Ann Lab Med 2019; 39(2): 209-213  https://doi.org/10.3343/alm.2019.39.2.209
Hemoglobin A1c Levels Are Slightly but Significantly Lower in Normoglycemic Subjects With the Hemoglobin E Phenotype
Busadee Pratumvinit, M.D.1, Kanit Reesukumal, M.D.1, Sithikan Hanyongyuth, B.P.H.1, Sujitra Wangchaijaroenkit, B.Sc.1, Julaporn Pooliam, M.Sc.2, Gerald J. Kost, M.D., Ph.D3, Panumas Kamkang, B.Sc.1, and Tze Ping Loh, M.D.4
1Department of Clinical Pathology and 2Division of Clinical Epidemiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 3Point-of-Care Testing Center for Teaching and Research (POCT∙CTR), School of Medicine, University of California, Davis, California, USA; 4Department of Laboratory Medicine, National University Hospital, Singapore
Corresponding author: Busadee Pratumvinit, M.D. https://orcid.org/0000-0002-5220-0552
Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University 2 Wang Lang Road, Bangkok Noi, Bangkok 10700, Thailand
Tel/Fax: +662-418-1367
E-mail: busadee.pra@mahidol.ac.th
Received: January 29, 2018; Revised: April 13, 2018; Accepted: October 12, 2018; Published online: March 1, 2019.
© Korean Society for Laboratory Medicine. All rights reserved.

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Abstract
Hb mutations can alter the structure, behavior, stability, or quantity of the globin chain produced. Some Hb variants shorten the erythrocyte life span, resulting in physiologically lower hemoglobin A1c (HbA1c) levels. The hemoglobin E (HbE) phenotype involves a single-nucleotide polymorphism that reduces β-globin chain synthesis. We compared the HbA1c levels of subjects with normal Hb (HbAA; N=131) and HbE (N=148) phenotypes, examining potential hematological and biochemical factors contributing to differences in HbA1c levels. All had normal fasting plasma glucose (<5.6 mmol/L), AST, ALT, and creatinine levels. Mean±SD HbA1c levels differed between HbAA and HbE subjects: 5.5±0.3% and 5.3±0.3% (P<0.001) according to an immunoassay, and 5.5±0.3% and 5.3±0.3% (P<0.001) according to cation-exchange HPLC, respectively. In multiple logistic regression, only mean corpuscular volume (P<0.001) contributed to the difference in HbA1c levels between groups. Although a 0.2% difference in HbA1c is relatively small and unlikely to alter clinical decisions, epidemiologically, this can lead to misclassification of a significant proportion of the population, especially since the threshold of non-diabetes HbA1c (≤5.6%) falls very close to the HbA1c median of the general population.
Keywords: Hemoglobin A1c, Hemoglobin E, HPLC, Immunoassay



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