Skip to main content
Top
Published in: International Journal of Diabetes in Developing Countries 4/2015

01-12-2015 | Original Article

Effects of hemoglobin S variants on the measurement of glycosylated hemoglobin A1c by four analytical methods

Authors: W. Tamimi, S. Aljasser, R. Kanan, R. Dafterdar, N. Aldegaither, M. Alrwali, A. Elfatah, W. Alsaeed, F. Q. Alenzi, R. Hasanato

Published in: International Journal of Diabetes in Developing Countries | Issue 4/2015

Login to get access

Abstract

Glycosylated hemoglobin (HbA1c) identifies the average plasma glucose concentration over 120 days. HbA1c test measurements can lead to false outcomes in patients with inherited hemoglobin variants as hemoglobin S, which is prevalent in the Middle Eastern population. Our aim was to evaluate four different methods for measuring the blood HbA1c levels in diabetic patients with sickle cell anemia (SCA) and sickle cell trait (SCT). Blood samples were collected in EDTA tubes from 38 diabetic patients with either SCA or SCT. HbA1c levels were measured on all samples at three different local hospitals using three different analyzers: the Cobas Integra700 (Roche, SZ), the Dimension RXL (Siemens, USA), and the DCA2000 (Siemens, USA). All methods were compared to the standard HPLC method Variant (Bio-Rad, USA). There was a good correlation (R 2) between HbA1c levels measured by the HPLC Variant II and immunoassay analyzers and between the immunoassay analyzers themselves in SCT, but not in SCA, patients. However, an excellent correlation was observed in the SCA group between the Dimension RXL and Cobas Integra analyzers (R 2 = 0.9918). Significant differences were observed in all the three immunoassay methods compared to the Variant HPLC (P <0.00001) and between the DCA2000+ and the Dimension RXL (P = 0.0144), as well as between the DCA2000+ and the Cobas Integra (P = 0.0247). We concluded that while HbA1c levels were undetected by some methods, other methods were able to measure HgbA1c with a high degree of accuracy. Therefore, we recommend that any affected HbA1c samples should be measured by two different methods.
Literature
1.
go back to reference Goldstein DE, Little RR, Lorenz RA, Ma- lone JI, Nathan D, Peterson CM. Tests of glycemia in diabetes. Diabetes Care. 2000;23 Suppl 1:S80–3. Goldstein DE, Little RR, Lorenz RA, Ma- lone JI, Nathan D, Peterson CM. Tests of glycemia in diabetes. Diabetes Care. 2000;23 Suppl 1:S80–3.
2.
go back to reference Martina WV, Martijn EG, van der Molen M, Schermer JG, Muskiet FAJ. β-N-terminal glycohemoglobins in subjects with common hemoglobinopathies: relation with fructosamine and mean erythrocyte age. Clin Chem. 1993;39:2259–65.PubMed Martina WV, Martijn EG, van der Molen M, Schermer JG, Muskiet FAJ. β-N-terminal glycohemoglobins in subjects with common hemoglobinopathies: relation with fructosamine and mean erythrocyte age. Clin Chem. 1993;39:2259–65.PubMed
3.
go back to reference Frank EL, Moulton L, Little RR, Wiedmeyer HM, Rohlfing C, Roberts WL. Effects of hemoglobin C and S traits on seven glycohemoglobin methods. Clin Chem. 2000;46:864–7.PubMed Frank EL, Moulton L, Little RR, Wiedmeyer HM, Rohlfing C, Roberts WL. Effects of hemoglobin C and S traits on seven glycohemoglobin methods. Clin Chem. 2000;46:864–7.PubMed
4.
go back to reference Weykamp CW, Penders TJ, Muskiet FA, van der Slik W. Influence of hemoglobin variants and derivatives on glycohemoglobin determinations, as investigated by 102 laboratories using 16 methods. Clin Chem. 1993;39:1717–23.PubMed Weykamp CW, Penders TJ, Muskiet FA, van der Slik W. Influence of hemoglobin variants and derivatives on glycohemoglobin determinations, as investigated by 102 laboratories using 16 methods. Clin Chem. 1993;39:1717–23.PubMed
5.
go back to reference Smaldone A. Glycemic control and hemoglobinopathy: when A1c may not be reliable. Diabetes Spectr. 2008;21:46–9.CrossRef Smaldone A. Glycemic control and hemoglobinopathy: when A1c may not be reliable. Diabetes Spectr. 2008;21:46–9.CrossRef
6.
go back to reference Malekiani CL, Ganesan A, Decker CF. Effect of hemoglobinopathies on hemoglobin A1c measurements. Am J Med. 2008;121(6):e5.CrossRefPubMed Malekiani CL, Ganesan A, Decker CF. Effect of hemoglobinopathies on hemoglobin A1c measurements. Am J Med. 2008;121(6):e5.CrossRefPubMed
7.
go back to reference Wiwanitkit V. Problem of using hemoglobin A1c measurement in endemic area of hemoglobinopathy. Prim Care Diabetes. 2007;1:173–5.CrossRefPubMed Wiwanitkit V. Problem of using hemoglobin A1c measurement in endemic area of hemoglobinopathy. Prim Care Diabetes. 2007;1:173–5.CrossRefPubMed
8.
go back to reference Sacks DB. Hemoglobin variants and hemoglobin A1c analysis: problems solved? Clin Chem. 2003;49:1245–7.CrossRefPubMed Sacks DB. Hemoglobin variants and hemoglobin A1c analysis: problems solved? Clin Chem. 2003;49:1245–7.CrossRefPubMed
10.
go back to reference Bry L, Chen PC, Sacks DB. Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Clin Chem. 2001;47:153–63.PubMed Bry L, Chen PC, Sacks DB. Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Clin Chem. 2001;47:153–63.PubMed
11.
go back to reference Chu CH, Wang MC, Sun TH, Lee JK, Lam HC. Very low HbA1c values in a patient with clinical silent hemoglobin variant (Hemoglobin J): a case report. J Intern Med Taiwan. 2007;18:45–50. Chu CH, Wang MC, Sun TH, Lee JK, Lam HC. Very low HbA1c values in a patient with clinical silent hemoglobin variant (Hemoglobin J): a case report. J Intern Med Taiwan. 2007;18:45–50.
12.
go back to reference Nigam PK, Sharma S, Sareen R, Paul V, Lal A. Lack of precision in HbA1c values on variant II in cases of hemoglobin Q India. Indian J Clin Biochem. 2006;21:72–5.PubMedCentralCrossRefPubMed Nigam PK, Sharma S, Sareen R, Paul V, Lal A. Lack of precision in HbA1c values on variant II in cases of hemoglobin Q India. Indian J Clin Biochem. 2006;21:72–5.PubMedCentralCrossRefPubMed
13.
go back to reference van den Ouweland JM, van Daal H, Klaassen CH, van Aarssen Y, Harteveld CL, Giordano PC. The silent hemoglobin alpha chain variant Hb Riccarton [alpha 51(CE9)Gly ->Ser] may affect HbA1c determination on the HLC-723 G7 analyzer. Clin Chem Lab Med. 2008;46:827–30.PubMed van den Ouweland JM, van Daal H, Klaassen CH, van Aarssen Y, Harteveld CL, Giordano PC. The silent hemoglobin alpha chain variant Hb Riccarton [alpha 51(CE9)Gly ->Ser] may affect HbA1c determination on the HLC-723 G7 analyzer. Clin Chem Lab Med. 2008;46:827–30.PubMed
14.
go back to reference Kilpatrick ES, Bloomgarden ZT, Zimmet PZ. Is hemoglobin A1c a step forward for diagnosing diabetes? BMJ. 2009;339(10):1288–90. Kilpatrick ES, Bloomgarden ZT, Zimmet PZ. Is hemoglobin A1c a step forward for diagnosing diabetes? BMJ. 2009;339(10):1288–90.
15.
go back to reference Schnedl WJ, Liebminger A, Roller RE, Lipp RW, Krejs GJ. Hemoglobin variants and determination of glycated hemoglobin (HbA1c). Diabetes Metab Res Rev. 2001;17:94–8.CrossRefPubMed Schnedl WJ, Liebminger A, Roller RE, Lipp RW, Krejs GJ. Hemoglobin variants and determination of glycated hemoglobin (HbA1c). Diabetes Metab Res Rev. 2001;17:94–8.CrossRefPubMed
16.
go back to reference Schnedl WJ, Krause R, Halwachs-Baumann G, Trinker M, Lipp RW, Krejs GJ. Evaluation of HbA1c determination methods in patients with hemoglobinopathies. Diabetes Care. 2000;23:339–44.CrossRefPubMed Schnedl WJ, Krause R, Halwachs-Baumann G, Trinker M, Lipp RW, Krejs GJ. Evaluation of HbA1c determination methods in patients with hemoglobinopathies. Diabetes Care. 2000;23:339–44.CrossRefPubMed
17.
go back to reference John WG, Braconnier F, Miedema K, Aulesa C, Piras G. Evaluation of the Menarini-Arkay HA 8140 hemoglobin A1c analyzer. Clin Chem. 1997;43:968–75.PubMed John WG, Braconnier F, Miedema K, Aulesa C, Piras G. Evaluation of the Menarini-Arkay HA 8140 hemoglobin A1c analyzer. Clin Chem. 1997;43:968–75.PubMed
18.
go back to reference Carta M, Dall’Olio G, Soffiati G. Determination of HbA1c in the presence of haemoglobin variants: comparison of three HPLC techniques. Eur J Clin Chem Biochem. 1997;35:923–5. Carta M, Dall’Olio G, Soffiati G. Determination of HbA1c in the presence of haemoglobin variants: comparison of three HPLC techniques. Eur J Clin Chem Biochem. 1997;35:923–5.
19.
go back to reference Weykamp CW, Penders TJ, Siebelder CW, Muskiet FA, van der Slik W. Interference of carbamylated and acetylated hemoglobins in assays of glycohemoglobin by HPLC, electrophoresis, affinity chromatography, and enzyme immunoassay. Clin Chem. 1993;39:138–42.PubMed Weykamp CW, Penders TJ, Siebelder CW, Muskiet FA, van der Slik W. Interference of carbamylated and acetylated hemoglobins in assays of glycohemoglobin by HPLC, electrophoresis, affinity chromatography, and enzyme immunoassay. Clin Chem. 1993;39:138–42.PubMed
20.
go back to reference Chang J, Hoke C, Ettinger B, Penerian G. Evaluation and interference study of hemoglobin A1c measured by turbidimetric inhibition immunoassay. Am J Clin Pathol. 1998;109:274–8.PubMed Chang J, Hoke C, Ettinger B, Penerian G. Evaluation and interference study of hemoglobin A1c measured by turbidimetric inhibition immunoassay. Am J Clin Pathol. 1998;109:274–8.PubMed
21.
go back to reference Roberts WL, Chiasera JM, Ward-Cook K. Glycohemoglobin results in samples with hemoglobin C or S trait: a comparison of four test systems [Technical Brief]. Clin Chem. 1999;45:906–9.PubMed Roberts WL, Chiasera JM, Ward-Cook K. Glycohemoglobin results in samples with hemoglobin C or S trait: a comparison of four test systems [Technical Brief]. Clin Chem. 1999;45:906–9.PubMed
22.
go back to reference Roberts WL, De BK, Brown D, Hanbury CM, Hoyer JD, John WG, et al. Effects of Hemoglobin C and S traits on eight glycohemoglobin methods. Clin Chem. 2002;48:383–5.PubMed Roberts WL, De BK, Brown D, Hanbury CM, Hoyer JD, John WG, et al. Effects of Hemoglobin C and S traits on eight glycohemoglobin methods. Clin Chem. 2002;48:383–5.PubMed
23.
go back to reference Miedema K, Lenters-Westra E, Horowitz G, Pistorino A, Patel R, Ng K, et al. Evaluation of the technical feasibility of Tina-quant HbA1c Gen.2. Assay on COBAS INTEGRA 800 [Abstract]. Clin Chem. 2005;51:A234. Miedema K, Lenters-Westra E, Horowitz G, Pistorino A, Patel R, Ng K, et al. Evaluation of the technical feasibility of Tina-quant HbA1c Gen.2. Assay on COBAS INTEGRA 800 [Abstract]. Clin Chem. 2005;51:A234.
24.
go back to reference Wang Y, Beckwith B, Smith C, Horowitz G. Misleading glycated hemoglobin results in a patient with hemoglobin SC disease. Clin Chem. 2007;53:1394–5.CrossRefPubMed Wang Y, Beckwith B, Smith C, Horowitz G. Misleading glycated hemoglobin results in a patient with hemoglobin SC disease. Clin Chem. 2007;53:1394–5.CrossRefPubMed
25.
go back to reference Watanabe T, Kato K, Yamada D, Midorikawa Sato W, Shiga M, Otsuka Y, et al. A nondiabetic case of hemoglobin variant (Hb Nigiata) with inappropriately high and low HbA1c titers detected by different methods. Clin Chem. 1998;44:1562–4.PubMed Watanabe T, Kato K, Yamada D, Midorikawa Sato W, Shiga M, Otsuka Y, et al. A nondiabetic case of hemoglobin variant (Hb Nigiata) with inappropriately high and low HbA1c titers detected by different methods. Clin Chem. 1998;44:1562–4.PubMed
26.
go back to reference Roberts WL, Safar-Pour S, De BK, Rohlfing CL, Weykamp CW, Little RR. Effects of hemoglobin C and hemoglobin S traits on glycohemoglobin measurements by eleven methods. Clin Chem. 2005;51:776–8.CrossRefPubMed Roberts WL, Safar-Pour S, De BK, Rohlfing CL, Weykamp CW, Little RR. Effects of hemoglobin C and hemoglobin S traits on glycohemoglobin measurements by eleven methods. Clin Chem. 2005;51:776–8.CrossRefPubMed
27.
go back to reference Mongia SK, Little RR, Rohlfing CL, Hanson S, Roberts RF, Owen WE, et al. Effects of hemoglobin C and S traits on 14 commercial glycated hemoglobin assays. Am J Clin Pathol. 2008;130:136–40.CrossRefPubMed Mongia SK, Little RR, Rohlfing CL, Hanson S, Roberts RF, Owen WE, et al. Effects of hemoglobin C and S traits on 14 commercial glycated hemoglobin assays. Am J Clin Pathol. 2008;130:136–40.CrossRefPubMed
28.
go back to reference Higgins T, Stewart D, Boehr E. Challenges in HbA1c analysis and reporting: an interesting case illustrating many pitfalls. Clin Biochem. 2008;41:1104–6.CrossRefPubMed Higgins T, Stewart D, Boehr E. Challenges in HbA1c analysis and reporting: an interesting case illustrating many pitfalls. Clin Biochem. 2008;41:1104–6.CrossRefPubMed
29.
go back to reference Lee KF, Szeto YT, Benzie IFF. Glycohaemoglobin measurement: methodological differences in relation to interference by urea. Acta Diabetol. 2002;39:35–9.CrossRefPubMed Lee KF, Szeto YT, Benzie IFF. Glycohaemoglobin measurement: methodological differences in relation to interference by urea. Acta Diabetol. 2002;39:35–9.CrossRefPubMed
30.
go back to reference Schnedl WJ et al. Determination of glycated hemoglobin in clinically silent hemoglobin variants. Diabetes Metab Res Rev. 2004;20:460–5.CrossRefPubMed Schnedl WJ et al. Determination of glycated hemoglobin in clinically silent hemoglobin variants. Diabetes Metab Res Rev. 2004;20:460–5.CrossRefPubMed
31.
go back to reference Nakanishi T, Iguchi K, Shimizu H. A method for hemoglobin A1c measurement based on peptide analysis by electrospray ionization mass spectrometry with deuterium-labeled synthetic peptides as internal standards. Clin Chem. 2003;49:829–31.CrossRefPubMed Nakanishi T, Iguchi K, Shimizu H. A method for hemoglobin A1c measurement based on peptide analysis by electrospray ionization mass spectrometry with deuterium-labeled synthetic peptides as internal standards. Clin Chem. 2003;49:829–31.CrossRefPubMed
32.
go back to reference Bisse E, Schauber C, Zorn N, Epting T, Eigel A, Van Dorsselaer A, et al. Hemoglobin Görwihl [α 2ß25(A2)Pro → Ala], an electrophoretically silent variant with impaired glycation. Clin Chem. 2003;49:137–43.CrossRefPubMed Bisse E, Schauber C, Zorn N, Epting T, Eigel A, Van Dorsselaer A, et al. Hemoglobin Görwihl [α 2ß25(A2)Pro → Ala], an electrophoretically silent variant with impaired glycation. Clin Chem. 2003;49:137–43.CrossRefPubMed
33.
go back to reference Friess U, Beck A, Kohne E, Lehmann R, Koch S, Haring H-U, et al. Novel hemoglobin variant [ß66(E10) Lys → Asn], with decreased oxygen affinity, causes falsely low hemoglobin A1c values by HPLC. Clin Chem. 2003;49:1412–5.CrossRefPubMed Friess U, Beck A, Kohne E, Lehmann R, Koch S, Haring H-U, et al. Novel hemoglobin variant [ß66(E10) Lys → Asn], with decreased oxygen affinity, causes falsely low hemoglobin A1c values by HPLC. Clin Chem. 2003;49:1412–5.CrossRefPubMed
Metadata
Title
Effects of hemoglobin S variants on the measurement of glycosylated hemoglobin A1c by four analytical methods
Authors
W. Tamimi
S. Aljasser
R. Kanan
R. Dafterdar
N. Aldegaither
M. Alrwali
A. Elfatah
W. Alsaeed
F. Q. Alenzi
R. Hasanato
Publication date
01-12-2015
Publisher
Springer India
Published in
International Journal of Diabetes in Developing Countries / Issue 4/2015
Print ISSN: 0973-3930
Electronic ISSN: 1998-3832
DOI
https://doi.org/10.1007/s13410-014-0257-0

Other articles of this Issue 4/2015

International Journal of Diabetes in Developing Countries 4/2015 Go to the issue