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Chemistry

Tolerance Testing

Tolerance testing, particularly the Oral Glucose Tolerance Test (OGTT), is designed to assess how the body handles a glucose load. It’s a dynamic test, meaning we’re not just looking at a single snapshot but rather how glucose levels change over time

Oral Glucose Tolerance Test (OGTT)

  • Principle: Measures the body’s ability to clear glucose from the blood over a set period after ingesting a specific amount of glucose. It assesses both insulin secretion and insulin sensitivity
  • Indications:
    • Diagnosis of diabetes mellitus (especially when fasting glucose is borderline)
    • Screening and diagnosis of gestational diabetes
    • Evaluation of insulin resistance
    • Assessment of reactive hypoglycemia

Patient Preparation

  • Dietary Instructions:
    • 3 Days Prior: The patient should consume a diet containing at least 150 grams of carbohydrates per day. This ensures that the body’s glucose handling mechanisms are primed
    • Rationale: Carbohydrate restriction before the test can impair insulin secretion and lead to false-positive results
  • Fasting
    • 8-12 Hours: The patient must fast for 8-12 hours before the test. Only water is allowed during this period
    • Rationale: Fasting ensures that the baseline glucose level is stable and not influenced by recent food intake
  • Medications
    • Hold Certain Medications: Some medications can affect glucose metabolism. The physician should advise the patient on whether to withhold medications like corticosteroids, diuretics, or oral contraceptives prior to the test
    • Rationale: These medications can alter glucose levels and interfere with test results
  • Activity Level
    • Avoid Strenuous Exercise: The patient should avoid strenuous exercise for at least 12 hours before the test
    • Rationale: Exercise can affect glucose metabolism and influence test results
  • Smoking
    • No Smoking: The patient should not smoke during the fasting period and throughout the test
    • Rationale: Nicotine can affect glucose levels and hormonal responses

Procedure

  • Baseline Sample
    • Collect a fasting blood sample (plasma or serum) to measure the baseline glucose level
    • Rationale: This establishes the starting point for glucose metabolism
  • Glucose Load Administration
    • Adults: Administer 75 grams of glucose in a liquid solution (usually 300 mL of water). The solution should be consumed within 5 minutes
    • Pregnant Women: A 75-gram or 100-gram glucose load may be used, depending on the guidelines followed for gestational diabetes screening
    • Children: Administer 1.75 grams of glucose per kilogram of body weight, up to a maximum of 75 grams
    • Rationale: The glucose load challenges the body’s ability to regulate glucose levels
  • Blood Sample Collection
    • Collect blood samples (plasma or serum) at specific intervals after the glucose load. Common time points include:
      • 30 minutes
      • 60 minutes (1 hour)
      • 120 minutes (2 hours)
      • Additional time points (e.g., 3 hours) may be required in certain cases
    • Rationale: These intervals capture the dynamic changes in glucose levels as the body responds to the glucose load
  • Patient Monitoring
    • Monitor the patient for any adverse reactions, such as nausea, vomiting, dizziness, or sweating
    • Rationale: Adverse reactions can affect the accuracy of the test and may require medical intervention

Specimen Handling

  • Collection Tubes
    • Use appropriate collection tubes (e.g., fluoride oxalate tubes) to prevent glycolysis
    • Rationale: Fluoride inhibits the enzymatic breakdown of glucose by blood cells
  • Processing
    • Promptly centrifuge blood samples and separate plasma or serum
    • Rationale: Delay in processing can lead to falsely low glucose values due to continued glycolysis
  • Storage
    • Analyze samples immediately or refrigerate. If samples cannot be analyzed within a few hours, freeze them
    • Rationale: Proper storage minimizes changes in glucose levels

Analytical Considerations

  • Glucose Measurement Methods
    • Use accurate and reliable glucose measurement methods, such as glucose oxidase or hexokinase assays
    • Rationale: Precise glucose measurement is essential for accurate OGTT interpretation
  • Quality Control
    • Follow strict quality control procedures to ensure the accuracy and precision of glucose measurements
    • Rationale: Quality control helps minimize errors and ensure reliable test results
  • Interfering Factors
    • Be aware of potential interfering factors, such as medications, stress, and acute illness, which can affect glucose levels
    • Rationale: Recognizing and accounting for these factors helps prevent misinterpretation of test results

Interpretation

  • Diagnostic Criteria
    • Diagnostic criteria for diabetes mellitus based on OGTT values (according to American Diabetes Association):
      • Normal: Fasting glucose < 100 mg/dL (5.6 mmol/L) and 2-hour glucose < 140 mg/dL (7.8 mmol/L)
      • Prediabetes: Fasting glucose 100-125 mg/dL (5.6-6.9 mmol/L) or 2-hour glucose 140-199 mg/dL (7.8-11.0 mmol/L)
      • Diabetes: Fasting glucose ≥ 126 mg/dL (7.0 mmol/L) or 2-hour glucose ≥ 200 mg/dL (11.1 mmol/L)
    • Gestational Diabetes:
      • Specific criteria vary by organization. One common set is the Carpenter-Coustan criteria, which uses a 100g load and has different cutoffs
  • Glucose Tolerance Curve
    • Evaluate the glucose tolerance curve, which plots glucose levels against time
    • Rationale: The shape of the curve provides insights into glucose metabolism and insulin response

Troubleshooting

  • Unexpected Results
    • If OGTT results are inconsistent with the patient’s clinical picture, repeat the test or consider alternative diagnostic methods
    • Rationale: OGTT results can be influenced by various factors, so confirmation may be needed
  • Adverse Reactions
    • If the patient experiences severe adverse reactions (e.g., vomiting, fainting), discontinue the test and provide appropriate medical care
    • Rationale: Patient safety is paramount
  • Technical Errors
    • If technical errors occur during the test (e.g., incorrect glucose load, missed sample collection), repeat the test on a different day
    • Rationale: Technical errors can compromise the accuracy of the test results

Special Considerations

  • Pregnancy
    • Gestational diabetes screening is typically performed between 24 and 28 weeks of gestation
    • The diagnostic criteria for gestational diabetes may differ from those for non-pregnant adults
    • The 1-hour glucose challenge test (GCT) is commonly used as a screening test. If the GCT is positive, a 3-hour OGTT is performed for diagnosis
  • Children
    • OGTT is rarely used in children except in specific cases, such as suspected insulin resistance or impaired glucose tolerance
    • The glucose load is adjusted based on body weight
  • Elderly
    • The elderly may have impaired glucose tolerance due to age-related changes in insulin sensitivity
    • Diagnostic criteria for diabetes are the same as for younger adults, but clinical judgment is needed

Key Terms

  • Glucose Load: The amount of glucose given to the patient during the test
  • Baseline Sample: The blood sample taken before administering the glucose load
  • Diagnostic Criteria: The specific glucose values used to diagnose diabetes
  • Glucose Tolerance Curve: A graph that plots glucose levels against time
  • Gestational Diabetes: Diabetes that develops during pregnancy
  • Insulin Resistance: A condition in which cells do not respond normally to insulin
  • Reactive Hypoglycemia: Low blood glucose levels that occur after a meal