hemoglobin A1c in red blood cells (Tina-quant HbA1cDx)
Indications
- assessment of glycemic control in patients with diabetes mellitus
- measure every 6 months[14]
- every 3 months if treatment is being adjusted to optimize glycemic control[11]
- measure every 6 months[14]
- evaluation of complications of diabetes mellitus
- diagnosis of diabetes mellitus
- used to estimate of average glucose concentration over the life span of erythrocytes (3 months)
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
- for each 1% increase in HgbA1c[1]
- risk of coronary artery disease increases* (RR = 1.2-1.3)
- risk of peripheral vascular disease increases (RR = 1.3)
- risk for stroke increases (RR = 1.2)
- risk of fatal myocardial infarction increases (RR = 1.2)
* significant for diabetes mellitus type 2, but not diabetes mellitus type 1
- variability in HgbA1c < 8% associated with increased risk of dementia[23]
- relative to A1c < 6%, risk (RR) of kidney disease is 2.5 fold for A1c 7-8% & 3.7 fold for A1C > 8%[5]
- HgbA1c 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
- diabetes mellitus
- postprandial hyperglycemia may account for differences in HgbA1c with average of blood glucose measurements by glucometer[11][12]
- uremia may increase hemoglobin A1c in some assays[11]
- increased erythrocyte survival due to:
- malondialdehyde, increased in iron deficiency anemia, enhances glycation of hemoglobin[22]
- chronic alcohol consumption results in formation of a hemoglobin-acetaldehyde compound (false elevation)[22]
Decreases
- erythrocyte transfusion[10]
- improved glycemic control
- hemolytic anemia (diminished half-life of erythrocytes)
- acute & chronic blood loss
- diminished half-life of erythrocytes & increased erythropoiesis with reticulocytosis due to erythropoiesis-stimulating agents may diminish hemoglobin A1c[11][16][22]
- iron supplementation[16]
- chronic kidney disease: anemia, erythopoietin use, transfusions[11]
- sickle-cell trait (5% decrease)[17]
- erythrocytes may have a shorter lifespan, allowing less time for glycation, thus reduced HbA1c
- other hemoglobinopathies[22]
- cirrhosis, alcoholic liver disease: hypersplenism
- pregnancy increases erythropoietin, decreases RBC survival
- myelodysplastic syndrome:[22]
- diminished half-life of erythrocytes, blood transfusions
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.
Notes
- if HgbA1c is unreliable (see Increases: & Decreases:), measure glycated albumin (fructosamine) in serum[22]
- measure glycated albumin when hemoglobinopathy or hemolytic anemia is suspected for incorrect hemoglobin A1c readings
- 2-hour postprandial glucose is 1st test (see glycemic control)
More general terms
Additional terms
- A1cNow
- ChoiceDM A1C Home Test
- glycemic control
- hemoglobin A1c in red blood cells (Tina-quant HbA1cDx)
Component of
References
- ↑ 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 - ↑ Bio-Rad
- ↑ 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)
- ↑ 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
- ↑ 5.0 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
- ↑ 6.0 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
- ↑ 7.0 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
- ↑ Mini Panel of 2 tests: Estimated Averge Glucose . Hemoglobin A1C Laboratory Test Directory ARUP: http://www.aruplab.com/guides/ug/tests/0070426.jsp
- ↑ 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
- ↑ 10.0 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
- ↑ 11.0 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 - ↑ 12.0 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
- ↑ 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
- ↑ 14.0 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 - ↑ 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
- ↑ 16.0 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
- ↑ 17.0 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 - ↑ 18.0 18.1 Monaco K FDA Clears 'Painless' Blood Draw. MedPage Today. Feb 27, 2017 http://www.medpagetoday.com/Endocrinology/Diabetes/63431
- ↑ 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 - ↑ Sacks DB. A1C versus glucose testing: a comparison. Diabetes Care. 2011 Feb;34(2):518-23. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21270207 Free PMC Article
- ↑ 21.0 21.1 Conlin PR, Colburn J, Aron D, Pries RM, Tschanz MP, Pogach L. Synopsis of the 2017 U.S. Department of Veterans Affairs/U.S. Department of Defense clinical practice guideline: Management of type 2 diabetes mellitus. Ann Intern Med 2017 Oct 24 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29059687
- ↑ 22.0 22.1 22.2 22.3 22.4 22.5 22.6 22.7 Pant V HbA1c Below the Reportable Range. Lab Med. 2022;53(2):e44-e47. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34611711 https://www.medscape.com/viewarticle/970349
- ↑ 23.0 23.1 Moran C et al HbA1c variability associated with dementia risk in people with type 2 diabetes. Whitmer RA, Dove Z et al Alzheimers Dement. 2024 Jul 3. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38959429 https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.14066