Insulin Tolerance Test

Mr. Arvind Kumar

Introduction

  1. The Insulin Tolerance Test (ITT) involves administering a controlled dose of insulin and measuring the body’s response, particularly the fall in blood glucose and the subsequent counter-regulatory response (including the release of growth hormone, cortisol, and glucagon).
  2. The test evaluates the ability of the body to handle a rapid reduction in blood glucose by assessing the counter-regulatory hormone release.
  3. In some clinical scenarios, the ITT is used to diagnose adrenal insufficiency, growth hormone deficiency, and insulin resistance.
  4. It is also used in research to evaluate insulin sensitivity and the hypothalamic-pituitary-adrenal axis.

 

Principle

The Insulin Tolerance Test (ITT) principle is based on administering a bolus dose of insulin to induce hypoglycemia. The body’s counter-regulatory mechanisms, which include glucagon secretion, growth hormone (GH), cortisol, and epinephrine, are activated to raise blood glucose levels. The test evaluates the recovery rate from hypoglycemia and the hormonal responses accompanying the fall in glucose.

A healthy individual will have a rapid hormonal response, including an increase in growth hormone and cortisol, and glucose levels should return to normal quickly. Delayed or absent responses to insulin-induced hypoglycemia may indicate endocrine dysfunction or insulin resistance.

 

Requirements

  1. Sample:
    • Blood samples are collected at baseline (before insulin administration) and at frequent intervals (usually at 30 minutes, 60 minutes, and 120 minutes) after insulin injection to monitor blood glucose levels and the levels of counter-regulatory hormones (GH, cortisol, glucagon).
  2. Reagents:
    • Insulin (rapid-acting insulin, usually regular insulin).
    • Glucose (for monitoring blood glucose levels).
    • Glucagon, growth hormone, cortisol, and epinephrine assays for evaluating hormonal responses.
  3. Apparatus:
    • Syringe for insulin injection.
    • Glucose meter for rapid blood glucose measurement.
    • Centrifuge (if sample separation is required for hormone assays).
    • Blood collection tubes for serum or plasma.
    • Spectrophotometer or other assays for growth hormone and cortisol levels.

 

Procedure

  1. Preparation of the Patient
    • The patient must fast for 8-12 hours before the test to ensure normal baseline glucose levels.
    • The test is typically performed in a hospital or clinical setting under supervised conditions due to the risks associated with induced hypoglycemia.
    • Baseline blood glucose is measured, and it should be within the normal range (70–100 mg/dL).
  1. Insulin Injection
    • A dose of 0.1-0.15 units/kg of body weight of regular insulin is administered intravenously. This dose is based on body weight and the clinical indication.
    • The goal is to induce hypoglycemia (blood glucose levels typically fall below 50 mg/dL or 2.8 mmol/L).
  1. Monitoring Blood Glucose and Hormonal Response
    • Blood glucose levels are monitored at regular intervals (usually every 30 minutes or every hour) to track the fall in glucose and the recovery from hypoglycemia.
    • Blood samples for counter-regulatory hormones (growth hormone, glucagon, cortisol) are also taken at specific intervals (e.g., 0, 30, 60, 90, and 120 minutes).
  1. Hypoglycemic Response
    • As insulin induces hypoglycemia, the body releases growth hormone, glucagon, and cortisol to counteract the low glucose levels and restore homeostasis.
    • The hypoglycemic response should cause an increase in glucose levels within 1-2 hours, depending on the individual’s insulin sensitivity and counter-regulatory hormone secretion.
  1. Termination of the Test
    • The test is terminated if the blood glucose level falls below 50 mg/dL (2.8 mmol/L) or if the patient exhibits hypoglycemia symptoms (e.g., shaking, dizziness, confusion).
    • If the glucose level does not return to normal after insulin administration or the counter-regulatory hormones do not respond adequately, the test may indicate insulin resistance or endocrine dysfunction.

 

Interpretation of Results

  1. Normal Response:
    • Blood glucose levels typically fall below 30-60 minutes after insulin injection.
    • The body should respond by releasing growth hormone, cortisol, and glucagon to stimulate the liver to produce glucose and restore blood glucose levels to normal within 1-2 hours.
    • Normal recovery is typically seen when glucose levels return to baseline levels after a peak in the counter-regulatory hormones.
  2. Abnormal Response:
    • Inadequate response: A blunted or absent release of growth hormone and cortisol in response to insulin-induced hypoglycemia can suggest growth hormone deficiency or adrenal insufficiency.
    • Delayed recovery: If glucose levels do not return to normal within a few hours, it may suggest insulin resistance or impaired counter-regulatory mechanisms.
    • Severe hypoglycemia without adequate recovery can also indicate insulin overdose or insulin sensitivity issues.
  3. Diagnosis:
    • If the blood glucose falls below 50 mg/dL (2.8 mmol/L) and does not recover appropriately, it may suggest hypopituitarism (especially growth hormone deficiency).
    • The failure to release growth hormone or cortisol despite hypoglycemia can point to hypothalamic-pituitary dysfunction or adrenal insufficiency.
    • Inadequate glucose recovery can indicate insulin resistance or diabetes.

 

Clinical Significance

  1. Diagnosis of Growth Hormone Deficiency:
    • The ITT is one of the most reliable tests for diagnosing growth hormone deficiency (GHD) in adults and children. A failure to increase growth hormone in response to insulin-induced hypoglycemia is a diagnostic feature.
  2. Adrenal Insufficiency and Cushing’s Syndrome:
    • The ITT is also used to assess the hypothalamic-pituitary-adrenal (HPA) axis. If the body does not respond to hypoglycemia by releasing cortisol, it may indicate adrenal insufficiency or hypopituitarism.
    • The ITT can help differentiate between Cushing’s syndrome (excessive cortisol) and adrenal insufficiency (low cortisol).
  3. Insulin Sensitivity and Insulin Resistance:
    • The ITT can provide valuable information regarding insulin resistance, often associated with type 2 diabetes and metabolic syndrome. If there is a delayed glucose recovery, it suggests insulin resistance.
  4. Monitoring of Hypoglycemia:
    • The test is also used to assess insulin sensitivity and help diagnose hypoglycemia in patients with unexplained low blood sugar levels.
  5. Research and Clinical Applications:
    • The ITT is widely used in research settings to assess insulin resistance and endocrine function. It also helps monitor the effectiveness of therapies in metabolic and endocrine disorders.

 

Limitations

  1. Risk of Hypoglycemia: The ITT can induce severe hypoglycemia, which can lead to symptoms of dizziness, confusion, or even seizures in rare cases.
  2. Patient Discomfort: The test is uncomfortable and may not be suitable for children, elderly, or patients with cardiac or vascular disease.
  3. Invasive: The test requires multiple blood draws, which can be inconvenient and stressful for some patients.
  4. False Results: Patients with conditions like severe liver disease, kidney failure, or chronic illness may have altered responses that complicate the interpretation of results.

 

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