How is diabetes mellitus defined according to the WHO and American Diabetes Association criteria?

Diagnostic Criteria for Diabetes Mellitus

Diabetes mellitus is diagnosed when any one of four criteria is met: HbA1c ≥6.5% (48 mmol/mol), fasting plasma glucose ≥7.0 mmol/L (126 mg/dL), 2-hour plasma glucose ≥11.1 mmol/L (200 mg/dL) during an oral glucose tolerance test, or random plasma glucose ≥11.1 mmol/L (200 mg/dL) in the presence of classic hyperglycemic symptoms. 1

Primary Diagnostic Thresholds

The American Diabetes Association and WHO have established four valid diagnostic criteria, any one of which is sufficient for diagnosis 1, 2:

• HbA1c ≥6.5% (≥48 mmol/mol) measured in an NGSP-certified laboratory standardized to the DCCT assay 1, 2
• Fasting plasma glucose ≥7.0 mmol/L (≥126 mg/dL) after at least 8 hours without caloric intake 1, 2
• 2-hour plasma glucose ≥11.1 mmol/L (≥200 mg/dL) during a 75-gram oral glucose tolerance test 1, 2
• Random plasma glucose ≥11.1 mmol/L (≥200 mg/dL) with classic symptoms of hyperglycemia 1, 2

Classic Symptoms of Hyperglycemia

The classic triad includes 1, 3:

• Polyuria (excessive urination) 1, 3
• Polydipsia (excessive thirst) 1, 3
• Unexplained weight loss 1, 3

Additional symptoms may include polyphagia, fatigue, and blurred vision 3

Confirmation Requirements

In the absence of unequivocal hyperglycemia (symptoms plus glucose ≥11.1 mmol/L or 200 mg/dL), two abnormal test results are required to confirm the diagnosis. 1, 2

The confirmation can be achieved through 1, 2:

• Two separate measurements of the same test on different days (e.g., two fasting glucose tests both ≥126 mg/dL) 1, 2
• Two different tests each exceeding their respective thresholds (e.g., one HbA1c ≥6.5% and one fasting glucose ≥126 mg/dL) 1, 2
• Two measurements from the same sample if both glucose and HbA1c are abnormal 1

When a patient presents with unequivocal hyperglycemia—defined as random plasma glucose ≥11.1 mmol/L (200 mg/dL) with classic symptoms or in hyperglycemic crisis—a single test is sufficient for immediate diagnosis without requiring confirmation. 1

Technical Specifications

HbA1c Testing Requirements

• Must be performed in an NGSP-certified laboratory standardized to the DCCT assay 1
• Point-of-care HbA1c assays should NOT be used for diagnostic purposes 1
• HbA1c should not be used for diagnosis in conditions that alter red blood cell turnover, including sickle-cell disease, pregnancy (second/third trimester), G6PD deficiency, hemodialysis, recent blood loss or transfusion, and erythropoietin therapy 1, 2

Fasting Plasma Glucose Requirements

• "Fasting" is defined as no caloric intake for at least 8 hours 1
• Plasma samples must be centrifuged and separated immediately after collection to avoid glycolysis, which produces falsely low results 2

Oral Glucose Tolerance Test Protocol

• Use 75 grams of anhydrous glucose dissolved in water 1
• For children, use 1.75 g/kg body weight (maximum 75 g) 3, 2
• Patients should consume a mixed diet with at least 150 g of carbohydrates for 3 days before testing 2
• Measure plasma glucose at 2 hours; diagnostic threshold is ≥11.1 mmol/L (200 mg/dL) 1

Random Plasma Glucose

• "Random" or "casual" means any time of day without regard to time since the last meal 1
• Must be accompanied by classic hyperglycemic symptoms for single-test diagnosis 1

Pre-Diabetes Categories

The WHO and ADA define intermediate states of hyperglycemia 1, 2:

• Impaired Fasting Glucose (IFG): Fasting plasma glucose 5.6–6.9 mmol/L (100–125 mg/dL) 1, 2
• Impaired Glucose Tolerance (IGT): 2-hour OGTT glucose 7.8–11.0 mmol/L (140–199 mg/dL) 1, 2
• HbA1c 5.7–6.4% (39–47 mmol/mol) indicates increased risk for diabetes 3, 2

These categories indicate increased risk for progression to diabetes and cardiovascular disease 1, 2

Critical Pitfalls to Avoid

• Do not use HbA1c alone in conditions with altered red blood cell turnover—plasma glucose criteria must be used instead 1, 2
• Do not rely on point-of-care HbA1c devices for diagnosis unless specifically FDA-cleared for diagnostic purposes 1
• Do not diagnose diabetes based on a single abnormal test unless the patient has unequivocal hyperglycemia with symptoms or is in hyperglycemic crisis 1, 2
• Ensure proper sample handling—plasma glucose samples must be processed immediately to prevent falsely low results from glycolysis 2
• Remember that HbA1c <6.5% does not exclude diabetes—glucose testing may still reveal diagnostic hyperglycemia 1

Screening Recommendations

• The ADA recommends screening all asymptomatic adults ≥45 years of age 1
• HbA1c, fasting plasma glucose, or 2-hour OGTT are all appropriate for screening 1
• Earlier and more frequent screening is indicated for individuals with risk factors including obesity, family history, high-risk ethnicity, history of gestational diabetes, hypertension, dyslipidemia, or physical inactivity 1