What is A1C in Diabetes
A1C (Hemoglobin A1C) is a blood test that measures your average blood glucose levels over the past 2-3 months by detecting the percentage of hemoglobin that has glucose attached to it, and it serves as both a diagnostic tool for diabetes (≥6.5%) and a monitoring tool for glycemic control. 1
How A1C Works
- A1C reflects glucose bound to hemoglobin over the 120-day lifespan of red blood cells, providing a "weighted" average that is more heavily influenced by recent glucose exposure. 1
- The test measures chronic glycemia rather than acute glucose fluctuations, making it fundamentally different from fingerstick glucose measurements. 1
- A1C correlates well with both microvascular complications (like retinopathy) and, to a lesser extent, macrovascular complications. 1
Diagnostic Criteria for Diabetes
An A1C of ≥6.5% diagnoses diabetes when performed in a laboratory using a method certified by the National Glycohemoglobin Standardization Program (NGSP) and standardized to the Diabetes Control and Complications Trial (DCCT) assay. 1, 2
- In the absence of unequivocal hyperglycemia, the diagnosis requires confirmation with a repeat test (either another A1C or a glucose-based test). 1, 2
- The 6.5% threshold was chosen because it represents an inflection point where retinopathy prevalence begins to increase. 1
- An A1C of 5.7-6.4% indicates prediabetes and identifies individuals who would benefit from diabetes prevention interventions. 2, 3
Key Advantages Over Glucose Testing
- No fasting is required, making it far more convenient for patients than fasting plasma glucose or oral glucose tolerance tests. 1
- Greater preanalytical stability compared to glucose samples, which must be processed immediately or kept on ice to prevent glycolysis. 1
- Less day-to-day variability and unaffected by acute factors like recent food intake, stress, illness, or physical activity. 1
- Lower within-person variability compared to glucose measurements. 1
Critical Limitations and When NOT to Use A1C
In conditions with altered red blood cell turnover or hemoglobin variants, plasma glucose criteria must be used exclusively for diagnosis. 1
Conditions requiring glucose-based testing instead:
- Hemoglobinopathies (including sickle cell disease and sickle cell trait requiring interference-free assays). 1
- Pregnancy (second and third trimesters and postpartum period). 1
- Anemia from hemolysis or iron deficiency. 1
- Glucose-6-phosphate dehydrogenase deficiency. 1
- HIV infection, hemodialysis, recent blood loss or transfusion, or erythropoietin therapy. 1
Additional important caveats:
- In rapidly evolving type 1 diabetes in children, A1C may not be significantly elevated despite frank diabetes. 1
- Point-of-care A1C devices should NOT be used for diagnosis unless specifically FDA-approved for diagnostic purposes and performed in CLIA-certified laboratories of moderate complexity or higher. 1, 2
- A1C at the 6.5% threshold identifies only about 30% of diabetes cases that would be detected using all three criteria (A1C, fasting glucose, and 2-hour glucose) collectively. 1, 2
When to Suspect Test Interference
Evaluate for assay interference when there is consistent and substantial discordance between blood glucose values and A1C results. 1
- Marked discordance should prompt consideration of using an interference-free assay or relying on plasma glucose criteria instead. 2, 4
- Ethnic and racial variations in A1C levels can occur independently of glucose levels (for example, African Americans may have higher A1C levels than non-Hispanic Whites with similar glucose levels). 1, 4
Relationship to Average Glucose
- A1C can be translated into estimated average glucose (eAG) using the formula: eAG (mg/dL) = 28.7 × A1C - 46.7. 5
- This allows patients to understand their A1C in the same units they use for daily glucose monitoring. 5
- For example, an A1C of 7% corresponds to an estimated average glucose of approximately 154 mg/dL. 5