What are the diagnostic tests for type 2 diabetes?

Diagnostic Tests for Type 2 Diabetes

Type 2 diabetes is diagnosed using any one of four laboratory tests: HbA1c ≥6.5%, fasting plasma glucose (FPG) ≥126 mg/dL, 2-hour plasma glucose ≥200 mg/dL during a 75-gram oral glucose tolerance test (OGTT), or random plasma glucose ≥200 mg/dL in patients with classic hyperglycemic symptoms. 1, 2, 3

Primary Diagnostic Tests

The following four tests are equally valid for diagnosis, though each has specific advantages and limitations:

1. Hemoglobin A1c (HbA1c)

• Diagnostic threshold: ≥6.5% (48 mmol/mol) 1, 2, 3
• Must be performed in a laboratory certified by the National Glycohemoglobin Standardization Program (NGSP) and standardized to the Diabetes Control and Complications Trial (DCCT) assay 1, 2, 3
• Point-of-care assays should NOT be used for diagnosis 1
• Reflects long-term blood glucose concentrations over approximately 2-3 months 1

2. Fasting Plasma Glucose (FPG)

• Diagnostic threshold: ≥126 mg/dL (7.0 mmol/L) 1, 2, 3
• Fasting is defined as no caloric intake for at least 8 hours 1, 2, 3
• This is the preferred screening test because it is faster, easier to perform, more convenient, acceptable to patients, and less expensive than OGTT 1, 3
• Blood should be drawn in the morning after overnight fasting 1

3. 2-Hour Plasma Glucose During OGTT

• Diagnostic threshold: ≥200 mg/dL (11.1 mmol/L) 1, 2, 3
• Requires a glucose load containing 75 grams of anhydrous glucose dissolved in water 1, 2, 4, 3
• Patient must fast for at least 8 hours prior to the test 4
• The 2-hour post-load sample is most critical for diagnosis 4
• OGTT may be necessary when FPG is normal but clinical suspicion remains high 1, 2

4. Random Plasma Glucose

• Diagnostic threshold: ≥200 mg/dL (11.1 mmol/L) 1, 2, 3
• Only valid in patients with classic symptoms of hyperglycemia: polyuria, polydipsia, unexplained weight loss, or hyperglycemic crisis 1, 2, 3
• "Casual" is defined as any time of day without regard to time since previous meal 1

Confirmation Requirements

In the absence of unequivocal hyperglycemia (symptomatic patient with random glucose ≥200 mg/dL), the diagnosis must be confirmed with a repeat test on a subsequent day 1, 2, 3

• Confirmation can be done by repeating the same test or performing a different diagnostic test 2, 3
• If two different tests (such as HbA1c and FPG) are both above the diagnostic threshold, this confirms the diagnosis without need for repeat testing 2
• The repeat test should be performed without delay, using a new blood sample 2

Critical Situations Where HbA1c Should NOT Be Used

Use only plasma glucose criteria (FPG or OGTT) in the following conditions: 2, 3

• Sickle cell disease 2, 3
• Pregnancy 2, 3
• Glucose-6-phosphate dehydrogenase deficiency 3
• HIV infection 3
• Hemodialysis 2, 3
• Recent blood loss or transfusion 2, 3
• Erythropoietin therapy 2, 3
• Iron-deficiency anemia 3
• Hemoglobin variants (hemoglobinopathies) 2, 3

These conditions are associated with increased red blood cell turnover or altered hemoglobin, which interferes with accurate HbA1c measurement 2, 3

Important Pitfalls to Avoid

Sample Handling for Glucose Testing

• Blood must be placed immediately in an ice-water slurry, and plasma should be separated from cells within 30 minutes 1
• If immediate separation cannot be achieved, use a tube containing a rapidly effective glycolysis inhibitor, such as citrate buffer 1
• Tubes with only enolase inhibitors, such as sodium fluoride, should NOT be relied upon to prevent glycolysis 1
• Using wrong collection tubes or delayed processing causes falsely low glucose values due to glycolysis 3

Discordant Results

• Marked discordance between measured HbA1c levels and plasma glucose levels should raise suspicion of interference in the HbA1c assay due to hemoglobin variants 2, 3
• In such cases, use an HbA1c assay without interference or switch to glucose-based criteria 3

Quality Standards

• All diagnostic testing should be performed in accredited laboratories 3
• Analytical precision for glucose measurement should have imprecision ≤2.4%, bias ≤2.1%, and total error ≤6.1% 3

Recommended Diagnostic Algorithm

Start with HbA1c and FPG in patients with risk factors 2

1. If either test is positive (HbA1c ≥6.5% or FPG ≥126 mg/dL), confirm with a second test 2
2. If both tests are positive on initial testing, diagnosis is confirmed 2
3. In case of discordance or high clinical suspicion with negative tests, perform an OGTT 2, 4
4. If patient presents with classic symptoms (polyuria, polydipsia, weight loss) and random glucose ≥200 mg/dL, diagnosis is confirmed without need for repeat testing 1, 2