What laboratory tests are required to diagnose type 2 diabetes?

Laboratory Tests for Diagnosing Type 2 Diabetes

You can diagnose type 2 diabetes using any one of four laboratory tests: fasting plasma glucose (FPG) ≥126 mg/dL, 2-hour plasma glucose ≥200 mg/dL during a 75-g oral glucose tolerance test (OGTT), hemoglobin A1C ≥6.5%, or random plasma glucose ≥200 mg/dL in symptomatic patients. 1

Primary Diagnostic Tests

You have four equally valid options for diagnosing diabetes, though each has specific advantages and limitations:

1. Fasting Plasma Glucose (FPG) - Most Practical First Choice

• Diagnostic threshold: ≥126 mg/dL (7.0 mmol/L) 1
• Requires no caloric intake for at least 8 hours 1
• This is the preferred screening test because it is faster, easier to perform, more convenient, acceptable to patients, and less expensive than OGTT 1, 2
• Must be measured in an accredited laboratory using enzymatic methods (hexokinase or glucose oxidase) 2
• Blood must be collected in tubes with glycolytic inhibitors (citrate buffer) and processed within 15-30 minutes if proper tubes unavailable 2

2. Hemoglobin A1C

• Diagnostic threshold: ≥6.5% (48 mmol/mol) 1, 3
• Must be performed using a method certified by the National Glycohemoglobin Standardization Program (NGSP) and standardized to the Diabetes Control and Complications Trial (DCCT) assay 1
• Major advantage: No fasting required, reflects longer-term glycemia 4
• Point-of-care assays should NOT be used for diagnosis 1

3. 2-Hour Plasma Glucose During OGTT

• Diagnostic threshold: ≥200 mg/dL (11.1 mmol/L) 1, 5
• Requires 75-g anhydrous glucose load dissolved in water 1, 5
• Patient must fast for at least 8 hours prior 5
• This test diagnoses more people with diabetes than FPG or A1C 1
• More accurate when there is discordance between A1C and glucose values 1

4. Random Plasma Glucose (Only for Symptomatic Patients)

• Diagnostic threshold: ≥200 mg/dL (11.1 mmol/L) 1
• Only valid in patients with classic symptoms: polyuria, polydipsia, unexplained weight loss, or hyperglycemic crisis 1

Confirmation Requirements - Critical to Avoid Misdiagnosis

Unless the patient has unequivocal hyperglycemia (symptomatic with random glucose ≥200 mg/dL), you MUST confirm the diagnosis with a second abnormal test result 1, 3

You have two confirmation options:

• Option 1: Repeat the same test on a different day 1, 3
• Option 2: Perform a different diagnostic test (e.g., if A1C is 7.0%, confirm with FPG ≥126 mg/dL) 1, 3

If both tests from the same sample or two different samples are above diagnostic thresholds, diagnosis is confirmed 1, 3

When NOT to Use A1C - Use Glucose Testing Instead

You must use only plasma glucose criteria (FPG or OGTT) in these specific situations: 1, 3

• Sickle cell disease 1
• Pregnancy (second and third trimesters and postpartum period) 1
• Glucose-6-phosphate dehydrogenase deficiency 1
• HIV (especially on certain medications) 1
• Hemodialysis 1
• Recent blood loss or transfusion 1
• Erythropoietin therapy 1
• Iron-deficiency anemia 1
• Hemoglobin variants (hemoglobinopathies) 1

Critical Pitfalls to Avoid

A1C Assay Interference

Marked discordance between A1C and plasma glucose should raise suspicion of A1C assay interference 1, 3. For patients with hemoglobin variants (like sickle cell trait), use an A1C assay without interference or switch to glucose-based criteria 1. Check www.ngsp.org/interf.asp for updated list of assays with interferences 1.

Sample Collection Errors

Using wrong collection tubes or delayed processing causes falsely low glucose values due to glycolysis 2. Blood must be in tubes with glycolytic inhibitors and processed promptly 2.

Misinterpreting Normal Reference Ranges

Do not confuse normal reference intervals (74-110 mg/dL) with diagnostic criteria for diabetes (≥126 mg/dL) 2.

Missing Diabetes with A1C Alone

A1C ≥6.5% as sole criterion misses a substantial number of people with type 2 diabetes, including some with fasting hyperglycemia 6. When A1C results are discordant with clinical picture or equivocal, perform plasma glucose testing 6.

Practical Algorithm for Diagnosis

Step 1: Start with FPG and A1C in patients with risk factors (age ≥35 years, BMI ≥25 kg/m², family history, high-risk ethnicity) 1, 3, 7

Step 2: If either test is positive, confirm with second test (repeat same test or different test) 3

Step 3: If discordance exists or high clinical suspicion with negative tests, perform OGTT 3

Step 4: If patient has conditions affecting A1C reliability (listed above), use only FPG or OGTT 1

Quality Standards

Analytical precision for glucose measurement should have imprecision ≤2.4%, bias ≤2.1%, and total error ≤6.1% 2. All diagnostic testing should be performed in accredited laboratories 2.