title: Haemoglobin variants may cause significant differences in haemoglobin A1c as measured by high-performance liquid chromatography and enzymatic methods in diabetic patients: a cross-sectional study.
abstract: Background We aimed to determine whether the discrepancy between haemoglobin A1c values determined by high-performance liquid chromatography and enzymatic haemoglobin A1c measurements in diabetic patients was clinically relevant. Methods We randomly recruited 1421 outpatients undergoing diabetic treatment and follow-up who underwent at least three haemoglobin A1c measurements between April 2014 and March 2015 at our clinic. In 6369 samples, haemoglobin A1c was simultaneously measured by HA-8160 and MetaboLead (enzymatic assay), and the values were compared. Results haemoglobin A1c measurements by high-performance liquid chromatography and enzymatic assay were strongly correlated (correlation coefficient: 0.9828, linear approximation curve y = 0.9986x - 0.2507). Mean haemoglobin A1c (6.8 ± 1.0%) measured by high-performance liquid chromatography was significantly higher than that measured by enzymatic assay (6.5 ± 1.0%, P < 0.0001). During the sample processing, four (0.3%) subjects presented consistently lower haemoglobin A1c values (<0.7%) by high-performance liquid chromatography than those from enzymatic assay. Of these, three had Hb Toranomon [β112 (G14) Cys→Trp]. The fourth had Hb Ube-2 [α68 (E17) Asn→Asp]. One other subject presented consistently higher haemoglobin A1c values (>1%) by high-performance liquid chromatography than those from enzymatic assay and was diagnosed with a -77 (T > C) mutation in the δ-globin gene. These unrelated asymptomatic subjects had normal erythrocyte profiles, without anaemia. Conclusions We showed that haemoglobin A1c values measured by high-performance liquid chromatography were significantly higher than those measured by enzymatic assay in diabetic subjects. However, when an oversized deviation (>0.7%) between glycaemic control status and haemoglobin A1c is apparent, clinicians should check the methods used to measure haemoglobin A1c and consider the possible presence of a haemoglobin variant.
authors: 1 Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.|2 Otabe Clinic, Fukuoka, Japan.
authors: Shuichi
authors: S
authors: Otabe
authors: 1 Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors: Hitomi
authors: H
authors: Nakayama
authors: 1 Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors: Tsuyoshi
authors: T
authors: Ohki
authors: 1 Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors: Eri
authors: E
authors: Soejima
authors: 1 Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors: Yuji
authors: Y
authors: Tajiri
authors: 1 Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors: Kentaro
authors: K
authors: Yamada
mesh_terms: D000328:Adult; D000368:Aged; D016477:Artifacts; D002851:Chromatography, High Pressure Liquid / Q000706:statistics & numerical data; D003920:Diabetes Mellitus / Q000097:blood / Q000175:diagnosis*; D057075:Enzyme Assays / Q000706:statistics & numerical data; D005260:Female; D015870:Gene Expression; D006442:Glycated Hemoglobin / Q000032:analysis / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000032:analysis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010045:Outpatients; D011786:Quality Control; D012680:Sensitivity and Specificity; D055545:gamma-Globins / Q000032:analysis / Q000235:genetics*
chemical_list: D006442:Glycated Hemoglobin; D006455:Hemoglobins, Abnormal; D055545:gamma-Globins; C517652:hemoglobin A1c protein, human; C104220:hemoglobin Toranomon; C033431:hemoglobin UBE-2
keywords: Diabetes; epidemiology studies; haemoglobin disorders