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Presents comprehensive coverage of the many microvascular complications of diabetes Diabetes remains one of the main causes, in the western world, of legal blindness, end stage renal disease, and amputation, despite the implementation of tight glycemic control and the great progress in the management and care of our patients. This book provides a useful and handy tool to professionals and students in the field of diabetes and its microvascular complications by integrating information from clinical settings as well as from the frontlines of diabetic research. It provides readers with up-to-date…mehr
Presents comprehensive coverage of the many microvascular complications of diabetes Diabetes remains one of the main causes, in the western world, of legal blindness, end stage renal disease, and amputation, despite the implementation of tight glycemic control and the great progress in the management and care of our patients. This book provides a useful and handy tool to professionals and students in the field of diabetes and its microvascular complications by integrating information from clinical settings as well as from the frontlines of diabetic research. It provides readers with up-to-date diagnostic criteria, classifications, and therapeutic approaches. and recent discoveries on mechanisms of disease, experimental therapeutic agents, and biomarkers of disease. Written by top experts in the field, Microvascular Disease in Diabetes offers in-depth chapters covering pathophysiology; the genetics of diabetic microvascular disease; and the epigenetics of diabetic microvascular disease. It then provides sections featuring both clinical and research information on diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, and diabetic foot. It also looks at coronary microvascular dysfunction and cerebral microvascular disease. * Integrates new and accessible material on diabetic microvascular comorbidities * Covers all relevant microvascular systems * Provides a much-needed resource synthesizing research and clinical applications to treating microvascular complications of diabetes * Presents current diagnostic criteria, classifications, and therapeutic approaches, as well as recent discoveries on the mechanisms of disease, experimental therapeutic agents, and biomarkers of disease Assembled in an easily consultable manner, Microvascular Disease in Diabetes is an excellent text for investigators, clinicians, and students looking to improve their understanding of diabetic complications.
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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.
Inhaltsangabe
Foreword to: Microvascular Disease in Diabetes xv
Editor Biography xvii
List of Contributors xix
1 Introduction 1 Andrea Giustina and Stefano Frara
References 3
2 Pathophysiology 5 Francesco Tecilazich
Introduction 5
Anatomo-Physiology of Microvessels 5
Regulation of Microvascular Tone 6
Endothelial-Dependent Vasodilation 6
Endothelial-Independent Vasodilation 6
Nerve Axon Reflex (NARV) 7
Myogenic Response 7
Functional Hyperemia 7
Venoarteriolar Response (VAR) 8
Structural Changes in the Microcirculation 8
Functional Changes in the Microcirculation 8
Endothelial Dysfunction 8
VSMC Dysfunction 9
NARV Impairment 9
Defective Myogenic Response 10
Reduced Functional Hyperemia 10
Endothelial Dysfunction 11
Role of the Immune System and Leukostasis 11
Role of Hyperglycemia 12
AGEs 12
Polyol Pathway 12
Oxidative Stress 13
PKC 13
Transforming Growth Factor (TGF)-ß 14
Hexosamine Pathway 14
PARP 14
ET-1 14
Vasoconstrictor Prostanoid Synthesis 15
Role of Insulin Resistance 15
Role of Inflammation 15
References 16
3 Genetics of Diabetic Microvascular Disease 23 Niina Sandholm and Carol Forsblom
Introduction 23
Genetics of DKD 23
Heritability of DKD 23
Candidate Genes for DKD 24
Linkage Studies for DKD 25
Genome-Wide Association Studies on DKD 25
Sequencing Efforts for DKD 29
Genetics of Diabetic Retinopathy 30
Heritability of Diabetic Retinopathy 30
Candidate Genes for Diabetic Retinopathy 30
Linkage Studies for Diabetic Retinopathy 31
GWAS on Diabetic Retinopathy 31
Sequencing Efforts for Diabetic Retinopathy 33
Genetics of Diabetic Neuropathy 33
Heritability of Diabetic Neuropathy 33
Candidate Genes for Diabetic Neuropathy 33
GWASs on Diabetic Neuropathy 34
Future Directions 34
Larger Studies are Needed 34
How to Define the Phenotype? 35
Variability in the Phenotypic Definitions 35
Criteria for Controls 36
Do Genetics of Microvascular Complications in T1D and T2D Differ? 36
Low-Frequency and Rare Variants May Affect Diabetic Complications 36
Sequencing of Rare and Low-Frequency Variants 36
Linkage Analysis with GWAS Data 37
Genetics May Reveal Biology and Infer Causality 37
Conclusions 37
References 37
4 Epigenetics of Diabetic Microvascular Disease 45 Luciano Pirola
Diabetic Complications Include Microvascular and Macrovascular Injury 45
The 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 46
DCCT/EDIC Study 46
The UKPDS Study 46
Models of Hyperglycemic Memory 47
Animal Models 47
Cell Culture Models 48
The "Epigenetic Code" 48
DNA Methylation 49
Histone Methylation in Models of Hyperglycemic Variability 49
Epigenetic Changes in Microvascular Models of Glycemic Memory 50
MiRNAs Contribute to the Control of Glucose Homeostasis and are Dysregulated in Diabetes 52
1 Introduction 1 Andrea Giustina and Stefano Frara
References 3
2 Pathophysiology 5 Francesco Tecilazich
Introduction 5
Anatomo-Physiology of Microvessels 5
Regulation of Microvascular Tone 6
Endothelial-Dependent Vasodilation 6
Endothelial-Independent Vasodilation 6
Nerve Axon Reflex (NARV) 7
Myogenic Response 7
Functional Hyperemia 7
Venoarteriolar Response (VAR) 8
Structural Changes in the Microcirculation 8
Functional Changes in the Microcirculation 8
Endothelial Dysfunction 8
VSMC Dysfunction 9
NARV Impairment 9
Defective Myogenic Response 10
Reduced Functional Hyperemia 10
Endothelial Dysfunction 11
Role of the Immune System and Leukostasis 11
Role of Hyperglycemia 12
AGEs 12
Polyol Pathway 12
Oxidative Stress 13
PKC 13
Transforming Growth Factor (TGF)-ß 14
Hexosamine Pathway 14
PARP 14
ET-1 14
Vasoconstrictor Prostanoid Synthesis 15
Role of Insulin Resistance 15
Role of Inflammation 15
References 16
3 Genetics of Diabetic Microvascular Disease 23 Niina Sandholm and Carol Forsblom
Introduction 23
Genetics of DKD 23
Heritability of DKD 23
Candidate Genes for DKD 24
Linkage Studies for DKD 25
Genome-Wide Association Studies on DKD 25
Sequencing Efforts for DKD 29
Genetics of Diabetic Retinopathy 30
Heritability of Diabetic Retinopathy 30
Candidate Genes for Diabetic Retinopathy 30
Linkage Studies for Diabetic Retinopathy 31
GWAS on Diabetic Retinopathy 31
Sequencing Efforts for Diabetic Retinopathy 33
Genetics of Diabetic Neuropathy 33
Heritability of Diabetic Neuropathy 33
Candidate Genes for Diabetic Neuropathy 33
GWASs on Diabetic Neuropathy 34
Future Directions 34
Larger Studies are Needed 34
How to Define the Phenotype? 35
Variability in the Phenotypic Definitions 35
Criteria for Controls 36
Do Genetics of Microvascular Complications in T1D and T2D Differ? 36
Low-Frequency and Rare Variants May Affect Diabetic Complications 36
Sequencing of Rare and Low-Frequency Variants 36
Linkage Analysis with GWAS Data 37
Genetics May Reveal Biology and Infer Causality 37
Conclusions 37
References 37
4 Epigenetics of Diabetic Microvascular Disease 45 Luciano Pirola
Diabetic Complications Include Microvascular and Macrovascular Injury 45
The 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 46
DCCT/EDIC Study 46
The UKPDS Study 46
Models of Hyperglycemic Memory 47
Animal Models 47
Cell Culture Models 48
The "Epigenetic Code" 48
DNA Methylation 49
Histone Methylation in Models of Hyperglycemic Variability 49
Epigenetic Changes in Microvascular Models of Glycemic Memory 50
MiRNAs Contribute to the Control of Glucose Homeostasis and are Dysregulated in Diabetes 52
Future Prospects 52
References
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