What is the diagnostic approach for diabetes?

Diagnosing Diabetes Mellitus

Diabetes mellitus is diagnosed when any one of the following criteria is met: fasting plasma glucose ≥126 mg/dL, 2-hour plasma glucose ≥200 mg/dL during an oral glucose tolerance test, A1C ≥6.5%, or random plasma glucose ≥200 mg/dL with classic symptoms of hyperglycemia. 1, 2

Diagnostic Criteria

Primary Diagnostic Tests

• Hemoglobin A1C ≥ 6.5% - Test should be performed in a laboratory using a method certified by the National Glycohemoglobin Standardization Program (NGSP) and standardized to the Diabetes Control and Complications Trial (DCCT) assay 3, 2
• Fasting Plasma Glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L) - Fasting is defined as no caloric intake for at least 8 hours 3, 1
• 2-hour Plasma Glucose ≥ 200 mg/dL (11.1 mmol/L) during a 75-g oral glucose tolerance test (OGTT) performed as described by the World Health Organization 3, 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 3, 1

Confirmation Requirements

• In the absence of unequivocal hyperglycemia with acute metabolic decompensation, diagnosis requires two abnormal test results from the same sample or in two separate test samples 3, 1
• If using two different tests (such as A1C and FPG) and both are above the diagnostic threshold, the diagnosis is confirmed 3
• If results are discordant from two different tests, the test with results above the diagnostic threshold should be repeated 3, 1
• No confirmation is needed when a patient presents with classic symptoms of hyperglycemia or hyperglycemic crisis and a random plasma glucose ≥ 200 mg/dL 3

Categories of Increased Risk for Diabetes (Prediabetes)

• Impaired Fasting Glucose (IFG): FPG 100-125 mg/dL (5.6-6.9 mmol/L) 3, 2
• Impaired Glucose Tolerance (IGT): 2-hour PG during OGTT 140-199 mg/dL (7.8-11.0 mmol/L) 3, 2
• A1C: 5.7-6.4% (39-47 mmol/mol) 2

Special Considerations for A1C Testing

Limitations of A1C

• A1C should not be used for diagnosis in conditions affecting red blood cell turnover 2:
  • Hemoglobinopathies and anemias
  • Pregnancy (second and third trimesters)
  • Recent blood loss or transfusion
  • Hemodialysis
  • Erythropoietin therapy
• In these conditions, only plasma glucose criteria should be used for diagnosis 3, 2
• Marked discrepancy between measured A1C and plasma glucose levels should raise the possibility of hemoglobin variants interfering with the assay 2

Point-of-Care A1C Testing

• While convenient for monitoring glycemic control, caution is advised when using point-of-care A1C testing for diagnosis 3, 1
• Point-of-care A1C assays may be used in CLIA-certified settings that meet quality standards 1

Screening Recommendations

• Screen adults aged 45 years and older 3, 1
• Screen overweight or obese adults (BMI ≥25 kg/m² or ≥23 kg/m² in Asian Americans) with one or more risk factors at any age 3
• If tests are normal, repeat testing at minimum 3-year intervals 3
• Consider earlier and more frequent screening for individuals at higher risk 1

Classification of Diabetes

• Type 1 diabetes: Usually caused by autoimmune destruction of pancreatic β-cells, resulting in absolute insulin deficiency 3
• Type 2 diabetes: Results from progressive insulin secretory defect on the background of insulin resistance; accounts for 90-95% of all diabetes cases 3, 1
• Gestational diabetes mellitus (GDM): Diabetes diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes 3
• Specific types of diabetes due to other causes: Monogenic diabetes syndromes, diseases of the exocrine pancreas, drug or chemical-induced diabetes 3

Clinical Pearls

• The concordance between FPG, 2-h PG, and A1C tests is imperfect; they do not necessarily detect diabetes in the same individuals 1
• Early diagnosis is crucial to prevent complications related to chronic hyperglycemia 1
• Misdiagnosis of diabetes type can occur in up to 40% of adults with new type 1 diabetes who are misdiagnosed as having type 2 diabetes 1
• 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 2