Table of Contents
Cover
Title Page
Section Editors
Copyright
Contributors
Preface
Section I: Epidemiology
Chapter 1: Classification of diabetes mellitus and other categories of glucose intolerance
Introduction
Historical perspective and current classifications
Type 1 process
Type 2 process
Other specific types
Classification of genetic disorders
Diabetes in children and youth
Diagnosis of diabetes using HbA1c
Diagnosis of gestational diabetes mellitus
Impaired glucose regulation (impaired glucose tolerance and impaired fasting glycemia)
Normoglycemia
Summary
References
Chapter 2: Epidemiology and risk factors for type 1 diabetes mellitus
Introduction
Prevalence and incidence
β-Cell autoimmunity and risk factors
Established type 1 diabetes
References
Chapter 3: Epidemiology and geography of type 2 diabetes mellitus
Age- and sex-specific prevalence of type 2 diabetes in different ethnic groups
Prevalence of impaired glucose tolerance and impaired fasting glycemia in different ethnic groups
Sex differences in prevalence of diabetes, IGT, and IFG
The ratio of IGT to diabetes
Secular trends in prevalence of type 2 diabetes
Type 2 diabetes in children
Modifiable risk factors for type 2 diabetes
Nontraditional modifiable risk factors for type 2 diabetes
References
Section II: Physiology of pancreatic function
Chapter 4: Development and maintenance of the islet β cell
Introduction
Pancreas development
Cytodifferentiation in the developing pancreas
Postnatal β-cell growth and maintenance
Conclusions and areas of future study
References
Chapter 5: Pancreatic morphology in normal and diabetic states
Pancreatic anatomy and morphology
Islet composition and morphology
Islet β cell regenerative potential
Disturbances in pancreas/islet morphology in diabetes
Mechanisms of β-cell loss in type 2 diabetes
Summary and future directions
Acknowledgments
References
Chapter 6: Insulin gene expression and biosynthesis
Introduction
Insulin gene expression
Insulin biosynthesis
Acknowledgments
References
Chapter 7: β-Cell biology of insulin secretion
Introduction
β-Cell metabolism
Metabolism-secretion coupling
Dynamics of insulin secretion
Modulation of insulin secretion by various intracellular signals
Pathophysiology of pancreatic β cells
Conclusions
References
Chapter 8: Normal β-cell function
Introduction
Methods for the Assessment of Insulin Secretion
β-Cell Response to Intravenous Glucose
β-Cell Response to Oral Glucose
β-Cell Response to Nonglucose Secretagogues
Slow β-Cell Response Modes and Adaptation Mechanisms
β-Cell Response to Hormones and the Nervous System
Pulsatile Secretion of Insulin
β-Cell Mass and Function
Insulin Clearance
β-Cell Function and Glucose Homeostasis
Conclusions
References
Chapter 9: Neuropeptides and islet hormone secretion
Introduction
Islet Parasympathetic Nerves
Gastrin-Releasing Polypeptide (GRP)
Vasoactive Intestinal Polypeptide (VIP)
Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)
Parasympathetic Effects and Mediation
Islet Sympathetic Nerves
Galanin
Neuropeptide Y (NPY)
Sympathetic Effects and Mediation
Islet Sensory Neuropeptides
Calcitonin Gene-Related Polypeptide (CGRP)
Substance P
Summary of Present-Day Knowledge
Questions for Future Research
Acknowledgments
References
Chapter 10: Biosynthesis, secretion, and action of glucagon
Introduction
Amino Acid Composition, Extraction, Synthesis, and Biosynthesis
Physiologic Effects of Glucagon
Other Effects of Glucagon
Control of Glucagon Release
Some Aspects of Glucagon Physiology and Pathophysiology
References
Chapter 11: Incretin physiology in health and disease
The incretin effect in health
Secretion of incretin hormones
Degradation and elimination of incretin hormones
Physiologic effects of incretin hormones
Other gastrointestinal hormones with potential incretin function
The incretin effect in patients with diabetes
Potential mechanisms of incretin dysfunction in type 2 diabetes
Summary and conclusions
References
Section III: Normal physiology of insulin action
Chapter 12: Mechanisms of Insulin Signal Transduction
Introduction
Insulin Receptors
Insulin Receptor Substrate Molecules
Ras/MAP Kinase Pathway: Mitogenic Signaling
PI-3 Kinase Pathways: Regulation of Metabolism and Gene Expression
PI-3 Kinase-Independent Pathways for Stimulation of Glucose Transport
The Glucose Transport Effector System
Insulin Resistance in Humans: Abnormalities in Insulin Signaling and in the Glucose Transport Effector System
Modulation of Insulin Action
Regulation of Gene Transcription
Acknowledgments
References
Chapter 13: Regulation of glucose metabolism in liver
Introduction
Hepatic glucose production
Hepatic glucose disposal
Summary
References
Chapter 14: Insulin actions in vivo: glucose metabolism
Introduction
Glucose metabolism
The basal state
The fed state
References
Chapter 15: Measuring insulin action in vivo
Historical perspective
The glucose clamp
Fasting insulin
Conclusions
Acknowledgments
References
Chapter 16: Protein metabolism in health and diabetes
Introduction
Integrative physiology of insulin action on protein metabolism
Effects of insulin on protein metabolism in specific tissues
Effects of insulin on whole body protein turnover
Pathophysiology of insulin action on protein metabolism
Protein metabolism in diabetes
Conclusions
Acknowledgments
References
Chapter 17: Lipid and lipoprotein metabolism, hypolipidemic agents, and therapeutic goals
Introduction
Lipoprotein metabolism in normal individuals and in type 2 diabetes mellitus
Therapeutic approaches to the dyslipidemia of insulin resistance and type 2 diabetes mellitus
References
Chapter 18: Metabolomics: applications in type 2 diabetes mellitus and insulin resistance
Introduction
What is “metabolomics?”
Altered metabolites and their potential origins in type 2 diabetes and insulin resistance
Future directions and potential application of metabolite profiling in type 2 diabetes
References
Section IV: NAFLD, NASH and non-traditional associations with diabetes
Chapter 19: Pathogenesis of nonalcoholic fatty liver disease (NAFLD)
Introduction
Pathogenesis of NAFLD
Consequences of NAFLD
Conclusions
References
Chapter 20: Treatment of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)
Introduction
Role of lifestyle intervention in NAFLD
Pharmacologic agents
Future directions
References
Chapter 21: Type 2 diabetes and cancer
Introduction
Epidemiology
Links between diabetes and cancer
Animal studies
Conclusions and future directions
References
Chapter 22: Diabetes and sleep apnea
Introduction
Definitions
OSA epidemiology and risk factors
OSA pathophysiology
OSA clinical features and diagnosis
OSA and glucose metabolism
Other OSA comorbidities
OSA management
Impact of T2DM on OSA
Summary and future directions
References
Section V: Pathogenesis
Chapter 23: The insulin resistance syndrome
What is insulin resistance?
Multiple roles of insulin
How do we measure insulin resistance?
Simple characteristics associated with insulin resistance
Concept of ectopic fat as a cause of tissue insulin resistance
Pathways linked to insulin resistance
Introducing insulin resistance to the clinic: the metabolic syndrome
What are the metabolic syndrome criteria?
The purpose of the metabolic syndrome concept
Statistical considerations and other issues
Treatment of patients with features of the metabolic syndrome
Current thinking regarding metabolic syndrome
Conclusion
References
Chapter 24: β-Cell mass and function in human type 2 diabetes
Introduction
β-Cell mass in type 2 diabetes
The role of β-cell death and regeneration
The dominance of β-cell functional impairment
Disruption of β-cell dialogue in the islet
Incretin defect
Additional aspects of β-cell dysfunction
Loss of β-cell functional identity
Conclusions
References
Chapter 25: Pathogenesis of type 2 diabetes mellitus
Normal glucose homeostasis
Natural history of type 2 diabetes
β-Cell function
Type 2 diabetes with hypoinsulinemia
First-phase insulin secretion
Pathogenesis of β-cell failure (Figure 25.4)
In utero fetal malnutrition
Insulin resistance and type 2 diabetes mellitus
Site of insulin resistance in type 2 diabetes
Cellular mechanisms of insulin resistance
The adipocyte, FFA metabolism, and lipotoxicity
Alpha cell and glucagon
The kidney: increased glucose reabsorption
The brain
Implications for therapy
References
Chapter 26: The genetics of type 2 diabetes
The diabetic spectrum
The diabetes epidemic
Heritability of T2DM
Identification of T2DM affecting genetic variants
Functions of associated genes
The missing heritability
Conclusions
References
Chapter 27: Glucose toxicity
Introduction
Hyperglycemia and glucose utilization
Chronic hyperglycemia as a cause of insulin resistance
Chronic hyperglycemia as a cause of impaired insulin secretion
Molecular mechanisms of glucose toxicity
Clinical significance of glucose toxicity
Acknowledgments
References
Chapter 28: Monogenic disorders of the β cell
Introduction
Monogenic β-cell disorders in key aspects of β-cell function
Clinical categories of monogenic β-cell disorders
Maturity-onset diabetes of the young
Neonatal diabetes: diabetes diagnosed within 6 months of life
Diabetes with extra-pancreatic features
Using molecular genetics in diabetes care
References
Chapter 29: Immunopathogenesis of type 1 diabetes in Western society
Introduction
Genetic studies provide clues about key disease mechanisms
Genes and environment: a moving target?
Multiple T-cell types and autoreactive T-cell specificities mediate T1DM
Autoimmunity persists in many patients even many years after diagnosis
Nonautoimmune factors
The relationship between pathogenic factors and β-cell destruction remains poorly understood
Conclusions
References
Chapter 30: Molecular genetics of type 1 diabetes
Introduction
The HLA complex
Other candidate genes for T1DM
Genome-wide analyses
Other genetic markers—the “missing heritability”
Clinical utility of T1DM susceptibility genes
Conclusion
References
Section VI: Obesity
Chapter 31: The relationship between obesity and type 2 diabetes—the role of gut factors
Introduction
The relationship of obesity to insulin resistance and diabetes
Gut hormone regulation of appetite, food intake, and insulin secretion
Role of gut hormones in obesity and type 2 diabetes
The role of microbiota in obesity and diabetes
Summary
References
Chapter 32: The role of energy metabolism in the regulation of energy balance
Introduction
Methods of measuring energy expenditure
Components of energy expenditure and their relevance for human obesity
Energy expenditure in the etiology of obesity
Molecular mechanisms of energy expenditure variability and avenues for treatment
Analysis of energy expenditure data in humans
Conclusions
References
Chapter 33: Treatment of obesity: lifestyle and pharmacotherapy
Introduction
Principles of diet-induced weight loss
Options for weight loss diets
Dietary weight maintenance programs
Weight management programs for the prevention of type 2 diabetes
Weight loss management in type 2 diabetes
Pharmacotherapy
Pharmaceutical compounds for diabetes treatment with weight loss properties
Other pharmacologic agents under development
References
Chapter 34: Treatment of obesity: bariatric surgery
Introduction
Current surgical approaches
Weight loss after bariatric surgery
Mechanisms of weight loss
Treatment of diabetes and related metabolic diseases
Bariatric surgery and other comorbidities
Mechanisms of diabetes remission and improvement in glucose homeostasis
Conclusion
References
Chapter 35: Animal models of obesity and type 2 diabetes
Introduction
Environmental influences
Genetic models
Fatty acid binding proteins
References
Chapter 36: The role of the hypothalamus in the maintenance of energy balance and peripheral glucose control
Introduction
Leptin and insulin signaling pathways in the hypothalamus
Hypothalamic leptin and insulin mediate food intake, energy expenditure, and glucose homeostasis
Leptin's and insulin's mechanisms of action in regulating energy and glucose homeostasis
References
Section VII: Clinical trial evidence in diabetes
Chapter 37: Prevention of type 1 diabetes
Introduction
Studies in established T1DM
Studies designed to prevent T1DM
Conclusions
References
Chapter 38: Prevention of type 2 diabetes
Prediabetes
Lifestyle interventions
Pharmaceutical intervention
Cost-effectiveness
Translation of diabetes prevention into routine primary care
High risk versus population
Conclusion
References
Chapter 39: Prevention of diabetic microvascular complications
Introduction
Diabetic nephropathy
Diabetic neuropathy
Diabetic retinopathy
Conclusion
References
Section VIII: Management of diabetes: diet, exercise and drugs
Chapter 40: Dietary management of diabetes mellitus in Europe and North America
Introduction
Total energy intake
Quantity and nature of dietary fat
Protein
Carbohydrate, dietary fiber, and glycemic index
Distribution of energy from macronutrients
Antioxidant nutrients, vitamins, and minerals
Alcohol
Sweeteners, supplements and functional foods
Implementation of diet therapy
References
Chapter 41: Exercise
Introduction
Exercise physiology
Metabolism during exercise in diabetics
Adaptations to training
Benefits, risks, and precautions associated with exercise in diabetes
Guidelines for training in diabetes
Exercise in the prevention of diabetes
References
Chapter 42: Sulfonylureas and meglitinides: insights into physiology and translational clinical utility
Historical perspective: the merger of clinical and basic science
Mechanism of action of sulfonylureas and meglitinides
Pharmacology and clinical pharmacology
Clinical aspects of sulfonylurea therapy
Similarities and differences among sulfonylureas
Adverse effects of sulfonylureas
Sulfonylureas as current therapeutic agents for type 2 diabetes
Interactions
Toxicity
Conclusion
References
Chapter 43: Metformin and other biguanides: pharmacology and therapeutic usage
Introduction
Pharmacology
Mechanism of action
Treatment of type 2 diabetes mellitus
Additional therapeutic potential
Adverse events, contraindications, and side effects
Conclusion
References
Chapter 44: PPAR agonists in the treatment of diabetes
Introduction
Mechanism of action
Glycemic effects
Metabolic effects
Cardiovascular effects
Other potential beneficial nonglycemic effects
Dose/drug interactions
Monitoring requirements/precautions/contraindications
Side effects
Future developments
Conclusion
Acknowledgments
References
Chapter 45: α-Glucosidase inhibitors
Introduction
Mechanism of action
Clinical efficacy of α-glucosidase inhibitors
Other effects of α-glucosidase inhibitors
Tolerability of acarbose
Other potential and demonstrated side effects related to α-glucosidase inhibitor therapy
Contraindications to α-glucosidase inhibitors
Indications for α-glucosidase inhibitors
Recommended doses are as follows
Conclusions
References
Chapter 46: Combination therapy in type 2 diabetes mellitus
Introduction
Natural history of type 2 diabetes
Beta-cell function
Insulin resistance
Implications for therapy
Combination therapy
Initial combination therapy in new onset diabetes
Combination therapy in T2DM patients inadequately controlled on antidiabetic therapy
Conclusion and recommendations
References
Chapter 47: New drugs for the treatment of diabetes mellitus
Introduction
Approaches to new antidiabetic agents
Inhibitors of intestinal carbohydrate digestion and absorption
Initiators of insulin secretion
Potentiators of insulin secretion
Increasing insulin action
Adipokines
Fibroblast growth factor 21
Selective PPAR modulators
Vitamins and minerals
Inhibitors of counterregulatory hormones
Direct modifiers of glucose metabolism
Modifiers of lipid metabolism
Sodium-glucose co-transporter inhibitors
Sirtuins
Conclusions
References
Chapter 48: Incretin-based therapies
Biologic actions of incretin hormones in patients with type 2 diabetes mellitus
GLP-1 as a parent compound for incretin-based antidiabetic drugs
Development of GLP-1 receptor agonists (incretin mimetics)
Agents under development
Efficacy of incretin mimetics as glucose-lowering agents (reduction in HbA1c)
Deceleration of gastric emptying
Inducing weight loss
Gastrointestinal adverse events
Antibody formation
Development of inhibitors of dipeptidyl peptidase-4 (DPP-4)
Efficacy as glucose-lowering agents (reduction in HbA1c)
Recommendations by guidelines for the treatment of type 2 diabetes
Future developments
References
Chapter 49: Insulin pumps
History
Efficacy, benefits, data supporting insulin pump therapy
Insulin pump use
Real-time continuous glucose monitoring (RT-CGM) linked to insulin pump
Adding RT-CGM to pump therapy
Future trends
Conclusion
Acknowledgment
References
Chapter 50: Innovative therapies in diabetes: colesevelam and bromocriptine
Colesevelam
Bromocriptine-QR
Acknowledgment
References
Section IX: Management of diabetes: monitoring and other interventions
Chapter 51: Implantable pumps and artificial and bio-artificial pancreas system
Introduction
The artificial pancreas
Future directions: bio-artificial pancreas
References
Chapter 52: Pancreas and islet transplantation
Role of pancreas and islet transplantation in management of diabetes
The pancreas transplantation procedure
The islet transplantation procedure
Success rates for pancreas and islet transplantation
Clinical outcomes on diabetes complications after successful pancreas and alloislet transplantation
References
Chapter 53: Hypoglycemia and other complications of insulin therapy
Introduction
Definition of hypoglycemia
Physiologic responses to hypoglycemia
Defects in counterregulation associated with diabetes treatments
Impaired awareness of hypoglycemia
The brain's responses to hypoglycemia
Risk for severe hypoglycemia
Consequences of hypoglycemia
Nocturnal hypoglycemia
Addressing hypoglycemia in insulin therapy
Management of hypoglycemia
Transplantation as a treatment for hypoglycemia
Barriers to avoidance of hypoglycemia and restoration of impaired hypoglycemia awareness
Nonhypoglycemic complications of insulin therapy
Injection site issues
Cancer
References
Chapter 54: Diabetic ketoacidosis and hyperosmolar state
Introduction
Diabetic ketoacidosis
Hyperglycemic hyperosmolar state
Treatment of hyperglycemic crises
Management of patients after resolution of hyperglycemic crisis
Prevention of hyperglycemic crises
Future prospects
Acknowledgments
References
Section X: Management of diabetes: glucose and lipid monitoring, specific subgroups
Chapter 55: Type 2 diabetes in obese adolescents: pathophysiology and treatment
Type 2 diabetes in obese youth: a growing challenge
Clinical characteristic of T2DM in youth
Beta-cell dysfunction: an early alteration in the development of T2DM
Natural history of IGT and the development of T2DM
Insulin resistance and T2DM: fat accumulation in all the wrong tissues
Treatment for T2DM: lessons from the TODAY study
References
Chapter 56: Diabetes in pregnancy
Maternal adaptation to pregnancy
Classification of glucose abnormalities in pregnancy
Epidemiology of diabetes in pregnancy
Diagnosis of gestational diabetes mellitus
Adverse pregnancy outcomes in gestations complicated by diabetes
Detection and treatment of diabetes in pregnancy
Preconception care for pregestational diabetes
Diet and behavioral adjustments
Insulin treatment
Oral antidiabetic agents
New technologies
Special considerations during pregnancy, labor, and delivery
References
Chapter 57: Aging and diabetes mellitus
Diabetes epidemiology in older adults
Pathophysiology of diabetes in the elderly
Prevention and management of diabetes and its comorbidities in older adults
Geriatric syndromes in older adults with diabetes
Diabetes education, self-management, and decision support in the elderly
References
Chapter 58: Psychological problems and management of patients with diabetes mellitus
Introduction
Depression
Anxiety
Eating disorders
Neurocognitive problems
Future research needs
Recommendations for clinical practice
Conclusions
References
Chapter 59: Glycated hemoglobin, serum proteins, and other markers as tools for monitoring
Introduction
Glycation reactions
Glycation of hemoglobin
Glycation in individuals with normal glucose tolerance
HbA1c testing for diabetes screening and monitoring in pregnancy
HbA1c and chronic complications of diabetes
Assays of glycated hemoglobin
Frequency of HbA1c testing
HbA1c testing affected by comorbid illnesses
Glycation of serum proteins
Monitoring of glycemia in pregnancy
1,5-Anhydroglucitol as a measure of glycemia
Advanced glycosylation end-products and diabetic complications
Artificial pancreas
Acknowledgments
References
Section XI: Complications of diabetes: general and microvasular
Chapter 60: Pathogenesis of diabetic microvascular complications
Introduction
Gene regulation
Hyperglycemia—too much fuel or not enough?
Hemodynamic pathways
Obesity and dyslipidemia
Protein modifications and turnover
Oxidative imbalances
Inflammation
Conclusion
References
Chapter 61: Diabetic retinopathy and other ocular complications
Introduction
Prevalence of diabetic retinopathy
Incidence and progression of diabetic retinopathy
Time trends in the epidemiology of diabetic retinopathy
Risk factors
Relationship with other complications
Pathogenesis
Clinical features and assessment
Investigations
Recommended timing and frequency of screening for diabetic retinopathy
Systemic treatment of diabetic retinopathy
Ocular therapy
Other ocular complications
Other retinal conditions
Future directions
References
Chapter 62: Diabetic nephropathy
Definition and classification of diabetic kidney disease (DKD)
Aetiology of DKD
Natural history of DKD
Predictive value of albuminuria below the microalbuminuric range
Hyperfiltration
Progression of DKD to ESRD
Gene variants in DKD
Histologic changes of DN
Prevention, screening, and monitoring of DKD
Management of DKD
References
Chapter 63: Pathology of human diabetic neuropathy
Introduction
Nerve biopsy
Myelinated fibers
Axonal atrophy
Axoglial dysjunction
Unmyelinated fibers
Microvessels
Extracellular matrix
Variants of diabetic neuropathy
Skin biopsy
Sudomotor innervation
Corneal confocal microscopy
References
Chapter 64: Autonomic neuropathy
Introduction
Epidemiology of Diabetic Autonomic Neuropathy
Pathogenesis of Diabetic Autonomic Neuropathy
Cardiovascular autonomic neuropathy
Gastrointestinal autonomic neuropathy
Genitourinary autonomic neuropathy
Autonomic neuropathy and the response to hypoglycemia
Conclusions
References
Chapter 65: Connective tissue disorders in diabetes
Introduction
Skeleton
Joints
Skin and periarticular tissue
Conclusion
References
Chapter 66: The diabetic foot
Introduction
Incidence and prevalence of diabetic foot ulcers
Peripheral vascular disease
Diabetic peripheral neuropathy
Distal symmetrical sensorimotor peripheral neuropathy
Peripheral sympathetic autonomic neuropathy
Other risk factors for foot ulceration
Nephropathy
Incidence of neuropathic foot ulcers
The pathway to foot ulceration
Identification of the high-risk foot
Infection and diabetic foot ulcers
Management of diabetic foot ulcers
Multidisciplinary team input
Patient education
Charcot neuroarthropathy
Diagnosis of Charcot neuroarthropathy
Medical management of Charcot neuroarthropathy
Surgical management of Charcot neuroarthropathy
Conclusion
References
Chapter 67: Erectile dysfunction in diabetes mellitus
Introduction
Epidemiology
Pathophysiology
ED: a marker for cardiovascular disease (CVD)
Management
Conclusions
References
Chapter 68: Periodontal disease and diabetes mellitus
Introduction
Periodontal diseases: assessment
Periodontal diseases and inflammation: localized and generalized
Periodontal disease and diabetes mellitus: a two-way relationship
Effect of diabetes on periodontal disease
Effect of diabetes intervention on periodontitis in type 2 diabetes
Effect of periodontal disease on diabetes
Effect of periodontal treatment on diabetes
Effect of periodontal disease on diabetes complications
Periodontal disease and diabetes-related medical care costs
Guidelines for oral health in people with diabetes
Co-management of patients with diabetes by dental and medical care providers
Future healthcare collaboration for diabetes prevention and lifelong management
References
Section XII: Complications of diabetes: macrovascular
Chapter 69: Epidemiology of macrovascular disease and hypertension in diabetes mellitus
Introduction
Hypertension
Coronary heart disease
Stroke and cerebrovascular diseases
Asymptomatic hyperglycemia and CVD risk
References
Chapter 70: Atherogenesis, coronary heart disease and insulin resistance syndrome in diabetes
Diabetes mellitus and the burden of cardiovascular disease
Insulin resistance (metabolic) syndrome
Hyperglycemia, glycemic control, and CVD
Diabetes and atherosclerosis
Pathogenesis linking metabolic syndrome, diabetes, and atherogenesis
Conclusion
References
Chapter 71: Endothelial function and metabolic syndrome
Introduction: the metabolic syndrome
Endothelial dysfunction and MetS
Endothelial microparticles (EMP)
Endothelial microparticles and MetS
Endothelial progenitor cells (EPC)
EPC and cardiovascular events
EPC and MetS
Conclusion
References
Chapter 72: Hemostatic abnormalities in diabetes mellitus
Introduction
Mechanisms of thrombosis
Mechanisms of thrombosis in diabetes
The effects of glucose and glycation on thrombosis
Inflammatory, thrombotic interactions
Circadian regulation of thrombotic mechanisms
Ameliorating thrombotic risk in diabetes
Summary and conclusions
References
Chapter 73: Clinical features and treatment of coronary heart disease in diabetes
Introduction
Key practical features of the relationship between CHD and diabetes
Specific clinical features of CHD in diabetes
Cardiovascular risk related to diabetes therapy
Management aspects
Concluding remarks
References
Chapter 74: Arterial hypertension in diabetes: etiology and treatment
Introduction
Genetics factors
Ion transport homeostasis
Extracellular sodium homeostasis
Sympathetic activity
Therapeutic considerations
Conclusion
References
Chapter 75: Peripheral vascular and cerebrovascular disease in diabetes mellitus
Introduction
Diabetes and risk of vascular disease
Diabetes and peripheral arterial disease
Diabetes and cerebrovascular disease
Conclusions
References
Section XIII: Diabetes and public health
Chapter 76: The diabetes challenge: from human and social rights to the empowerment of people with diabetes
Introduction
The right to health
Human and social rights of people with diabetes
Rights and responsibilities on diabetes information and education
Conclusion: the way forward
References
Chapter 77: The economics of diabetes care: a global perspective
Introduction
The scope of this chapter
The economic impact of diabetes
The cost effectiveness and cost utility of interventions
The information that we have is not what we need most
Acknowledgments
References
Index
End User License Agreement
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Guide
Cover
Table of Contents
Preface
Section I: Epidemiology
Begin Reading
List of Illustrations
Figure 1.1
Figure 2.1
Figure 2.2
Figure 2.3
Figure 2.4
Figure 3.1
Figure 3.2
Figure 3.3
Figure 3.4
Figure 3.5
Figure 3.6
Figure 3.7
Figure 3.8
Figure 3.9
Figure 3.10
Figure 3.11
Figure 4.1
Figure 4.2
Figure 4.3
Figure 5.1
Figure 5.2
Figure 5.3
Figure 5.4
Figure 5.5
Figure 6.1
Figure 6.2
Figure 6.3
Figure 6.4
Figure 6.5
Figure 7.1
Figure 7.2
Figure 7.3
Figure 8.1
Figure 8.2
Figure 8.3
Figure 8.4
Figure 8.5
Figure 9.1
Figure 10.1
Figure 10.2
Figure 11.1
Figure 11.2
Figure 11.3
Figure 11.4
Figure 11.5
Figure 12.1
Figure 12.2
Figure 12.3
Figure 12.4
Figure 12.5
Figure 12.6
Figure 12.7
Figure 13.1
Figure 13.2
Figure 13.3
Figure 13.4
Figure 13.5
Figure 13.6
Figure 13.7
Figure 13.8
Figure 14.1
Figure 14.2
Figure 14.3
Figure 14.4
Figure 14.5
Figure 14.6
Figure 14.7
Figure 14.8
Figure 14.9
Figure 14.10
Figure 14.11
Figure 14.12
Figure 14.13
Figure 14.14
Figure 14.15
Figure 14.16
Figure 14.17
Figure 14.18
Figure 14.19
Figure 15.1
Figure 15.2
Figure 15.3
Figure 15.4
Figure 15.5
Figure 15.6
Figure 15.7
Figure 15.8
Figure 15.9
Figure 15.10
Figure 16.1
Figure 18.1
Figure 18.2
Figure 19.1
Figure 19.2
Figure 19.3
Figure 19.4
Figure 20.1
Figure 22.1
Figure 22.2
Figure 22.3
Figure 23.1
Figure 23.2
Figure 23.3
Figure 24.1
Figure 24.2
Figure 24.3
Figure 24.4
Figure 24.5
Figure 24.6
Figure 24.7
Figure 24.8
Figure 24.9
Figure 24.10
Figure 24.11
Figure 24.12
Figure 24.13
Figure 25.1
Figure 25.2
Figure 25.3
Figure 25.4
Figure 25.5
Figure 25.6
Figure 25.7
Figure 25.8
Figure 25.9
Figure 25.10
Figure 25.11
Figure 25.12
Figure 25.13
Figure 25.14
Figure 25.15
Figure 25.16
Figure 25.17
Figure 26.1
Figure 26.2
Figure 27.1
Figure 27.2
Figure 27.3
Figure 27.4
Figure 27.5
Figure 28.1
Figure 28.2
Figure 28.3
Figure 28.4
Figure 28.5
Figure 29.1
Figure 29.2
Figure 30.1
Figure 30.2
Figure 30.3
Figure 30.4
Figure 31.1
Figure 31.2
Figure 31.3
Figure 32.1
Figure 32.2
Figure 33.1
Figure 33.2
Figure 33.3
Figure 33.4
Figure 33.5
Figure 34.1
Figure 34.2
Figure 34.3
Figure 34.4
Figure 35.1
Figure 36.1
Figure 36.2
Figure 39.1
Figure 39.2
Figure 41.1
Figure 41.2
Figure 41.3
Figure 41.4
Figure 41.5
Figure 41.6
Figure 41.7
Figure 42.1
Figure 42.2
Figure 42.3
Figure 42.4
Figure 42.5
Figure 42.6
Figure 43.1
Figure 43.2
Figure 43.3
Figure 44.1
Figure 44.2
Figure 44.3
Figure 44.4
Figure 45.1
Figure 45.2
Figure 45.3
Figure 45.4
Figure 46.1
Figure 46.2
Figure 46.3
Figure 46.4
Figure 46.5
Figure 46.6
Figure 46.7
Figure 46.8
Figure 47.1
Figure 47.2
Figure 47.3
Figure 47.4
Figure 47.5
Figure 47.6
Figure 47.7
Figure 47.8
Figure 47.9
Figure 47.10
Figure 48.1
Figure 48.2
Figure 48.3
Figure 48.4
Figure 48.5
Figure 52.1
Figure 52.2
Figure 52.3
Figure 52.4
Figure 52.5
Figure 52.6
Figure 53.1
Figure 53.2
Figure 53.3
Figure 53.4
Figure 54.1
Figure 54.2
Figure 54.3
Figure 55.1
Figure 55.2
Figure 56.1
Figure 56.2
Figure 57.1
Figure 59.1
Figure 59.2
Figure 59.3
Figure 60.1
Figure 60.2
Figure 61.1
Figure 61.2
Figure 62.1
Figure 62.2
Figure 63.1
Figure 63.2
Figure 63.3
Figure 63.4
Figure 63.5
Figure 63.6
Figure 63.7
Figure 63.8
Figure 63.9
Figure 64.1
Figure 64.2
Figure 64.3
Figure 64.4
Figure 64.5
Figure 65.1
Figure 65.2
Figure 66.1
Figure 66.2
Figure 66.3
Figure 67.1
Figure 67.2
Figure 67.3
Figure 67.4
Figure 68.1
Figure 68.2
Figure 68.3
Figure 68.4
Figure 69.1
Figure 70.1
Figure 70.2
Figure 70.3
Figure 70.4
Figure 72.1
Figure 72.2
Figure 72.3
Figure 73.1
Figure 74.1
Figure 74.2
Figure 75.1
Figure 76.1
Figure 77.1
List of Tables
Table 1.1
Table 1.2
Table 1.3
Table 1.4
Table 1.5
Table 1.6
Table 1.7
Table 2.1
Table 3.1
Table 3.2
Table 3.3
Table 3.4
Table 4.1
Table 4.2
Table 4.3
Table 7.1
Table 9.1
Table 9.2
Table 9.3
Table 10.1
Table 10.2
Table 12.1
Table 14.1
Table 14.2
Table 15.1
Table 15.2
Table 15.3
Table 17.1
Table 17.2
Table 20.1
Table 20.2
Table 20.3
Table 20.4
Table 20.5
Table 21.1
Table 21.2
Table 21.3
Table 22.1
Table 22.2
Table 22.3
Table 22.4
Table 23.1
Table 23.2
Table 23.3
Table 23.4
Table 23.5
Table 23.6
Table 24.1
Table 24.2
Table 25.1
Table 25.2
Table 26.1
Table 28.1
Table 28.2
Table 28.3
Table 28.4
Table 30.1
Table 33.1
Table 33.2
Table 35.1
Table 35.2
Table 38.1
Table 38.2
Table 38.3
Table 39.1
Table 40.1
Table 40.2
Table 40.3
Table 41.1
Table 41.2
Table 41.3
Table 42.1
Table 42.2
Table 42.3
Table 42.4
Table 43.1
Table 43.2
Table 43.3
Table 44.1
Table 44.2
Table 45.1
Table 46.1
Table 46.2
Table 47.1
Table 47.2
Table 47.3
Table 48.1
Table 48.2
Table 49.1
Table 50.1
Table 50.2
Table 50.3
Table 51.1
Table 51.2
Table 53.1
Table 53.2
Table 54.1
Table 54.2
Table 54.3
Table 54.4
Table 54.5
Table 54.6
Table 56.1
Table 56.2
Table 56.3
Table 56.4
Table 56.5
Table 56.6
Table 56.7
Table 56.8
Table 57.1
Table 59.1
Table 59.2
Table 59.3
Table 61.1
Table 61.2
Table 61.3
Table 61.4
Table 62.1
Table 62.2
Table 62.3
Table 62.4(a)
Table 62.4(b)
Table 62.4(c)
Table 64.1
Table 64.2
Table 65.1
Table 66.1
Table 66.2
Table 67.1
Table 67.2
Table 67.3
Table 67.4
Table 67.5
Table 67.6
Table 67.7
Table 67.8
Table 68.1
Table 68.2
Table 68.3
Table 69.1
Table 69.2
Table 69.3
Table 70.1
Table 72.1
Table 73.1
Table 73.2
Table 73.3
Table 74.1
Table 75.1
Table 75.2
Table 75.3
Table 75.4
Table 77.1
Table 77.2
Table 77.3
International Textbook of Diabetes Mellitus
Fourth Edition
Editors-In-Chief
Ralph DeFronzo MD
Professor of Medicine and Chief, Diabetes Division The University of Texas Health Science Center at San Antonio (UTHSCSA) Deputy Director, Texas Diabetes Institute San Antonio, TX, USA
Ele Ferrannini MD
Professor of Internal Medicine Department of Clinical and Experimental Medicine University of Pisa Pisa, Italy
Paul Zimmet AO, MD, PhD, FRACP, FRCP, FTSE
Director Emeritus, Victor Smorgon Diabetes Centre Baker IDI Heart and Diabetes Institute Adjunct Professor, Monash University Honorary President, International Diabetes Federation Chair, Programme Committee, World Diabetes Congress 2013 Melbourne, VIC, Australia
K. George M. M. Alberti MA, DPhil, PRCP, FRCPath, FRCP
Senior Research Investigator, Imperial College, London, UK Chair of King's College Hospital NHS Foundation Trust Emeritus Professor of Medicine, University of Newcastle upon Tyne Newcastle upon Tyne, UK
Knut Borch-Johnsen MD, DMSc
Professor of Quality in Health Care
Medical Director, Holbæk Hospital
Holbaek, Denmark
Mark Cooper MD, PhD, FRACP
Deputy Director and Chief Scientific Officer
Baker IDI Heart and Diabetes Institute
Melbourne, VIC, Australia
Stefano Del Prato MD
Professor of Endocrinology and Metabolism
School of Medicine, University of Pisa;
Chief, Section of Diabetes and Metabolic Diseases
University of Pisa
Pisa, Italy
Robert H. Eckel MD
Charles A. Boettcher Endowed Chair in Atherosclerosis
Professor of Medicine
Division of Endocrinology, Metabolism and Diabetes, and Cardiology
Professor of Physiology and Biophysics
University of Colorado School of Medicine
Aurora, CO, USA
W. Timothy Garvey MD, FACE
Butterworth Professor and Chair,
Department of Nutrition Sciences
University of Alabama at Birmingham
Director, UAB Diabetes Research Center
GRECC Investigator and Staff Physician
Birmingham VA Medical Center
Birmingham, AL, USA
Rury R. Holman FRCP
Professor of Diabetic Medicine
Director, University of Oxford Diabetes Trials Unit
Oxford Centre for Diabetes, Endocrinology and Metabolism
Churchill Hospital
University of Oxford
Oxford, UK
Steven E. Kahn MB, ChB
Professor of Medicine
Division of Metabolism, Endocrinology and Nutrition
Director, Diabetes Research Center
University of Washington
VA Puget Sound Health Care System
Seattle, WA, USA
James B. Meigs MD
Massachusetts General Hospital
Boston, MA, USA
Eric Ravussin PhD
Associate Executive Director, Obesity & Diabetes
Pennington Biomedical Research Center
Baton Rouge, LA, USA
Jay S. Skyler MD, MACP
Professor of Medicine, Pediatrics, & Psychology
Division of Endocrinology, Diabetes, & Metabolism
Deputy Director— Diabetes Research Institute
University of Miami Miller School of Medicine
Miami, FL, USA
Hannele Yki-Järvinen MD, FRCP
Professor of Medicine
University of Helsinki;
Minerva Foundation Institute for Medical Research
Helsinki, Finland
Bernard Zinman CM, MD, FRCPC, FACP
Director, Leadership Sinai Centre for Diabetes
Sam and Judy Pencer Family Chair in Diabetes Research
Senior Scientist, Samuel Lunenfeld Research Institute
Professor of Medicine, University of Toronto Mount Sinai Hospital
Toronto, ON, Canada
This edition first published 2015 © 2004, 2015 by John Wiley & Sons Ltd.
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Library of Congress Cataloging-in-Publication Data
International textbook of diabetes mellitus / edited by Ralph A. DeFronzo, Ele Ferrannini, K. George M.M. Alberti, Paul Zimmet.— 4th edition.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-470-65861-1 (cloth)
I. DeFronzo, Ralph A., editor. II. Ferrannini, Eleuterio, editor. III. Alberti, K. G. M. M. (Kurt George Matthew Mayer), editor. IV. Zimmet, Paul, editor.
[DNLM: 1. Diabetes Mellitus. WK 810]
RC660
616.4′62– dc23
2014037412
A catalogue record for this book is available from the British Library.