Interference of hemoglobin variants in HbA_1c quantification

Fasting blood glucose and glycated hemoglobin (HbA_1c) are routine biomarkers to screen and monitor diabetes mellitus. HbA_1c results from glycation at the N-terminus of the β globin chain of tetrameric human hemoglobin. Fasting blood glucose level varies with the nature and amount of food intake, physical exercise, etc., and, accordingly, is a short-term measure of glucose control. In contrast, HbA_1c provides an average measure of glucose control for the long-term (8-12 weeks). Unfortunately, genetic variants of hemoglobin may interfere with HbA_1c quantification using ion exchange chromatography, capillary electrophoresis, immunoassay and boronate affinity chromatography. Mass spectrometry, however, measures total glycation of hemoglobin across both α and β globin chains and correlates well with the ion exchange based method. Additionally, mass spectrometry based quantification is not impacted by the presence of genetic variants of hemoglobin and thus might be a better analytical choice for diabetes mellitus.