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The glucose tolerance test (GTT, not to be confused with GGT test) is a
medical test A medical test is a medical procedure performed to detect, diagnose, or monitor diseases, disease processes, susceptibility, or to determine a course of treatment. Medical tests such as, physical and visual exams, diagnostic imaging, genetic te ...
in which
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
is given and
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
samples taken afterward to determine how quickly it is cleared from the blood. The test is usually used to test for
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
,
insulin resistance Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood gluco ...
, impaired
beta cell Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dimini ...
function, and sometimes
reactive hypoglycemia Reactive hypoglycemia, postprandial hypoglycemia, or sugar crash is a term describing recurrent episodes of symptomatic hypoglycemia occurring within four hours"Hypoglycemia." It can also be referred to as "sugar crash" or "glucose crash." Nati ...
and
acromegaly Acromegaly is a disorder that results from excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There may also be an enlargement of the forehead, jaw, and nose. Other ...
, or rarer disorders of
carbohydrate metabolism Carbohydrate metabolism is the whole of the biochemistry, biochemical processes responsible for the metabolic anabolism, formation, catabolism, breakdown, and interconversion of carbohydrates in life, living organisms. Carbohydrates are central t ...
. 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. 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. 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, 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.


Testing

Since the 1970s, the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
and other organizations interested in diabetes agreed on a standard dose and duration.


Preparation

The patient is instructed not to restrict
carbohydrate In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ma ...
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 A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test result ...
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. Medication such as large doses of
salicylates Salicylic acid is an organic compound with the formula HOC6H4CO2H. A colorless, bitter-tasting solid, it is a precursor to and a metabolite of aspirin (acetylsalicylic acid). It is a plant hormone, and has been listed by the EPA Toxic Substa ...
,
diuretics A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...
,
anticonvulsants Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
, and
oral contraceptives Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control. Female Two types of female oral contraceptive pill, taken once per day, are widely available: * The combin ...
affect the glucose tolerance test.


Procedure

# A zero time (baseline) blood sample is drawn. # The patient is then given a measured dose (below) of glucose solution to drink within a 5-minute time frame. # Blood is drawn at intervals for measurement of glucose (
blood sugar Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...
), and sometimes
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
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.


Dose of glucose and variations

* 75 g of oral dose is the recommendation of the
WHO Who or WHO may refer to: * Who (pronoun), an interrogative or relative pronoun * Who?, one of the Five Ws in journalism * World Health Organization Arts and entertainment Fictional characters * Who, a creature in the Dr. Seuss book '' Horton He ...
to be used in all adults, and is the main dosage used in the United States. The dose is adjusted for weight only in children. The dose should be drunk within 5 minutes. * A variant is often used in
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
to screen for
gestational diabetes Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, it increases the risk of pre-eclampsia, depression, and of ...
, with a screening test of 50 g over one hour. If elevated, this is followed with a test of 100 g over three hours. * In UK general practice, the standard glucose load was provided by 394 ml of the energy drink
Lucozade Lucozade is a British brand of soft drink manufactured and marketed by the Japanese company Suntory. Created as "Glucozade" in the UK in 1927 by a Newcastle-upon-Tyne, Newcastle pharmacist, William Walker Hunter (trading as W. Owen & Son), it ...
with original carbonated flavour, but this is being superseded by purpose-made drinks.


Substances measured and variations

If
renal glycosuria Renal glycosuria is a rare condition in which the simple sugar glucose is excreted in the urine despite normal or low blood glucose levels. With normal kidney (renal) function, glucose is excreted in the urine only when there are abnormally elevat ...
(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 5.6 mmol/L (100 mg/dL). Fasting levels between 5.6 and 6.9 mmol/L (100 and 125 mg/dL) indicate prediabetes ("
impaired fasting glucose Impaired fasting glucose is a type of prediabetes, in which a person's blood sugar levels during fasting are consistently above the normal range, but below the diagnostic cut-off for a formal diagnosis of diabetes mellitus. Together with impaired ...
"), and fasting levels repeatedly at or above 7.0 mmol/L (>126 mg/dL) are diagnostic of diabetes. * For a 2 hour GTT with 75 g intake, a glucose level below 7.8 mmol/L (140 mg/dL) is normal, whereas higher levels indicate
hyperglycemia Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200  mg/dL), but symptoms may not start to become noticeable until even ...
. Blood plasma glucose between 7.8 mmol/L (140 mg/dL) and 11.1 mmol/L (200 mg/dL) indicate "
impaired glucose tolerance Prediabetes is a component of the metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms but people with prediabetes often have obesit ...
", and levels at or above 11.1 mmol/L at 2 hours confirm a diagnosis of diabetes. For
gestational diabetes Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, it increases the risk of pre-eclampsia, depression, and of ...
, the
American College of Obstetricians and Gynecologists The American College of Obstetricians and Gynecologists (ACOG) is a professional association of physicians specializing in obstetrics and gynecology in the United States. Several Latin American countries are also represented within Districts of ...
(ACOG) recommends a two-step procedure, wherein the first step is a 50 g glucose dose. If after 1 hour the blood glucose level is more than 7.8 mmol/L (140 mg/dL), it is followed by a 100 g glucose dose. The diagnosis of gestational diabetes is then defined by a blood glucose level meeting or exceeding the cutoff values on at least two intervals, with cutoffs as follows: * Before glucose intake (fasting): 5.3 mmol/L (95 mg/dL) * 1 hour after drinking the glucose solution: 10.0 mmol/L (180 mg/dL) * 2 hours: 8.6 mmol/L (155 mg/dL) * 3 hours: 7.8 mmol/L (140 mg/dL)


Sample method

The diagnosis criteria stated above by the World Health Organization (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. The diagnosis criteria issued by the WHO are only suitable 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 no conversion factor had 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 normal levels do not preclude the diagnosis, abnormal levels do not prove that the patient's other symptoms are related to a demonstrated atypical OGTT, and 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 Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, it increases the risk of pre-eclampsia, depression, and of ...
. It can be done at any time of day, not on an empty stomach. The test involves 50 g of glucose, with a reading after one hour.


Limitations of OGTT

The OGTT does not distinguish between insulin resistance in peripheral tissues and reduced capacity of the pancreas beta-cells to produce insulin. The OGTT is less accurate than the hyperinsulinemic-euglycemic clamp technique (the "gold standard" for measuring insulin resistance), or the
insulin tolerance test An insulin tolerance test (ITT) is a medical diagnostic procedure during which insulin is injected into a patient's vein, after which blood glucose is measured at regular intervals. This procedure is performed to assess pituitary function, adrenal ...
, but is technically less difficult. Neither of the two technically demanding tests can be easily applied in a clinical setting or used in epidemiological studies. HOMA-IR (
homeostatic model assessment The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta-cell function. It was first described under the name HOMA by Matthews ''et al.'' in 1985. Derivation The HOMA authors used data from physiological stu ...
) is a convenient way of measuring insulin resistance in normal subjects, which can be used in epidemiological studies, but can give erroneous results for diabetic patients.


References

{{Diabetes Diabetes-related tests Blood tests Dynamic endocrine function tests