Classification of variant forms of haemoglobin according to the ratio of glycated haemoglobin to glycated albumin

Abstract

Background Asymptomatic variant haemoglobin is increasingly being found in the measurement of glycated haemoglobin (HbA1c) for the management of diabetes mellitus. We compared the HbA1c concentrations measured by high-performance liquid chromatography (HPLC) and immunoassay and glycated albumin (GA) concentrations and calculated the respective ratios in order to classify the variant haemoglobin. Methods Twenty different haemoglobin variants from 43 subjects were identified by mass spectrometry and DNA analysis. Since GA accurately reflects glycaemic control in patients with variant haemoglobin, we calculated respective ratios of HbA1c and GA. Haemoglobin variants causing a low ratio of HbA1c measured by HPLC (HPLC-HbA1c) to GA with a normal ratio of HbA1c measured by immunoassay (IA-HbA1c) to GA were classified as C1. A further classification of α and β was used with abnormalities of the α chain or β chain in the haemoglobin gene. Other haemoglobin variants were classified as non-C1. Eight diabetic patients with stable glycaemic control were used as controls. Results Twenty forms of variant haemoglobins were classified as C1 α (2 variants; I-Interlaken and Hb J-Meerut), C1 β (15 variants) and non-C1 (3 variants; Hb Himeji, Hb Woolwich, Hb Peterborough). Positive correlations between GA and HPLC-HbA1c or IA-HbA1c were seen in the C1 β patients with diabetes mellitus. The regression line between GA and HPLC-HbA1c, but not that between GA and IA-HbA1c, showed a downward shift in comparison with the data obtained from the diabetic controls. Conclusions Variant haemoglobin could be classified by calculating the ratios of HPLC-HbA1c, IA-HbA1c and GA.