What A1c (glycated hemoglobin) level is diagnostic for type 2 diabetes?

Diagnostic A1C Threshold for Type 2 Diabetes

An A1C level of 6.5% (48 mmol/mol) or higher is diagnostic for type 2 diabetes when performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay. 1

Diagnostic Criteria for Type 2 Diabetes

The American Diabetes Association (ADA) guidelines clearly establish the following criteria for diagnosing diabetes:

1. A1C ≥ 6.5% (48 mmol/mol)

   • Test must be performed in a laboratory using NGSP certified method
   • Standardized to the DCCT assay

2. Alternative diagnostic criteria (any one of these is also diagnostic):

   • Fasting plasma glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L) after at least 8 hours of fasting
   • 2-hour plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during oral glucose tolerance test
   • Random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) in patients with classic symptoms of hyperglycemia 1

Confirmation Requirements

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

• It is recommended that the same test be repeated or a different test be performed without delay using a new blood sample
• For example, if A1C is 7.0% and a repeat result is 6.8%, the diagnosis of diabetes is confirmed
• If two different tests (such as A1C and FPG) are both above the diagnostic threshold, this also confirms the diagnosis 1

Prediabetes Range

The ADA defines prediabetes as:

• A1C 5.7–6.4% (39–47 mmol/mol) 1
• This range identifies individuals at high risk for diabetes and cardiovascular outcomes

Important Considerations When Using A1C for Diagnosis

Several factors can affect A1C measurement and interpretation:

1. Hemoglobinopathies: Hemoglobin variants can interfere with A1C measurement. Marked discrepancies between measured A1C and plasma glucose levels should prompt consideration that the A1C assay may not be reliable for that individual. 1

2. Race/Ethnicity: A1C levels may vary with race/ethnicity independently of glycemia. For example:

   • African Americans may have higher A1C levels than non-Hispanic whites with similar glucose levels
   • African Americans heterozygous for HbS may have lower A1C by about 0.3% 1

3. Red Blood Cell Turnover: In conditions with increased red blood cell turnover (sickle cell disease, pregnancy, hemodialysis, blood loss, transfusion, erythropoietin therapy), only plasma glucose criteria should be used to diagnose diabetes. 1

4. Age: The epidemiological studies that formed the basis for recommending A1C to diagnose diabetes included only adult populations. 1

Clinical Approach to Diagnosis

When evaluating a patient for possible diabetes:

1. Obtain A1C measurement from a reliable laboratory
2. If A1C ≥ 6.5%, either:
   • Repeat A1C test for confirmation, or
   • Confirm with an alternative test (FPG or OGTT)
3. If results are discordant, repeat the test that is above diagnostic threshold
4. For patients with test results near diagnostic thresholds, follow closely and repeat testing in 3-6 months

Common Pitfalls to Avoid

• Relying on point-of-care A1C testing for diagnosis: These are not standardized for diagnostic purposes
• Failing to confirm borderline results: Unless classic symptoms are present, confirmation is required
• Ignoring factors that affect A1C reliability: Hemoglobinopathies, anemia, and other conditions can affect results
• Not considering alternative diagnostic criteria: In situations where A1C may be unreliable, use glucose-based criteria

The diagnostic threshold of A1C ≥ 6.5% has been established based on the inflection point for increased risk of microvascular complications, particularly retinopathy, which aligns with similar thresholds observed for FPG and 2-hour PG values.