Method-dependent HbA1c values in a family with hemoglobin Himeji

Abstract

BackgroundHb Himeji is variant hemoglobin associated with increased glycation in a mutated β chain. We measured HbA1c using various methods in a family with Hb Himeji. MethodsThe proband was a 42-y female. While receiving treatment for Graves' disease, an oral glucose tolerance test showed normal glucose tolerance, but HbA1c by enzymatic assay was abnormally elevated (11.6%). Hemoglobin gene analysis identified Hb Himeji [β140 (H18) Ala→Asp]. ResultsHbA1c values measured by high-performance liquid chromatography (HPLC; HLC-723G8 and HA-8160 instruments), immunoassay, enzymatic assay, affinity method, and electrospray ionization/mass spectrometry were 3.2%, 5.2%, 11.5%, 9.7%, 7.2%, and 9.6%, respectively. Glycation product of the variant hemoglobin measured by HPLC, using HLC-723G8 and HA-8160, was 9.1% and 4.5%, respectively. The proband's father with type 2 diabetes was the first reported case of Hb Himeji. HbA1c by affinity method was markedly elevated (18.0%), but it was 5.3% by HPLC. The proband's two sisters also had Hb Himeji variant and similar method-dependent discrepancies in HbA1c values were observed. ConclusionsIn the patients with Hb Himeji, discrepancies occur between plasma glucose and HbA1c with all measurement methods because of differences in HPLC mobility, increased glycation, and antigenic changes of the variant β chain.