Microvascular Disease in Diabetes

Herausgegeben:Tecilazich, Francesco

• Gebundenes Buch

Produktbeschreibung

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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Produktdetails

• Verlag: Wiley & Sons / Wiley-Blackwell
• Artikelnr. des Verlages: 1W119309600
• 1. Auflage
• Seitenzahl: 280
• Erscheinungstermin: 5. Mai 2020
• Englisch
• Abmessung: 244mm x 170mm x 18mm
• Gewicht: 680g
• ISBN-13: 9781119309604
• ISBN-10: 1119309603
• Artikelnr.: 56711643

Autorenporträt

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

Future Prospects 52

References