Biomarkers in Diabetes

Preface
Contents
About the Editors
Contributors
Part I: General Aspects
1 Linking Variants of Hemoglobin A1C and Glycemic Status
Introduction
Overview of Genome-Wide Association Studies of HbA1c
Functional Characterization of HbA1c-Associated Genetic Variants
Glycemic-Related Genetic Variants
Erythrocyte-Related Genetic Variants
Unclassified Genetic Variants
Erythrocyte-Related HbA1c Variants and Glycemic Status Screening
G6PD: rs1050828 and rs76723693
HBB-rs334
G6PD-rs1050828 and HBB-rs334
Cumulative Effect of Erythrocyte-Related Genetic Variants
Conclusion
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of HbA1c
Summary Points
Reference
2 Treatment Regimes in Diabetes and Their Impact on Biomarkers
Lipid Profile and T2DM
Introduction to Lipids and T2DM
The Relationship Between Obesity and Lipids
The Relationship Between Lipids and T2DM
Lipid Intermediates and Insulin Resistance
Role of Exercise on Lipid Metabolism in T2DM
Acute Effects of Exercise on Muscle Lipid Content
Acute Effects of Exercise on Muscle Lipid Intermediates
Chronic Effects of Exercise on Muscle Lipid Content
Chronic Effects of Exercise on Muscle Lipid Intermediates
Effect of Exercise on Liver Lipid Content
Exercise Interventions and Classic Lipid Biomarkers
Inflammatory Profile and T2DM
Introduction to Inflammation and T2DM
The Relationship Between Obesity and Inflammation
The Relationship Between Inflammation and T2DM
TNF-α and T2DM
IL-6 and T2DM
IL-1β and T2DM
Anti-inflammatory Effects of Exercise
Acute Effects of Exercise and Anti-inflammatory Mechanisms
Chronic Effects of Exercise and Anti-inflammatory Mechanisms
Exercise Interventions and Inflammatory Biomarkers
Applications to Other Diseases or Conditions
Conclusion
Mini-Dictionary of Terms
Key Facts on Exercise and the Lipid Profile
Key Facts on Exercise and Inflammation
Summary Points
References
Part II: Circulating and Body Fluid Biomarkers: Impact of Diabetes on Pathology
3 Resistin as a Biomarker and Applications to Prediabetes
Introduction
Diabetes
Prediabetes: Definition and Related Diseases
The Role of Adipokines at Energy Balance
Resistin As a Biomarker at Different Types of Disease
Resistin As a Biomarker in Cardiovascular Disorders
Resistin As a Biomarker in Obesity
Resistin As a Biomarker in Diabetes
Resistin As a Biomarker in Cancer
The Association Between Resistin and Prediabetes and Outcomes
Conclusion
Key Facts of Resistin
Summary Points
References
4 Altered Metabolome of Amino Acids Species: A Source of Signature Early Biomarkers of T2DM
Introduction
Diabetes Mellitus
The Need for New Biomarkers for Diabetes
Amino Acids in Metabolic Signaling and Insulin Resistance
Altered Amino Acid Profiles in Insulin Resistance and Diabetes
Amino Acids Metabolic Intermediates As Markers for Insulin Resistance and Diabetes
Conclusions
Applications to Prognosis, Other Diseases, or Conditions
Mini Dictionary of Terms
Key Facts of Amino acids
Summary Points
References
5 Components of the Purine Metabolism Pathways as Biomarkers for the Early Diagnosis of Diabetes
Introduction
Purine Metabolism
Xanthine Oxidase
Adenosine Metabolizing Enzymes, Inosine and Adenosine
Inosine-5′-Monophosphate Dehydrogenase
Uric Acid
Conclusion
Applications to Prognosis, Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of Purine Enzymes and Related Metabolites
Summary Points
References
6 Serpin A12 (Vaspin) as a Serine Protease Inhibitor
Introduction
Type 2 Diabetes and the Importance of Biomarkers
Vaspin as a Diabetes Biomarker
Biochemical Characterization
Main Sources of Vaspin
Vaspin and Anti-Inflammatory Effects
Glucose Intolerance and Vaspin
Insulin Role and Vaspin Action
Circulating Vaspin Level, Type 2 Diabetes, and Obesity
Metabolic Syndrome (MetS) and Vaspin
Applications to Prognosis, Other Diseases, and Conditions
Conclusion
Mini-Dictionary of Terms
Key Facts of Type 2 Diabetes
Summary Points
References
7 Advanced Glycation End Products in Diabetes
Introduction
Advanced Glycation End Products (AGEs)
AGE Receptors
Effects of AGEs
AGE Measurements
Effects of AGEs in Diabetes
Nephropathy in Diabetes
Cardiomyopathy and Arterial Alterations in Diabetes
Neuropathy in Diabetes
Retinopathy in Diabetes
Cancer and Diabetes
Cross Talk Between AGEs and Oxidative Stress in Diabetes
AGEs in Other Diseases
Applications to Other Diseases or Conditions
Mini Dictionary of Terms
Key Facts of Diabetes: Where Advanced Glycation End Products Is the Topic
Summary Points
References
8 Markers of Liver Function and Insulin Resistance
Introduction
Applications to Diagnosis
Mini-Dictionary of Terms
Summary Points (5-10)
Markers of Liver Function and Insulin Resistance
Visceral Fat and Insulin Resistance
NAFLD, IR Y T2DM
Hepatokines
DPP4 (Dipeptidyl Peptidase-4)
Pharmacological DPP-4 Inhibitors
Fetuin A (AHSG)
Fetuin B
Selenoprotein P
LECT-2
Hepassocin, Also Called Hepatocyte-Derived Fibrinogen-Related Protein 1, HPS, and HFREP1
Pigment Epithelium-Derived Factor
Tsukushi (TSK)
Conclusions
References
9 Biological Markers of Insulin Sensitivity Links with Dietary Antioxidant
Introduction
Applications to Diagnosis
Mini Dictionary of Terms
Key Facts of Insulin Sensitivity, Biomarkers, and Dietary Antioxidants
Summary Points
Markers of Liver Function and Insulin Resistance
Insulin Sensitivity
Adiponectin
Adropin, Angiopoietin-lLike Protein 4 (ANGPTL4)
DPP4, GLP-1
Fetuin-A and Fetuin-B
FGF21
HMBG1, Myostatin
Interleukins, Irisin, RBP4
Minerals in Insulin Resistance Sensitivity
Calcium, Magnesium
Chromiun, Selenium, Zinc
Vitamins in Insulin Sensitivity
Vitamin C, E
Vitamin D, K, B
Conclusions
References
10 Serum Uric Acid and Metabolic Markers in Diabetes
Introduction
Metabolic Markers in Diabetes
Uric Acid
Uric Acid in Diabetes Pathophysiology
Uric Acid as a Biomarker in Diabetes
Serum Uric Acid as a Predictor of Diabetes Risk
Serum Uric Acid, Blood Glucose Level, and HbA1c
Uric Acid in Diabetic Complications
Uric Acid in Macrovascular Complications
Uric Acid in Microvascular Complications
eGFR and Serum Uric Acid Levels
Applications to Prognosis and Other Diseases or Conditions
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of Serum Uric Acid and Metabolic Markers in Diabetes: eGFR, HbA1c, and Beyond
Key Facts of Uric Acid and Diabetes
Key Facts of Uric Acid and Diabetic Complications
Summary Points
References
11 Urinary Interleukins and Kidney Damage in Diabetes
Introduction
Inflammation and Diabetic Kidney Disease
Urinary Interleukins
Interleukin 1
Interleukin 6
Interleukin 8
Interleukin 10
Interleukin 18
Potential Applications to Prognosis, Other Diseases, or Conditions
Mini-dictionary of Terms
Key Facts of Diabetes, Kidney Damage, and Urinary Interleukins
Summary Points
References
12 Serum Homocysteine as a Biomarker in Diabetes
Introduction
Homocysteine and Its Role in the Body
Biosynthesis and Metabolism of Homocysteine
Factors Causing Hyperhomocysteinemia
Diabetes Mellitus Cellular Metabolism Disturbance and Micronutrient Status in Diabetes Mellitus
Hyperhomocysteinemia and Diabetes Mellitus
Cognitive Dysfunction in Diabetes Mellitus
Cognitive Function
Factors That Affect Cognitive Function
Hyperhomocysteinemia and Cognitive Function
Compliance in Diabetes Management and Cognitive Dysfunction
Applications to Prognosis
Mini-Dictionary of Terms
Key Facts of Serum Homocysteine as a Biomarker in Diabetes: Links with Variables Such as Cognition
Summary Points
References
13 3-Hydroxyisobutyrate (3-HIB): Features and Links as a Biological Marker in Diabetes
Introduction
BCAA Catabolism in Adipose Tissue
3-HIB in Interorgan Metabolic Crosstalk
3-HIB Reflects Hepatic Fatty Acid Oxidation
Conclusion and Future Perspectives
Applications to Prognosis, Other Diseases, or Conditions
Mini-Dictionary of Terms
Key Facts of Diabetes
Summary Points
References
14 Proteomic Biomarkers: What They Are and How Type 2 Diabetes Mellitus Has Similarities with Other Diseases
Introduction
Proteomic Biomarkers and Type 2 Diabetes Mellitus
Proteomics in Type 2 Diabetes Mellitus Complications
Diabetic Retinopathy
Diabetic Kidney Disease
Diabetic Neuropathy and Chronic Wounds
Proteomics in Type 2 Diabetes Mellitus and Other Diseases
Type 2 Diabetes Mellitus and Obesity
Type 2 Diabetes Mellitus and Cardiovascular Diseases
Type 2 Diabetes Mellitus and Metabolic Diseases
Type 2 Diabetes Mellitus and Pancreatic Cancer
Type 2 Diabetes Mellitus and Neurologic Disorders
Conclusion
Applications to Prognosis and Other Diseases or Conditions
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Key Factors of Proteomic Biomarkers in Diabetes Mellitus
Summary Points
References
15 Salivary C-Reactive Protein as a Biomarker and Implications for Diabetes
Introduction
Biomarkers of Type 2 Diabetes
C-Reactive Protein and Pathogenesis
Type 2 Diabetes and CRP
Human Saliva as Diagnostic Fluid for Biomarkers
Salivary Biomarkers in Type 2 Diabetes
Identification of Diabetes-Associated Serum Proteins Found in Saliva
Measurement of Diabetes-Related Serum Protein Markers in Saliva of Diabetic Patients
Correlation of the CRP Levels in Saliva and Serum
Diagnostic Methods of Salivary Biomarker Identification
Enzyme-Linked Immunosorbent Assay (ELISA)
Multiplex Analysis
Other Detection Methods
Applications to Prognosis, Other Diseases, or Conditions
Mini-dictionary of Terms
Key Facts of C-Reactive Protein
Summary Points
References
16 Assessing Insulin Sensitivity in People with Type 1 Diabetes Without Euglycemic-Hyperinsulinemic Clamps
Introduction
Euglycemic-Hyperinsulinemic Clamp
Estimation of Insulin Sensitivity
Estimation of GDR in Type 1 Diabetes
Application to Prognosis and Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts
Summary Points
References
17 Serum Betatrophin: What It Shows and How It Alters in Gestational Diabetes Mellitus
Gestational Diabetes Mellitus: Definition and Prevalence
GDM Incidence
GDM Risk Factors
GDM Treatment
Glucose Regulation During Healthy Pregnancy
GDM Physiology
The Adipose Tissue in the Pathophysiology of Gestational Diabetes Mellitus
Betatrophin
Betatrophin in Gestational Diabetes Mellitus
Applications to Prognosis, Other Diseases or Conditions
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini Dictionary of Terms
Key Facts of Betatrophin
Summary Points
References
18 Biomarkers in Disease: Diabetes Methods, Discoveries, and Applications
Introduction
Risk Prediction of Diabetes and the Role of Lipoproteins
The Role of Large VLDL Particles (High Density of VLDL1 Particles) in Risk Prediction of Diabetes: Results from Clinical Studi...
The Role of Large VLDL Particles (High Density of VLDL1 Particles) in Risk Prediction of Diabetes: Rationale Suggesting a Caus...
The Role of VLDL Particles and Triglycerides in Risk Prediction of Diabetes: What is the Role of Genetics?
The Role of Large VLDL Particles (High Density of VLDL1 Particles) in Risk Prediction of Diabetes: Genetics as a Fundamental P...
Lipidomics as Tool to Study TRL Metabolism and the Risk of Diabetes
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of Type 2 Diabetes and Hypertriglyceridemia
Summary Points
References
19 Correlations Between Renal Biomarkers and the Treatment Outcomes in Diabetes: Ophthalmic Aspects
Introduction
Correlations Between Renal Biomarkers and Diabetic Retinopathy
Serum Creatinine and Estimated Glomerular Filtration Rate
Albuminuria
Erythropoietin
Correlations Between Renal Biomarkers and Diabetic Macular Edema
Serum Creatinine and Estimated Glomerular Filtration Rate
Albuminuria
Body Fluid Status
Correlations Between Renal Biomarkers and Treatment Outcomes of Diabetic Macular Edema
Serum Creatinine and Estimated Glomerular Filtration Rate
Albuminuria
Effects of Diabetic Nephropathy Treatment on Diabetic Retinopathy and Diabetic Macular Edema
Glycemic Control
Glucagon-Like Peptide-1 (GLP-1) Agonists
Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
Sodium-Glucose Co-Transporter-2 (SGLT-2) Inhibitors
Renal Replacement Therapy
Kidney Transplantation
Correlations Between Renal Biomarkers and Other Ocular Manifestations in Diabetes
Diabetic Keratopathy and Corneal Nerve Degeneration
Renal Biomarkers Versus Diabetic Keratopathy
Effects of Renal Replacement Therapy or Kidney Transplantation on Diabetic Keratopathy
Glaucoma in Diabetes
Renal Biomarkers Versus Glaucoma in Diabetes
Effects of Renal Replacement Therapy or Kidney Transplantation on Glaucoma
Renal Biomarkers Versus Cataract in Diabetes
Effects of Renal Replacement Therapy or Kidney Transplantation on Cataract
Conclusions
Applications of Renal Biomarkers to Prognosis
Mini-dictionary of Terms
Key Facts of Diabetic Retinopathy
Key Facts of Diabetic Macular Edema
Summary Points
References
20 Serum Paraoxonase 1 as a Biomarker: Features and Applications in Type 2 Diabetes Mellitus
Introduction
Structure of PON1
Functions and Physiological Roles of PON1
PON1 Polymorphisms
PON1 Polymorphisms in T2DM
PON1 and T2DM
Conclusions
Application in Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts
Summary Points
References
21 The Ratio of Omega-6/Omega-3 Fatty Acid: Implications and Application as a Marker to Diabetes
Introduction
Fatty Acids
General Metabolism of n-3 and n-6 PUFA
PUFA Composition and Cell Membrane
Role of PUFA in Cellular Function
Diet and Polyunsaturated Fatty Acids
Omega-6/Omega-3 Ratio
Significance of Omega-6/Omega-3 Ratio in Type 2 Diabetes Mellitus
Applications to Prognosis, Other Diseases, or Conditions
Obesity
Cardiovascular Diseases
Cancer
Pulmonary Disorders
Skin
Brain-Related Functions
Autoimmune Disease
Key Facts
Summary
References
22 Engulfment and Cell Motility Protein (ELMO)-1 as a Biomarker in Type II Diabetes
Introduction
A Genetic Variant of ELMO-1 as the Risk for DN in T2DM
The Role of ELMO-1 in Diabetic Nephropathy, Studies in the Animal Model, and Cell Culture
ELMO-1 in Circulation and Renal Tissue in Humans as a Potential Biomarker of DN in T2DM
Application to Prognosis, Other Diseases or Condition
Mini-Dictionary
Key Facts
Key Facts of Albuminuria
Key Facts of ELMO-1 Protein
Key Facts of ELMO-1 Genetic Variant rs741301
Summary Points
References
23 Brain-Derived Neurotrophic Factor and Vascular Endothelial Growth Factor A: Biomarkers Potential in Diabetes
Introduction
Brain-Derived Neurotrophic Factor: Mechanisms of Action and Functions
Vascular Endothelial Growth Factor A: Mechanisms of Action and Functions
Diagnostic and Therapeutic Potential of Brain-Derived Neurotrophic Factor in Metabolic Disturbances of Type 2 Diabetes Mellitus
Study of Serum Concentrations of BDNF in Human Populations
Inflammation and Brain-Derived Neurotrophic Factor
Diagnostic and Therapeutic Potential of Vascular Endothelial Growth Factor and Type 2 Diabetes Mellitus
Type 1 Diabetes Mellitus and Growth Factors
Serum BDNF and VEGFA as Biomarkers of Diabetes Complications
Study of Serum Concentrations of BDNF and VEGFA in Human Populations in Diabetic Polyneuropathy
Differences in Serum Levels of Neurotrophins in Diabetic Polyneuropathy in Type 1 and Type 2 Diabetes Mellitus
Modulation of Neuropathic Pain by BDNF in Diabetic Neuropathy
Central Nervous System Disturbances in DM: The Role of Growth Factors
Applications to Prognosis, Other Diseases, or Conditions
Key Facts of Brain-Derived Neurotrophic Factor and Vascular Endothelial Growth Factor A: Biomarkers´ Potential in Diabetes
Mini-Dictionary of Terms
Summary Points
References
24 The Role of Glycated Albumin as a Biomarker of Glycemic Control in Diabetes and Chronic Kidney Disease
Introduction
Albumin Discovery and Structure
Albumin Glycation Process
Diabetes Mellitus (DM)
Diabetes Mellitus and Glycation
The Use of Glycated Albumin in Monitoring Metabolic Control
Pitfalls of Conventional Measures of Glycemia
Fructosamine and Glycated Albumin
CKD and Diabetes
HbA1c for Glycemic Control in CKD
GA and Dialysis
Challenges and Pitfalls in the Measurement of Glycated Albumin
Conclusions, Limitations, and Recommendations
Applications to Prognosis and Other Diseases and Conditions
Key Facts of Glycated Albumin
Mini-Dictionary of Terms
Summary Points
References
Part III: Genetic, Molecular, and Cellular Variables
25 Epigenetics and 5-Hydroxymethylcytosines as a Biomarker in Type 2 Diabetes
Introduction
Novel Epigenetic Modifications beyond DNA Methylation
Technical Advances Enable Discovery of Hydroxymethylation Biomarkers
TAB-Seq
oxBS-Seq
The 5hmC as Novel Epigenetic Biomarkers for T2D Complications
Vascular Complications
Diabetic Retinopathy
Diabetic Nephropathy
Conclusions
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of Diabetic Complications
Summary Points
References
26 Adult Stem Cells as a Biomarker in Diabetes
Introduction
Why Adult Stem Cells
Effect of Exercise on Endothelial Progenitor Cells (EPCs)
Effects on EPC
Age Is Another Major Factor Behind Reduction of EPC Numbers
Effect of Novel Diabetes Medications on Endothelial Progenitor Cells (EPCs)
Effect of HIV Medication Regimens on Endothelial Progenitor Cells (EPCs)
Effects on Exercise on MSCs
Conclusion
Applications to Other Diseases or Conditions
Mini-dictionary of Terms
References
27 The Search for Immunological Biomarkers in Type 1 Diabetes Mellitus (T1DM) and Multiple Sclerosis (MS): Th40 Cells Provide ...
Mini Dictionary of Terms
Key Facts
Summary Points
References
28 Epigenetically Modified DNA Fragments
Introduction
Epigenetic Modifications
Cell-Free DNA and Epigenetically Modified DNA Fragments
Technologies for DNA Methylation Detection
Differentially Methylated cfDNA as a Biomarker for β-Cell Death
Advancing Technologies to Measure Differentially Methylated cfDNA
Differentially Methylated cfDNA Beyond T1D
Limitations to Measuring Differentially Methylated cfDNA as a Biomarker for β-Cell Death
Applications to Prognosis, Other Diseases, or Conditions
Mini-Dictionary of Terms
Key Facts of Diabetes
Key Facts of Cell-Free DNA (cfDNA)
Summary Points
References
29 Urinary Glucose Excretion as a Biomarker for Precision Medicine in Diabetes
Introduction
The Role of the Kidney in Glucose Homeostasis
Physiology of Glucosuria
Clinical Determinants of Urinary Glucose Excretion in the Diabetic State
Sodium-Glucose Cotransporters and Glucosuria
Mutations in the SGLT2 Gene and Urinary Glucose Excretion
Common Variants of the SGLT2 Gene
SLC5A2 and Diabetes-Related Phenotypes
Association of SGLT2 Gene with Susceptibility to Type 2 Diabetes Mellitus
Application to Prediction
SLC5A2 rs9934336 Polymorphism as a Genetic Marker of Diabetes-Related Phenotypes
Mini-Dictionary of Terms
Key Facts of Urinary Glucose Excretion
Summary Points
References
30 Secreted Frizzled-Related Proteins 4 and 5: What They Are and Can They Be Used as a Biomarker in Gestational Diabetes Melli...
Glucose Homeostasis During Pregnancy
Gestational Diabetes Mellitus
Adverse Pregnancy Outcomes GDM and Treatment
Secreted Frizzled-Related Protein Family
Secreted Frizzled-Related Protein Family During Pregnancy
sFRP4 and sFRP5 in Glucose Homeostasis
Biomarker for Gestational Diabetes Mellitus
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of Secreted Frizzled-Related Proteins 4 and 5: What They Are and Can They Be Used as a Biomarker in Gestational Diab...
Key Facts of Gestational Diabetes Mellitus
Key Facts of Secreted Frizzled-Related Proteins (sFRPs)
Summary Points
References
31 Insights into the World of MicroRNAs
Introduction
miRNA Biogenesis
Circulating miRNAs
Circulating miRNAs and Diabetes
Circulating miRNAs and DR
miR-1281 as a Novel Circulating Biomarker in Patients with DR
Conclusions
Key Facts of miRNAs
Summary Points
References
32 Genomic Ancestry as Biomarkers
Introduction
How to Determine Ethnicity?
How to Assess Genetic Ancestry?
Short Tandem Repeats (STRs)
SNPs
INDELs
AIMs
The Role of Ancestry in DR: What Do We Know so Far?
Conclusions
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of Genomic Ancestry as a Biomarker in Diabetic Retinopathy
Summary Points
References
33 Hp1-1 as a Genetic Marker in Diabetes: Measures, Applications, and Correlations
Key Facts of Haptoglobin Phenotype
Introduction
Structure and Polymorphic Variants of Haptoglobin
Biological Functions of Haptoglobin
Correlations of Haptoglobin
The Relationship Between the Haptoglobin Variant and Cardiovascular Disease
The Relationship Between the Haptoglobin Variant and the Development of Diabetic Complications
Relationship Between the Haptoglobin Variant and Neurodegenerative Diseases
The Relationship Between the Haptoglobin Variant and the Development of Infection
The Relationship Between the Haptoglobin Variant and the Development of Immune-Mediated Diseases
Conclusion
Summary Points
References
Part IV: Functional Variables, Physiological Variables, and Platforms
34 Day-by-Day Home Blood Pressure Monitoring as a Biomarker in Diabetes
Introduction
Diabetes and BPV
Different Types of BPV and Related Evidence
Day-by-Day HBPV and Target Organ Damage or CVD
Current Status of DKD
Association Between HBP, Day-by-Day HBPV, and DKD
Association Between HBP Level and Albuminuria
Association Between Day-by-Day Home BPV and Albuminuria
Association Between HBP Level and eGFR
Association Between Day-by-Day Home BPV and eGFR
Perspectives on HBPM
Conclusion
Applications to Prognosis and Other Diseases or Conditions
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms (5-15 terms)
Key Facts
Summary Points
References
35 Methods for Measuring Blood Pressure and Applications to Diabetes
Introduction
Diagnosis of Hypertension and Blood Pressure Measurement
Office Blood Pressure Measurement
Types of OBPM
Devices for OBPM
Number of Measurements per Occasion
Blood Pressure Measurement Technique
Twenty-Four-Hour Ambulatory Blood Pressure Monitoring (Table 1)
Home Blood Pressure Monitoring (Table 2)
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of ``Methods for Measuring Blood Pressure and Applications to Diabetes: A Focus on Children, Adolescents, and Young ...
Summary Points
References
36 Carotid Bodies: Use of Chemosensitivity as a Biomarker in Prediabetes
The Carotid Bodies
Role of CB in Metabolic Diseases
CB Dysfunction in Prediabetes and Type 2 Diabetes
What Is the Trigger for CB Dysfunction in Metabolic Diseases?
Insulin
Leptin
Evaluation of CB Chemosensitivity in Humans
Evaluation of Hypertonicity of Peripheral Chemoreceptors
Evaluation of Hyperreflexivity of Peripheral Chemoreceptors
Biomarkers of Prediabetes
Hyperinsulinemia and Obesity as Risk Factors for Prediabetes
Early Diagnosis of Prediabetes
Questionnaires and Scales
Biochemical Markers
CB Chemosensitivity as a Biomarker of Prediabetes
Evaluation of CB Hypertonicity by the Dejours Test
CBmeter: A New Medical Device for Early Detection of Prediabetes
Future Perspectives
Applications to Prognosis, Other Diseases, or Conditions
Mini-Dictionary of Terms
Key Facts of Carotid Bodies: Use of Chemosensitivity as a Biomarker in Prediabetes
Summary Points
References
37 Optical Coherence Tomography Angiography for Biomarker Indices in Diabetes
Introduction
Principles of Optical Coherence Tomography Angiography
Visualization Methods of Optical Coherence Tomography Angiography
Diabetic Retinopathy
Optical Coherence Tomography Angiography Features of Diabetic Retinopathy
Diabetic Eyes Without Clinical Retinopathy
Correlation with Other Biomarkers of Diabetic Retinopathy
Nonproliferative Diabetic Retinopathy
Proliferative Diabetic Retinopathy
Diabetic Macular Edema
Applications to Prognosis and Other Diseases or Conditions
Application to Diabetic Retinopathy Screening and Its Monitoring
Application to Retinal Vascular Diseases
Limitations of OCTA
Mini-Dictionary of Terms
Key Facts of Optical Coherence Tomography Angiography (OCTA) in Diabetic Retinopathy (DR)
Summary Points
References
38 Urinary Profiling with Liquid Chromatography-Mass Spectrometry
Introduction
Urine as Diagnosis Specimen
Animal Model in Studying Human Disease
Liquid Chromatography-Mass Spectrometry
Application of Orthogonal Partial Least Squares Discriminant Analysis (OPLA-DA) to Prediabetes Diagnosis
Benefits of Physical Activity and Dietary Control
Proteomics Analysis of Urinary Proteins
Common Protein Biomarkers for Diagnosis of Diabetes
Application of Major Urinary Proteins and Histone H4 as Prediabetes Biomarker Proteins
Conclusion
Key Facts of Prediabetes
Mini-Dictionary Terms
Summary Points
References
39 Physiologic Measures in Diabetes: QTc Prolongation
Introduction
ECG and the Myocardial Action Potential
QT Interval
Genetics of the QT Interval
Early ECG Changes in Diabetes
Glycemic Variability and the QT Interval
QT Interval in Diabetes Mellitus
QT Interval and Sudden Cardiac Death
QT Interval and Atrial Fibrillation
QT Dispersion
Pathologic Q Waves: Diabetic Risk of Silent Myocardial Infarction
REGARDS Study
Applications to Prognosis and Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of QT Interval
Key Facts of Atrial Fibrillation
Key Facts of Malignant Arrhythmias
Key Facts of Sudden Cardiac Death
Summary Points
References
40 Biomarkers of Myocardial Fibrosis in Diabetes, Echocardiography, and Magnetic Resonance Imaging
Introduction
Heart Disease in Diabetes
Heart Failure with Preserved Ejection Fraction
Imaging Biomarkers of Myocardial Function in Diabetes and HFpEF
Epidemiology of Diabetic Heart Disease
Diabetic Cardiomyopathy
Treatment of Diabetes in Relation to Cardiomyopathy
Treatment of HFpEF
Myocardial Fibrosis in Diabetes
Cardiac Metabolism in Diabetes
The Heart´s Interaction with the Peripheral Circulation
The Myocardial Extracellular Volume
Animal Models of Cardiac Fibrosis in Diabetes
Magnetic Resonance Imaging of Fibrosis and the Extracellular Volume
The Two CMR Techniques of Fibrosis Quantitation
Tissue T1 Times
Gadolinium Contrast
Myocardial Blood Flow Determination with CMR
Determination of the Extracellular Volume
The Late Gadolinium Enhancement Technique
CMR Determination of Fibrosis in Cardiomyopathies
Ischemic Versus Non-ischemic Cardiomyopathy with LGE
Extracellular Volume and Fibrosis in Diabetes by CMR
Cardiac Fibrosis and Extracellular Volume in Patients with T2DM
Relation of Cardiac Fibrosis to Markers of Diastolic Function
Myocardial Blood Flow in T2DM
The Relation of Fibrosis to Myocardial Blood Flow
Looking to the Future
Longitudinal Studies
CMR for Screening of DM Patients?
Validation of Serum Biomarkers of Fibrosis
Applications to Prognosis
Key Facts of Diabetic Cardiomyopathy
Key Facts of Cardiac Magnetic Resonance Imaging of Fibrosis
Mini-Dictionary of Terms
Summary Points
References
41 Measures of Endothelial Function in Type 2 Diabetes: A Focus on Non-circulatory Methods of Measurement
Introduction
Noncirculatory Measures of Endothelial Function
Venous Occlusion Plethysmography (VOP)
Flow-Mediated Dilatation
Peripheral Artery Tonometry (PAT)
Aortic Pulse Wave Velocity (PWV)
Laser Doppler Flowmetry (LDF)
Skin Autofluorescence (SAF)
Applications to Diabetes
Mini-dictionary of Terms
Key Facts of Endothelial Dysfunction in Type 2 Diabetes Mellitus
Summary Points
References
42 Measures of Endothelial Function in Type 2 Diabetes: A Focus on Circulatory Biomarkers
Introduction
Circulatory Biomarkers as Measures of Endothelial Function
Nitric Oxide Metabolites and Asymmetric Dimethylarginine (ADMA)
High-Sensitivity C-Reactive Protein (hsCRP)
Adhesion Molecules and Chemokines
Endothelial Progenitor Cells (EPC)
Endothelial Microparticles (EMP)
Advanced Glycosylation End Products
Endocan
External Counterpulsation (ECP) Therapy on Measures of Endothelial Function
Applications to Diabetes
Mini-Dictionary of Terms
Summary Points
References
Part V: Biomarkers in Specific Conditions or Scenarios of Diabetes
43 Biomarkers of Diabetes-Induced Nephropathy
Introduction
Overview of Pathogenesis of Diabetic Nephropathy
Stages of Diabetic Nephropathy
First Stage
Second Stage
Third Stage
Fourth Stage
Fifth Stage
Conventional Biomarker of Diabetic Nephropathy
New Biomarkers of Diabetic Nephropathy
Biomarkers of Glomerular Damage
Biomarkers of Tubular Damage
Inflammatory Biomarkers
Biomarkers of Oxidative Stress Associated with Diabetic Nephropathy
Future Perspectives in the Diagnosis and Prognosis of Diabetic Nephropathy
NADPH Oxidase
MicroRNA (miRNAs)
Proteomics
Metabolomics
Genomics
Mini-Dictionary of Terms
Key Facts of Biomarkers of Diabetes-Induced Nephropathy
Summary Points
References
44 Serum Vitamin D As a Biomarker in Diabetic: Applications and Associations with Retinopathy
Introduction
Vitamin D Deficiency
Vitamin D and Diabetes Mellitus
Vitamin D and Diabetic Retinopathy Development and Severity
Diabetic Retinopathy Pathophysiology - Where Does Vitamin D Stand?
Vitamin D Supplementation for DR Prevention - What Is the Current Evidence?
Applications to Prognosis
Conclusion
Key Facts
Mini Dictionary of Terms
Summary Points
References
45 Markers of Bacterial Translocation in Type 2 Diabetes Mellitus
Introduction
Gut Microbiome
The Gut Barrier´s Defense Mechanisms
The Gut Barrier Is Composed of Multiple Layers: (Fig. 1)
Factors Affecting the Gut Barrier Integrity
Mechanisms of Gut Barrier Disruption
Consequences of Gut Barrier Disruption/Dysfunction
Bacterial Translocation
Markers of Bacterial Translocation
Lipopolysaccharide (LPS)
Bacteria and Bacterial DNA
Other Bacterial Translocation Markers
Applications to Other Diseases/Conditions
Mini-Dictionary of Terms
Key Facts
Summary Points
References
46 Serum Leptin as a Biomarker in Diabetes
Diabetes Mellitus
Complications of Diabetes Mellitus
Insulin Resistance and β-Cell Function in Type 2 Diabetes Mellitus
Diabetes Mellitus and Acromegaly
Acromegaly Comorbidities
Metabolic Complications
Cardiovascular Disease
Insulin Resistance and Leptin in Type 2 Diabetes Mellitus
Leptin Resistance in Type 2 Diabetes Mellitus
Leptin in Acromegaly
Medical Therapy
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of Hyperinsulinemia
Key Facts of Human Leptin
Key Facts of Acromegaly
Summary Points
References
47 Vitreous Biomarkers: What They Are and How They May Be Used to Advance the Management of Diabetic Retinopathy
Introduction
Diabetic Retinopathy
Pathogenesis and Pathophysiology
Clinical Grading
Clinical Management
Assessing Local Molecular Biomarkers for DR
Ocular Liquid Biopsy
Sample Selection and Method of Analysis
Vitreous Molecular Biomarkers of DR
Cytokines
Kinin-Kallikrein System (KKS)
Complement System (CS)
MicroRNA (miRNA)
Metabolites
Applications to Prognosis and Other Diseases and Conditions
Key Facts of Vitreous Biomarkers in Diabetic Retinopathy (DR)
Mini-Dictionary of Terms
Summary Points
References
48 Protein Pyrrole Adducts in Diabetes Mellitus
Introduction
Diabetic Distal Symmetrical Polyneuropathy
DSPN: Central-Peripheral Distal Axonopathy
DSPN Etiology and Pathogenesis
Existing DSPN Biomarkers
Protein Pyrrole Adducts
Cross-Linking of γ-Diketone-Derived Pyrroles
Cross-Linking of Protein Pyrrole Adduct: Links with DSPN
Detection of Pyrrole Adducts
Applications to Peripheral Neuropathy
Occupational n-Hexane/2-Hexanone Neuropathy
Diabetic Polyneuropathy
Conclusions
Mini-Dictionary of Terms
Key Facts
Summary Points
References
49 Biomarkers in Gestational Diabetes
Application to Prognosis, Other Diseases or Conditions
Application to Prognosis
Application to Other Diseases or Conditions
Introduction
Noncontinuous Versus Continuous Glucose Monitoring:
Postprandial Versus Preprandial Glucose Monitoring:
Updated Guidelines
Conclusion
Mini Dictionary of Terms
Key Facts
Summary Points
References
50 Metabolomic Biomarkers, Metabolite Patterns, and Gestational Diabetes Mellitus
Introduction
Epidemiology, Etiology, and Consequences of Gestational Diabetes Mellitus
Epidemiology
Etiology
Consequences
Screening and Diagnosis
Metabolic Heterogeneity Among GDM Cases
Applications of Metabolomics in Gestational Diabetes Mellitus
Prevention/Prediction
Treatment/Prognosis
Amino Acid Profile
Amino Acids and Applications to GDM Treatment
Amino Acids and Applications to GDM Prognosis
Lipid Profile
Lipids and Applications to GDM Treatment
Lipids and Applications to GDM Prognosis
Carbohydrates
Future Directions
Mini-Dictionary of Terms
Key Facts of Gestational Diabetes Mellitus
Summary Points
References
51 Neuroinflammatory Biomarkers in Diabetic Encephalopathy: Linking Cholinergic and Cognitive Dysfunction
Introduction
Diabetes and Brain
Neuroinflammation and Diabetes
Mechanistic Insights Involved in Diabetes-Induced Neuroinflammation
Cognitive Impairment and Neuroinflammation in Diabetic Animal Models
Conclusion
Application to Prognosis, Other Diseases, or Conditions
Key Facts
Mini Dictionary
Summary Points
References
Part VI: Diet and Diabetes
52 Selenium and Risk of Diabetes
Introduction
Association Between Selenium and the Risk of T2DM
Recent Updates on Clinical Studies
Selenium and Gestational Diabetes
Selenium and Diabetes Complications
Potential Mechanisms of Action of Selenium on Glucose Homeostasis
Conclusion
Summary Points
References
Part VII: Models and Modeling in Diabetes
53 Models of Diabetes in Rats: A Focus on Diabetic Neuropathy and Biomarkers
Introduction
Rat Model of Diabetic Neuropathy
Biomarkers of Diabetic Neuropathy in Rat Models
Oxidative Stress Markers
Adiponectin
Immune Cells
Glial Cells in Peripheral and Central Nervous Systems
Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB)
Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNF-α)
Monocyte Chemoattractant Protein-1 (MCP-1)
Cell Receptors
Transient Receptor Potential Vanilloid-1 (TRPV1)
N-Methyl-d-Aspartate Receptors (NMDARs)
Gamma-Amino Butyric Acid (GABA) Receptors
Enzyme-Related Markers
Nicotinamide Adenine Dinucleotide Phosphate Oxidase (NOX)
Heme Oxygenase-1 (HO-1)
Other Protein
Caveolin-1 (CAV-1)
Conclusion
Applications to Prognosis, Other Diseases or Conditions
Mini-dictionary of Terms
Key Facts
Key Facts of Diabetic Neuropathy
Key Facts of Rat Model of Diabetic Neuropathy
Summary Points
References
54 Biomarkers in Experimental Diabetes: Studies with Syzygium Cumini (L.) and Links with the Sulfonylurea 1 Receptor
Introduction
Pathophysiology of Diabetes Mellitus
Clinically Used Biomarkers in Diabetes Mellitus
Animal Models for Experimental Diabetes
Experimental Models for Type 1 DM
Experimental Models for Type 2 DM
Experiments with Syzygium Cumini
Fasting Blood Glucose (FBG)
Serum Insulin and C Peptide Levels
Glycosylated Hemoglobin (HbA1C)
Homeostatic Model of Assessment (HOMA)
Liver Glycogen
Lipid Profile
Adiponectin
Glucagon-Like Peptide 1 (GLP 1)
Markers of Oxidative Stress
Inflammatory Biomarkers
Histopathology of Islets of Pancreas
PPARs (Peroxisome Proliferator-Activated Receptors)
Hexokinase
Biomarkers for Evaluating Molecular Mechanisms
Molecular Docking Study of Syzygium Cumini extract Components on Sulfonylurea Receptor (SUR1)
Applications to Prognosis
Mini Dictionary of Terms
Key Facts: Biomarkers in Experimental Diabetes: Studies with Syzygium Cumini (L.) and Links with the Sulfonylurea 1 Receptor
Summary
References
Part VIII: Resources
55 Recommended Resources for Biomarkers in Diabetes: Methods, Discoveries, and Applications
Introduction
Resources
Other Resources
Summary Points
References
Index