What is the preferred diagnostic test for diabetes, a one-hour glucose tolerance test (GTT) or an A1c test?

Diagnostic Testing for Diabetes: OGTT vs. A1C

The oral glucose tolerance test (OGTT) is considered a first-line diagnostic test for diabetes, with the 2-hour plasma glucose measurement being the reference standard against which other tests are compared. 1

Comparison of Diagnostic Tests

Oral Glucose Tolerance Test (OGTT)

• Considered the reference standard for diagnosing diabetes 1
• Higher sensitivity for detecting diabetes compared to A1C
• 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) is diagnostic
• Recent evidence supports the value of 1-hour plasma glucose during OGTT:
  • 1-hour plasma glucose ≥11.6 mmol/L has excellent sensitivity (92%) and specificity (91%) for detecting type 2 diabetes 2
• Limitations:
  • Poor reproducibility
  • Requires patient fasting for 8 hours
  • Requires 75g glucose load followed by blood draw 2 hours later
  • Less convenient for patients 1

A1C Testing

• Advantages:
  • Greater convenience (no fasting required)
  • Greater preanalytical stability
  • Less day-to-day perturbations during stress, illness, or dietary changes 1
• Limitations:
  • Lower sensitivity compared to OGTT
  • A1C ≥6.5% identifies one-third fewer cases of undiagnosed diabetes than fasting glucose criteria 1
  • Unreliable in conditions with altered red blood cell turnover (hemoglobinopathies, pregnancy, anemia, hemodialysis, etc.) 1, 3
  • Racial/ethnic variations can affect results 1

Current Diagnostic Criteria

According to the American Diabetes Association (ADA) guidelines, diabetes may be diagnosed based on any of the following criteria 1:

1. A1C ≥6.5% (48 mmol/mol)
2. Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L)
3. 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during OGTT
4. Random plasma glucose ≥200 mg/dL (11.1 mmol/L) with classic symptoms of hyperglycemia

In the absence of unequivocal hyperglycemia, diagnosis requires two abnormal test results from the same sample or in two separate test samples 1.

Diagnostic Algorithm

1. Initial Assessment:

   • For patients with risk factors for diabetes, either OGTT or A1C can be used
   • OGTT is preferred when maximum sensitivity is required
   • A1C is preferred when convenience is prioritized

2. Special Populations - Use OGTT only:

   • Patients with hemoglobinopathies (sickle cell disease/trait)
   • Pregnancy (second and third trimesters)
   • Anemia or conditions with abnormal red cell turnover
   • Hemodialysis patients
   • Recent blood loss, transfusion, or erythropoietin therapy 1, 3

3. Confirmation:

   • If initial test is positive, confirm with a second test
   • Preferably use the same test for confirmation
   • If two different tests both show results above diagnostic thresholds, diagnosis is confirmed 1

Clinical Implications

• The OGTT detects more cases of early diabetes and impaired glucose tolerance than fasting glucose or A1C alone 4
• Studies show that more diabetic patients are identified from populations with normal fasting glucose than from those with impaired fasting glucose 4
• The 2-hour glucose value during OGTT appears crucial as a diagnostic tool 4
• A1C testing may miss approximately one-third of diabetes cases that would be detected by glucose criteria 1, 5

Common Pitfalls to Avoid

• Relying solely on A1C in patients with conditions affecting red blood cell turnover
• Using point-of-care A1C testing for diagnostic purposes (not standardized)
• Failing to confirm abnormal results with a second test
• Overlooking discordance between A1C and glucose-based tests, which may indicate hemoglobin variants or other interfering factors
• Not ensuring adequate carbohydrate intake (at least 150g/day) for 3 days prior to OGTT testing 1

In conclusion, while both tests have their place in diabetes diagnosis, the OGTT remains the reference standard with higher sensitivity, particularly when the 2-hour plasma glucose measurement is used. The A1C offers convenience but at the cost of lower sensitivity and reliability in certain populations.