A1C Diagnostic Threshold for Diabetes
An A1C level of ≥6.5% (48 mmol/mol) is diagnostic of diabetes. 1
Diagnostic Criteria
The American Diabetes Association established A1C ≥6.5% as one of the acceptable criteria for diagnosing diabetes in 2010, and this remains the current standard. 1 This threshold was selected based on its relationship to microvascular complications, particularly retinopathy risk.
Confirmation Requirements
In the absence of unequivocal hyperglycemia (random glucose >200 mg/dL with classic symptoms), diagnosis requires two abnormal test results. 1
The confirmation can come from:
If discordant results occur between two different tests, repeat the test that exceeded the diagnostic threshold. 1
If A1C confirms diabetes but glucose does not (or vice versa), the patient should still be considered diabetic based on the confirmed abnormal test. 1
Test Performance Characteristics
A1C ≥6.5% demonstrates high specificity (97-98%) but moderate sensitivity (47-67%) for detecting diabetes compared to glucose-based criteria. 2 This means:
- A1C will miss some individuals who meet glucose-based diabetes criteria (lower sensitivity) 2
- When A1C is elevated ≥6.5%, diabetes is highly likely (high specificity) 2
- Against repeated fasting glucose measurements, A1C sensitivity improves to 67% while maintaining 97% specificity 2
Critical Clinical Caveats
When A1C Should NOT Be Used
A1C is unreliable and should not be used for diagnosis in these conditions: 1
- Sickle cell disease
- Pregnancy (second and third trimesters)
- Glucose-6-phosphate dehydrogenase deficiency
- Hemodialysis
- Recent blood loss or transfusion
- Erythropoietin therapy
- Postpartum state
- HIV treated with certain drugs
- Iron-deficiency anemia
In these situations, use only plasma glucose criteria for diagnosis. 1
Prediabetes Range
For context, A1C of 5.7-6.4% defines prediabetes (increased diabetes risk). 3 Individuals with A1C 6.0-6.4% have particularly high risk, with 25-50% developing diabetes within 5 years. 3
Prognostic Value of Combined Testing
When both A1C ≥6.5% AND fasting glucose ≥126 mg/dL are present, the 10-year risk of diagnosed diabetes is 88%, compared to only 55% when fasting glucose alone is elevated but A1C is 5.7-6.4%. 2 This supports using both tests when feasible for risk stratification.
Practical Algorithm
- Measure A1C in patients being evaluated for diabetes
- If A1C ≥6.5%: Repeat A1C or perform fasting glucose to confirm diagnosis 1
- If A1C 5.7-6.4%: Diagnose prediabetes and initiate prevention strategies 3
- If conditions affecting red blood cell turnover exist: Skip A1C entirely and use glucose-based testing 1
- If results are near diagnostic margins: Discuss symptoms with patient and retest in 3-6 months 1