HbA1c and Diagnostic Management of Diabetes Mellitus

No parameter in diabetology - other than blood glucose - has gained the importance and popularity of glycated hemoglobin, also called HbA1c or A1C. The global aim of this book is to give proof to this statement.
Major studies such as DCCT, UKPDS or ACCORD, but even more so every-day diabetes care, are driven by HbA1c as the crucial working tool. HbA1c likewise governs pathophysiology, education, epidemiology, guidelines and individual counselling.
The author of this monograph was one of the pioneers in the field of HbA1c application and glycation research in Germany and accompanied HbA1c development from the solution of early-stage analytical problems to the exploration of its kinetics and later on to its standardization as an applied method in diabetes care.
This textbook is of interest to those who are engaged in HbA1c or glycation in particular and in diabetes or metabolic syndrome in general.

Inhaltsverzeichnis

Contents
1. Introduction 10
1.1. Why Write or Read a Book on HbA1c? 10
1.2. The Reliability of HbA1c 12
1.3. References 12
2. History of HbA1c 13
2.1. The Timetable 13
2.2. Glycation of Hemoglobin 14
2.2. Glycation of Hemoglobin in Relation to Diabetes Mellitus 14
2.2.2. HbA1c in Relation to Late Complications of Diabetes 16
2.3. Annex 18
2.4. References 20
3. Definition and Terminology 23
3.1. References 23
4. Chemistry and Kinetics of Hemoglobin Glycation, Biomathematical Models 25
4.1. Protein Glycation 25
4.2. Glycation of Hemoglobin 25
4.2.1. Reactants or Substrates 25
4.2.1.1. Hemoglobin (Hb) and the Hemoglobin Family 25
4.2.1.1.1. Physiological Hemoglobin Variants 26
4.2.1.1.2. Pathological Hemoglobin Variants 27
4.2.1.2. Glucose and further Monosaccharides and their Derivatives 28
4.2.2. The Reaction Conditions 29
4.2.2.1. Reaction Space/Compartment and Time 29
4.2.2.2. Reaction Milieu 30
4.2.2.2.1. Hydrogen Ion Concentration 30
4.2.2.2.2. Effects of Temperature on Glycation 31
4.2.3. The Glycation Process 31
4.2.3.1. Maillard's Reaction 31
4.2.3.2. The Chemical Reaction Steps / Pathway 31
4.2.3.2.1. The HbA1c Aldimine 32
4.2.3.2.2. The HbA1c Ketoamine 34
4.2.3.3. Kinetics 36
4.2.3.3.1. In Vitro Glycation Model 36
4.2.3.3.2. In Vivo Glycation Model 37
4.2.3.3.3. Clinical Studies 38
4.2.3.4. Biomathematical Modeling of Hb Glycation 39
4.2.3.5. Consequences of Glycation on Hemoglobin 43
4.2.3.6. Advanced Glycation 44
4.2.3.6.1. Advanced Glycation End Products (AGEs) 44
4.2.3.7. HbA1c Disappearance 48
4.3. References 49
5. HbA1c Determination 57
5.1. Determination Principles and Classification 57
5.2. Methods / Assays 58
5.2.1. Cation Ion Exchange Chromatography (Conventional) 58
5.2.2. Electrophoresis and Isoelectric Focusing 63
5.2.3. Affinity Chromatography 65
5.2.4. Colorimetric Method (Thiobarbituric Acid, Photometry) 66
5.2.5. Immunological Methods 66
5.2.6. Point-of-Care Testing (POCT) Devices 73
5.2.7. Rarely Applied Principles / Methods 73
5.3. References 73
6. HbA1c - Preanalytical and External Influences 82
6.1. Material 82
6.1.1. Sampling of Material 82
6.1.2. Processing of Material 83
6.2. Patient- or Donor-Related Influences 85
6.2.1. Interferences of Hematological Origin 85
6.2.2. Interferences of Non-Hematological Origin 89
6.2.2.1. Interaction with Drugs, Vitamins or Alcohol 91
6.2.2.2. Other Disease States and their Influence on HbA1c Results 92
6.2.2.3. Additives or Pharmacological Agents and their Influence on HbA1c Results 94
6.2.2.4. Postmortem Influences on HbA1c Results 95
6.3. References 95
7. HbA1c - Standardization 103
7.1. HbA1c: Trueness, Precision, Comparability, Traceability 103
7.2. Quality Assessment and Reliability 103
7.2.1. Background 103
7.2.2. The Problem 103
7.2.3. The Solution(s) 104
7.3. Regional Standardization Schemes 105
7.3.1. The National Glycohemoglobin Standardization Program (NGSP) 105
7.4. International Standardization Schemes 108
7.4.1. International Federation of Clinical Chemistry Standardization (IFCC) 108
7.5. Harmonization Efforts between Schemes 111
7.6. Summary 116
7.7. References 116
8. Biological Influences on Glycation Other Than Glycemia 120
8.1. Mechanisms for Diversification in Glycation of Hemoglobin 121
8.1.1. HbA1c Accumulation / Appearance 121
8.1.2. HbA1c Clearance / Disappearance 121
8.2. Clinical Impact of Biological Variability 122
8.2.1. Quantitative Biological Variability 122
8.2.2. Qualitative Variability 123
8.3. Fluctuations, Instability 126
8.4. The Impact of Biological Variability on Diabetes Screening and Monitoring 127
8.5. Impact of Biological Variability on Specific Microangiopathic Complications of Diabetes in Eyes and Kidney 128
8.6. References 129
9. Pathophysiology: Glycation of Hemoglobin and Other Substrates 133
9.1. Glycation In "Normal" and Pathological Circumstances 133
9.2. Pathobiochemistry of Chronic Hyperglycemia 134
9.3. Effects of Glycation on Hemoglobin and Related Blood Constituents 136
9.4. Glycation Effects on Non-Hemoglobin Protein Substrates and Related Blood Constituents 138
9.5. Relationship of Glycation to Diabetic (Late) Complications 146
10. Clinical Application of HbA1c Determination 163
10.1. The Rationale of HbA1c Testing and Application 163
10.2. Clinical Application of HbA1c Testing - the Why, Where and When of Testing 169
10.3. HbA1c in Detection of Disease 169
10.3.1. HbA1c in Screening Procedures/Projects on Population Base 169
10.3.2. (Initial) Clinical Diabetes Diagnostics 170
10.4. Monitoring of Metabolic Control in (Treated) Diabetes 171
10.4.1. The Goal of Testing 171
10.4.2. HbA1c in the Big Diabetes Studies 171
10.4.3. HbA1c within the Diabetes Control System 173
10.4.4. Relation of HbA1c to the Mode of Treatment in Diabetes 174
10.4.5. Relation of HbA1c to Metabolic Instability 176
10.5. Recommendations / Guidelines for HbA1c Application 177
10.5.1. Recommendations Concerning Targets 177
10.5.2. Recommendations Concerning Time Intervals of HbA1c Determinations 178
10.6. Point-of-Care Testing (POCT) = "Near-Patient Testing" 180
10.7. Psychological Aspects Around HbA1c 182
10.7.1. Physician and Caregiver Views 183
10.7.2. Patient Views 183
10.8. HbA1c and Pregnancy 189
10.8.1. Diabetic Pregnancy (Pregnancy in Women with Diabetes) 189
10.8.2. HbA1c in Non-Diabetic Pregnancy (During Pregnancy in Women Without Diabetes) 191
10.8.3. HbA1c and Gestational Diabetes Mellitus (GDM) 192
10.9. HbA1c in Postmortem Analysis 193
10.10. HbA1c in Diseases Other Than Diabetes Mellitus 193
10.11. Summary 194
10.12. References 194
11. Glossary 202
Index 204

Produktdetails

• Autoren: Helmut R. Henrichs
• Verlag: Uni-Med
• Sprache: Deutsch
• Produktform: Fester Einband
• Erschienen: 31.12.2017
• EAN: 9781848151253
• ISBN: 978-1-84815-125-3
• Seiten: 207
• Abmessung: 177 mm x 245 mm x 23 mm
• Gewicht: 513 g
• Serien: UNI-MED Science; UNI-MED Science