hemoglobin A1c in red blood cells (Tina-quant HbA1cDx)

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Indications

Reference interval

  • normal: < 6.0% (5.7%)
  • target based on health status:[11]
    • < 7.0% if mild or no microvascular complications & life expectancy > 10 years
    • 7%-8.5% if microvascular or macrovascular complications, comorbid conditions, or life expectancy of 5-10 years
    • 8%-9% if advanced microvascular or macrovascular complications, severe comorbid conditions, difficulties with self-management, or life expectancy < 5 years[21]

Average serum glucose value estimated from Hgb A1c[11]

Hgb A1c glucose (mg/dL)
6% 126
7% 154
8% 180
9% 210
10% 240
11% 270
12% 300
13% 330

* for discrepancy in fasting glucose values with HbA1c see glycemic control

comments

  • variability in serum glucose increases HbA1c for any given average glucose level[6] does not rise as steeply as it does for fasting plasma glucose increments below that threshold[7]
  • at any given level of fasting serum glucose, HbA1c will likely be lower in patients who take oral hypoglycemics, compared with untreated patients[7]

Principle

Hemoglobin A1c (HbA1), or glycosylated hemoglobin, is a modified form of adult hemoglobin (HbA). Hemoglobin A1 is also known as 'fast' hemoglobin because, under the right conditions, it will move down a cation exchange resin column at a quicker rate than HbA. Hemoglobin A makes up over 90% of the total hemoglobin in a normal adult. Hemoglobin A1 is a minor hemoglobin & is composed of at least 3 subfractions--HbA1a, HbA1b & HbA1c. These 3 subfractions account for ~7% of the total hemoglobin in the normal adult with HbA1c being the major subfraction. Levels of the 3 subfractions are increased proportionately in diabetes mellitus where they may double, or even triple, depending upon the degree of glycemic control. Hemoglobin A1c is an objective test of glycemic control which is independent of patient cooperation, time of day, insulin administration, meals, or exercise, & provides the physician with an unbiased indication of the efficacy of prescribed therapy.

In the Bio-Rad Hemoglobin A1c by column assay, a small quantity of whole blood is mixed with a hemolysis reagent. The hemolysis reagent simultaneously lyses the red blood cells to free the contained hemoglobin & initiate the removal of the Schiff base. An aliquot of the hemolysate is then applied to a weakly acidic cation exchange resin in a disposable column. A low ionic strength borate/phosphate buffer reagent is then added to the column. This 1st buffer elutes the HbA1a & HbA1b & further dissociates the labile Schiff base (aldimine) fraction. The HbA1c is then eluted independently from the remaining hemoglobin fraction by the addition of the second elution/developing reagent.

While the hemoglobin fractions are being separated, a total hemoglobin tube is prepared by mixing an aliquot of the hemolysate with the second elution developing reagent. After collecting the column eluate containing the glycosylated Hemoglobin A1c, the relative % concentrations of total hemoglobin & HbA1c are determined spectrophotometrically at 415 nm.

Clinical significance

* significant for diabetes mellitus type 2, but not diabetes mellitus type 1

relative to A1c < 6%, risk (RR) of kidney disease is 2.5 fold for A1c 7-8% & 3.7 fold for A1C > 8%[5]

HbA1c levels at which the risk for retinopathy begins to increase are lower in black adults than in white adults[9] (5.5% vs 6.0%)

average HbA1c levels are 0.4% higher for black people than white people for any given mean serum glucose

in higher range, difference may be greater 9.1% vs 8.3%[19]

Increases

Decreases

Specimen

No special patient preparation is required. At least 100 uL of venous blood is required for this test. The whole blood specimens should be collected in a vacuum blood collection tube containing an anticoagulant & thoroughly mixed. Tubes containing EDTA or potassium oxalate & sodium fluoride are acceptable. The specimens may be stored up to seven (7) days at 2-8 degrees C. Heparinized samples are less stable & should be assayed within two days when stored at 2-8 degrees C. Avoid hemolysis with all anticoagulants. Specimens containing EDTA have been frozen at -20 C & found to be stable for 15 days.

  • push-button device collects 100 uL of blood from upper arm
    • device billed as "virtually painless"
    • FDA cleared for use with HgbA1c measurement[18]

Notes

More general terms

Additional terms

Component of

References

  1. 1.0 1.1 Journal Watch 24(21):159, 2004
    Selvin E, Marinopoulos S, Berkenblit G, Rami T, Brancati FL, Powe NR, Golden SH. Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med. 2004 Sep 21;141(6):421-31. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15381515
    Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N. Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk. Ann Intern Med. 2004 Sep 21;141(6):413-20. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15381514
    Gerstein HC. Glycosylated hemoglobin: finally ready for prime time as a cardiovascular risk factor. Ann Intern Med. 2004 Sep 21;141(6):475-6. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15381522
  2. Bio-Rad
  3. Qaseem A, Vijan S, Snow V, Cross JT, Weiss KB, Owens DK; Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Glycemic control and type 2 diabetes mellitus: the optimal hemoglobin A1c targets. A guidance statement from the American College of Physicians. Ann Intern Med. 2007 Sep 18;147(6):417-22. Summary for patients in: Ann Intern Med. 2007 Sep 18;147(6): I52. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/17876024 <Internet> http://www.annals.org/cgi/content/abstract/147/6/417?etoc (Corresponding NGC guideline withdrawn Dec 2012)
  4. Prescriber's Letter 15(8): 2008 COMMENTARY: A1c: How Low Should You Go? GUIDELINES: ADA Position Statement on Standards of Medical Care in Diabetes - 2008 GUIDELINES: CDA Clinical Practice Guidelines on Monitoring Glycemic Control Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=240801&pb=PRL (subscription needed) http://www.prescribersletter.com
  5. 5.0 5.1 Bash LD et al, Poor glycemic control in diabetes and the risk of incident chronic kidney disease even in the absence of albuminuria and retinopathy. Atherosclerosis Risk in Communities (ARIC Study Ann Intern Med. 168(22):2440-2447, 2008 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19064828
  6. 6.0 6.1 Kuenen JC et al. Does glucose variability influence the relationship between mean plasma glucose and HbA1c levels in type 1 and type 2 diabetic patients? Diabetes Care 2011 Aug; 34:1843. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21700921
  7. 7.0 7.1 7.2 Ramachandran A et al. Relationship between A1C and fasting plasma glucose in dysglycemia or type 2 diabetes: An analysis of baseline data from the ORIGIN trial. Diabetes Care 2012 Apr; 35:749 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22323416
  8. Mini Panel of 2 tests: Estimated Averge Glucose . Hemoglobin A1C Laboratory Test Directory ARUP: http://www.aruplab.com/guides/ug/tests/0070426.jsp
  9. 9.0 9.1 Tsugawa Y et al Should the Hemoglobin A1c Diagnostic Cutoff Differ Between Blacks and Whites?: A Cross-sectional Study Annals of Internal Medicine August 7, 2012, Vol. 157. No. 3 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22868832 <Internet> http://annals.org/article.aspx?articleid=1305508
  10. 10.0 10.1 Spencer DH, Grossman BJ, Scott MG. Red cell transfusion decreases hemoglobin A1c in patients with diabetes. Clin Chem. 2011 Feb;57(2):344-6 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21059826
  11. 11.0 11.1 11.2 11.3 11.4 11.5 11.6 11.7 Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 18, 19. American College of Physicians, Philadelphia 2012, 2015, 2018, 2022
    Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  12. 12.0 12.1 Nathan DM, Kuenen J, Borg R, Zheng H et al Translating the A1C assay into estimated average glucose values. Diabetes Care. 2008 Aug;31(8):1473-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18540046
  13. FDA News Release: May 23, 2013 FDA allows marketing of first A1c test labeled for diagnosing diabetes. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm353653.htm
  14. 14.0 14.1 McCoy RG et al HbA1c overtesting and overtreatment among US adults with controlled type 2 diabetes, 2001-13: observational population based study. BMJ 2015;351:h6138 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26646052 <Internet> http://www.bmj.com/content/351/bmj.h6138
    Hayward RA Excessive testing of adults with type 2 diabetes. BMJ 2015;351:h6549 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26646164 <Internet> http://www.bmj.com/content/351/bmj.h6549
  15. Cowie CC, Rust KF, Byrd-Holt DD et al Prevalence of diabetes and high risk for diabetes using A1C criteria in the U.S. population in 1988-2006. Diabetes Care. 2010 Mar;33(3):562-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20067953 Free PMC Article
  16. 16.0 16.1 16.2 Ng JM, Cooke M, Bhandari S, Atkin SL, Kilpatrick ES The effect of iron and erythropoietin treatment on the A1C of patients with diabetes and chronic kidney disease. Diabetes Care. 2010 Nov;33(11):2310-3 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20798337 Free PMC Article
  17. 17.0 17.1 Lacy ME, Wellenius GA, Sumner AE et al Association of Sickle Cell Trait With Hemoglobin A1c in African Americans. JAMA. 2017;317(5):507-515 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28170479 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2600468
    Bleyer AJ, Aloi JA Sickle Cell Trait and Interpretation of Hemoglobin A1c Levels. JAMA. 2017;317(5):481-482 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28170462 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2600446
  18. 18.0 18.1 Monaco K FDA Clears 'Painless' Blood Draw. MedPage Today. Feb 27, 2017 http://www.medpagetoday.com/Endocrinology/Diabetes/63431
  19. 19.0 19.1 Bergenstal RM, Gal RL, Connor CG et al Racial Differences in the Relationship of Glucose Concentrations and Hemoglobin A1c Levels. Ann Intern Med. June 13, 2017. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28605777 <Internet> http://annals.org/aim/article/2631725/racial-differences-relationship-glucose-concentrations-hemoglobin-1c-levels
    Selvin E, Sacks DB Variability in the Relationship of Hemoglobin A1c and Average Glucose Concentrations: How Much Does Race Matter? Ann Intern Med. June 13, 2017. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28605752 <Internet> http://annals.org/aim/article/2631189/variability-relationship-hemoglobin-1c-average-glucose-concentrations-how-much-does
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Patient information

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