Diagnostic utility of glycated hemoglobin (HbA1c) measurement in prediabetes and type 2 diabetes. A critical review of the evidence and its applicability in real- life settings

Authors

  • María Natalia Forte National University of La Plata (UNLP), La Plata, Buenos Aires Province, Argentina
  • Lucas Damián Costa National University of the Litoral, Santa Fe, Argentina
  • Jorge Federico Elgart Associated Center of the Scientific Research Commission of the Province of Buenos Aires (CICPBA), La Plata, Province of Buenos Aires, Argentina
  • Luis Emilio Flores Associated Center of the Scientific Research Commission of the Province of Buenos Aires (CICPBA), La Plata, Province of Buenos Aires, Argentina

DOI:

https://doi.org/10.47196/diab.v60i2.1358

Keywords:

HbA1c, glycated hemoglobin, diabetes diagnosis, prediabetes, standardization, HPLC

Abstract

For decades, glycated hemoglobin (HbA1c) has been the reference biomarker for assessing chronic glycemic control in people with diabetes mellitus (DM). Following an international consensus reached over the last decade, its utility as a diagnostic criterion for both DM and prediabetes has gained particular significance. This review examines the evolution of HbA1c usage, its biochemical basis, measurement and standardization methods, and the evidence both supporting and challenging its diagnostic value. It highlights the marker's analytical and clinical advantages, as well as limitations stemming from biological, methodological, and contextual factors—particularly in middle-income countries.

Author Biographies

María Natalia Forte, National University of La Plata (UNLP), La Plata, Buenos Aires Province, Argentina

National University of La Plata (UNLP), La Plata, Buenos Aires Province, Argentina; Medical Specialist in Internal Medicine; Master's Degree in Diabetes, Favaloro University; Faculty Member, Women's Studies Chair (UNLP); Director of the University Course at Universidad del Este (UDE), CEDIAB-MEPRIN, La Plata, Buenos Aires Province, Argentina

Lucas Damián Costa, National University of the Litoral, Santa Fe, Argentina

Department of Biostatistics, Faculty of Medical Sciences

Jorge Federico Elgart, Associated Center of the Scientific Research Commission of the Province of Buenos Aires (CICPBA), La Plata, Province of Buenos Aires, Argentina

Center for Experimental and Applied Endocrinology (CENEXA), National University of La Plata–National Scientific and Technical Research Council (UNLP-CONICET), School of Medical Sciences

Luis Emilio Flores, Associated Center of the Scientific Research Commission of the Province of Buenos Aires (CICPBA), La Plata, Province of Buenos Aires, Argentina

Center for Experimental and Applied Endocrinology (CENEXA), National University of La Plata–National Scientific and Technical Research Council (UNLP-CONICET), School of Medical Sciences

References

I. International Diabetes Federation. IDF Diabetes Atlas. 11th ed. Brussels: International Diabetes Federation; 2025.

II. Allen DW, Schroeder WA, Balog J. Observations on the chromatographic heterogeneity of normal adult and fetal human hemoglobin. J Am Chem Soc. 1958;80(7):1628-34.

III. Rahbar S. An abnormal hemoglobin in red cells of diabetics. Clin Chim Acta. 1968 Oct;22(2):296-8. doi: 10.1016/0009-8981(68)90372-0.

IV. Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, et al; Diabetes Control and 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 Sep 30;329(14):977-86. doi: 10.1056/NEJM199309303291401.

V. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837-853.

VI. Weykamp C, John WG, Mosca A, Hoshino T, Little R, Jeppsson JO, et al. The IFCC reference measurement system for HbA1c: a 6-year progress report. Clin Chem 2008 Feb;54(2):240-488. doi: 10.1373/clinchem.2007.097402.

VII. World Health Organization. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus: abbreviated report of a WHO consultation. Geneva: World Health Organization; 2011.

VIII. American Diabetes Association. 2. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes 2021. Diabetes Care. 2021 Jan;44(Suppl 1):S15-S33. doi: 10.2337/dc21-S002. Erratum in: Diabetes Care. 2021 Sep;44(9):2182. doi: 10.2337/dc21-ad09.

IX. International Expert Committee. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009;32(7):1327-34. doi: 10.2337/dc09-9033.

X. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010 Jan;33 Suppl 1(Suppl 1):S62-9. doi: 10.2337/dc10-S062. Erratum in: Diabetes Care. 2010 Apr;33(4):e57.

XI. Lorenzo-Medina M, Uranga-Múgica B, Rus-Martínez A, et al. Comparación entre 2 sistemas analíticos para la determinación de la hemoglobina A1c: inmunoturbidimetría versus cromatografía líquida de alta eficiencia. Rev Lab Clin 2013;6(4):145–50.

XII. Chaila MZ, Viniegra M, Gagliardino JJ, Martínez A, Simesen de Bielke MG, Frusti M, Monaco L, Salgado P, Buso C, González CD, Commendatore VF. Glycated hemoglobin measurement. Comparison of three methods versus high performance liquid chromatography. J Diabetes Sci Technol. 2022 May;16(3):724-731. doi: 10.1177/1932296821997179.

XIII. Hoelzel W, Weykamp C, Jeppsson JO, Miedema K, Barr JR, Goodall I, et al; IFCC Working Group on HbA1c Standardization. IFCC reference system for measurement of hemoglobin A1c in human blood and the national standardization schemes in the United States, Japan, and Sweden: a method-comparison study. Clin Chem. 2004 Jan;50(1):166-74. doi: 10.1373/clinchem.2003.024802.

XIV. García-Alcalá H, Ruiz-Argüelles A, Cedillo-Carvallo B. Effect of the method to measure levels of glycated hemoglobin on individual clinical decisions: comparison of an immunoassay with high-performance liquid chromatography. Am J Clin Pathol 2009 Sep;132(3):332-5. doi: 10.1309/AJCPIWRO1ST6HCIY.

XV. Diabetes.co.uk. HbA1c conversion calculator [Internet]. Disponible en: https://www.diabetes.co.uk/hba1c-units-converter.html.

XVI. Campuzano-Maya G, Latorre-Sierra G. La HbA1c en el diagnóstico y en el manejo de la diabetes. Med Lab 2010;16:211-4.

XVII. Cohen RM, Haggerty S, Herman WH. HbA1c for the diagnosis of diabetes and prediabetes: is it time for a mid-course correction? J Clin Endocrinol Metab 2010 Dec;95(12):5203-6. doi: 10.1210/jc.2010-2352. PMID: 21131541; PMCID: PMC2999978.

XVIII. El-Agouza I, Abu Shahla A, Sirdah M. The effect of iron deficiency anaemia on the levels of haemoglobin subtypes: possible consequences for clinical diagnosis. Clin Lab Haematol. 2002 Oct;24(5):285-9. doi: 10.1046/j.1365-2257.2002.00464.x.

XIX. Kaur G, Lakshmi PVM, Rastogi A, Bhansali A, Jain S, Teerawattananon Y, et al. Diagnostic accuracy of tests for type 2 diabetes and prediabetes. A systematic review and meta-analysis. PLoS One. 2020 Nov 20;15(11):e0242415. doi: 10.1371/journal.pone.0242415.

XX. De’Marziani G, Elbert AE. Hemoglobina glicada (HbA1c). Utilidad y limitaciones en pacientes con enfermedad renal crónica. Rev Nefrol Dial Traspl 2018;38(1):65-83.

XXI. Davidson MB, Schriger DL. Effect of age and race/ethnicity on HbA1c levels in people without known diabetes mellitus: implications for the diagnosis of diabetes. Diabetes Res Clin Pract. 2010 Mar;87(3):415-21. doi: 10.1016/j.diabres.2009.12.013.

XXII. Gómez-Pérez FJ, Valles-Sánchez VE, López-Alvarenga JC, Choza-Romero R, Ibarra Pascuali JJ, González Orellana R, et al. Vitamin E modifies neither fructosamine nor HbA1c levels in poorly controlled diabetes. Rev Invest Clin 1996 Nov-Dec;48(6):421-4. PMID: 9028151.

XXIII. Gómez-Pérez FJ, Aguilar-Salinas CA, Almeda-Valdes P, Cuevas-Ramos D, Lerman Garber I, Rull JA. HbA1c for the diagnosis of diabetes mellitus in a developing country. A position article. Arch Med Res. 2010 May;41(4):302-8. doi: 10.1016/j.arcmed.2010.05.007.

XXIV. Battelino T, Danne T, Bergenstal RM, Amiel SA, Beck R, Biester T et al. Clinical targets for continuous glucose monitoring data interpretation. Recommendations from the International Consensus on Time in Range. Diabetes Care 2019;42(8):1593-1603. doi: 10.2337/dci19-0028.

XXV. Yoshii H, Mita T, Katakami N, Okada Y, Osonoi T, Aso K, et al. The importance of continuous glucose monitoring-derived metrics beyond HbA1c for optimal individualized glycemic control J Clin Endocrinol Metab. 2022;107(10):e3990-e4003. doi:10.1210/clinem/dgac459.

XXVI. American Diabetes Association Professional Practice Committee. 6. Glycemic goals and hypoglycemia: Standards of Care in Diabetes 2025. Diabetes Care. 2025;48(Suppl 1):S128-S145.

XXVII. Sabanayagam C, Liew G, Tai ES, Shankar A, Lim SC, Subramaniam T, et al. Relationship between glycated haemoglobin and microvascular complications: is there a natural cut-off point for the diagnosis of diabetes? Diabetologia. 2009 Jul;52(7):1279-89. doi: 10.1007/s00125-009-1360-5.

XXVIII. Maselli M, Llanos I, Lucarelli C, Fenili C, Ruibal G, Valdez S. Opiniones y recomendaciones de la Sociedad Argentina de Diabetes. Hemoglobina A1c. Rev Soc Arg Diab 2023; 57(1):20-23

XXIX. Buell C, Kermah D, Davidson MB. Utility of A1C for diabetes screening in the 1999 2004 NHANES population. Diabetes Care. 2007; 30(9):2233-2235. doi: 10.2337/dc07-0585.

XXX. Tanaka Y, Atsumi Y, Matsuoka K, Mokubo A, Asahina T, Hosokawa K, et al. Usefulness of stable HbA(1c) for supportive marker to diagnose diabetes mellitus in Japanese subjects. Diabetes Res Clin Pract. 2001 Jul;53(1):41-5. doi: 10.1016/s0168-8227(01)00226-1.

XXXI. Kim KS, Kim SK, Lee YK, Park SW, Cho YW. Diagnostic value of glycated haemoglobin HbA(1c) for the early detection of diabetes in high-risk subjects. Diabet Med. 2008 Aug;25(8):997-1000. doi: 10.1111/j.1464-5491.2008.02489.x.

XXXII. NHS Health Check. Vascular risk assessment and management: best practice guidance. London: Department of Health; 2009 Apr. Disponible en: http://www.dh.gov.uk

XXXIII. Cavagnolli G, Comerlato J, Comerlato C, Renz PB, Gross JL, Camargo JL. HbA(1c) measurement for the diagnosis of diabetes: is it enough? Diabet Med. 2011 Jan;28(1):31-5. doi: 10.1111/j.1464-5491.2010.03159.x.

XXXIV. Gagliardino JJ, Elgart JF, Bourgeois M, Etchegoyen G, Fantuzzi G, Ré M, et al. Diabetes primary prevention program: New insights from data analysis of recruitment period. Diabetes Metab Res Rev. 2018 Jan;34(1). doi: 10.1002/dmrr.2943.

XXXV. Bennett CM, Guo M, Dharmage SC. HbA(1c) as a screening tool for detection of Type 2 diabetes: a systematic review. Diabet Med. 2007 Apr;24(4):333-43. doi: 10.1111/j.1464-5491.2007.02106.x. Epub 2007 Mar 15. Erratum in: Diabet Med. 2007 Sep;24(9):1054.

XXXVI. Gerstein HC, Santaguida P, Raina P, Morrison KM, Balion C, Hunt D, et al. Annual incidence and relative risk of diabetes in people with various categories of dysglycemia: a systematic overview and meta-analysis of prospective studies. Diabetes Res Clin Pract. 2007 Dec;78(3):305-12. doi: 10.1016/j.diabres.2007.05.004.

XXXVII. Ko GT, Chan JC, Yeung VT, Chow CC, Tsang LW, Li JK, et al. Combined use of a fasting plasma glucose concentration and HbA1c or fructosamine predicts the likelihood of having diabetes in high-risk subjects. Diabetes Care. 1998 Aug;21(8):1221-5. doi: 10.2337/diacare.21.8.1221.

XXXVIII. Chaila MZ, Viniegra M, Gagliardino JJ, Lucarelli C, Maccallini G, Frusti M, Elbarcha O, Louzan S, Salgado P, González CD, Commendatore VF. Glucemia en ayunas entre 100 y 109 mg/dL versus prediabetes según hemoglobina glicosilada. Rev Soc Arg Diab 2022;56(2):51-6.

XXXIX. Chan L, Yu EYT, Wan EYF, Wong SYS, Chao DVK, Ko WWK, et al. Improving type 2 diabetes detection among at-risk individuals comparing the effectiveness of active opportunistic screening using spot capillary-HbA1c testing and venous HbA1c testing: a cluster randomized controlled trial. BMC Med. 2025;23:190. doi:10.1186/s12916-025-04007-z.

XL. Kasujja FX, Daivadanam M, Mayega RW, Nuwaha F, Kusolo R, Ekirapa E. Glycated haemoglobin versus fasting plasma glucose for type 2 diabetes point of care screening: a decision model cost-effectiveness analysis. BMC Health Serv Res 2025;25:664. doi:10.1186/s12913-025-12840-4.

XLI. Shao Q, Xie X, Wang L, Gao L, Hu Y, Zhang Y. Point-of-care Testing HbA1c screening for type 2 diabetes in urban and rural areas of China: a cost-effectiveness analysis. Front Public Health. 2024 Jul 30;12:1438945. doi: 10.3389/fpubh.2024.1438945.

XLII. Gaidhane S, Sah R, Zahiruddin QS, Khatib N, Telrandhe S, Choudhari S, et al. Hemoglobin A1c to detect prediabetes or type 2 diabetes mellitus in a rural population of Wardha district in India. J Diabetol 2024;15(2):195-203. doi:10.4103/jod.jod_122_23.

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Published

2026-07-29

Issue

Vol. 60 No. 2 (2026): May–August

Section

Review

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