Abstract
Objectives
Hemoglobin A1c (HbA1c) and glycated albumin (GA) are glycemic control status indicators in patients with diabetes mellitus. Hemoglobin H (HbH) disease is a moderately severe form of α-thalassemia. Here we examine the usefulness of HbA1c and GA in monitoring glycemic control in patients with HbH disease.
Methods
HbA1c, GA, and an oral glucose tolerance test were performed in 85 patients with HbH disease and 130 healthy adults. HbA1c was measured using five methods, including two systems based on cation-exchange high-performance liquid chromatography (Variant II Turbo 2.0 and Bio-Rad D100), a capillary zone electrophoresis method (Capillarys 3 TERA), a boronate affinity HPLC method (Premier Hb9210), and an immunoassay (Cobas c501).
Results
Significant lower levels of HbA1c were observed in patients with HbH disease than in healthy adults. In contrast, GA showed no statistically significant differences between participants with and without HbH disease. A considerable number of diabetic patients with HbH disease would be missed if using HbA1c as a diagnostic criterion for diabetes mellitus.
Conclusions
GA but not HbA1c is suitable for monitoring glycemic control in patients with HbH disease that can modify the discriminative ability of HbA1c for diagnosing diabetes.
-
Research funding: None declared.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: Authors state no conflict of interest.
-
Informed consent: Informed consent was obtained from all individuals included in this study.
-
Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the Ethics Committee of the Shenzhen Longhua District Central Hospital.
References
1. Diabetes Control Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–86.10.1056/NEJM199309303291401Search in Google Scholar PubMed
2. UK Prospective Diabetes Study (UKPDS) Group. Intensive bloodglucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS33). Lancet 1998;352:837–53.10.1016/S0140-6736(98)07019-6Search in Google Scholar
3. American Diabetes Association. Standards of medical care in diabetes–2011. Diabetes Care 2011;34:S11–61.10.2337/dc11-S011Search in Google Scholar PubMed PubMed Central
4. Fitzgibbons, JF, Koler, RD, Jones, RT. Red cell age-related changes of hemoglobins AIa+b and AIc in normal and diabetic subjects. J Clin Invest 1976;58:820–4.10.1172/JCI108534Search in Google Scholar PubMed PubMed Central
5. Koga, M, Morita, S, Saito, H, Mukai, M, Kasayama, S. Association of erythrocyte indices with glycated haemoglobin in pre-menopausal women. Diabet Med 2007;24:843–7.10.1111/j.1464-5491.2007.02161.xSearch in Google Scholar PubMed
6. Koga, M, Hashimoto, K, Murai, J, Saito, H, Mukai, M, Ikegame, K, et al.. Usefulness of glycated albumin as an indicator of glycemic control status in patients with hemolytic anemia. Clin Chim Acta 2011;412:253–7.10.1016/j.cca.2010.10.014Search in Google Scholar PubMed
7. Fucharoen, S, Viprakasit, V. Hb H disease: clinical course and disease modifiers. Hematology Am Soc Hematol Educ Program 2009;26–34. https://doi.org/10.1182/asheducation-2009.1.2620008179.Search in Google Scholar PubMed
8. Piel, FB, Weatherall, DJ. The α-thalassemias. N Engl J Med 2014;371:1908–16.10.1056/NEJMra1404415Search in Google Scholar PubMed
9. Chui, DH. Alpha-thalassemia: Hb H disease and Hb Barts hydrops fetalis. Ann N Y Acad Sci 2005;1054:25–32.10.1196/annals.1345.004Search in Google Scholar PubMed
10. Laosombat, V, Viprakasit, V, Chotsampancharoen, T, Wongchanchailert, M, Khodchawan, S, Chinchang, W, et al.. Clinical features and molecular analysis in Thai patients with HbH disease. Ann Hematol 2009;88:1185–92.10.1007/s00277-009-0743-5Search in Google Scholar PubMed
11. Cohen, RM, Franco, RS, Khera, PK, Smith, EP, Lindsell, CJ, Ciraolo, PJ, et al.. Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c. Blood 2008;112:4284–91.10.1182/blood-2008-04-154112Search in Google Scholar PubMed PubMed Central
12. Rhea, JM, Molinaro, R. Pathology consultation on HbA(1c) methods and interferences. Am J Clin Pathol 2014;141:5–16.10.1309/AJCPQ23GTTMLAEVLSearch in Google Scholar PubMed
13. Bry, L, Chen, PC, Sacks, DB. Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Clin Chem 2001;47:153–63.10.1093/clinchem/47.2.153Search in Google Scholar
14. Desmons, A, Jaisson, S, Leroy, N, Gillery, P, Guillard, E. Labile glycated haemoglobin and carbamylated haemoglobin are still critical points for HbA1c measurement. Biochem Med 2017;27:378–86.10.11613/BM.2017.039Search in Google Scholar PubMed PubMed Central
15. Xu, A, Chen, W, Xia, Y, Zhou, Y, Ji, L. Effects of common hemoglobin variants on HbA1c measurements in China: results for α- and β-globin variants measured by six methods. Clin Chem Lab Med 2018;56:1353–61.10.1515/cclm-2017-1211Search in Google Scholar PubMed
16. Panzer, S, Kronik, G, Lechner, K, Bettelheim, P, Neumann, E, Dudczak, R. Glycosylated hemoglobins (GHb): an index of red cell survival. Blood 1982;59:1348–50.10.1182/blood.V59.6.1348.1348Search in Google Scholar
17. Kameyama, M, Takeuchi, S, Ishii, S. Steady-state relationship between average glucose, HbA1c and RBC lifespan. J Theor Biol 2018;447:111–7.10.1016/j.jtbi.2018.03.023Search in Google Scholar PubMed
18. Rohlfing, C, Hanson, S, Weykamp, C, Siebelder, C, Higgins, T, Molinaro, R, et al.. Effects of hemoglobin C, D, E and S traits on measurements of hemoglobin A1c by twelve methods. Clin Chim Acta 2016;455:80–3.10.1016/j.cca.2016.01.031Search in Google Scholar PubMed PubMed Central
19. Miyamoto, H, Tao, X, Kohzuma, T, Ohnishi, A. Influences of anemia, kidney disease, thyroid dysfunction, and liver disease on the ratio of glycated albumin to hemoglobin A1c. J Diabetes Sci Technol 2018;12:1082–3.10.1177/1932296818767452Search in Google Scholar PubMed PubMed Central
20. Little, RR, La’ulu, SL, Hanson, SE, Rohlfing, CL, Schmidt, RL. Effects of 49 different rare Hb variants on HbA1c measurement in eight methods. J Diabetes Sci Technol 2015;9:849–56.10.1177/1932296815572367Search in Google Scholar PubMed PubMed Central
21. Weykamp, C, Kemna, E, Leppink, S, Siebelder, C. Glycation rate of haemoglobins S, C, D, E, J and G, and analytical interference on the measurement of HbA1c with affinity chromatography and capillary electrophoresis. Clin Chem Lab Med 2015;53:207–10.10.1515/cclm-2014-1134Search in Google Scholar PubMed
22. Shapiro, R, McManus, MJ, Zalut, C, Bunn, HF. Sites of nonenzymatic glycosylation of human hemoglobin A. J Biol Chem 1980;255:3120–7.10.1016/S0021-9258(19)85860-XSearch in Google Scholar
23. Kabytaev, K, Connolly, S, Rohlfing, CL, Sacks, DB, Stoyanov, AV, Little, RR. Higher degree of glycation of hemoglobin S compared to hemoglobin A measured by mass spectrometry: potential impact on HbA1c testing. Clin Chim Acta 2016;458:40–3.10.1016/j.cca.2016.04.027Search in Google Scholar PubMed PubMed Central
24. Roberts, NB, Amara, AB, Morris, M, Green, BN. Long-term evaluation of electrospray ionization mass spectrometric analysis of glycated hemoglobin. Clin Chem 2001;47:316–21.10.1093/clinchem/47.2.316Search in Google Scholar
25. Xu, A, Xie, W, Wang, Y, Ji, L. Potential of MALDI-TOF mass spectrometry to overcome the interference of hemoglobin variants on HbA1c measurement. Clin Chem Lab Med 2021;59:233–9. https://doi.org/10.1515/cclm-2020-0724.Search in Google Scholar PubMed
26. Lacy, ME, Wellenius, GA, Sumner, AE, Correa, A, Carnethon, MR, Liem, RI, et al.. Association of sickle cell trait with hemoglobin A1c in African Americans. JAMA 2017;317:507–15.10.1001/jama.2016.21035Search in Google Scholar PubMed PubMed Central
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2020-1563).
© 2021 Walter de Gruyter GmbH, Berlin/Boston
