Standardization of HbA1c and Optimal Range of Monitoring.

The IFCC has established a working group on HbA1c standardization, which developed a reference system to act as basis for global standardization of all glycohemoglobin/HbA1c assays. The reference system is based on HbA1c, defined as beta-N-1-deoxy fructosyl haemoglobin as component. Two reference methods specifically measure the glycated N-terminal residue of the beta chain of haemoglobin. The assay principle is peptide mapping after proteolytic cleavage of the molecule followed by measurement of the ratio of the glycated and non-glycated ss-N-terminal hexapeptides by HPLC/MS or HPLC/CE. An international network of 12 reference laboratories is in place. An overall CV below 2% is achieved in comparison studies, which guarantees a reliable value assignment to secondary reference materials. For implementation of the system, the relationship between IFCC and the existing Designated Comparison Methods in the US (NGSP), Sweden (MonoS) and Japan was calculated in seven method comparisons. In all cases, the correlation was exactly the same, making recalculation of the various systems to one IFCC reference system possible. IFCC values will be a reference range of 3-4% HbA1c with a target value of optimal treatment of 5% and change of therapy proposed at values >6%. The last item of the IFCC WG on HbA1c standardization is the adjustment of all the commercial methods to this new reference system. Three method comparison studies with all the major manufacturer methods were performed. This allowed us to first anchor all commercial methods to the IFCC reference system and thereafter recalculate the results to the new IFCC system. Secondary reference materials and a transfer protocol are provided to enable manufacturers to adjust their routine tests to the new reference system. The IFCC reference system for HbA1c will make it possible to improve the performance of routine HbA1c assays. The goal of this improved analytical performance is a within and between run CV of 2%. If this can be achieved, then the HbA1c results can be incorporated into the diagnostic strategies for detecting diabetes mellitus.