HbA1c Diagnostic Thresholds for Diabetes and Prediabetes
An HbA1c of ≥6.5% (≥48 mmol/mol) indicates diabetes, while values between 5.7-6.4% (39-46 mmol/mol) indicate prediabetes or high risk for developing diabetes. 1
Diagnostic Categories
The American Diabetes Association establishes clear HbA1c thresholds using NGSP-certified laboratory methods 1:
- Normal: <5.7% (<39 mmol/mol) 1
- Prediabetes: 5.7-6.4% (39-46 mmol/mol) 1
- Diabetes: ≥6.5% (≥48 mmol/mol) 1
The normal reference interval for HbA1c centers around a mean of 5% (31 mmol/mol), typically ranging from 4.5-5.6% 1. Many laboratories have lowered the upper limit of the reference interval to 5.6% 1.
Prediabetes Risk Stratification
Not all prediabetes values carry equal risk—the relationship between HbA1c and diabetes progression is a continuum with disproportionately greater risk at higher values. 1, 2
- HbA1c 5.7-6.0%: 5-year diabetes incidence of 9-25%, representing 3-8 fold higher risk than the general population 1
- HbA1c 6.0-6.4%: 5-year diabetes incidence of 25-50%, with relative risk 20 times higher compared to HbA1c of 5.0% 1, 2
Individuals with HbA1c >6.0% should be considered at very high risk and warrant the most intensive interventions and vigilant follow-up 1, 2.
Confirmation Requirements
For diabetes diagnosis, confirmation with a second HbA1c test on a different sample or a glucose-based test is recommended. 1, 3
Testing must be performed using an NGSP-certified method in an accredited laboratory 1, 2. Point-of-care HbA1c devices should be restricted to FDA-approved devices at CLIA-certified laboratories performing moderate complexity testing or higher, and should not be used for initial diagnosis 1.
Clinical Advantages of HbA1c Testing
HbA1c reflects average glucose levels over the preceding 60-90 days based on the 120-day lifespan of red blood cells 1, 3. The test offers several technical advantages over glucose-based testing 1, 3:
- Greater preanalytical stability (no fasting required)
- Lower biological variability
- No need for glucose loading
- Increased patient convenience and adherence
Important Caveats and Limitations
Laboratories must be aware of potential interferences that can affect HbA1c results depending on the assay method used. 1
Conditions that can interfere with HbA1c measurements include 4:
- Anemia
- Hemoglobinopathies (hemoglobin variants)
- Uremia
- Red blood cell destruction
Laboratories should verify by repeat testing any specimens with HbA1c results below the lower limit of the reference interval or greater than 15% 1. Results less than 4% or greater than 15% should prompt investigation for hemoglobin variants 1.
Small changes in HbA1c (±0.3%) over time may reflect assay variability rather than true changes in glycemic status 1.
Sensitivity Limitations for Prediabetes
While HbA1c performs well for diabetes diagnosis, it has modest sensitivity for identifying prediabetes and will miss a substantial proportion of individuals with impaired fasting glucose or impaired glucose tolerance. 5, 6
Research demonstrates that HbA1c 5.7-6.4% alone identifies only 28.5-65.3% of patients with glucose-defined prediabetes 5. The combination of both HbA1c and fasting plasma glucose testing identifies individuals at highest risk for progression to diabetes more effectively than either test alone 6.