What are the diagnostic criteria for diabetes mellitus (DM) and pre-diabetes based on fasting glucose and Hemoglobin A1c (HbA1c) levels?

Diagnostic Criteria for Diabetes Mellitus and Pre-diabetes Based on Fasting Glucose and HbA1c

Diabetes mellitus is diagnosed with fasting plasma glucose ≥7.0 mmol/L (126 mg/dL), HbA1c ≥6.5% (48 mmol/mol), or 2-hour post-load glucose ≥11.1 mmol/L (200 mg/dL) during an oral glucose tolerance test (OGTT). 1

Diagnostic Criteria for Diabetes Mellitus

Venous Plasma Glucose Criteria:

• Fasting plasma glucose (FPG): ≥7.0 mmol/L (126 mg/dL)
• 2-hour post-load glucose (2hPG): ≥11.1 mmol/L (200 mg/dL) during OGTT
• Random plasma glucose: ≥11.1 mmol/L (200 mg/dL) with symptoms of hyperglycemia

HbA1c Criteria:

• HbA1c: ≥6.5% (48 mmol/mol)

Diagnostic Criteria for Pre-diabetes

Venous Plasma Glucose Criteria:

• Impaired Fasting Glucose (IFG):
  • WHO definition: FPG 6.1-6.9 mmol/L (110-125 mg/dL)
  • ADA definition: FPG 5.6-6.9 mmol/L (100-125 mg/dL)
• Impaired Glucose Tolerance (IGT): 2hPG 7.8-11.0 mmol/L (140-199 mg/dL)

HbA1c Criteria:

• Pre-diabetes: HbA1c 5.7-6.4% (39-47 mmol/mol) 1

Important Considerations

Confirmation Requirements

• A diagnosis of diabetes requires either:
  • Two abnormal test results from the same sample (e.g., FPG and HbA1c)
  • Two abnormal test results from separate testing occasions
  • One abnormal test result in the presence of symptoms 1

Testing Methodology

• Venous plasma is the recommended standard for glucose determination
• Point-of-care HbA1c testing should be restricted to FDA-approved devices at certified laboratories 1
• Laboratory-based HbA1c testing using NGSP-certified methods is preferred for diagnosis 1

Discrepancies Between Tests

• Studies show that using HbA1c alone may identify different populations than using glucose-based criteria 2, 3
• When FPG and HbA1c results are discordant, OGTT is recommended to clarify the diagnosis 1
• Patients with HbA1c ≥6.5% but FPG <126 mg/dL tend to be older and may have reduced kidney function 3

Special Populations

• In conditions affecting red blood cell turnover (hemoglobinopathies, pregnancy, recent blood loss, hemolytic anemia), HbA1c is unreliable and only glucose criteria should be used 1
• In pregnancy, different diagnostic thresholds apply for gestational diabetes mellitus 1

Practical Algorithm for Diagnosis

1. Initial Testing:

   • Measure both FPG and HbA1c in patients at risk
   • If both tests are concordant (both normal, both pre-diabetes, or both diabetes), diagnosis is established

2. If Results Are Discordant:

   • Perform an OGTT with 75g glucose load
   • The more severe category should generally be assigned (e.g., if one test indicates diabetes and another pre-diabetes, diagnose as diabetes)

3. Confirmation:

   • Repeat testing on a different day if the initial result is in the diabetes range without symptoms
   • No need for confirmation in symptomatic patients with unequivocal hyperglycemia

This approach ensures accurate diagnosis while minimizing the risk of missing cases that could benefit from early intervention to prevent complications related to chronic hyperglycemia.

By using standardized diagnostic criteria and appropriate testing methods, clinicians can identify patients with diabetes and pre-diabetes early, allowing for timely intervention to reduce morbidity and mortality associated with these conditions.