Background: Asymptomatic variant haemoglobin is increasingly being found in the measurement of glycated haemoglobin (HbA(1c)) for the management of diabetes mellitus. We compared the HbA(1c) 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 HbA(1c) and GA. Haemoglobin variants causing a low ratio of HbA(1c) measured by HPLC (HPLC-HbA(1c)) to GA with a normal ratio of HbA(1c) measured by immunoassay (IA-HbA(1c)) 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 C1α (2 variants; I-Interlaken and Hb J-Meerut), C1β (15 variants) and non-C1 (3 variants; Hb Himeji, Hb Woolwich, Hb Peterborough). Positive correlations between GA and HPLC-HbA(1c) or IA-HbA(1c) were seen in the C1β patients with diabetes mellitus. The regression line between GA and HPLC-HbA(1c), but not that between GA and IA-HbA(1c), 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-HbA(1c), IA-HbA(1c) and GA.