetic Patients, Support the Existence of the Hyperglycemic Memory Phenomenon 46DCCT/EDIC Study 46The UKPDS Study 46Models of Hyperglycemic Memory 47Animal Models 47Cell Culture Models 48The "Epigenetic Code" 48DNA Methylation 49Histone Methylation in Models of Hyperglycemic Variability 49Epigenetic Changes in Microvascular Models of Glycemic Memory 50MiRNAs Contribute to the Control of Glucose Homeostasis and are Dysregulated in Diabetes 52Future Prospects 52References 545 Diabetic Retinopathy - Clinical 59Francesco Bandello, Rosangela Lattanzio, Alessandro Marchese, and Emanuela AragonaIntroduction 59Epidemiology 60Screening 60Risk Factors 61Clinical Patterns 61Non-Proliferative Diabetic Retinopathy (NPDR) 61Clinical Findings 62Diagnostic Tools 64Treatment Strategies 65Proliferative Diabetic Retinopathy (PDR) 65Clinical Findings 65Diagnostic Tools 67Treatment Strategies 67Diabetic Macular Edema (DME) 69Classification 70Clinical Findings 71Diagnostic Tools 71Treatment Strategies 71Conclusions 73References 746 Diabetic Retinopathy - Research 79Gopalan GnanaguruRetina and Induction of Hyperglycemia 79Hyperglycemia and Retinal Microvasculature 80Hyperglycemia and Reactive Gliosis 80Hyperglycemia and Neurodegeneration 81Hyperglycemia and Inflammation 81References 827 Diabetic Nephropathy - Clinical 85Gianpaolo ZerbiniEpidemiology 85Natural History 86Stages of DN 86Morphologic Changes 87Pathophysiology 88Clinical Course 89Treatment 90Primary Prevention 90Secondary Prevention 91Tertiary Prevention 91Perspectives 91References 928 Diabetic Nephropathy - Research 97Silvia Maestroni and Gianpaolo ZerbiniEssential Hypertension and DN 97Role of Genetics in the Pathogenesis of DN 99Polyol Pathway and Non-Enzymatic Glycation 100Environment 100Perspectives 101Sodium-Glucose Cotransporter-2 (SGLT2) and DN 101B7-1 and DN 101Animal Models 102DN in Induced Model of Type 1 Diabetes Mellitus (T1DM) 102DN in Spontaneous Model of T1DM 103Ins2¯Akita Mice 103Non-Obese Diabetic (NOD) Mice 104OVE26 Friend leukemia virus B (FVB) Mice 104DN in Spontaneous Models of T2DM 105db/db Mice 105References 1059 Diabetic Neuropathy - Clinical 111Christopher H. GibbonsIntroduction 111Classification of Diabetic Neuropathies 111Distal Symmetric Polyneuropathy (DSPN) 112Diagnosis 113Management 113Small Fiber Neuropathy 114Diagnosis 115Management 115Autonomic Neuropathy 116Diagnosis 117Management 117Treatment-Induced Neuropathy of Diabetes (TIND) 119Diagnosis 119Management 120Diabetic Radiculoplexopathy 120Diagnosis 120Management 121Mononeuropathies 121Diagnosis 121Management 121Cranial Neuropathies 121Diagnosis 121Management 122Screening for Neuropathy 122Summary of Management of Diabetic Neuropathy 122References 12310 Diabetic Neuropathy - Research 129Krish Chandrasekaran, Lindsay A. Zilliox, and James W. RussellBasic and Translational Research in Diabetic Neuropathy 129Animal Models of Diabetic Neuropathy 129Basic Pathophysiology of Diabetic Neuropathy 131Changes in Redox Potential 131Role of Mitochondrial Dysfunction in Diabetic Neuropathy 133Protein Kinase C (PKC) and Neuropathy 137Advanced Glycation End Products 137Modifying Molecular Chaperones 138Inflammation and Neuropathy 138TGF-ß and Neuropathy 138Metabotropic Glutamate Receptors (mGluRs) and Oxidative Injury 139Growth Factors and Diabetes 139Clinical Research in Diabetic Neuropathy 140Treatment of Hypertension 141Improved Glycemic Control 141Diet and Lifestyle Interventions 142Alpha-Lipoic Acid 144Benfotiamine and Neuropathy 145Treatment of Neuropathic Pain 145Acknowledgments 146References 14711 Diabetic Foot - Clinical 157Cristian NicolettiIntroduction and Size of the Problem 157Pathogenesis of Diabetic Foot Complications 158Neuropathy 158Peripheral Vascular Disease 158Other Risk Factors 159Prevention 159Treatment 160Treatment of Neuropathic Diabetic Foot Ulcers: Offloading 160Treatment of PAD: Revascularization 161Diabetic Foot Infections (DFIs) 163Introduction 163Diagnosis 163Treatment 164Wound Healing 166Debridement 166Dressings 167Topical Negative Pressure Wound Therapy (NPWT) 167Other Topical Treatments 167References 16712 Diabetic Foot - Research 173Georgios Theocharidis and Aristidis VevesIntroduction 173Anatomy of the Skin and Microcirculation 174Structural Changes in the Microcirculation 174Functional Changes in the Microcirculation 175Functional Changes in the Diabetic Foot 176Vasodilation 176Endothelium-Dependent Vasodilation 177Endothelium-Independent Vasodilation 178Nerve Axon Reflex 179Mechanisms of Endothelial Dysfunction 180Endothelial Dysfunction and Hyperglycemia 180Endothelial Dysfunction and Insulin Resistance 182Endothelial Dysfunction and Inflammation 183Pathophysiology of Diabetic Wound Healing 184Hyperglycemia 184Chronic Inflammation 184Impaired Angiogenesis and Vasculogenesis 186Hypoxia 186Impaired Neuropeptide Signaling 186Adjunctive Treatment Options 186Bioengineered Skin Substitutes 187Growth Factors 187Hyperbaric Oxygen Therapy 188Negative Pressure Wound Therapy 188Electrical Stimulation and Shockwave Therapy 189Future Therapeutic Perspectives 189Gene Therapies 189Stem Cell Therapies 189Norleu3-Angiotensin-(1-7) 190Neuropeptides 190Cytokine Inhibition 190Conclusion 191References 19113 Coronary Microvascular Dysfunction in Diabetes - Clinical and Research 201Guglielmo Gallone, Francesco Moroni, and Marco MagnoniIntroduction 201Clinical Classification and Mechanisms of CMD 202CMD in Diabetic Patients 203Clinical Assessment of CMD 205Non-Invasive Imaging Technique for the Assessment of CMD 205Transthoracic Doppler Evaluation 205Contrast Echocardiography 206Cardiovascular Magnetic Resonance (CMR) Imaging 206Positron Emission Tomography (PET) 207Invasive Techniques for the Evaluation of CBF 207Indicator Dilution-Based Methods 207Thermodilution 208Gas Wash Out Method 208Intracoronary Doppler Flow Wire 208Treatment for CMD 210The Effects of Glucose-Lowering Drugs on CMD 211Future Perspectives for the Treatment of CMD in Diabetes 211References 21214 Cerebral Microvascular Disease in Diabetes - Clinical and Research 221Eelco van Duinkerken and Richard G. IJzermanIntroduction 221Postmortem Studies of the Brain in Diabetes 222Cerebral Small Vessel Disease on MRI 223MRI-Measured Cerebral Small Vessel Disease in Type 1 Diabetic Patients 224White Matter Hyperintensities 224Cerebral Microbleeds 226Summary 226Type 2 Diabetes and Cerebral Small Vessel Disease 227Lacunar Infarcts 227White Matter Hyperintensities 228Cerebral Microbleeds 230Synthesis 230Clinical Impact of Cerebral Small Vessel Disease in Diabetes 231Cognitive Functioning 231Stroke 233Dementia 234The Influence of Microvascular Disease on the Structure and Functioning of the Diabetic Brain 235Type 1 Diabetes 236Type 2 Diabetes 237Conclusions and Future Directions 239References 240Index 247

O autorze

FRANCESCO TECILAZICH, MD, PhD, is a physician and scientist in the Endocrinology and Metabolic Diseases department of the Ospedale San Raffaele-Vita Salute San Raffaele University in Milan, Italy.