Biological Variation of Hemoglobin A1c: Consequences for Diagnosing Diabetes Mellitus

To the Editor:For optimal monitoring and diagnosing of patients with diabetes by use of glycated hemoglobin (Hb A1c)1 measurements, the analytical CV (CVa) of the Hb A1c assay and the within-person biological variation (CVwp) are of relevance. CVwp refers to an inherent biological variation around an individual patient's set point of a biological parameter. Several studies have been published assessing the CVwp of Hb A1c (1–3). However, none of those studies used >1 Hb A1c method to determine the CVwp. The aim of this study was to apply 4 different IFCC and National Glycohemoglobin Standardization Program (NGSP) certified secondary reference measurement procedures (SRMPs) using different assay principles and calibrated in SI units (mmol/mol) and Diabetes Control and Complications Trial (DCCT) units (% Hb A1c) to see whether there were differences in the CVwp obtained. In addition, we addressed the consequences for diagnosing diabetes mellitus of the CVwp found.We recruited 21 presumed healthy hospital employees to participate in the study (11 men and 10 women). Five K2EDTA-treated whole blood samples were collected from each individual every 2 weeks for 2 months. On collection, aliquots of each sample were immediately stored at −80 °C. Full analysis was performed at the end of the 2-month collection period. The samples were analyzed in a single run in duplicate using the following 4 SRMPs: