CoChat
Sign Up
Cited by 361Clinical Laboratory Practices and Quality ControlDiabetes Management and ResearchAdvanced Glycation End Products research

Pitfalls in Hemoglobin A1c Measurement: When Results may be Misleading

Open access
Radin, Michael S.·2014·Journal of General Internal Medicine
DOI 10.1007/s11606-013-2595-xPMC PMC3912281
Open this paper in CoChat — free accountOpen PDF

Abstract

Since the beginning of clinical use in the 1970s, hemoglobin A1c (A1c) has become the standard tool for monitoring glycemic control in patients with diabetes. The role of the A1c test was broadened in 2010, when the American Diabetes Association added A1c as a diagnostic criterion for diabetes. Because of hemoglobin A1c's integral role in diagnosis and treatment, it is important to recognize clinical scenarios and interfering factors that yield false results. The purpose of this review is to describe the A1c measurement, outline clinical scenarios or factors that may yield false results, and describe alternative laboratory biomarkers.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s11606-013-2595-x

Cites

9 of 9 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In conditions with altered erythrocyte turnover or hemoglobinopathies, HbA1c does not reflect mean glucose.

    “In several conditions, however, HbA 1c does not reflect mean glucose; these are mainly situations where erythrocyte turnover is altered or in the presence of hemoglobinopathies (Table 4) (67).”

    From The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2021) · cites this paper as [67]

    The FALSELY LOWERED A1C and FALSELY ELEVATED A1C sections explain that altered red-cell turnover can make HbA1c misrepresent average glycemia. The HEMOGLOBIN VARIANTS section says variants can also distort HbA1c, but qualifies the claim: measurement can be used for heterozygous variants when an appropriate assay is used. The citing sentence overgeneralizes the hemoglobinopathy part. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 42

  1. Sacks DB. Measurement of Hemoglobin A1c. Diabetes Care. 2012;35:2674-80.
  2. International Expert Committee. International Expert Committee report on the role of A1C assay in the diagnosis of diabetes. Diabetes Care. 2009;32:1327-34.
  3. Steinberg MH, Benz EJ Jr, Adewoye AH, Ebert BL. Hemoglobin synthesis, structure, and function. In: Hematology: Basic Principles and Practice. 5th ed. Philadelphia, PA: Churchill Livingstone Elsevier; 2009. Chap 33.
  4. Bunn HF, Haney DN, Kamin S, Gabbay KH, Gallop PM. The biosyn- thesis of hemoglobin A1c: slow glycosylation of hemoglobin in vitro. J Clin Invest. 1976;57:1652-9.
  5. Saudek CD, Brick JC. Clinical advances in hemoglobin A1c measure- ment: the clinical use of hemoglobin A1c. J Diabetes Sci Technol. 2009;3(4):629-34.
  6. Nathan DM, Kuenen J, Borg R, et al. Translating the A1c assay into estimated average glucose values. Diabetes Care. 2008;31(8):1473-8.
  7. Homa K, Majkowska L. Difficulties in interpreting HbA1c results. Pol Arch Med Wewn. 2010;120:148-54.
  8. Little RR, Roberts WL. Laboratory advances in hemoglobin A1c measurement: a review of variant hemoglobins interfering with hemo- globin A1c measurement. J Diabetes Sci Technol. 2009;3(3):446-51.
  9. Chang A, Frank J, Knaebel J, Fullam J, Pardo S, Simmons DA. Evaluation of an over-the-counter glycated hemoglobin (A1c) test kit. J Diabetes Sci Technol. 2010;4(6):1495-503.
  10. Al-Ansary L, Farmer A, Hirst J, et al. Point-of-care testing for HbA1c in the management of diabetes: a systematic review and metaanalysis. Clin Chem. 2011;57(4):568-76.
  11. Herman WH, Cohen RM. Racial and ethnic differences in the relation- ship between HbA1c and blood glucose: Implications for the diagnosis of diabetes. J Clin Endocrinol Metab. 2012;97(4):1067-72.
  12. Brooks AP, Metcalfe J, Day JL, Edwards MS. Iron deficiency and glycosylated haemoglobin A. Lancet. 1980;2:141.
  13. Coban E, Ozdogan M, Timuragaoglu A. Effect of iron deficiency anemia on the levels of hemoglobin A1c in nondiabetic patients. Acta Haematol. 2004;112:126-8.
  14. Nitin S. HbA1c and factors other than diabetes mellitus affecting it. Singap Med J. 2010;51:616-22.
  15. Arnold JG, McGowan HJ. Delay in diagnosis of diabetes mellitus due to inaccurate use of hemoglobin A1c levels. J Am Board Fam Med. 2007;20:93-6.
  16. Spencer DH, Grossman BJ, Scott MG. Red cell transfusion decreases hemoglobin A1c in patients with diabetes. Clin Chem. 2011;57(2):344-6.
  17. Falko JM, O'Dorisio TM, Cataland S. Spurious elevations in glycosylated hemoglobin (HbA1) secondary to hypertriglyceridemia. Arch Intern Med. 1982;142(7):1370-1.
  18. Hoberman HD, Chiodo SM. Elevation of the hemoglobin A1 fraction in alcoholism. Alcohol Clin Exp Res. 1982;6(2):260-6.
  19. Hazelette SE, Liebelt RA, Brown WJ, Androulakakis V, Jarjoura D, Truitt EB Jr. Evaluation of acetaldehyde-modified hemoglobin and other markers of chronic heavy alcohol use: effects of gender and hemoglobin concentration. Alcohol Clin Exp Res. 1998;22(8):1813-9.
  20. Rastelli G, Gerra G, Mineo F, et al. Homeostasis of blood glucose and abuse of exogenous opiates: evaluation of fructosamine and glycosylated hemoglobin. Minerva Med. 1987;78(17):1291-6.
  21. Tran HA, Silva D, Petrovsky N. Case study: potential pitfalls of using hemoglobin A1c as the sole measure of glycemic control. Clin Diabetes. 2004;22(3):141-3.
  22. Joy MS, Cefalu WT, Hogan SL, Nachman PH. Long-term glycemic control measurements in diabetic patients receiving hemodialysis. Am J Kidney Dis. 2002;39(2):297-307.
  23. Lurie S, Mamet Y. Red blood cell survival and kinetics during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2000;93(2):185-92.
  24. Lind T, Cheyne GA. Effect of normal pregnancy upon glycosylated haemoglobins. Br J Obstet Gynaecol. 1979;86:210-3.
  25. Hanson U, Hagenfeldt L, Hagenfeldt K. Glycosylated hemoglobins in normal pregnancy: sequential changes and relation to birth weight. Obstet Gynecol. 1983;62:741-4.
  26. Phelps RL, Honig GR, Green D, Metzger BE, Frederiksen MC, Freinkel N. Biphasic changes in hemoglobin A1c concentrations during normal human pregnancy. Am J Obstet Gynecol. 1983;147:651-3.
  27. Gross BN, Cross LB, Foard JC, Wood YA. Falsely low hemoglobin A1c levels in a patient receiving ribavirin and peginterferon alpha-2b for hepatitis C. Pharmacotherapy. 2009;29(1):121-3.
  28. Greenberg PD, Rosman AS, Eldeiry LS, Naqvi Z, Bräu N. Decline in haemoglobin A1c values in diabetic patients receiving interferon-alpha and ribavirin for chronic hepatitis C. J Viral Hepat. 2006;13(9):613-7.
  29. 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.
  30. Sacks DB. A1c versus glucose testing: a comparison. Diabetes Care. 2011;34(2):518-23.
  31. Smaldone A. Glycemic control and hemoglobinopathy: when A1c may not be reliable. Diabetes Spectrum. 2008;21:46-9.
  32. Ambruster DA. Fructosamine: structure, analysis, and clinical useful- ness. Clin Chem. 1987;33(12):2153-63.
  33. Goldstein DE, Little RR, Lorenz RA, Malone JI, Nathan D, Peterson CM, Sacks DB. Tests of glycemia in diabetes. Diabetes Care. 2004;27(7):1761-73.
  34. Chen HS, Wu TE, Lin HD, et al. Hemoglobin A1c and fructosamine for assessing glycemic control in diabetic patients with CKD stages 3 and 4. Am J Kidney Dis. 2010;55:867-74.
  35. Inaba M, Okuno S, Kumeda Y, et al. Glycated albumin is a better glycemic indicator than glycated hemoglobin values in hemodialysis patients with diabetes: effect of anemia and erythropoietin injection. J Am Soc Nephrol. 2007;18:896-903.
  36. Beck R, Steffes M, Xing D, et al. The interrelationships of glycemic control measures: HbA1c, glycated albumin, fructosamine, 1,5- anhydroglucitrol, and continuous glucose monitoring. Pediatr Diabetes. 2011;12(8):690-5.
  37. Dungan KM. 1,5-anhydroglucitol (GlycoMark TM ) as a marker of short- term glycemic control and glycemic excursions. Expert Rev Mol Diagn. 2008;8(1):9-19.
  38. McGill JB, Cole TJ, Nowatzke W, et al. Circulating 1,5-anhydroglucitol levels in adult patients with diabetes reflect longitudinal changes of glycemia. Diabetes Care. 2004;27:1859-65.
  39. Nielsen JK. Continuous subcutaneous glucose monitoring shows a close correlation between mean glucose and time spent in hypergly- cemia and hemoglobin A1c. J Diabetes Sci Technol. 2007;1(6):857- 63.
  40. Vaddiraju S, Burgess DJ, Tomazos I, Jain FC, Papadimitrakopoulos F. Technologies for continuous glucose monitoring: current problems and future promises. J Diabetes Sci Technol. 2010;4(6):1540-62.
  41. Lucarelli F, Ricci F, Caprio F, et al. GlucoMen Day continuous glucose monitoring system: a screening for enzymatic and electrochemical interferents. J Diabetes Sci Technol. 2012;6(5):1172-81.
  42. Klonoff DC, Buckingham B, Christiansen JS, Montori VM, Tamborlane WV, Vigersky RA, Wolpert H, Endocrine Society. Con- tinuous glucose monitoring: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96(10):2968-79.

Cited by

Sorted by citations

Authors
Radin, M. S.
Affiliations
Winthrop-University Hospital (US)
Corresponding author
Radin, Michael S.
Venue
Journal of General Internal Medicine
Publisher
Springer Science and Business Media LLC
Published
2013-09-04
Volume
29
Issue
2
Pages
388-394
ISSN
  • 0884-8734 (ISSN-L)
  • 1525-1497
DOI
10.1007/s11606-013-2595-x
PMC
PMC3912281
OpenAlex
W1970777186
Cited by
361
References
9
Citations by year
2026: 43 · 2025: 37 · 2024: 46 · 2023: 36 · 2022: 35 · 2021: 44 · 2020: 43 · 2019: 25 · 2018: 21 · 2017: 15 · 2016: 8 · 2015: 4 · 2014: 2 · 2013: 1
FWCI
3.48
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Journal of General Internal Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
Keywords
HbA1c, glycemic control monitoring, diabetes diagnosis, false results, interfering factors, laboratory biomarkers, diabetes mellitus
MeSH terms
Blood Glucose, Diabetes Mellitus, Type 2, Female, Glycated Hemoglobin, Humans, Middle Aged, Biomarkers

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review