HbA1c

American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and International Diabetes Federation (IDF) consensus statement on the worldwide standardization of the hemoglobin A1c measurement

A reference method that specifically measures hemoglobin (Hb) A_1c is an essential part of the reference system for the international standardization of Hb A_1c/glycohemoglobin. We have developed a new method for quantification, based on the specific N-terminal residue of the hemoglobin β-chains. Enzymatic cleavage of the intact hemoglobin molecule with endoproteinase Glu-C has been optimized to obtain the b-N-terminal hexapeptides of Hb A_1c and Hb A₀. These peptides have been separated by reversed-phase HPLC and quantitated by electrospray ionization-mass spectrometry (method A) or by capillary electrophoresis (method B). With these peptides and hyphenated separation techniques, it has been possible to overcome the insufficient resolution of currently used protein separation systems for Hb A_1c.

The HbA_1c assay has become the gold-standard measurement of chronic glycaemia for over two decades. Anchored in the knowledge that elevated HbA_1c values increase the likelihood of the microvascular complications of diabetes (and perhaps macrovascular complications as well), clinicians have used the HbA_1c test results to guide treatment decisions, and the assay has become the cornerstone for the assessment of diabetes care.

The clinical world has assumed that the HbA1c assay reflects average glycaemia over the preceding few months.

• Beurteilung der Glykämiekontrolle in Umbruch
• Vom Analyseartefakt zum Goldstandard der Diabeteskontrolle
• Weltweite HbA1c –Standardisierung nach IFCC Fakten und Hintergründe
• Labors messen weiter wie gewohnt
• Beurteilung der Stoffwechselkontrolle HbA_1c ist nicht alles
• HbA_1c als Kriterium für die Diabetesdiagnose
• Probleme der HbA_1c –Bestimmung bei Nierenversagen

The measurement of glycated hemoglobin is central in the monitoring of glycemic control in patients with diabetes. There are at least 30 different laboratory assays commercially available to measure the proportion of HbA_1c in blood. In 1995 the IFCC established a Working Group (IFCC WG-HbA_1c) to achieve international standardization of HbA_1c measurement. The main achievements can be summarized as follows: a) a reference measurement procedure has been established with purified primary calibrators; b) a network of reference laboratories has been developed worldwide; and c) work has begun on implementation of traceability to the IFCC reference system. The IFCC WG-HbA_1c recognizes the recommendation of the IFCC-IUPAC Committee on Nomenclature, Properties and Units that the analyte measured by the IFCC reference measurement procedure has been defined as βN1-deoxyfructosylhemoglobin and that the recommended measurement units are mmol/mol. The IFCC WG-HbA_1c recommends maintaining the use of the name HbA_1c in clinical practice.

Clin Chem Lab Med 2007;45:1077–80.

The measurement of glycated hemoglobin is central in the monitoring of glycemic control in patients with diabetes. There are at least 30 different laboratory assays commercially available to measure the proportion of HbA_1c in blood. In 1995 the IFCC established a Working Group (IFCC WG-HbA_1c) to achieve international standardization of HbA_1c measurement. The main achievements can be summarized as follows: a) a reference measurement procedure has been established with purified primary calibrators; b) a network of reference laboratories has been developed worldwide; and c) work has begun on implementation of traceability to the IFCC reference system. The IFCC WG-HbA_1c recognizes the recommendation of the IFCC-IUPAC Committee on Nomenclature, Properties and Units that the analyte measured by the IFCC reference measurement procedure has been defined as βN1-deoxyfructosylhemoglobin and that the recommended measurement units are mmol/mol. The IFCC WG-HbA_1c recommends maintaining the use of the name HbA_1c in clinical practice.

Clin Chem Lab Med 2007;45:1077–80.

IFCC Reference System for Measurement of Hemoglobin A_1c in Human Blood and the National Standardization Schemes in the United States, Japan, and Sweden: A Method-Comparison Study

Implementation of hemoglobin A_1c results traceable to the IFCC reference system: the way Forward

The IFCC has recently approved a reference measurment procedure for measuring the propertf often designated "HbA1c". This analytially specific procedure involving single molecular species allows calculation of measurement results as "amount-of-substance fraction" rather than mass fraction. In addition it provides well-defined metrological traceability to the International System of Units (SI).

As the numerical values of the measurement results will change with the new measurement proceddure, it is timely to reconsider the current termsfor the property in terms of system, component, and kind-of-property, as well as the expression of the measurement result.

Significant analytical improvements have occurred since glycated haemoglobin (GHb), measured as total HbA₁, was first used in routine clinical laboratories around 1977. Following the publication of the Diabetes Control and Complications Trial (DCCT) study in 1993 the issue of international standardisation became an important objective for scientists and clinicians. The lack of international standardisation led several countries to develop national standardisation programs. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Working Group on Standardisation of HbA_1c established a true international reference measurement system for HbA_1c and the successful preparation of pure HbA_1c calibration material that should lead to further improvements in inter-method and inter-laboratory variability. Reporting of HbA_1c has been agreed using the units of mmol/mol (IFCC) and percent (National Glycohemoglobin Standardization Program, NGSP).

Relating to the Implementation of the IFCC, ADA, EASD and IDF Consensus Statement of on reporting of HbA_1c

Statistical Methods for Monitoring the Relationship between the IFCC Reference Measurement Procedure for Hemoglobin A_1c and the Designated Comparison Methods in the United States, Japan, and Sweden.