Standardization and analytical goals for glycated hemoglobin measurement

Abstract Glycated hemoglobin (HbA1c) plays a key role in diagnosing diabetes and monitoring the glycemic state. To guarantee the reliability of its measurement at the global level, the IFCC has defined a reference measurement system, based on the definition of the measurand as hemoglobin molecules having a special hexapeptide in common, which is the stable adduct of glucose to the N-terminal valine of the hemoglobin β-chain. In addition to the traceability of HbA1c results to the reference system, the establishment of analytical goals to make HbA1c measurements clinically reliable becomes crucial. However, allowable goals will depend on the assay specificity (i.e., selectivity) and, consequently, on units in which HbA1c results are expressed [mmol/mol for IFCC-aligned systems or % for National Glycohemoglobin Standardization Program (NGSP) converted numbers]. In this regard, analytical goals derived from biological variability studies in which the determination of HbA1c has been carried out by an assay providing the same selectivity for the measurand as defined by the IFCC are recommended. Only these targets should be used for evaluating the performance of commercial assays traceable to the IFCC system and of clinical laboratories using them through appropriately structured quality assessment schemes. Analytical systems following different calibration hierarchies (e.g., the NGSP-aligned assays) will require different analytical goals, possibly derived from clinical outcome data.