Hemoglobin A1c units, diagnostic limits and quality aspects updated.

Volume 4, Issue 6, December 2019     |     PP. 191-208      |     PDF (502 K)    |     Pub. Date: October 6, 2019
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Penttilä Ilkka, Kuopio Research Institute of Exercise Medicine, 70100 Kuopio, Finland
Penttilä Karri, Finnish Medicines Agency FIMEA, 70210 Kuopio, Finland
Ranta Päivi, Labquality Ltd., 00530 Helsinki, Finland
Törrönen Jukka, Kuopio Research Institute of Exercise Medicine, 70100 Kuopio, Finland
Savonen Kai, Kuopio Research Institute of Exercise Medicine, 70100 Kuopio, Finland

In this report the use of the units, diagnostic limits and the quality aspects of hemoglobin A1c (HbA1c) were studied in worldwide clinical laboratory practice. In addition, the quality aspects were calculated for the target values from the surveys of Labquality Ltd. and ERLGH. The use of HbA1c units and the diagnostic limits for diabetes were examined using e-mail and mail inquiries to 37–51 societies of laboratory medicine (mainly clinical chemistry) from 2009 to 2019. The parametric statistical programs of Labquality Ltd. and commercial programs of SPSS® 13.0 and MS Excel 2013 (Microsoft® Co., Cambridge, MA, USA) were used.The IFCC system for HbA1c as mmol/mol unit slowly but constantly gaining acceptance in Europe, but remains quite rare outside Europe whereas the DCCT/NGSP system as a per cent unit was reduced. The mean round values of Labquality Ltd. and the corresponding values of the European Reference Laboratory for Glycohemoglobin (ERLGH) were calculated for the target values with ±6% intervals for the per cent results and ±8% intervals for the mmol/mol results. To avoid confusion, the overall use of mmol/mol unit only for HbA1c by the IFCC system could be the best one in the future.

diabetes, HbA1c, IFCC recommendation, quality aspects, target limits

Cite this paper
Penttilä Ilkka, Penttilä Karri, Ranta Päivi, Törrönen Jukka, Savonen Kai, Hemoglobin A1c units, diagnostic limits and quality aspects updated. , SCIREA Journal of Clinical Medicine. Volume 4, Issue 6, December 2019 | PP. 191-208.


[ 1 ] Penttilä I, Penttilä K, Holm P, Laitinen H, Rauramaa R. Hemoglobin A1c reported in units and cutoffs in relation to international recommendations. Clin Chem Lab Med 2015;53:e277-e279.
[ 2 ] Holmquist WR, Schroeder WA. A new N-terminal blocking group involving a Schiff base in hemoglobin A1c. Biochemistry 1966;5:2489-2503.
[ 3 ] Rabhar S. An abnormal hemoglobin in red cells of diabetes. Clin Chim Acta. 1968;22:296-298.
[ 4 ] Trivelli LA, Ranney HM, Lai H-T. Hemoglobin components in patients with diabetes mellitus. New Engl J Med. 1971;284:353-357.
[ 5 ] Weykamp CW, Penders TJ, Muskiet FAJ, van der Silk W. Effect of calibration on dispersion of glycohemoglobin values determined from 111 laboratories using 21 methods. Clin Chem. 1994;40:138-144.
[ 6 ] Jensen ON, de Fine Olivarius N, Hyltoft Petersen P, Klitgaard NA, Blaabjerg O, Hørder M. Discrepancy in HbA1c measurements performed at different local laboratories and selected central reference laboratory. Uppsala J Med Sci 1993;98:275-282.
[ 7 ] Little RR, Rohlfing CL, Wiedmeyer HM, Myers GL, Sacks DB, Goldstein DE; NGSP Steering Committee. The National Glycohemoglobin Standardization Program: A five-year progress report. Clin Chem. 2001;47:1985-1192.
[ 8 ] Finke A, Kobold U, Hoelzel W, Weykamp C, Miedema K, Jeppsson J-O. Preparation of a candidate primary reference material for the international standardization of HbA1c determinations. Clin Chem Lab Med. 1998;36:299-308.
[ 9 ] Jeppsson J-O, Kobold U, Barr J, Finke A, Hoelzel W, Hashino T, Miedema K, Mosca A, Mauri P, Paroni R, Thienpont L, Umemoto M, Weykamp C. Approved IFCC reference method for the measurement of HbA1c in human blood. Clin Chem Lab Med. 2002;40:78-89.
[ 10 ] Hoelzel W, Miedema K. Development of a reference system for the international standardization of HbA1c/glycohemoglobin determinations. J Int Fed Clin Chem. 1996;9:62-67.
[ 11 ] Hoelzel W, Weykamp C, Jeppsson J-O, Miedema K, Barr JR, Goodali I, Hoshino T, John WG, Kobold U, Little R, Mosca A, Pierluigi M, Paroni R, Susanto F, Takei I, Tienpont L, Umemoto M, Wiedmeyer H-M on behalf of the IFCC Working Group on HbA1c Standardization. IFCC reference system for measurement of HbA1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: a method-comparison study. Clin Chem. 2004;50:166-174.
[ 12 ] American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33(Suppl 1):S62-S69.
[ 13 ] Hanas R, John WG; International HbA1c Consensus Committee. 2013 Update on the worldwide standardization of the hemoglobin A1c measurement. Pediatr Diabetes. 2014;15:e1-e2.
[ 14 ] Penttilä I, Penttilä K, Holm P, Laitinen H, Ranta P, Törrönen J, Rauramaa R. Methods, units and quality requirements for the analysis of haemoglobin A1c in diabetes mellitus. World J Methdol. 2016;6:133-142.
[ 15 ] Labquality Ltd., Helsinki, Finland; www.labquality.fi.
[ 16 ] Penttilä I, Penttilä K, Laitinen H, Ranta P, Törrönen J, Rauramaa R. Hemoglobin A(1c) Reporting Units and Diagnostic Cut-Offs in Relation to International Recommendations. Int J Clin Exper Med Sci 2019; 5: 18-25.
[ 17 ] Weykamp C, Lenters-Westra E, van der Vuurst H, Slingerland R, Siebelder C, Visser-Dekkers W. Evaluation of the Menarini/ARKRAY ADAMS A1c HA-8180V analyzer for HbA1c. Clin Chem Lab Med. 2011;49:647-651.
[ 18 ] Little RR, Rohlfing CL, Sacks DB for the NGSP Committee. Status of hemoglobin A1c measurement and goals for improvement: from chaos to order for improving diabetes care. Clin Chem. 2011;57:205-214.
[ 19 ] Lindblad B, Nordin G. External quality assessment of HbA1c and kits effect on comparison between Swedish pediatric diabetes clinics. Experiences from the Swedish pediatric diabetes quality register (Swediabkids) and Equalis. Clin Chem Lab Med. 2013;51:2045-2052.
[ 20 ] Lenters-Westra E, Boraas T, Schindhelm RK, Slingerland RJ, Sandberg S. Biological variation of hemoglobin A1c: consequences for diagnosis of diabetes mellitus. Clin Chem. 2014;60:1570-1572.
[ 21 ] Finnish Society of Clinical Chemistry. ww.skky.fi
[ 22 ] DGKL (Deutsche Vereinte Gesellschaft für Klinische Chemie und Laboratoriums-medizin). Stellungnahme der Deutschen Diabetes Gesellschaft, diabetes und des Kompetenznetzes Diabetes mellitus zur Verwendung des HbA1c-Wertes als Biomarker zur Diabetesdiagnose; www.diabetesde.org/
[ 23 ] Nordin G, Dybkaer R. Recommendation for term and measurement unit for “HbA1c”. Clin Chem Lab Med. 2007;45:1081-1082.
[ 24 ] Weykamp CW, Mosca A, Gillery P, Panteghini M. The analytical goals for hemoglobin A1c measurement in IFCC units and in National Glycohemoglobin Standardization Program units are different. Clin Chem. 2011;57:1204-1206.
[ 25 ] Nielsen AA, Petersen PH, Green A, Christensen C, Christensen H, Brandslund I. Changing from glucose to HbA1c for diabetes diagnosis: predictive values of one test and importance of analytical bias and imprecision. Clin Chem Lab Med. 2014;52:1069-1077.
[ 26 ] Lenters-Westra E, English E. Evaluating new HbA1c methods for adoption by the IFCC and NGSP reference networks using international quality targets. Clin Chem Lab Med. 2017;55:1426-1434.
[ 27 ] EurA1c Group. The European HbA1c Trial to Investigate the Performance of HbA1c Assays in 2166 Laboratories across 17 Countries and 24 Manufacturers by Use of the IFCC Model for Quality Targets. Clin Chem 2018;64:1183-1192
[ 28 ] Little RR, Rohlfing C, Sacks DB. The National Glycohemoglobin Standardization Program: Over 20 Years of Improving Hemoglobin A1c Measurement. Clin Chem 2019;65:839-848.