Does an HbA1c of 6.5% and a fasting plasma glucose of 7.5 mmol/L (≈135 mg/dL) meet diagnostic criteria for diabetes mellitus?

Diagnosis of Diabetes with HbA1c 6.5% and Fasting Glucose 7.5 mmol/L

Yes, this meets diagnostic criteria for diabetes mellitus. An HbA1c of exactly 6.5% (≥6.5%) is diagnostic for diabetes, and while the fasting plasma glucose of 7.5 mmol/L (135 mg/dL) falls below the 7.0 mmol/L (126 mg/dL) threshold, the HbA1c alone is sufficient to establish the diagnosis. 1

Diagnostic Criteria Met

The HbA1c of 6.5% meets the diabetes diagnostic threshold. According to current American Diabetes Association guidelines, an HbA1c value ≥6.5% (≥48 mmol/mol) measured by an NGSP-certified laboratory method is diagnostic of diabetes. 1

• The fasting glucose of 7.5 mmol/L (135 mg/dL) is elevated but does not reach the diagnostic threshold of ≥7.0 mmol/L (≥126 mg/dL) for diabetes. 1
• However, when one test meets diagnostic criteria, diabetes can be confirmed even if another test does not, provided the diagnostic test is repeated or confirmed. 1

Confirmation Requirements

The diagnosis should be confirmed with a repeat test before initiating treatment, unless the patient presents with classic symptoms of hyperglycemia or hyperglycemic crisis. 1

Confirmation Options:

• Repeat the HbA1c test on a different sample—if the second HbA1c is also ≥6.5%, diabetes is confirmed. 1
• Alternatively, perform a different glucose-based test (fasting glucose or 2-hour oral glucose tolerance test) to provide concordant evidence. 1
• If both the repeat HbA1c and the original HbA1c are ≥6.5%, the diagnosis is established regardless of the fasting glucose value. 1

Understanding the Discordance

The discordance between HbA1c and fasting glucose suggests post-prandial hyperglycemia. HbA1c reflects average glucose exposure over the preceding 2-3 months, integrating all daily glucose fluctuations including post-meal spikes, whereas fasting glucose captures only the basal state. 2, 3

• HbA1c weights glucose exposure 50% to the most recent month, 25% to 30-60 days prior, and 25% to 60-120 days prior, emphasizing recent glycemia and post-prandial excursions. 2, 4
• An HbA1c of 6.5% corresponds to an estimated average glucose of approximately 140 mg/dL (7.8 mmol/L), which is higher than the observed fasting value of 7.5 mmol/L (135 mg/dL). 2
• This pattern indicates that glucose levels are likely elevated significantly after meals, even though fasting levels remain relatively controlled. 3, 5

Important Caveats Before Finalizing Diagnosis

Rule out conditions that falsely elevate HbA1c before confirming diabetes, particularly if clinical suspicion is low:

• Iron deficiency anemia prolongs red blood cell survival, increasing glycation time and producing falsely elevated HbA1c. 3
• Hemoglobin variants (HbS, HbC, HbE) can cause spuriously high HbA1c depending on the assay method. 3
• African American ethnicity is associated with HbA1c values approximately 0.4% higher than white individuals at comparable glucose levels. 4, 3
• Age-related increases of approximately 0.1% per decade after age 30 occur even without diabetes. 4, 3

Recommended Screening:

• Obtain a complete blood count to detect anemia, particularly iron deficiency. 3
• Consider hemoglobin electrophoresis if hemoglobinopathy is suspected, especially in at-risk ethnic groups. 3
• Ensure the laboratory uses NGSP-certified HbA1c assays to avoid assay-related bias. 1, 3

Clinical Pitfalls to Avoid

• Do not dismiss the elevated HbA1c as "false" without evaluating post-prandial glucose, since post-prandial hyperglycemia is the most common true cause of HbA1c-fasting glucose discordance. 3
• Do not assume normal fasting glucose excludes diabetes—among individuals with HbA1c 6.0-7.0%, a substantial proportion meet diabetes criteria on oral glucose tolerance testing despite normal fasting values. 3, 5
• Using fasting glucose alone misses a significant proportion of diabetes cases—in screening studies, HbA1c ≥6.5% identifies approximately one-third fewer cases than fasting glucose ≥126 mg/dL, but conversely, fasting glucose alone misses many cases identified by HbA1c. 1, 2, 6

Practical Next Steps

1. Repeat the HbA1c test using an NGSP-certified laboratory method to confirm the diagnosis. 1
2. Obtain post-prandial glucose measurements (2-hour post-meal or 2-hour OGTT) to document the glucose elevations driving the elevated HbA1c. 3
3. Screen for conditions affecting HbA1c reliability with a complete blood count and assessment of renal function. 3
4. If HbA1c reliability is questionable due to anemia or hemoglobinopathy, rely on glucose-based criteria (fasting glucose, OGTT, or continuous glucose monitoring) for diagnosis. 1, 3