At what Hemoglobin A1c (HbA1c) level can diabetes be diagnosed?

Diagnosis of Diabetes Using HbA1c

Diabetes can be definitively diagnosed with an HbA1c value of ≥6.5% (≥48 mmol/mol) when measured using a standardized, NGSP-certified laboratory method. 1

Diagnostic Criteria for Diabetes

The American Diabetes Association (ADA) has established the following diagnostic criteria for diabetes:

• HbA1c ≥6.5% (≥48 mmol/mol) using a method that is NGSP certified and standardized to the DCCT assay 1
• Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L) after at least 8 hours of fasting 1
• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test (OGTT) 1
• Random plasma glucose ≥200 mg/dL (11.1 mmol/L) in patients with classic symptoms of hyperglycemia or hyperglycemic crisis 1

Confirmation Requirements

Unless there is a clear clinical diagnosis (e.g., patient with hyperglycemic crisis or classic symptoms with random glucose ≥200 mg/dL), a second test is required for confirmation 1:

• Ideally, the same test should be repeated for confirmation
• If two different tests (e.g., HbA1c and FPG) are both above diagnostic thresholds, this also confirms the diagnosis
• When results are discordant, the test that is above the diagnostic threshold should be repeated

Advantages of Using HbA1c for Diagnosis

• Greater convenience (no fasting required)
• Better preanalytical stability
• Less day-to-day perturbations during periods of stress and illness 1
• Reflects average glycemia over the preceding 60-90 days 1

Limitations and Precautions

HbA1c testing should not be used for diagnosis in the following situations:

• Conditions with abnormal red blood cell turnover:
  • Pregnancy (second and third trimesters)
  • Hemolytic anemia
  • Recent blood loss or transfusion
  • Hemodialysis
  • Erythropoietin therapy 1
• Hemoglobinopathies (use assays without interference or use glucose criteria instead)
• Marked discordance between measured A1C and plasma glucose levels 1

Prediabetes Classification

Individuals with HbA1c levels between 5.7% and 6.4% (39-46 mmol/mol) are classified as having prediabetes 1, 2:

• HbA1c 5.7-6.0%: 3-8 fold increased risk of developing diabetes 2
• HbA1c 6.0-6.4%: approximately 20 times higher risk of developing diabetes 2

Testing Considerations

• Only NGSP-certified methods should be used for diagnosis 1
• Point-of-care HbA1c testing should not be used for diagnosis unless using FDA-approved devices at CLIA-certified laboratories that perform testing of moderate complexity or higher 1
• Laboratory standardization is critical for accurate diagnosis 1

Clinical Pearls

• The HbA1c cut-off of 6.5% has high specificity but lower sensitivity compared to glucose-based criteria 3
• When using HbA1c for diagnosis, approximately one-third fewer cases of undiagnosed diabetes are identified compared to using fasting glucose criteria 1
• However, the greater convenience of HbA1c testing may lead to wider application and potentially increase the overall number of diagnoses 1
• Marked discrepancies between measured HbA1c and plasma glucose levels should prompt consideration that the HbA1c assay may not be reliable for that individual 1

By understanding these diagnostic criteria and their limitations, clinicians can appropriately diagnose diabetes using HbA1c while recognizing situations where glucose-based testing may be more appropriate.