Things to Consider When Evaluating A1c Test Results

Hemoglobin A1c (known as A1c) is considered a cornerstone of diabetes diagnosis and management. However, one rule to remember that is most important is to "treat the patient, not just the number".

Hemoglobin A1c has many confounders that can alter, misrepresent or provide false or misleading results.

The Critical Role of Hemoglobin Variants

If you have any abnormal hemoglobins, it is vital to have your A1c levels analyzed by either an interference-free method or a specific method that detects silent variants such as abnormal hemoglobins.

In addition, it is important to confirm via a CBC that your red blood cells (RBCs) are normal in a specific range so as to rule out anemia (too few) or polycythemia (too many). In either case the A1c value can be altered by an abnormal RBC count. In one case reported lower than normal and the other reported higher than normal. This can result in an underestimate or overestimated A1c value.

In addition, giving blood can alter the A1c value. You should wait a full 90 days after giving blood or receiving a transfusion prior to a new A1c analysis.

The Danger of Non-FDA Approved Tests

Using a disposable A1c meter or a non-FDA approved Laboratory Developed Test (LDT) A1c test that is incapable of either detecting or compensating abnormal variants is known to have serious flaws resulting in a false A1c value.

In order to avoid a false A1c value, you should use a CLIA approved lab that is considered moderate complexity with an analytical method such as HPLC-IE that is FDA/OTC approved.

Comprehensive List of A1c Confounders

In addition, here are other confounders to consider when using A1c to judge the most recent inference of glycemic control (A1c) analysis:

• Use of steroids will increase the A1c level. It can take 90 days after discontinuing the use of these drugs to return to normal glycemic status.
• Anemia: Different types can affect the test. Iron deficiency anemia can lead to falsely elevated A1c levels, while conditions with rapid red blood cell turnover like hemolytic anemia can cause falsely lower results.
• Kidney failure can cause inaccurate results due to production of carbamylated hemoglobin, while chronic liver disease can lead to falsely lower results.
• Blood disorders that result in disturbed erythrocyte kinetics such as sickle cell anemia, thalassemia, and many other hemoglobinopathies can interfere with accurate test results.
• Pregnancy: The lifespan of red blood cells changes during pregnancy, making A1c results less reliable.
• Medications: Certain drugs, such as some HIV medications, opioids, and ribavirin/interferon-alpha, can interfere with A1c results. Administration of erythropoietin treatment can alter A1c results.
• Blood loss and transfusions: Recent blood loss or a blood transfusion can temporarily skew the A1c results.
• Vitamin deficiencies: Deficiencies in vitamins B12 or iron can impact A1c results.
• High doses of certain vitamins: Large doses of Vitamin C or E can cause falsely low readings with some measurement methods.
• Alcoholism (falsely increases)
• Use of anti-coagulant drugs (falsely lowers)
• EPO deficiency (lowers)
• Exposure to lead poisoning (increases)
• Cystic fibrosis (not useful)

Summary and Alternative Testing Options

A1c is an important tool in the diagnosis and management of diabetes. However, the clinician must consider any of the possible confounders that could affect the accuracy of the actual A1c value. If the A1c value as estimated by the eAG does not agree with the average daily glucose values, alternate means to measure the patient's glycemic average can be considered. These consist of:

• Fructosamine: Reflects average blood glucose over the past 2-3 weeks
• Glycated albumin: Another shorter-term glycemic marker
• CGM (Continuous Glucose Monitoring): Provides real-time glucose data and trends

The AccuBase Advantage

AccuBase A1c testing uses FDA-cleared HPLC-IE methodology that can detect and flag many hemoglobin variants, helping ensure you get accurate results even if you have variant hemoglobins. Our moderate complexity CLIA-certified laboratory follows strict quality protocols to minimize the impact of confounders on your results.

Remember: Understanding these potential confounders helps you and your healthcare provider interpret your A1c results more accurately. If you suspect any of these factors might be affecting your results, discuss them with your healthcare team.