The hemoglobin A1C (HbA1c) test has become one of the cornerstones of modern diabetes management. It provides a long-term picture of blood sugar control, averaging glucose levels over a two- to three-month period. Unlike a single glucose test, which reflects one moment in time, A1C captures the broader story of how well diabetes is being managed day-to-day.
A recent article by the Association for Diagnostics & Laboratory Medicine (ADLM) highlights a growing need to better understand what A1C really measures—and where it can be misleading. For patients and providers alike, understanding these nuances is essential to avoid misinterpretation and guide better care.
What the A1C Test Actually Measures
Hemoglobin A1C reflects the percentage of hemoglobin molecules in red blood cells that have glucose attached to them. Since red blood cells live for about 120 days, A1C values represent the average exposure of these cells to glucose during that lifespan.
The American Diabetes Association (ADA) recommends using an HbA1c level of 6.5% or higher as one diagnostic threshold for diabetes. Lowering A1C levels through medication, diet, and lifestyle changes can help reduce the risk of complications like kidney disease, neuropathy, and cardiovascular events.
However, while A1C is a valuable clinical tool, it is not perfect—and several factors can distort its accuracy.
Why A1C Results Can Be Misleading
1. Differences Between Laboratory Methods
Not all A1C tests are performed the same way. Laboratories use a variety of techniques—each with its own strengths and vulnerabilities:
- Charge-based methods (such as HPLC or electrophoresis) separate hemoglobin molecules based on their electrical charge. These can sometimes misidentify common hemoglobin variants, leading to inaccurate results.
- Immunoassays, which use antibodies to detect glycated hemoglobin, are widespread but can be affected by elevated levels of fetal hemoglobin (HbF) or structural hemoglobin variants.
- Boronate affinity chromatography (BAC) is more specific and less affected by interference.
- Mass spectrometry remains the most accurate, but it is expensive and mainly used as a reference method rather than in routine testing.
- Point-of-care (POC) A1C devices, often used in clinics, offer rapid results but vary in precision and may not meet diagnostic accuracy standards.
Even when performed correctly, results from different labs may vary slightly. The ADLM notes that most laboratories strive for a coefficient of variation (CV) below 1.5% within the same lab and under 2.5% across different labs.
2. Biological Factors That Affect Accuracy
Even with ideal laboratory practices, individual biology can still distort A1C readings.
- Shortened red blood cell lifespan – Conditions like hemolytic anemia or recent blood loss can falsely lower A1C because red blood cells have less time to accumulate glucose.
- Prolonged red blood cell lifespan – In kidney disease or after transfusion, A1C may appear falsely elevated.
- Hemoglobin variants and elevated HbF – Certain genetic conditions change the structure of hemoglobin and interfere with test results.
- Comorbidities and medications – Liver disease, iron or B12 deficiency, alcoholism, and high doses of vitamin C or E can all alter results.
In these cases, clinicians may rely on alternative glycemic markers such as fructosamine or glycated albumin, which better reflect short-term glucose control and aren’t affected by red blood cell turnover.
A1C in Context: How Clinicians and Patients Can Interpret It More Wisely
For healthcare professionals, an A1C test is not just a number—it’s a data point that must be viewed in context. If a patient’s A1C seems inconsistent with their daily glucose readings, or if it shifts unexpectedly after a blood transfusion or new medication, further investigation is warranted.
When reviewing trends, clinicians are advised to:
- Consider laboratory method consistency over time.
- Recognize the possibility of biological interference.
- Use complementary measures like self-monitoring, continuous glucose monitoring (CGM), or fructosamine testing when appropriate.
For patients, the takeaway is simple but important: A1C is a guide, not a grade. A slightly higher or lower value does not always mean your management plan is failing or succeeding. Communicating with your care team about health changes, medications, or unusual results is key to avoiding confusion.
The Future of A1C and Glycemic Monitoring
As testing technologies improve, more standardized methods are reducing variability between laboratories. Meanwhile, innovations in continuous glucose monitoring (CGM) are helping clinicians correlate A1C with real-time data more effectively.
The ADLM’s recent insights underscore that A1C remains invaluable for both diagnosing and managing diabetes—but it should never be interpreted in isolation. Accurate diagnosis depends on using the right testing methods, understanding biological influences, and maintaining clear communication between labs, clinicians, and patients.
Key Takeaways
- A1C provides a long-term picture of glucose control but can be influenced by both lab methods and individual biology.
- Different assays yield slightly different results, so consistent testing methods are important.
- Certain health conditions or medications can falsely raise or lower A1C values.
- Alternative markers like fructosamine may offer more reliable data for some patients.
- Context matters—use A1C trends, not single results, to guide care.
Source:
Navigating Hemoglobin A1C Measurements for Diabetes Care. Clinical Laboratory News, September–October 2025. Association for Diagnostics & Laboratory Medicine (ADLM).
https://myadlm.org/cln/articles/2025/septemberoctober/navigating-hemoglobin-a1c-measurements-for-diabetes-care
