Diagnostic Criteria for Diabetes Mellitus
Diabetes is diagnosed when any one of the following criteria is met: A1C ≥6.5%, fasting plasma glucose ≥126 mg/dL, 2-hour plasma glucose ≥200 mg/dL during an oral glucose tolerance test, or random plasma glucose ≥200 mg/dL with classic symptoms of hyperglycemia. 1
Primary Diagnostic Criteria
A1C ≥6.5% (48 mmol/mol): The test should be performed in a laboratory using a method that is NGSP-certified and standardized to the Diabetes Control and Complications Trial (DCCT) assay 2, 1
Fasting Plasma Glucose (FPG) ≥126 mg/dL (7.0 mmol/L): Fasting is defined as no caloric intake for at least 8 hours 2
2-hour Plasma Glucose ≥200 mg/dL (11.1 mmol/L) during an Oral Glucose Tolerance Test (OGTT): The test should be performed using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water 2
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 2
Confirmation Requirements
In the absence of unequivocal hyperglycemia with acute metabolic decompensation, the diagnosis requires confirmation with repeat testing 2, 3
Confirmation can be done by:
If two different tests are both above the diagnostic threshold, this confirms the diagnosis 2
If results from two different tests are discordant, the test with results above the diagnostic threshold should be repeated 2
No confirmation is needed when a patient has classic symptoms of hyperglycemia with a random plasma glucose ≥200 mg/dL (11.1 mmol/L) 2
Special Considerations for A1C Testing
A1C should NOT be used for diagnosis in conditions affecting red blood cell turnover, including: 2, 1
- Hemoglobinopathies
- Pregnancy (second and third trimesters)
- Glucose-6-phosphate dehydrogenase deficiency
- HIV treated with certain drugs
- Hemodialysis
- Recent blood loss or transfusion
- Erythropoietin therapy
- Iron-deficient anemia
In these conditions, only plasma glucose criteria should be used for diagnosis 2, 1
Marked discordance between measured A1C and plasma glucose levels should raise the possibility of hemoglobin variants interfering with the assay 2
A1C levels may vary with race/ethnicity independently of glycemia; for example, African Americans may have higher A1C levels than non-Hispanic whites with similar glucose levels 2
Prediabetes Criteria
Fasting Plasma Glucose: 100-125 mg/dL (5.6-6.9 mmol/L) - Impaired Fasting Glucose (IFG) 1, 3
2-hour Plasma Glucose during OGTT: 140-199 mg/dL (7.8-11.0 mmol/L) - Impaired Glucose Tolerance (IGT) 1, 3
Practical Testing Considerations
For OGTT, individuals should consume a mixed diet with at least 150g of carbohydrates in the 3 days preceding the test to avoid falsely elevated glucose levels 1
Plasma glucose samples should be spun and separated immediately after they are drawn to prevent preanalytic variability 2
If test results are near the margins of the diagnostic threshold, repeat the test in 3-6 months 2
Combined use of FPG and A1C may improve sensitivity for detecting diabetes compared to using either test alone 4, 5
Common Pitfalls and Caveats
The concordance between FPG, 2-h PG, and A1C tests is imperfect; they do not necessarily detect diabetes in the same individuals 2
Point-of-care A1C testing, while convenient for monitoring glycemic control, should be used with caution for diagnostic purposes 3
Misdiagnosis of diabetes type can occur in up to 40% of adults with new type 1 diabetes who are initially misdiagnosed as having type 2 diabetes 3
The ADA criteria using fasting glucose alone has been shown to have relatively low sensitivity (48.3%) for diagnosing diabetes compared to WHO definitions that include OGTT 5
Early diagnosis is critical as even undiagnosed patients are at increased risk of developing macrovascular and microvascular complications 3