What is the purpose and procedure of an oral glucose tolerance test (OGTT) in diagnosing and managing diabetes?

Oral Glucose Tolerance Test (OGTT)

Primary Purpose

The OGTT is a diagnostic test used to identify diabetes and prediabetes by measuring the body's ability to metabolize a standardized glucose load, with a 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) confirming diabetes. 1, 2

The test serves three main diagnostic functions:

• Diabetes diagnosis when fasting plasma glucose or HbA1c results are equivocal or unavailable 1
• Gestational diabetes mellitus (GDM) screening in pregnant women at 24-28 weeks gestation 1
• Prediabetes identification through detection of impaired glucose tolerance (IGT), defined as 2-hour glucose 140-199 mg/dL 2, 1

Standard OGTT Procedure for Diabetes Diagnosis

Pre-Test Requirements

• Patient must fast for at least 8 hours before the test, with no caloric intake 1, 2
• The test should be performed in the morning 1
• Normal physical activity and unrestricted carbohydrate intake (≥150g/day) for 3 days prior is recommended 3

Test Administration

• Collect baseline fasting plasma glucose sample 2
• Administer 75g anhydrous glucose dissolved in water as specified by the World Health Organization 1, 2
• Collect plasma glucose at 2 hours post-glucose load for standard diabetes diagnosis 1
• Some protocols measure additional timepoints at 30,60, and 90 minutes for more detailed assessment 4

Diagnostic Thresholds for Diabetes

The OGTT diagnoses diabetes when the 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) 1, 2. This must be confirmed on a subsequent day in the absence of unequivocal hyperglycemia 1, 2.

Impaired glucose tolerance (prediabetes) is diagnosed when 2-hour glucose is 140-199 mg/dL (7.8-11.0 mmol/L) 2, 1, identifying individuals at high risk for progression to diabetes who may benefit from lifestyle interventions 1.

OGTT in Gestational Diabetes Screening

Two Competing Strategies

The American Diabetes Association recognizes both one-step and two-step approaches, though the one-step strategy using IADPSG criteria is recommended to optimize gestational outcomes 1.

One-Step Strategy (Preferred by ADA)

• Perform 75g OGTT at 24-28 weeks gestation in women not previously diagnosed with diabetes 1
• Test after overnight fast of at least 8 hours 1
• GDM diagnosed if ANY of the following thresholds are met or exceeded: 1, 2
  • Fasting: 92 mg/dL (5.1 mmol/L)
  • 1-hour: 180 mg/dL (10.0 mmol/L)
  • 2-hour: 153 mg/dL (8.5 mmol/L)

Two-Step Strategy (Alternative)

Step 1: Perform nonfasting 50g glucose load test (GLT) at 24-28 weeks 1, 5

• If 1-hour glucose ≥140 mg/dL (or ≥130 or ≥135 mg/dL depending on institutional protocol), proceed to Step 2 1, 5
• The 140 mg/dL threshold identifies ~80% of GDM cases, while 130 mg/dL increases sensitivity to ~90% 5

Step 2: Perform fasting 100g OGTT 1

• GDM diagnosed when at least TWO of four values meet or exceed: 1, 5
  • Fasting: 95 mg/dL (5.3 mmol/L)
  • 1-hour: 180 mg/dL (10.0 mmol/L)
  • 2-hour: 155 mg/dL (8.6 mmol/L)
  • 3-hour: 140 mg/dL (7.8 mmol/L)

Clinical Advantages and Limitations

Why OGTT Remains Important

The OGTT is more sensitive than fasting glucose alone for detecting diabetes, particularly in populations where post-load hyperglycemia predominates 6. Many individuals with normal fasting glucose (<126 mg/dL) but elevated 2-hour values would be missed by fasting glucose screening alone 6.

The test identifies individuals with IGT who have increased cardiovascular risk and can benefit from preventive interventions 1.

Practical Limitations

• Less convenient than fasting glucose due to time requirements (2-3 hours) and fasting requirement 1
• Poor reproducibility compared to HbA1c or fasting glucose 1
• Rarely performed in routine practice outside of pregnancy screening due to inconvenience 1
• Results can be affected by recent illness, medications, or inadequate carbohydrate intake 3

Critical Confirmation Requirements

In the absence of unequivocal hyperglycemia (symptoms plus random glucose ≥200 mg/dL), any abnormal OGTT result must be confirmed by repeat testing on a different day 1, 2. This applies to both diabetes and prediabetes diagnoses.

A single abnormal OGTT can diagnose diabetes if accompanied by: 1

• Classic symptoms of hyperglycemia (polyuria, polydipsia, unexplained weight loss), OR
• HbA1c ≥6.5% by NGSP-certified laboratory method, OR
• Unequivocal diabetic retinopathy

Common Pitfalls to Avoid

• Never use point-of-care glucose meters for diagnostic OGTT - only laboratory venous plasma glucose measurements are acceptable 1
• Do not perform OGTT during acute illness or stress as results will be falsely elevated 3
• Ensure adequate carbohydrate intake before testing - carbohydrate restriction can cause false positive results 3
• Do not use OGTT to diagnose reactive hypoglycemia - this is not a validated indication 7
• In pregnancy, do not confuse the nonfasting 50g screening test with the diagnostic OGTT - these serve different purposes 5

Special Population Considerations

For children and adolescents at risk for type 2 diabetes, testing should be performed every 3 years starting at age 10 (or onset of puberty) in overweight youth (BMI >85th percentile) with additional risk factors 1, 2.

For women with history of GDM, lifelong screening for diabetes or prediabetes should occur at least every 3 years using OGTT or other tests (not HbA1c immediately postpartum) 1.