What are the diagnostic criteria for diabetes mellitus?

Diagnostic Criteria for Diabetes Mellitus

Diabetes mellitus is diagnosed when any one of four criteria is met: A1C ≥6.5%, fasting plasma glucose (FPG) ≥126 mg/dL, 2-hour plasma glucose ≥200 mg/dL during a 75-g oral glucose tolerance test (OGTT), or random plasma glucose ≥200 mg/dL in a patient with classic hyperglycemic symptoms or crisis. 1, 2

Primary Diagnostic Thresholds

The American Diabetes Association establishes four distinct pathways to diagnose diabetes in non-pregnant adults: 1, 2

• A1C ≥6.5% (≥48 mmol/mol) 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 1, 2

• Fasting Plasma Glucose (FPG) ≥126 mg/dL (≥7.0 mmol/L), where fasting is defined as no caloric intake for at least 8 hours 1, 2

• 2-hour Plasma Glucose ≥200 mg/dL (≥11.1 mmol/L) during a 75-g OGTT performed as described by the World Health Organization 1, 2

• Random Plasma Glucose ≥200 mg/dL (≥11.1 mmol/L) in an individual with classic symptoms of hyperglycemia (polyuria, polydipsia, unexplained weight loss) or hyperglycemic crisis (diabetic ketoacidosis or hyperglycemic hyperosmolar state) 1, 3

Confirmation Requirements: The Critical Two-Test Rule

In the absence of unequivocal hyperglycemia (hyperglycemic crisis with symptoms), diagnosis requires two abnormal test results. 1, 2 This is where many clinicians make errors, so understanding the confirmation algorithm is essential:

When Confirmation is Required:

• Any single abnormal test result in an asymptomatic patient or patient without hyperglycemic crisis must be confirmed 1, 2
• Confirmation can be achieved by repeating the same test on a different day 1
• Alternatively, two different tests (e.g., A1C and FPG) performed on the same sample, both above diagnostic thresholds, confirm the diagnosis 1

When Confirmation is NOT Required:

• A patient presenting with classic symptoms of hyperglycemia (polyuria, polydipsia, weight loss) or hyperglycemic crisis AND random plasma glucose ≥200 mg/dL requires no confirmatory testing 1, 3

Managing Discordant Results:

When two different tests yield conflicting results (one above, one below diagnostic threshold): 1

• Repeat the test that was above the diagnostic threshold 1
• If the repeated test remains elevated, diagnose diabetes based on the confirmed abnormal test 1
• If a patient has A1C ≥6.5% confirmed on repeat testing but FPG <126 mg/dL, that person still has diabetes 1

Test Selection: Practical Considerations

FPG is the preferred test in most clinical settings due to ease of administration, convenience, patient acceptability, and lower cost compared to OGTT. 2 However, the three tests (A1C, FPG, 2-hour PG) reflect different aspects of glucose metabolism and have incomplete concordance—they do not identify diabetes in the same individuals. 1, 3

The 2-hour plasma glucose during OGTT diagnoses more people with diabetes and prediabetes compared to FPG and A1C cut points. 1 This is particularly relevant in populations where post-prandial hyperglycemia predominates.

Critical Limitations of A1C Testing

A1C should NOT be used for diagnosis in the following conditions affecting red blood cell turnover: 2, 3

• Hemoglobinopathies (sickle cell disease, thalassemia) 1, 2
• Hemolytic anemias 2, 3
• Pregnancy 2, 3
• Recent blood loss or blood transfusion 2, 3
• Hemodialysis 2, 3
• Erythropoietin therapy 2, 3

In these conditions, only plasma glucose criteria (FPG, 2-hour PG, or random glucose) should be used for diagnosis. 2, 3 For patients with abnormal hemoglobins but normal red cell turnover (such as sickle cell trait), use an A1C assay without interference from abnormal hemoglobins. 1

Point-of-Care A1C Testing Caution:

While point-of-care A1C assays may be used in CLIA-certified settings meeting quality standards, caution is advised when using them for diagnosis—they are better suited for monitoring glycemic control. 2 Diagnostic A1C testing should be performed in accredited laboratories using venous plasma. 3

Prediabetes Categories: Identifying High-Risk Individuals

The American Diabetes Association recognizes three categories of increased risk for diabetes (prediabetes): 1

• Impaired Fasting Glucose (IFG): FPG 100-125 mg/dL (5.6-6.9 mmol/L) 1, 2
• Impaired Glucose Tolerance (IGT): 2-hour PG 140-199 mg/dL (7.8-11.0 mmol/L) during 75-g OGTT 1, 2
• A1C: 5.7-6.4% 1, 2

For all three prediabetes categories, risk is continuous and becomes disproportionately greater at the higher ends of the range. 1

Common Pitfalls and How to Avoid Them

Pitfall #1: Using Capillary Blood Glucose for Diagnosis

Never use capillary blood glucose testing as a stand-alone diagnostic test—it performs poorly for diagnosis with high specificity (92-98%) but low sensitivity (39-55%). 2 All diagnostic testing must be performed using venous plasma in accredited laboratories. 3

Pitfall #2: Ignoring Test Variability

Due to preanalytic and analytic variability, when a test above the diagnostic threshold is repeated, the second value may fall below the cut point. 1 This is least likely for A1C, somewhat more likely for FPG, and most likely for 2-hour PG. 1 Such patients likely have results near diagnostic margins—consider close follow-up and repeat testing in 3-6 months. 1

Pitfall #3: Lower Sensitivity of A1C

The A1C cut point of ≥6.5% identifies approximately one-third fewer cases of undiagnosed diabetes compared to FPG ≥126 mg/dL when applied to population screening. 1 However, the greater practicality and convenience of A1C may increase the actual number of diagnoses made in real-world practice. 1

Pitfall #4: Rapidly Evolving Diabetes

In rapidly evolving diabetes, such as new-onset type 1 diabetes in children, A1C may not be significantly elevated despite frank hyperglycemia. 1 In these cases, rely on plasma glucose criteria for diagnosis.

Screening Recommendations

Testing should be considered in: 1

• All adults aged 45 years and older, with repeat testing at minimum 3-year intervals if normal 1, 3
• Overweight or obese adults (BMI ≥25 kg/m² or ≥23 kg/m² in Asian Americans) with one or more additional risk factors at any age 1
• Adults with sustained blood pressure >135/80 mmHg 3

Additional risk factors include: physical inactivity, first-degree relative with diabetes, high-risk ethnicity (African American, Latino, Native American, Asian American, Pacific Islander), history of gestational diabetes or delivering a baby >9 lb, hypertension (≥140/90 mmHg or on therapy), HDL cholesterol <35 mg/dL and/or triglycerides >250 mg/dL, polycystic ovary syndrome, previous A1C ≥5.7%, and history of cardiovascular disease. 1, 3