Best Test for Diagnosing Diabetes
For diagnosing diabetes in adults, use fasting plasma glucose (FPG) as your first-line test—it is faster, easier, more convenient, less expensive, and more acceptable to patients than alternatives. 1, 2
Primary Diagnostic Options
All three tests below are acceptable for diagnosing diabetes, but they differ in practicality 1:
- Fasting Plasma Glucose (FPG) ≥126 mg/dL (no caloric intake for ≥8 hours) 1, 3
- Hemoglobin A1C ≥6.5% (must be NGSP-certified and DCCT-standardized) 1, 3
- 2-hour Oral Glucose Tolerance Test (OGTT) ≥200 mg/dL (after 75g glucose load) 1, 3
- Random plasma glucose ≥200 mg/dL (only in patients with classic hyperglycemic symptoms) 1, 3
Why FPG is Preferred for Initial Testing
FPG wins on practical grounds 1, 2:
- No fasting required for A1C sounds convenient, but FPG is still faster to perform in clinical workflow
- FPG costs significantly less than A1C testing 1
- Patient acceptability is higher with FPG 1
- FPG has better reproducibility than OGTT 2
When A1C Becomes Problematic
A1C is unreliable and should NOT be used in these conditions 1, 2:
- Hemoglobinopathies (sickle cell disease, thalassemia)
- Pregnancy (second/third trimester and postpartum)
- Anemia or conditions with altered red cell turnover
- Recent blood loss or transfusion
- Hemodialysis patients
- Erythropoietin therapy
- Glucose-6-phosphate dehydrogenase deficiency
In these situations, use only plasma glucose criteria (FPG or OGTT). 1
Critical Testing Nuances
Racial/Ethnic Considerations
- African Americans may have A1C levels 0.3% higher than non-Hispanic Whites at the same glucose levels 1, 4
- Certain genetic variants (G6PD G202A) can lower A1C by 0.7-0.8% 1
- When A1C and glucose values are markedly discordant, trust the glucose measurement 1
Confirmation Requirements
In the absence of unequivocal hyperglycemia, you must confirm with repeat testing 1, 2:
- Repeat the same test on a different day (preferred approach) 1
- If two different tests both exceed diagnostic thresholds, diabetes is confirmed 1
- If results are discordant between tests, repeat the abnormal test 1
The OGTT: When to Use It
Reserve OGTT for specific scenarios 1, 3:
- When FPG is <126 mg/dL but clinical suspicion remains high 1
- The 2-hour value diagnoses more people with diabetes than FPG or A1C alone 1
- Requires adequate carbohydrate intake (≥150g/day) for 3 days prior to testing 1, 5
OGTT is more cumbersome: it takes 2+ hours, requires patient preparation, and has poor patient acceptability compared to FPG 1
Common Pitfalls to Avoid
Glucose Sample Handling
- Plasma must be separated immediately or kept on ice to prevent glycolysis 5, 3
- Glucose has poor preanalytical stability compared to A1C 1, 6
- This is why many labs reject improperly handled glucose samples
Point-of-Care A1C Testing
- Do NOT use point-of-care A1C for diagnosis 1
- POC assays lack mandated proficiency testing 1
- Only laboratory-based, NGSP-certified methods are acceptable for diagnosis 1
The A1C Advantage Myth
While A1C doesn't require fasting and has better preanalytical stability 1, 6, these advantages are offset by:
- Higher cost 1
- Limited availability in some settings 1
- Incomplete correlation with average glucose in certain individuals 1
- Multiple conditions that invalidate results 1
Practical Algorithm
- Start with FPG in most adults 1, 2
- If FPG ≥126 mg/dL: Repeat on different day to confirm (unless patient has classic symptoms) 1, 2
- If FPG 100-125 mg/dL: Patient has prediabetes; consider OGTT if high clinical suspicion 1, 3
- If FPG <100 mg/dL but suspicion remains: Perform OGTT 1
- Use A1C only when: Patient cannot fast reliably, or you need additional diagnostic information 1
- Never use A1C when: Hemoglobinopathies, pregnancy, anemia, or altered RBC turnover present 1
The bottom line: FPG remains the workhorse diagnostic test for diabetes in clinical practice, with A1C and OGTT reserved for specific clinical scenarios. 1, 2