Glucose Tolerance Test – Principle, Procedure, Types, Applications

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What is a Glucose Tolerance Test?

Glucose Tolerance Test (GTT) is a medical test which is used to measure how effectively the body processes the glucose (sugar) from blood into the tissues. It is most commonly performed as Oral Glucose Tolerance Test (OGTT). It is mainly used for diagnosis of metabolic conditions like prediabetes type 2 diabetes and gestational diabetes (during pregnancy). It can also be used for evaluation of insulin resistance reactive hypoglycemia and a rare hormonal disorder called acromegaly.

In this test the fasting blood sample is taken first. This is done after patient has not taken food or drink for at least 8 hours and this is referred to as baseline blood sugar level. After this the patient is given a sweet syrupy glucose solution which contains a fixed amount of glucose (usually 75 g for non pregnant adults). It is consumed within five minutes.

After drinking glucose solution the blood samples are taken at specific time intervals. These samples are taken at one hour two hour and sometimes three hour after drink to check how quickly insulin clears the glucose from blood. If the blood sugar level remains abnormally high during these intervals (for example 200 mg/dL or higher at 2 hour mark) then it indicates that the body is not utilizing insulin properly and diagnosis of diabetes can be confirmed.

Principle of Glucose Tolerance Test

Principle of Glucose Tolerance Test (GTT) is based on dynamic evaluation of glucose insulin feedback loop. It is done by measuring how pancreas secretes insulin and how peripheral tissues shows insulin sensitivity after glucose load. When a standardized oral glucose solution is given it triggers incretin effect. In this process gastrointestinal tract senses glucose and gut hormones are released like GIP (Gastric inhibitory polypeptide) and GLP-1 (Glucagon like peptide-1). These hormones are carried to pancreas and insulin secretion is stimulated and this accounts for about 50% to 70% of total insulin released after oral glucose intake.

In normal healthy person a biphasic insulin response is produced. First phase is immediate rapid release of stored insulin within first 10 minutes and it helps in stopping liver to produce more glucose. Second phase is prolonged steady release of newly synthesized insulin for next few hours. This sustained release drives glucose from blood into skeletal muscle and fat tissues for energy and storage.

By simulating a meal like physiological stress and tracking how efficiently glucose is cleared from blood the metabolic dysfunctions can be exposed. These includes loss of early phase insulin release or peripheral insulin resistance which is not detected by static fasting tests.

Types of Glucose Tolerance Test

Types of Glucose Tolerance Test are as follows–

  1. Oral Glucose Tolerance Test (OGTT)
    It is most common type of glucose tolerance test. In this test glucose rich drink is given and blood samples are taken at regular intervals. Standard diagnostic test is 2 hour OGTT and it is usually done with 75 g glucose load.
  2. Intravenous Glucose Tolerance Test (IVGTT)
    In this test glucose bolus is administered directly into bloodstream through IV line and digestive system is bypassed. It is mainly used in research for evaluation of beta cell function or when oral intake is not feasible.
  3. Gestational Glucose Tolerance Tests
    These are used for screening and diagnosis of gestational diabetes during pregnancy. These includes–
    • One hour glucose challenge test – It is screening test in which 50 g glucose is given without prior fasting.
    • Three hour glucose tolerance test – It is follow up diagnostic test. It requires 8 hour fasting and 100 g glucose drink is given. Blood sample is taken at 1 hour 2 hour and 3 hour after ingestion.
  4. Extended Oral Glucose Tolerance Test (5 hour or 6 hour OGTT)
    It is prolonged version of standard OGTT. It is used for evaluation of reactive (postprandial) hypoglycemia and late stage drop in blood sugar can be detected.
  5. Acromegaly Glucose Tolerance Test
    It is special test used for diagnosis of acromegaly. After glucose liquid is consumed the human growth hormone (HGH) level is measured instead of only blood sugar. It is done to see whether glucose suppresses HGH production or not.

Materials Required

Materials Required for Glucose Tolerance Test are as follows–

  1. Standardized oral glucose solution
    It is sweet syrupy glucose drink. It is sometimes referred as Glucola and commercial alternatives are Lucozade and Polycal. It contains precise amount of dissolved glucose and usually 50 g 75 g or 100 g glucose is present depending on test variation.
  2. Blood collection tubes
    These are used for collection and preservation of blood samples. Gray top tubes are commonly used and it contains glycolytic inhibitor (sodium fluoride and potassium oxalate) to prevent glucose degradation. Lithium Heparin plasma separator tubes can also be used. For special evaluations like acromegaly test yellow top flox tubes for glucose and brown top gel tubes for hormone testing may be used.
  3. Intravenous (IV) cannula and line
    It is required in Intravenous Glucose Tolerance Test (IVGTT) for injecting glucose bolus directly into bloodstream. It can also be used for frequent blood sampling in tests like acromegaly GTT.
  4. Urine specimen containers
    It is required in some extended glucose tolerance protocols. Urine samples are collected along with scheduled blood draws.
  5. Centrifuge
    It is laboratory equipment used to spin blood samples and separate plasma from blood cells. It is done within 30 to 60 minutes after collection for accurate glucose measurement.

Requirements for Glucose Tolerance Test (GTT)

Requirements for Glucose Tolerance Test (GTT) are as follows–

  1. Diet
    Unrestricted diet should be taken before test. It should contain at least 150 g carbohydrates per day for 3 days before the test.
  2. Physical activity
    Normal physical activity is maintained. Unusual or strenuous exercise is avoided for at least 12 hours before the test.
  3. Medications
    Some drugs can interfere with result. It is checked with healthcare provider and some medications may be discontinued for few days before the test.
  4. Health status
    Test should not be done when patient is hospitalized or on bed rest. If acute illness trauma or surgery has occurred then test is done after at least 2 weeks.
  5. Fasting
    Fasting is required for 8 to 14 hours before test. During fasting only plain water is allowed and no food or other drinks is taken.
  6. Hydration
    Patient should be well hydrated with water before test.
  7. Timing of test
    Test is scheduled in morning. It is preferably done between 7:00 AM to 9:00 AM because natural daily variation in glucose tolerance can affect result.
  8. Substances to avoid
    Smoking is avoided during fasting period. Caffeine is also not consumed during fasting.
  9. Drinking glucose solution
    Whole glucose drink provided by clinic is consumed within 5 minutes.
  10. Inactivity during test
    Patient remains seated and relatively inactive for whole duration of test. Walking around or exercise is not done because muscle glucose utilization can alter result.
  11. No eating or smoking during test
    Eating is not allowed during the test. Smoking is also not allowed while test is ongoing.
  12. Vomiting
    If glucose solution is vomited then test must be discontinued.

Procedure of Glucose Tolerance Test

Procedure of standard Glucose Tolerance Test

Procedure of standard Glucose Tolerance Test is as follows–

  1. Pre test preparation
    Normal diet is taken before test. Unrestricted diet containing at least 150 g carbohydrates per day is consumed for 3 days before test. Strenuous or unusual exercise is avoided for at least 12 hours before appointment. Overnight fasting is done for 8 to 14 hours and only plain water is allowed. Medications which affect blood sugar are consulted with doctor and morning medications are not taken on day of test until procedure is finished.
  2. Morning arrival
    Test is scheduled early in morning. It is usually done between 7:00 AM to 9:00 AM.
  3. Baseline blood draw
    Initial blood sample is collected from a vein in arm. This is done to establish fasting blood glucose level.
  4. Drinking glucose solution
    Sweet syrupy glucose solution is given. Standard amount of glucose is present and usually 75 g glucose dissolved in water is used for non pregnant adults. Whole drink is consumed within 5 minutes.
  5. Waiting and resting
    Patient is asked to remain seated and relatively inactive for duration of test. Walking around is not allowed. Eating and smoking are also not allowed during test.
  6. Interval blood draws
    Additional blood samples are collected at specific intervals. It is usually taken at 1 hour and 2 hour after finishing the glucose drink to track body response. In some variations sample is taken at 3 hour or more.
  7. After the test
    After final blood sample is collected patient can eat and drink immediately and regular medications can be taken. Snack can be taken after test. Patient is allowed to leave clinic and normal daily activities can be resumed.

Procedure of Oral Glucose Tolerance Test (OGTT)

Procedure of Oral Glucose Tolerance Test (OGTT) is as follows–

  1. Preparation before test
    Normal unrestricted diet is taken and at least 150 g carbohydrate per day is consumed for 3 days before test. Normal physical activity is maintained but strenuous or unusual exercise is avoided for at least 12 hours before appointment. Fasting is done for 8 to 14 hours before test and only plain water is allowed. Test is scheduled in early morning and it is preferably between 7:00 AM to 9:00 AM. Medications are consulted with healthcare provider and morning medications are skipped till the test is completed.
  2. Baseline blood draw
    Initial blood sample is collected from vein to establish fasting blood glucose level.
  3. Glucose drink
    Sweet glucose solution is given to drink. For non pregnant adults it usually contains 75 g glucose dissolved in 250 to 300 mL water. In children dose is adjusted according to body weight (up to 75 g). Whole drink is consumed within 5 minutes and the time of finishing drink is counted as time zero.
  4. Waiting period
    Patient is asked to sit and rest for duration of test. Walking and exercising is not allowed. Eating and smoking is also prohibited during test. If glucose drink is vomited then test must be discontinued.
  5. Interval blood draws
    Blood samples are collected at specific intervals to measure glucose processing. In standard 2 hour OGTT blood is drawn at exactly 1 hour and 2 hour after finishing drink.
  6. After the test
    After final blood sample is collected test is completed and patient can return to normal daily activities. Patient can eat and drink immediately and regular medications can be taken. Snack is often recommended after test is done.

Procedure of Intravenous Glucose Tolerance Test (IVGTT)

Procedure of Intravenous Glucose Tolerance Test (IVGTT) is as follows–

  1. Intravenous administration
    In this test glucose is administered directly into bloodstream through intravenous (IV) line. Gastrointestinal tract is bypassed completely.
  2. Glucose dosage
    Standard glucose dose is given according to body weight. It is usually 0.5 g per kg body weight and maximum dose is up to 35 g.
  3. Infusion time
    Whole glucose bolus is infused quickly into vein. It is usually completed within about 3 minutes.
  4. Frequent blood sampling
    After glucose injection blood samples are collected at very frequent short intervals. It is done to measure intrinsic pancreatic beta cell response.
  5. Specific intervals
    Blood samples are taken at 1 minute 3 minute 5 minute 7 minute and 10 minute after glucose administration. This rapid sampling is designed to capture First Phase Insulin Response (FPIR).
  6. Post test monitoring
    After test patient is monitored for complications related to IV line. Thrombophlebitis (inflammation of vein) can occur at injection site and it is checked.

Procedure of Gestational Glucose Tolerance Tests

Procedure of Gestational Glucose Tolerance Tests is as follows–

  1. Timing of test
    Gestational glucose tolerance tests are usually performed between 24 to 28 weeks of pregnancy. Two main strategies are used for screening and diagnosis of gestational diabetes. These are one step strategy and two step strategy.
  2. One step strategy (75 g 2 hour test)
  • Fasting is done overnight for 8 hours before test.
  • Baseline blood sample is collected to measure fasting blood glucose.
  • Glucose drink containing 75 g sugar is given and it is consumed.
  • Blood samples are collected at 1 hour and 2 hour after finishing drink to evaluate glucose processing.
  1. Two step strategy

Step 1 – One hour glucose challenge test (50 g)

  • Fasting is not required before this screening test.
  • Initial baseline blood sample is taken and measured.
  • Glucose drink containing 50 g sugar is given.
  • After exactly 1 hour blood sample is collected to check blood sugar level.
  • If blood sugar meets or exceeds threshold (usually 130 mg/dL or 140 mg/dL) then Step 2 is required for definitive diagnosis.

Step 2 – Three hour glucose tolerance test (100 g)

  • Fasting is done overnight for 8 hours before this follow up diagnostic test.
  • Baseline fasting blood sample is collected to establish baseline blood sugar.
  • Concentrated glucose solution containing 100 g sugar is given to drink.
  • Patient remains in clinic or lab waiting area for whole duration of test.
  • Blood samples are collected at 1 hour 2 hour and 3 hour after drinking solution. Gestational diabetes is usually diagnosed when at least two values are higher than expected.

Procedure of Extended Oral Glucose Tolerance Test (5-hour or 6-hour OGTT)

Procedure of Extended Oral Glucose Tolerance Test is as follows–

  1. Pre test fasting
    Overnight fasting is done. It is started after evening meal or after midnight. Eating and drinking is not done and only water is allowed till test begins.
  2. Baseline samples
    Patient arrives at medical facility in fasting condition. Initial blood sample is collected for baseline level. Urine specimen is also collected to establish baseline.
  3. Glucose drink
    Sweet glucose beverage is given to drink. It is often called Glucola. It contains specifically measured amount of glucose.
  4. Interval sampling
    After finishing drink blood sample is collected at fixed intervals. Urine specimen is also collected along with blood. Sample is taken at 30 minutes after drink then at 1 hour and then every hour till 5 hour or 6 hour is completed. In some protocols samples are collected at half hour intervals or at 30 60 90 120 180 and 300 minutes depending on doctor protocol.
  5. Symptom monitoring
    During prolonged test patient must observe symptoms properly. Symptoms of reactive hypoglycemia like sweating dizziness weakness racing heart and confusion are noted. Exact time of symptoms is written down.
  6. Immediate sampling for symptoms
    If severe or uncomfortable symptoms occurs between scheduled intervals then staff is informed and blood is collected immediately. This is crucial step because lowest blood sugar reading is captured at time of symptoms and it is not delayed till next scheduled sample.

Procedure of Acromegaly Glucose Tolerance Test

Procedure of Acromegaly Glucose Tolerance Test is as follows–

  1. Pre test preparation
    Unrestricted carbohydrate diet is followed for 3 days before test. Fasting is started from 10:00 PM night before test and fasting of more than 10 hours is maintained. Water is allowed during fasting. Morning medications are not taken before test and if patient is on insulin then it is also omitted. Medications are taken after test is finished.
  2. Morning arrival and setup
    Patient arrives early in morning usually around 8:30 AM. IV cannula is inserted into vein at least 10 minutes before test begins so that multiple blood samples can be collected easily. Patient remains seated throughout test and smoking is strictly prohibited.
  3. Baseline blood draw (Time 0)
    Initial blood sample is collected through IV. Baseline level of growth hormone (GH) Insulin like growth factor-1 (IGF-1) and glucose is measured.
  4. Glucose solution
    Sweet glucose drink is given containing 75 g glucose load. If glucose solution is vomited then test must be discontinued.
  5. Interval blood draws
    Blood samples are collected through IV at 30 minutes 60 minutes 90 minutes and 120 minutes after finishing drink. These samples are used to see whether glucose suppresses growth hormone level or not.
  6. After the test
    After 120 minute blood sample is collected breakfast is given. Patient can take usual morning medications after test is completed.

Uses of Glucose Tolerance Test

Uses of Glucose Tolerance Test are as follows–

  • It is used for screening and diagnosis of impaired fasting glucose impaired glucose tolerance prediabetes and type 2 diabetes. It is especially used when fasting blood glucose level is borderline.
  • It is used as standard test for screening and diagnosis of gestational diabetes mellitus (GDM) during pregnancy.
  • It is used for diagnosis of acromegaly. It is considered as definitive biochemical test to diagnose acromegaly and it is also used to monitor treatment success.
  • It is used for evaluation of reactive (postprandial) hypoglycemia. Late stage drop in blood sugar is captured and it helps in diagnosis.
  • It is used for evaluation of insulin resistance. Peripheral insulin resistance and impaired pancreatic beta cell function is evaluated.
  • Intravenous form (IVGTT) is used in research settings to predict onset of type 1 diabetes in at risk individuals.
  • It is used for diagnosis of rare carbohydrate metabolism disorders.
  • It is used to evaluate glycosuria (sugar in urine) without hyperglycemia like renal glycosuria.
  • It can be applied for investigation of unexplained hypertriglyceridemia neuropathy impotence retinopathy or diabetes like renal disease.
  • Abnormal carbohydrate metabolism identified by this test can help in predicting perinatal morbidity and risk of fetal abnormalities during pregnancy.

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