Glycated hemoglobin and alternative glycation biomarkers - a review from the perspective of laboratory medicine
Authors:
D. Stejskal; Z. Švagera; K. Janochová
Authors‘ workplace:
Lékařská fakulta, Ostravská univerzita
; Lab4Life Ostrava FNOU, Ostrava, Česká republika
; Ústav laboratorní medicíny, Fakultní nemocnice Ostrava
Published in:
Klin. Biochem. Metab., 34, 2026, No. 3, p. 1-8
Overview
Objective: This review provides a comprehensive overview of the current status of glycated hemoglobin (HbA1c) diagnostics and alternative glycation biomarkers from the perspective of laboratory medicine as of March 2026. The work summarizes analytical methods for HbA1c determination, their standardization, limitations in specific clinical settings, and the potential of alternative biomarkers for complementary assessment of diabetes mellitus compensation.
Design: Review article.
Setting: Department of Laboratory Medicine, University Hospital Ostrava; Faculty of Medicine, University of Ostrava; Lab4Life Ostrava FNOU, Ostrava, Czech Republic.
Material and Methods: A targeted, narratively structured literature search was conducted in PubMed, Web of Science, and Scopus databases covering the period 2015-2026, focusing on HbA1c analytical methods, standardization, point-of-care testing (POCT), alternative glycation biomarkers (fructosamine, glycated albumin, 1,5-anhydroglucitol, advanced glycation end-products, skin autofluorescence), and emerging markers. Original research articles, meta-analyses, systematic reviews, and professional society guidelines were analyzed.
Results: HbA1c remains an established reference parameter for diabetes diagnosis and monitoring; however, it shows significant limitations in patients with hemoglobinopathies, chronic kidney disease (CKD), pregnancy, post-bariatric surgery, and other conditions affecting erythrocyte turnover. Alternative biomarkers provide complementary glycemic information over different time windows. Glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) reflect shorter-term glycemic control over 1-3 weeks. Advanced glycation end-products (AGEs) and skin autofluorescence (SAF) capture cumulative metabolic burden. POCT device quality shows high variability - in a comprehensive study by Lenters-Westra et al. (2025) [14], only 5 of 19 tested devices met both IFCC and NGSP acceptance criteria. The JSCC reference measurement procedure for GA demonstrated an overall precision with a CV of 1.0 % and very high interlaboratory agreement (r = 0.999) in the validation study; in addition, a regression equation was established to enable conversion of JSCC RMP values to HPLC-derived va-lues. A multimarker approach combining HbA1c with GA, 1,5-AG, and SAF is proposed for CKD patients.
Conclusion: A multimarker approach combining HbA1c with alternative glycation biomarkers represents a promising direction, particularly for patient populations where HbA1c determination is unreliable. Integration of short-term markers (GA, 1,5-AG), cumulative damage markers (AGEs, SAF), and continuous glucose monitoring (CGM) data enables more comprehensive assessment of metabolic compensation and prediction of chronic diabetic complications.
Keywords:
glycated hemoglobin – glycated albumin – fructosamine – 1,5-anhydroglucitol – advanced glycation end-products
Sources
1. NGSP. IFCC Standardization of HbA1c [online]. [odkaz].
2. Eyth, E., Zubair, M., Naik, R. Hemoglobin A1C. In: StatPearls [online]. Treasure Island: StatPearls Publishing; aktualizováno 2. 6. 2025 [odkaz].
3. American Diabetes Association Professional Practice Committee. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes – 2025. Diabet. Care, 2025, 48(1), S27–S49. [odkaz]
4. American Diabetes Association Professional Practice Committee. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes – 2026. Diabet. Care, 2026, 49(1), S27–S49. [odkaz]
5. Davies, M. J., Aroda, V. R., Collins, B. S. et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia, 2022, 65(12), 1925–1966. [odkaz]
6. Friedecký, B., Kratochvíla, J., Springer, D. et al. Diabetes mellitus – laboratorní diagnostika a sledování stavu pacientů (společné doporučení ČSKB ČLS JEP a ČDS ČLS JEP). Klin. Biochem. Metab., 2019, 27(1), 32–47. [odkaz]
7. Hanas, R., John, G. 2010 consensus statement on the worldwide standardization of the hemoglobin A1c measurement. Ann. Clin. Biochem., 2010, 47(4), 290–291. [odkaz]
8. Samajdar, S. S., Joshi, S. R., Misra, A. et al. The limitations and fallacies of relying on glycosylated hemoglobin for diagnosing and monitoring diabetes in Indian populations [Viewpoint]. Lancet Reg. Health Southeast Asia, 2026, 45, 100724. [odkaz]
9. Okpete, U. E., Byeon, H. Limitations of glycated hemoglobin and emerging biomarkers for diabetes care after bariatric surgery. World J. Diabet., 2025, 16(7), 107928. [odkaz]
10. Li, M., Ge, S., Shu, X. et al. Interference of hemoglobin variants with HbA1c measurements by six commonly used HbA1c methods. Lab. Med., 2024, 55(6), 708–712. [odkaz]
11. Little, R. R., Rohlfing, C. L., Sacks, D. B. The National Glycohemoglobin Standardization Program: Over 20 Years of Improving Hemoglobin A1c Measurement. Clin. Chem., 2019, 65(7), 839–848. [odkaz]
12. EurA1c Trial Group. EurA1c: 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(8), 1183–1192. [odkaz]
13. Friedecký, B., Kratochvíla, J., Wiewiorka, O. Stav analytické a postanalytické harmonizace u měření glykovaného hemoglobinu HbA1c. Klin. Biochem. Metab., 2023, 31(3), 137–141. [odkaz]
14. Lenters-Westra, E., Singh, P., Vetter, B. et al. Challenges in Hb A1c point-of-care testing: only 5 of 19 HbA1c point-of-care devices meet IFCC and NGSP certification criteria on independent evaluation. Clin. Chem., 2025, 71(7), 775–788. [odkaz]
15. Stavelin, A., Flesche, K., Tollånes, M. et al. Performance of Afinion HbA1c measurements in general practice as judged by external quality assurance data. Clin. Chem. Lab. Med., 2020, 58(4), 588–596. [odkaz]
16. Wei, Y., Gu, M., Ren, Y. et al. Comparison of point-of-care HbA1c devices with laboratory HPLC methods: a systematic review and meta-analysis. Biomed. Rep., 2026, 24(4), 47. [odkaz]
17. Gounden, V., Anastasopoulou, C., Zubair, M., Jialal, I. Clinical Utility of Fructosamine and Glycated Albumin (Glycated Serum Protein). In: StatPearls [online]. Treasure Island: StatPearls Publishing, 2025. [odkaz]
18. Selvin, E., Rawlings, A. M., Lutsey, P. L. et al. Fructosamine and Glycated Albumin and the Risk of Cardiovascular Outcomes and Death. Circulation, 2015, 132(4), 269–277. [odkaz]
19. Ku, K. C., Zhong, J., Song, E. et al. Clinical utility of glycated albumin and 1,5-anhydroglucitol in the screening and prediction of diabetes: a multi-center study. World J. Diabetes, 2025, 16(4), 102867. [odkaz]
20. Meguro, S., Iwasaki, Y., Ueda, J. et al. Validation of the Japan Society of Clinical Chemistry (JSCC) recommended reference measurement procedure for glycated albumin determination. Ann. Clin. Biochem., 2026, 63(2), 123–131. [odkaz]
21. Xu, H., Chen, R., Hou, X. et al. The clinical potential of 1,5-anhydroglucitol as biomarker in diabetes mellitus. Front. Endocrinol., 2024, 15, 1471577. [odkaz]
22. Ni, J., Chen, L., Su, H. et al. Low serum 1,5-anhydroglucitol is associated with increased risk of all-cause and cardiovascular mortality in type 2 diabetes. Diabet. Obes. Metab., 2026, 28(1), 434–442. [odkaz]
23. Mishra, N., Saxena, S., Shukla, R. K. et al. Advanced glycation end products are biomolecular biomarkers for proliferative diabetic retinopathy. Indian J. Ophthalmol., 2025, 73(6), 906–911. [odkaz]
24. Wang, Z. H., Zhang, Z. J., Wang, Y. F. et al. Serum advanced glycation end products as a putative biomarker in Type 2 DKD patients’ prognosis. Front. Physiol., 2025, 16, 1541198. [odkaz]
25. Meerwaldt, R., Links, T., Graaff, R. et al. Simple noninvasive measurement of skin autofluorescence. Ann. N. Y. Acad. Sci., 2005, 1043, 290–298. [odkaz]
26. Hosseini, M. S., Razavi, Z., Ehsani, A. H., Firooz, A., Afazeli, S. Clinical Significance of Non-Invasive Skin Autofluorescence Measurement in Patients with Diabetes: A Systematic Review and Meta-Analysis. E Clin. Med., 2021, 42, 101194. [odkaz]
27. Borghi, S., Nencini, F., Giurranna, E. et al. Fibrinogen glycosylation and glycation: molecular insights into thrombosis and vascular disease. Front. Mol. Biosci., 2025, 12, 1680332. [odkaz]
28. Valk, T., McMorrow, C. A proposed model using glycation metrics and circulating biomarkers for the prevention of cardiovascular disease. Front. Med., 2025, 12, 1624682. [odkaz]
29. DePasquale, H., DeLucenay, A., Ahmed-Sarwar, N. Correlation of HbA1c and continuous glucose monitor time in range. J. Pharm. Technol., 2025, 87551225251348832. [odkaz]
30. Rizos, E. C., Markozannes, G., Charitakis, N. et al. Continuous glucose monitoring in type 1 diabetes, type 2 diabetes, and diabetes during pregnancy: a systematic review with meta-analysis of randomized controlled trials. Diabet. Technol. Ther., 2025, 27(7), 537–552. [odkaz]
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Clinical biochemistry Nuclear medicine Nutritive therapistArticle was published in
Clinical Biochemistry and Metabolism
2026 Issue 3
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