What A1C value defines diabetes in a non‑pregnant adult when measured in an NGSP‑certified laboratory?

A1C Cutoff for Diabetes Diagnosis

An A1C value of ≥6.5% defines diabetes in non-pregnant adults when measured in an NGSP-certified laboratory. 1, 2, 3

Diagnostic Threshold and Laboratory Requirements

• The diagnostic cutoff is A1C ≥6.5% (≥48 mmol/mol), a threshold endorsed by the American Diabetes Association based on recommendations from an International Expert Committee. 1

• The test must be performed in a laboratory using a method certified by the National Glycohemoglobin Standardization Program (NGSP) and standardized or traceable to the Diabetes Control and Complications Trial (DCCT) reference assay. 1, 2

• Point-of-care A1C assays are not sufficiently accurate for diagnostic purposes and should never be used to diagnose diabetes. 1, 2, 3

Rationale for the 6.5% Threshold

• The 6.5% cutoff was selected because it corresponds to an inflection point for retinopathy prevalence, the same epidemiologic relationship seen with fasting plasma glucose ≥126 mg/dL and 2-hour glucose ≥200 mg/dL. 1

• This threshold reflects chronic glycemic exposure over 2–3 months and correlates well with both microvascular and macrovascular complications. 1

Confirmation Protocol

• In the absence of unequivocal hyperglycemia (such as hyperglycemic crisis with classic symptoms), an abnormal A1C result must be confirmed by repeat testing. 1, 2, 3

• The preferred approach is to repeat the same A1C test; if both results are ≥6.5%, diabetes is confirmed. 1, 2

• Alternatively, if two different tests (e.g., A1C ≥6.5% and fasting plasma glucose ≥126 mg/dL) both exceed their diagnostic thresholds, diabetes is confirmed without further testing. 1, 2, 3

• If results are discordant between two different tests, repeat the test that exceeded the diagnostic threshold to establish the diagnosis. 1

When A1C Should NOT Be Used

A1C is unreliable and should not be used for diagnosis in the following conditions:

• Hemoglobinopathies (e.g., sickle cell disease, sickle cell trait, HbS, HbC) that interfere with the assay—use an A1C method without hemoglobin interference if red cell turnover is normal, or rely exclusively on glucose criteria. 1, 2, 3

• Conditions with altered red blood cell turnover, including:

  • Pregnancy (second and third trimester) 2, 3
  • Recent blood loss or transfusion 1, 2, 3
  • Hemolytic anemia 1
  • Iron-deficiency anemia 1, 2
  • Hemodialysis 2, 3
  • Erythropoietin therapy 2, 3
  • G6PD deficiency 3

• In all these situations, use glucose-based diagnostic criteria exclusively: fasting plasma glucose ≥126 mg/dL (≥7.0 mmol/L) or 2-hour OGTT ≥200 mg/dL (≥11.1 mmol/L). 1, 2, 3

Alternative Glucose-Based Diagnostic Criteria

The following glucose thresholds remain valid and can be used instead of or alongside A1C:

• Fasting plasma glucose ≥126 mg/dL (7.0 mmol/L) after at least 8 hours of fasting. 1, 3

• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during a 75-gram oral glucose tolerance test. 1, 3

• Random plasma glucose ≥200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycemia (polyuria, polydipsia, unexplained weight loss) or hyperglycemic crisis. 1, 3

Advantages and Limitations of A1C

Advantages:

• Greater convenience—no fasting required. 1
• Greater preanalytical stability and less day-to-day variability during stress or illness compared to glucose measurements. 1
• Already familiar to clinicians as a marker of glycemic control. 1

Limitations:

• Lower sensitivity than fasting glucose: A1C ≥6.5% identifies approximately one-third fewer cases of undiagnosed diabetes than fasting glucose ≥126 mg/dL in population screening. 1
• Higher cost and limited availability in some regions. 1
• Incomplete correlation between A1C and average glucose in certain individuals. 1
• Can vary by ethnicity and is unreliable in conditions affecting red cell turnover. 1, 2, 3
• May not be significantly elevated in rapidly evolving type 1 diabetes in children despite frank hyperglycemia. 1

Common Pitfalls and How to Avoid Them

• Never diagnose diabetes on a single A1C value unless the patient is in hyperglycemic crisis with unequivocal symptoms. 2, 3

• Do not use point-of-care A1C devices for diagnosis—only certified laboratory methods are acceptable. 1, 2

• Always consider conditions that invalidate A1C (hemoglobinopathies, anemia, recent transfusion, pregnancy)—in these cases, switch to glucose criteria. 1, 2, 3

• Plasma glucose samples must be centrifuged and separated immediately after collection to prevent glycolysis, which causes falsely low results. 3

• If A1C and glucose results are markedly discordant, investigate for assay interference or conditions affecting red cell turnover. 2, 3

• For patients with test results near the diagnostic margin (e.g., A1C 6.4–6.6%), consider close follow-up and repeat testing in 3–6 months. 1