Editing Insulin resistance (section)

==Diagnosis==
===Glucose tolerance testing===
During a [[glucose tolerance test]] (GTT), which may be used to diagnose diabetes mellitus, a fasting patient takes a 75&nbsp;gram oral dose of glucose. Then blood glucose levels are measured over the following two hours.

Interpretation is based on [[WHO]] guidelines. After two hours a [[blood sugar|glycemia]] less than 7.8&nbsp;mmol/L (140&nbsp;mg/dL) is considered normal, a glycemia of between 7.8 and 11.0&nbsp;mmol/L (140 to 197&nbsp;mg/dL) is considered as [[impaired glucose tolerance]] (IGT), and a glycemia of greater than or equal to 11.1&nbsp;mmol/L (200&nbsp;mg/dL) is considered [[diabetes mellitus]].

An [[oral glucose tolerance test]] (OGTT) may be normal or mildly abnormal in simple insulin resistance. Often, there are raised glucose levels in the early measurements, reflecting the loss of a postprandial peak (after the meal) in insulin production. Extension of the testing (for several more hours) may reveal a [[hypoglycemia|hypoglycemic]] "dip," that is a result of an overshoot in insulin production after the failure of the physiologic postprandial insulin response.{{Citation needed|date=October 2010}}

===Fasting insulin levels===
A fasting serum insulin level greater than 29 microIU/mL or 174 pmol/L indicates insulin resistance.<ref name="pmid30318910">{{cite journal | vauthors = Knopp JL, Holder-Pearson L, Chase JG | title = Insulin Units and Conversion Factors: A Story of Truth, Boots, and Faster Half-Truths | journal = J Diabetes Sci Technol | volume = 13 | issue = 3 | pages = 597–600 | date = May 2019 | pmid = 30318910 | pmc = 6501531 | doi = 10.1177/1932296818805074 }}</ref>{{Failed verification|date=January 2024|reason=this paper has no discussion about insulin resistance at all: it's a paper about the proper conversion of mass-based to bioactivity-based measures of insulin}} The same levels apply three hours after the last meal.

===Hyperinsulinemic euglycemic clamp===
The [[gold standard (test)|gold standard]] for investigating and quantifying insulin resistance is the "hyperinsulinemic euglycemic clamp," so-called because it measures the amount of [[glucose]] necessary to compensate for an increased [[insulin]] level without causing [[hypoglycemia]].<ref name = Anders_1979>{{cite journal | vauthors = DeFronzo RA, Tobin JD, Andres R | title = Glucose clamp technique: a method for quantifying insulin secretion and resistance | journal = The American Journal of Physiology | volume = 237 | issue = 3 | pages = E214-23 | date = September 1979 | pmid = 382871 | doi = 10.1152/ajpendo.1979.237.3.e214 | s2cid = 7192984 }}</ref> It is a type of [[glucose clamp technique]]. The test is rarely performed in clinical care, but is used in medical research, for example, to assess the effects of different medications. The rate of glucose infusion commonly is referred to in diabetes literature as the GINF value.<ref name="Muniyappa">{{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 Journal of Physiology. Endocrinology and Metabolism | volume = 294 | issue = 1 | pages = E15-26 | date = January 2008 | pmid = 17957034 | doi = 10.1152/ajpendo.00645.2007 | s2cid = 848540 }}</ref>

The procedure takes about two hours. Through a [[peripheral vein]], [[insulin]] is infused at 10–120 mU per m<sup>2</sup> per [[minute]]. In order to compensate for the insulin [[intravenous|infusion]], [[glucose]] 20% is infused to maintain blood sugar levels between 5 and 5.5&nbsp;mmol/L. The rate of glucose infusion is determined by checking the [[blood sugar]] levels every five to ten minutes.<ref name="Muniyappa" />

The insulin sensitivity is determined by the rate of glucose infusion during the last thirty minutes of the test. If high levels (7.5&nbsp;mg/min or higher) are needed, the patient is considered insulin-sensitive. Conversely, very low levels (4.0&nbsp;mg/min or lower) indicate insulin resistance. Levels falling between 4.0 and 7.5&nbsp;mg/min are not conclusive and suggest "impaired glucose tolerance," which is an early indication of insulin resistance.<ref name="Muniyappa" />

This fundamental technique can be greatly enhanced through the utilization of glucose tracers. Glucose can be labeled with either stable or radioactive atoms. Commonly employed tracers include 3-3H glucose (radioactive), 6,6 2H-glucose (stable), and 1-13C glucose (stable). Prior to initiating the hyperinsulinemic phase, a 3-hour tracer infusion allows for the determination of the basal rate of glucose production. Throughout the clamp, the plasma tracer concentrations facilitate the computation of whole-body insulin-stimulated glucose metabolism, as well as the production of glucose by the body. (i.e., endogenous glucose production).<ref name="Muniyappa" />

===Modified insulin suppression test===
Another measure of insulin resistance is the modified insulin suppression test developed by [[Gerald Reaven]] at Stanford University. The test correlates well with the euglycemic clamp, with less operator-dependent error. This test has been used to advance the large body of research relating to the metabolic syndrome.<ref name = "Muniyappa" />

Patients initially receive 25 μg of [[octreotide]] (Sandostatin) in 5 mL of normal saline over 3 to 5 minutes via intravenous infusion (IV) as an initial bolus, and then, are infused continuously with an intravenous infusion of [[somatostatin]] (0.27 μg/m<sup>2</sup>/min) to suppress endogenous insulin and glucose secretion. Next, insulin and 20% glucose are infused at rates of 32 and 267&nbsp;mg/m<sup>2</sup>/min, respectively. Blood glucose is checked at zero, 30, 60, 90, and 120 minutes, and thereafter, every 10 minutes for the last half-hour of the test. These last four values are averaged to determine the steady-state plasma glucose level (SSPG). Subjects with an SSPG greater than 150&nbsp;mg/dL are considered to be insulin-resistant.<ref name="Muniyappa" />

===Static function tests===
Given the complicated nature of the "clamp" technique (and the potential dangers of [[hypoglycemia]] in some patients), alternatives have been sought to simplify the measurement of insulin resistance. The first was the [[homeostatic model assessment|Homeostatic Model Assessment]] (HOMA),<ref name="pmid3899825">{{cite journal | vauthors = Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC | title = Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man | journal = Diabetologia | volume = 28 | issue = 7 | pages = 412–9 | date = July 1985 | pmid = 3899825 | doi = 10.1007/BF00280883 | s2cid = 24872571 | doi-access = free }}</ref> and more recent methods include the [[Quantitative insulin sensitivity check index]] (QUICKI)<ref name="pmid10902785">{{cite journal | vauthors = Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ | title = Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans | journal = J Clin Endocrinol Metab | volume = 85 | issue = 7 | pages = 2402–10 | date = July 2000 | pmid = 10902785 | doi = 10.1210/jcem.85.7.6661 | s2cid = 7612943 | doi-access = free }}</ref> and [[SPINA-GR]], a measure for insulin sensitivity.<ref name="pmid36271244">{{cite journal | vauthors = Dietrich JW, Dasgupta R, Anoop S, Jebasingh F, Kurian ME, Inbakumari M, Boehm BO, Thomas N | title = SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell function | journal = Sci Rep | volume = 12 | issue = 1 | pages = 17659 | date = October 2022 | pmid = 36271244 | doi = 10.1038/s41598-022-22531-3 | pmc = 9587026 | bibcode = 2022NatSR..1217659D }}</ref> All of these calculated markers employ [[fasting]] [[insulin]] and [[glucose]] levels to calculate insulin resistance, and all correlate reasonably with the results of clamping studies.

====Interpretation of results====
** HOMA-IR < 2: normal insulin sensitivity
** HOMA-IR > 2: possible insulin resistance
** HOMA-IR > 2,5: probable insulin resistance
** HOMA-IR > 5: typical results for type 2 diabetes<ref>{{cite web |last1=DocCheck |title=Homeostasis Model Assessment |url=https://flexikon.doccheck.com/de/Homeostasis_Model_Assessment |website=DocCheck Flexikon |language=de}}</ref>
** SPINA-GR 1,41–9,00&nbsp;mol/s: normal insulin sensitivity
** SPINA-GR ≤ 1,40&nbsp;mol/s: insulin resistance
** SPINA-GR < 1,35&nbsp;mol/s: typical results for type 2 diabetes<ref name="pmid36271244"/>