Editing Glucose tolerance test

{{Short description|Medical test of how quickly glucose is cleared from the blood}}
{{Infobox diagnostic
| name            = Glucose tolerance test
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| purpose         = To determine how quickly glucose is cleared from blood
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The '''glucose tolerance test''' ('''GTT''', not to be confused with [[GGT 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.<ref>{{MeshName|Glucose+Tolerance+Test}}</ref> The test is usually used to test for [[Diabetes mellitus|diabetes]], [[insulin resistance]], impaired [[Pancreatic beta cell function|beta cell function]],<ref name="pmid21802577">{{cite journal|vauthors=DeFronzo RA, Abdul-Ghani M|title=Assessment and treatment of cardiovascular risk in prediabetes: impaired glucose tolerance and impaired fasting glucose|journal=[[American Journal of Cardiology]]|volume=108|issue=3&nbsp;Suppl|year=2011|pages=3B–24B |doi=10.1016/j.amjcard.2011.03.013|pmid=21802577}}</ref> 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.<ref name=IQWiG-GTT>{{cite web|last=Institute for Quality and Efficiency in Health Care|title=Glucose tolerance test: how does it work exactly?|url=https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0010385/|work=Informed Health Online|publisher=Institute for Quality and Efficiency in Health Care|access-date=22 June 2013}}</ref> 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]].<ref>{{cite journal|author=Conn, JW.|title=Interpretation of the glucose tolerance test. The necessity of a standard preparatory diet|journal= Am J Med Sci |year=1940 |volume=199 |pages=555–64|doi=10.1097/00000441-194004000-00014}}</ref>

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,<ref>{{cite journal | title=Jacobsen ATB. Untersuchungen über den Einfluss verschiedener Nahrungsmittel auf den Blutzucker bei normalen, zuckerkranken und graviden Personen. Biochem Z 1913; 56:471–94}}</ref> 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.<ref>{{cite journal|author=Traugott, K.|title=Über das Verhalten des Blutzuckerspiegels bei wiederholter und verschiedener Art enteraler Zuckerzufuhr and dessen Bedeutung für die Leberfunktion |journal=Klin. Wochenschr. |volume=1 |page=892 |year=1922|issue=18 |doi=10.1007/BF01715866 |s2cid=32368110 }}</ref><ref>{{cite journal|last=Staub |first=H. |title=Bahnung im intermediaren Zuckerstoffwechsel |journal=Biochem. Z. |year=1921 |volume=118 |page=93}}</ref>

==Testing==
Since the 1970s, the [[World Health Organization]] and other organizations interested in diabetes agreed on a standard dose and duration.<ref>{{Cite journal |title=Standards of Medical Care in Diabetes—2013 |journal=Diabetes Care |year=2013 |volume=36 |issue=Suppl 1 |pages=S11–S66 |doi=10.2337/dc13-S011 |issn=0149-5992 |pmc=3537269 |pmid=23264422|author1=American Diabetes Association }}</ref>

===Preparation===
The patient is instructed not to restrict [[carbohydrate]] intake in the days or weeks before the test.<ref>{{cite journal|doi=10.1210/jendso/bvab049|title=Carbohydrate Intake Prior to Oral Glucose Tolerance Testing |year=2021 |last1=Klein |first1=Klara R. |last2=Walker |first2=Christopher P. |last3=McFerren |first3=Amber L. |last4=Huffman |first4=Halie |last5=Frohlich |first5=Flavio |last6=Buse |first6=John B. |journal=Journal of the Endocrine Society |volume=5 |issue=5 |pages=bvab049 |pmid=33928207 |pmc=8059359 |doi-access=free }}</ref> 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&nbsp;kg (94&nbsp;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 [[fasting|fast]] (water is allowed) for 8–12 hours prior to the tests. Medication such as large doses of [[salicylates]], [[diuretics]], [[anticonvulsants]], and [[oral contraceptives]] affect the glucose tolerance test.<ref>{{Cite journal |last1=Salvaggio |first1=Heather L |last2=Zaenglein |first2=Andrea L |date=2010-08-09 |title=Examining the use of oral contraceptives in the management of acne |journal=International Journal of Women's Health |volume=2 |pages=69–76 |doi=10.2147/ijwh.s5915 |issn=1179-1411 |pmc=2971728 |pmid=21072299 |doi-access=free }}</ref>

===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]]), 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.

===Dose of glucose and variations===
* 75&nbsp;g of oral dose is the recommendation of the [[World Health Organization|WHO]] to be used in all adults,<ref name=who/> and is the main dosage used in the United States.<ref name=ADAstandards2020/> The dose is adjusted for weight only in children.<ref name=who>{{cite book|author=World Health Organization and International Diabetes Federation|title=Definition, diagnosis and classification of diabetes mellitus and its complications|location=Geneva, Switzerland|publisher=World Health Organization|year=1999}}</ref> 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&nbsp;g over one hour. If elevated, this is followed with a test of 100&nbsp;g over three hours.<ref name=ADAstandards2020/>
* In UK general practice, the standard glucose load was provided by 394&nbsp;ml of the energy drink [[Lucozade]] with original carbonated flavour, but this is being superseded by purpose-made drinks.<ref>
{{cite web|url=http://www.salforddiabetescare.co.uk/index2.php?nav_id=443|title=Glucose Tolerance Tests in Primary Care|author=Salford Royal NHS Trust|access-date=2012-06-20}}</ref><ref>{{cite web|url=http://www.erypct.nhs.uk/upload/HERHIS/East%20Riding%20PCTs/Document%20Store/Policies/diabetes_OGT_protocol&guidance_final_apr09.pdf|title=Oral Glucose Tolerance Tests: Protocol and Guidance|author=Jane Patmore|year=2009|publisher=Hull and East Riding Diabetes Network, Hull NHS teaching hospitals trust|access-date=2012-06-20|archive-url=https://web.archive.org/web/20120506131302/http://www.erypct.nhs.uk/upload/HERHIS/East%20Riding%20PCTs/Document%20Store/Policies/diabetes_OGT_protocol%26guidance_final_apr09.pdf|archive-date=2012-05-06|url-status=dead}}</ref>

===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.<ref>{{Cite web |title=Glucose - Urine |url=https://www.ucsfhealth.org/Medical%20Tests/003581 |access-date=2022-10-17 |website=ucsfhealth.org |language=en}}</ref>

==Results==
* ''Fasting plasma glucose'' (measured before the OGTT begins) should be below 5.6&nbsp;mmol/L (100&nbsp;mg/dL). Fasting levels between 5.6 and 6.9&nbsp;mmol/L (100 and 125&nbsp;mg/dL) indicate prediabetes ("[[impaired fasting glucose]]"), and fasting levels repeatedly at or above 7.0&nbsp;mmol/L (>126&nbsp;mg/dL) are diagnostic of diabetes.<ref name=ADAstandards2020>{{cite journal |title=2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020 |journal=Diabetes Care |date=20 December 2019 |volume=43 |issue=Supplement 1 |pages=S14–S31 |doi=10.2337/dc20-S002 |pmid=31862745 |url=https://care.diabetesjournals.org/content/43/Supplement_1/S14 |access-date=26 February 2020|doi-access=free |author1=American Diabetes Association }}</ref>
* For a ''2 hour GTT'' with 75&nbsp;g intake, a glucose level below 7.8&nbsp;mmol/L (140&nbsp;mg/dL) is normal, whereas higher levels indicate [[hyperglycemia]]. Blood plasma glucose between 7.8&nbsp;mmol/L (140&nbsp;mg/dL) and 11.1&nbsp;mmol/L (200&nbsp;mg/dL) indicate "[[impaired glucose tolerance]]", and levels at or above 11.1&nbsp;mmol/L at 2 hours confirm a diagnosis of diabetes.<ref name=ADAstandards2020/>

For [[gestational diabetes]], the [[American College of Obstetricians and Gynecologists]] (ACOG) recommends a two-step procedure, wherein the first step is a 50&nbsp;g glucose dose.<ref name=ADAstandards2020/><ref>{{cite journal|date=February 2018|title=ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus|journal=Obstetrics & Gynecology|volume=131|issue=2|pages=e49–e64|doi=10.1097/AOG.0000000000002501|pmid=29370047|author1=Committee on Practice Bulletins—Obstetrics|s2cid=3395229 }}</ref> If after 1 hour the blood glucose level is more than 7.8&nbsp;mmol/L (140&nbsp;mg/dL),<ref name=ADAstandards2020/> it is followed by a 100&nbsp;g glucose dose.<ref name=ADAstandards2020/> The diagnosis of gestational diabetes is then defined by a blood glucose level meeting or exceeding the cutoff values on at least two intervals,<ref name=ADAstandards2020/> with cutoffs as follows:<ref name=ADAstandards2020/>
* Before glucose intake (fasting): 5.3&nbsp;mmol/L (95&nbsp;mg/dL)
* 1 hour after drinking the glucose solution: 10.0&nbsp;mmol/L (180&nbsp;mg/dL)
* 2 hours: 8.6&nbsp;mmol/L (155&nbsp;mg/dL)
* 3 hours: 7.8&nbsp;mmol/L (140&nbsp;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.<ref name=nevander>{{cite journal | last1=Nevander | first1=Sofia | last2=Landberg | first2=Eva | last3=Blomberg | first3=Marie | last4=Ekman | first4=Bertil | last5=Lilliecreutz | first5=Caroline | title=Comparison of Venous and Capillary Sampling in Oral Glucose Testing for the Diagnosis of Gestational Diabetes Mellitus: A Diagnostic Accuracy Cross-Sectional Study Using Accu-Chek Inform II | journal=Diagnostics| volume=10 | issue=12 | date=26 November 2020 | issn=2075-4418 | doi=10.3390/diagnostics10121011|doi-access=free | page=1011| pmid=33255868 | pmc=7760160 }}</ref> 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 {{As of|2017|lc=y}} no conversion factor had been issued by the WHO, despite some medical professionals adopting their own.{{citation needed|date=November 2021}} A 2020 study on pregnant women for gestational diabetes mellitus (GDM) found that 0-hour venous and capillary levels were similar, but that 2-hour samples were different. The authors compared their study with others, and concluded that capillary samples could be used for diagnosis of GDM during pregnancy using corrected cutoffs with acceptable accuracy in an antenatal care setting.<ref name=nevander/><!--older WHO documents find fairly consistently that capillary values are similar at 0h, and about 1.1mmol/l higher at 2 hours, reasonably consistent with Nevander et al. https://apps.who.int/iris/rest/bitstreams/51753/retrieve (1994). https://applications.emro.who.int/dsaf/dsa509.pdf (2006). This could be added to the article, but should perhaps be discussed first.-->

==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.<ref>{{Cite journal |last1=Lv |first1=Xue |last2=Fang |first2=Kun |last3=Hao |first3=Wenqing |last4=Han |first4=Yuxin |last5=Yang |first5=Nailong |last6=Yu |first6=Qing |date=2020-12-02 |title=Identification of Reactive Hypoglycemia with Different Basic BMI and Its Causes by Prolonged Oral Glucose Tolerance Test |journal=Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy |volume=13 |pages=4717–4726 |doi=10.2147/DMSO.S280084 |issn=1178-7007 |pmc=7719337 |pmid=33293845 |doi-access=free }}</ref>

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.<ref>{{Cite journal |last1=Pant |first1=Vivek |last2=Mathema |first2=Safala |last3=Jha |first3=Sandeep |last4=Paudel |first4=Sujay Dutta |last5=Baral |first5=Suman |date=2021-12-07 |title=The Detection of Postprandial Hypoglycemia with 5-Hour Oral Glucose Tolerance Test |journal=EJIFCC |volume=32 |issue=4 |pages=451–457 |issn=1650-3414 |pmc=8751404 |pmid=35046763}}</ref>

==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]].<ref name=IQWiG-GTT /><ref name=AHRQ-GDM>{{cite book|last=Hartling|first=L|title=Screening and Diagnosing Gestational Diabetes Mellitus|url=https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0050423/|work=Evidence Reports/Technology Assessments, No. 210|publisher=Agency for Healthcare Research and Quality|access-date=22 June 2013|author2=Dryden, DM |author3=Guthrie, A |date=October 2012|issue=210|pages=1–327|pmid=24423035|pmc=4781607|display-authors=etal}}</ref> It can be done at any time of day, not on an empty stomach.<ref name=IQWiG-GTT /> The test involves 50&nbsp;g of glucose, with a reading after one hour.<ref name=IQWiG-GTT />

==Limitations of OGTT==
The OGTT does not distinguish between insulin resistance in peripheral tissues and reduced capacity of the pancreas [[Beta cell|beta-cells]] to produce insulin. The OGTT is less accurate than the [[Glucose clamp technique|hyperinsulinemic-euglycemic clamp technique]] (the "gold standard" for measuring insulin resistance), or the [[insulin tolerance test]], 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]]) 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.<ref name="pmid17957034">{{cite journal|vauthors=Muniyappa R, Lee S, Chen H, Quon MJ|title=Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage|journal=[[American Physiological Society#Publications|American Journal of Physiology. Endocrinology and Metabolism]]|volume=294|issue=1|pages=E15–E26|year=2008|doi=10.1152/ajpendo.00645.2007|url=http://ajpendo.physiology.org/content/294/1/E15.long|pmid=17957034|s2cid=848540|url-access=subscription|access-date=2017-02-13|archive-date=2017-08-17|archive-url=https://web.archive.org/web/20170817172932/http://ajpendo.physiology.org/content/294/1/E15.long|url-status=dead}}</ref><ref name="pmid21435930">{{cite journal|vauthors=Antuna-Puente B, Disse E, Rabasa-Lhoret R, Laville M, Capeau J, Bastard JP|title=How can we measure insulin sensitivity/resistance?|journal= Diabetes & Metabolism|volume=37|issue=5|pages=179–88|year=2011|doi=10.1016/j.diabet.2011.01.002|url=http://www.em-consulte.com/article/296652/alertePM|pmid=21435930|url-access=subscription}}</ref>

== See also ==
* [[Metabolic Score for Insulin Resistance (METS-IR)]]
* [[Homeostatic model assessment]]
* [[SPINA-GBeta]]
* [[SPINA-GR]]
* [[Disposition index]]
* [[Diabetes mellitus]]
* [[Diabetes management]]

==References==
{{Reflist}}

{{Diabetes}}
{{Authority control}}

[[Category:Diabetes-related tests]]
[[Category:Blood tests]]
[[Category:Dynamic endocrine function tests]]