Hemoglobin A1c In Red Blood Cells

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Contents 1 Indications 2 Reference-interval 3 Principle 4 Clinical-significance 5 Increases 6 Specimen 7 More General Terms 8 Additional Terms 9 References

Indications

• assessment of glycemic control in patients with diabetes mellitus
• used to estimate of average glucose concentration over the life span of erythrocytes (3 months)

Reference-interval

• normal: < 6.0%
• target: < 7.0% (diabetes mellitus)
• high risk: > 8.5%

* Hgb A1c    glucose (mg/dL) 
*  6%          120  
*  7%          150 
*  8%          180 
*  9%          210 
* 10%          240 
* 11%          270 
* 12%          300 
* 13%          330

• Variability in serum glucose increases HbA1c for any given average glucose level [6]
• As fasting serum glucose increases above 162 mg/dL, HbA1c does not rise as steeply as it does for FPG 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
  
• relative to A1c < 6%, risk ( RR) of kidney disease is 2.5 fold for A1c 7-8% & 3.7 fold for A1C > 8% [5]

Increases

• diabetes mellitus

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.

More General Terms

• special chemistry test

Additional Terms

• A1cNow
• ChoiceDM A1C Home Test
• glycemic control
• hemoglobin A1c in red blood cells

References

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: [1]
   - 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: [2]
   - 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: [3]
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: [4] <Internet> [5]
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#: [6] (subscription needed) [7]
5. 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: [8]
6. 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: [9]
7. 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: [10]

hemoglobin A1c in red blood cells