Glucose tolerance test

The glucose tolerance test is a medical test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood.^[1] The test is usually used to test for diabetes, insulin resistance, impaired beta cell function,^[2] and sometimes reactive hypoglycemia and acromegaly, or rarer disorders of carbohydrate metabolism. In the most commonly performed version of the test, an oral glucose tolerance test (OGTT), a standard dose of glucose is ingested by mouth and blood levels are checked two hours later.^[3] Many variations of the GTT have been devised over the years for various purposes, with different standard doses of glucose, different routes of administration, different intervals and durations of sampling, and various substances measured in addition to blood glucose.

History

The glucose tolerance test was first described in 1923 by Jerome W. Conn.^[4]

The test was based on the previous work in 1913 by A. T. B. Jacobson in determining that carbohydrate ingestion results in blood glucose fluctuations,^[5] and the premise (named the Staub-Traugott Phenomenon after its first observers H. Staub in 1921 and K. Traugott in 1922) that a normal patient fed glucose will rapidly return to normal levels of blood glucose after an initial spike, and will see improved reaction to subsequent glucose feedings.^[6][7]

Testing

Since the 1970s, the World Health Organization and other organizations interested in diabetes agreed on a standard dose and duration.

Preparation

The patient is instructed not to restrict carbohydrate intake in the days or weeks before the test. The test should not be done during an illness, as results may not reflect the patient's glucose metabolism when healthy. A full adult dose should not be given to a person weighing less than 42.6 kg (94 lb), or the excessive glucose may produce a false positive result. Usually the OGTT is performed in the morning as glucose tolerance can exhibit a diurnal rhythm with a significant decrease in the afternoon. The patient is instructed to fast (water is allowed) for 8–12 hours prior to the tests

Procedure

1. A zero time (baseline) blood sample is drawn.
2. The patient is then given a measured dose (below) of glucose solution to drink within a 5 minute time frame.
3. Blood is drawn at intervals for measurement of glucose (blood sugar), and sometimes insulin levels. The intervals and number of samples vary according to the purpose of the test. For simple diabetes screening, the most important sample is the 2 hour sample and the 0 and 2 hour samples may be the only ones collected. A laboratory may continue to collect blood for up to 6 hours depending on the protocol requested by the physician.#gtt

Dose of glucose and variations

• In the US, dosing is by weight, and since the late 1970s has been 1.75 grams of glucose per kilogram of body weight, to a maximum dose of 75g. Prior to 1975 a dose of 100g was often used.
• The WHO recommendation is for a 75g oral dose in all adults: the dose is adjusted for weight only in children.^[8] The dose should be drunk within 5 minutes.
• A variant is often used in pregnancy to screen for gestational diabetes, with a screening test of 50 grams over one hour. If elevated, this is followed with a test of 100 grams over three hours.
• In UK General Practice, the standard glucose load is provided by 394ml of the sports drink Lucozade (original flavour only), which the patient is asked to supply.^[9][10]
• In Portugal, the standard glucose load is provided by the clinical laboratory or hospital by 200 ml of a PET bottle. The most well known brand and used is TopStar, produced in Portugal. The recommendation is for a 75g oral dose in all adults and is adjusted for weight in children. However is also used the concentrations of 50g and 100g and usually in 3 flavors and aroma (orange, lemon and cola).

Substances measured and variations

If renal glycosuria (sugar excreted in the urine despite normal levels in the blood) is suspected, urine samples may also be collected for testing along with the fasting and 2 hour blood tests.

Results

• Fasting plasma glucose (measured before the OGTT begins) should be below 6.1 mmol/L (110 mg/dL). Fasting levels between 6.1 and 7.0 mmol/L (110 and 125 mg/dL) are borderline ("impaired fasting glycaemia"), and fasting levels repeatedly at or above 7.0 mmol/L (126 mg/dL) are diagnostic of diabetes.
• A 1 hour GTT (Glucose Tolerance Test) glucose level below 10 mmol/L (180 mg/dL) is considered normal.^[11][12]
• A 2 hour GTT (Glucose Tolerance Test) glucose level below 7.8 mmol/L (140 mg/dL) is normal, whereas higher glucose levels indicate hyperglycemia. Blood plasma glucose between 7.8 mmol/L (140 mg/dL) and 11.1 mmol/L (200 mg/dL) indicate "impaired glucose tolerance", and levels above 11.1 mmol/L (200 mg/dL) at 2 hours confirm a diagnosis of diabetes.

In the 75g OGTT that diagnoses for Gestational Diabetes: Fasting level should be below 5.1 mmol/L;2 hour level should be below 8.5 mmol/L.^[12]

Sample method

It is important to stress that the diagnosis criteria stated above by the World Health Organisation (WHO) are for venous samples only (a blood sample taken from a vein in the arm). An increasingly popular method for measuring blood glucose is to sample capillary or finger-prick blood, which is less invasive, more convenient for the patient and requires minimal training to conduct. Though fasting blood glucose levels have been shown to be similar in both capillary and venous samples, postprandial blood glucose levels (those measured after a meal) can vary. Therefore, the diagnosis criteria issued by the WHO should only be used for venous blood samples. Given the increasing popularity of capillary testing, the WHO has recommended that a conversion factor between the two sample types be calculated, but to date no conversion factor has been issued by the WHO despite some medical professionals adopting their own.

Variations

A standard two-hour GTT (Glucose Tolerance test) is sufficient to diagnose or exclude all forms of diabetes mellitus at all but the earliest stages of development. Longer tests have been used for a variety of other purposes, such as detecting reactive hypoglycemia or defining subsets of hypothalamic obesity. Insulin levels are sometimes measured to detect insulin resistance or deficiency.

The GTT (Glucose Tolerance Test) is of limited value in the diagnosis of reactive hypoglycemia, since (1) normal levels do not preclude the diagnosis, (2) abnormal levels do not prove that the patient's other symptoms are related to a demonstrated atypical OGTT, and (3) many people without symptoms of reactive hypoglycemia may have the late low glucose.

Oral glucose challenge test

The oral glucose challenge test (OGCT) is a short version of the OGTT, used to check pregnant women for signs of gestational diabetes.^[3][13] It can be done at any time of day, not on an empty stomach.^[3] The test involves 50g of glucose, with a reading after one hour.^[3]

References

1. Glucose Tolerance Test at the US National Library of Medicine Medical Subject Headings (MeSH)
2. DeFronzo RA, Abdul-Ghani M (2011). "Assessment and treatment of cardiovascular risk in prediabetes: impaired glucose tolerance and impaired fasting glucose". American Journal of Cardiology 108 (3 Suppl): 3B–24B. doi:10.1016/j.amjcard.2011.03.013. PMID 21802577.
3. Institute for Quality and Efficiency in Health Care. "Glucose tolerance test: how does it work exactly?". Informed Health Online. Institute for Quality and Efficiency in Health Care. Retrieved 22 June 2013.
4. "Conn JW. Interpretation of the glucose tolerance test. The necessity of a standard preparatory diet. Am J Med Sci. 1940; 199: 555-564".
5. "Jacobsen ATB. Untersuchungen uber den Einfluss verschiedener Nahrungsmittel auf den Blutzucker bei normalen, zuckerkranken und graviden Personen. Biochem Z 1913;56:471–494".
6. "TRAUGOTT K. Uber das verhalten des blutzucker spiegels bei wiederholter und verschiedener art enteraier zuchersufuhr and dessen. Bedeutung fur die leberfunction. Klin. Wochenschr. 1: 892, 1922.".
7. "Staub, H., Biochem. Z., 1921, cxviii, 93.".
8. World Health Organization and International Diabetes Federation (1999). Definition, diagnosis and classification of diabetes mellitus and its complications. Geneva, Switzerland: World Health Organization.
9. Salford Royal NHS Trust. "Glucose Tolerance Tests in Primary Care". Retrieved 2012-06-20.
10. Dr Jane Patmore (2009). "Oral Glucose Tolerance Tests: Protocol and Guidance" (PDF). Hull and East Riding Diabetes Network, Hull NHS teaching hospitals trust. Retrieved 2012-06-20.
11. http://www.mayoclinic.org/tests-procedures/glucose-tolerance-test/basics/results/prc-20014814
12. https://labtestsonline.org/understanding/analytes/glucose/tab/test
13. Hartling, L; Dryden, DM; Guthrie, A; et al. (October 2012). "Screening and Diagnosing Gestational Diabetes Mellitus". Evidence Reports/Technology Assessments, No. 210. Agency for Healthcare Research and Quality. Retrieved 22 June 2013.