HbA1c – Glycated Hemoglobin and Diabetes Mellitus

01.08.2009

Englisch

9783895998515

UNI-MED

UNI-MED Science

Nein

Helmut R Henrichs

208

1

Gebundene Ausgabe

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

240 mm

17 cm