{{cs1 config|name-list-style=vanc}} thumb|alt=Hyperbolic relationship between insulin sensitivity and beta cell function showing dynamical compensation in "healthy" insulin resistance (transition from A to B) and the evolution of type 2 diabetes mellitus (transition from A to C). |Hyperbolic relationship between insulin sensitivity and beta cell function showing dynamical compensation in "healthy" insulin resistance (transition from A to B) and the evolution of type 2 diabetes mellitus (transition from A to C). Disposition metrics integrate beta cell function and insulin sensitivity in a way so that the results remain constant across dynamical compensation. Changed from Cobelli et al. 2007 and Hannon et al. 2018<ref name="Cobelli_2007">{{cite journal |last1=Cobelli |first1=C |last2=Toffolo |first2=GM |last3=Dalla Man |first3=C |last4=Campioni |first4=M |last5=Denti |first5=P |last6=Caumo |first6=A |last7=Butler |first7=P |last8=Rizza |first8=R |title=Assessment of beta-cell function in humans, simultaneously with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests. |journal=American Journal of Physiology. Endocrinology and Metabolism |date=July 2007 |volume=293 |issue=1 |pages=E1–E15 |doi=10.1152/ajpendo.00421.2006 |pmid=17341552|hdl=11577/2434950 |hdl-access=free }}</ref><ref name="Hannon_2018">{{cite journal |last1=Hannon |first1=TS |last2=Kahn |first2=SE |last3=Utzschneider |first3=KM |last4=Buchanan |first4=TA |last5=Nadeau |first5=KJ |last6=Zeitler |first6=PS |last7=Ehrmann |first7=DA |last8=Arslanian |first8=SA |last9=Caprio |first9=S |last10=Edelstein |first10=SL |last11=Savage |first11=PJ |last12=Mather |first12=KJ |last13=RISE |first13=Consortium |author-link2=Steven Kahn (endocrinologist) |title=Review of methods for measuring β-cell function: Design considerations from the Restoring Insulin Secretion (RISE) Consortium. |journal=Diabetes, Obesity & Metabolism |date=January 2018 |volume=20 |issue=1 |pages=14–24 |doi=10.1111/dom.13005 |pmid=28493515|pmc=6095472 }}</ref>

The '''Disposition index''' ('''DI''') is a measure for the loop gain of the insulin-glucose feedback control system. It is defined as the product of insulin sensitivity times the amount of insulin secreted in response to blood glucose levels.<ref name="pmid11815482">{{cite journal | vauthors=Bergman RN, Ader M, Huecking K, Van Citters G | title=Accurate assessment of beta-cell function: the hyperbolic correction | journal= Diabetes | volume=51 | issue=Supp 1 | pages=S212–S220 | year=2002 | url = http://diabetes.diabetesjournals.org/content/51/suppl_1/S212.long | pmid = 11815482 | doi=10.2337/diabetes.51.2007.s212| doi-access=free }}</ref><ref name="Ferrannini_and_Mari_2004">{{cite journal |last1=Ferrannini |first1=E |last2=Mari |first2=A |title=Beta cell function and its relation to insulin action in humans: a critical appraisal. |journal=Diabetologia |date=May 2004 |volume=47 |issue=5 |pages=943–56 |doi=10.1007/s00125-004-1381-z |pmid=15105990|doi-access=free }}</ref> "Metabolically healthy" Insulin resistant individuals can maintain normal responses to blood glucose due to the fact that higher levels of insulin are secreted as long as the beta cells of the pancreas are able to increase their output of insulin to compensate for the insulin resistance. But the ratio of the incremental increase in plasma insulin associated with an incremental increase in plasma glucose (disposition index) provides a better measure of beta cell function than the plasma insulin response to a glucose challenge.<ref name="pmid19336687 ">{{cite journal | author=Defronzo RA | title=Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus | journal=Diabetes | volume=58 | issue=4 | pages=773–795 | year=2009 | url=https://diabetes.diabetesjournals.org/content/58/4/773.long | doi = 10.2337/db09-9028 | pmc= 2661582 | pmid=19336687 }}</ref> Loss of function of the beta cells, reducing their capacity to compensate for insulin resistance, results in a lower disposition index.<ref name="pmid11815482" />

The term was proposed in 1981 by Bergman, Phillips and Cobelli to introduce an integrated measure of glucose tolerance, which includes the quantitative contributions of beta-cell function and insulin sensitivity<ref>{{cite journal |last1=Bergman |first1=RN |last2=Phillips |first2=LS |last3=Cobelli |first3=C |title=Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. |journal=The Journal of Clinical Investigation |date=December 1981 |volume=68 |issue=6 |pages=1456–67 |doi=10.1172/jci110398 |pmid=7033284|pmc=370948 |bibcode=1981JCliI..68.1456B }}</ref>.

== Methods of determination ==

The disposition index can be obtained on the basis of data that provide information on insulin sensitivity and beta cell function. Suitable sources include:

* Hyperglycemic glucose clamp investigations<ref name="Shah2016">{{cite journal |last1=Shah |first1=SS |last2=Ramirez |first2=CE |last3=Powers |first3=AC |last4=Yu |first4=C |last5=Shibao |first5=CA |last6=Luther |first6=JM |title=Hyperglycemic clamp-derived disposition index is negatively associated with metabolic syndrome severity in obese subjects. |journal=Metabolism: Clinical and Experimental |date=June 2016 |volume=65 |issue=6 |pages=835–42 |doi=10.1016/j.metabol.2016.02.011 |pmid=27173462|pmc=4867079 }}</ref> * Frequently-sampled intravenous glucose tolerance testing (IVGTT or FSIGT) <ref name="Cobelli_2007"/> * Frequently-sampled oral glucose tolerance testing (OGTT or FSOGT)<ref name="Matsuda_1999">{{cite journal |last1=Matsuda |first1=M |last2=DeFronzo |first2=RA |title=Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. |journal=Diabetes Care |date=September 1999 |volume=22 |issue=9 |pages=1462–70 |doi=10.2337/diacare.22.9.1462 |pmid=10480510}}</ref><ref name="DeFronzo 2010">{{cite journal |last1=DeFronzo |first1=RA |last2=Matsuda |first2=M |title=Reduced time points to calculate the composite index. |journal=Diabetes Care |date=July 2010 |volume=33 |issue=7 |pages=e93 |doi=10.2337/dc10-0646 |pmid=20587713|doi-access=free }}</ref> * Simultaneous fasting measurements of insulin and glucose in conjunction with mathematical modelling (SPINA)<ref name="Dietrich_2024">{{cite journal |last1=Dietrich |first1=Johannes W. |last2=Abood |first2=Assjana |last3=Dasgupta |first3=Riddhi |last4=Anoop |first4=Shajith |last5=Jebasingh |first5=Felix K. |last6=Spurgeon |first6=R. |last7=Thomas |first7=Nihal |last8=Boehm |first8=Bernhard O. |title=A novel simple disposition index (SPINA-DI) from fasting insulin and glucose concentration as a robust measure of carbohydrate homeostasis |journal=Journal of Diabetes |date=2 January 2024 |volume=16 |issue=9 |article-number=e13525 |doi=10.1111/1753-0407.13525 |pmid=38169110|doi-access=free |pmc=11418405 }}</ref>

If clamp investigations are used the disposition index is defined as the product of the area under the insulin response curve (<math>AUC_{\Delta Insulin}</math>) and the insulin sensitivity index (''ISI<sub>Clamp</sub>'', average glucose infusion rate divided by average insulin concentration) with

<math>DI_{Clamp}=AUC_{\Delta Insulin} \cdot ISI_{Clamp}</math>.<ref name="Shah2016"/>

Determining the disposition index on the basis of an FSIGT requires fitting the timeseries of insulin and glucose concentrations to the minimal model of insulin-glucose homeostasis.<ref name="Bergman_2020">{{cite journal |last1=Bergman |first1=RN |title=Origins and History of the Minimal Model of Glucose Regulation. |journal=Frontiers in Endocrinology |date=2020 |volume=11 |article-number=583016 |doi=10.3389/fendo.2020.583016 |doi-access=free |pmid=33658981|pmc=7917251 }}</ref> The disposition index is then calculated as

<math>{DI}_{FSIGT}={\varphi }_{1}\cdot{S}_{I}</math>

from the first phase response of plasma insulin to the glucose injection (<math>{\varphi }_{1}</math>) and the insulin sensitivity index (''S<sub>I</sub>'').<ref name="Bergman_2020"/>

Based on an oral glucose tolerance test a disposition index can be calculated with

<math>{DI}_{FSOGT}=IGI\cdot ISI_{composite}</math>

from the insulinogenic index (''IGI'') and the insulin sensitivity index (''ISI<sub>composite</sub>'').<ref name="Matsuda_1999"/><ref name="DeFronzo 2010"/>

The fasting-based disposition index (SPINA-DI) can be obtained from the product of the secretory capacity of pancreatic beta cells (<math>G_\beta</math> or SPINA-GBeta) times the insulin receptor gain (<math>G_R</math> or SPINA-GR):

<math>DI_f = G_\beta \cdot G_R</math>.<ref name="Dietrich_2024"/>

The four approaches deliver slightly different information. Although the results of clamp-, IVGTT-, OGTT- and SPINA-derived disposition indices significantly correlate with each other the correlations are only modest.<ref>{{cite journal |last1=Retnakaran |first1=R |last2=Qi |first2=Y |last3=Goran |first3=MI |last4=Hamilton |first4=JK |title=Evaluation of proposed oral disposition index measures in relation to the actual disposition index. |journal=Diabetic Medicine |date=December 2009 |volume=26 |issue=12 |pages=1198–203 |doi=10.1111/j.1464-5491.2009.02841.x |pmid=20002470|s2cid=9477335 }}</ref><ref>{{cite journal |last1=Sjaarda |first1=LG |last2=Bacha |first2=F |last3=Lee |first3=S |last4=Tfayli |first4=H |last5=Andreatta |first5=E |last6=Arslanian |first6=S |title=Oral disposition index in obese youth from normal to prediabetes to diabetes: relationship to clamp disposition index. |journal=The Journal of Pediatrics |date=July 2012 |volume=161 |issue=1 |pages=51–7 |doi=10.1016/j.jpeds.2011.12.050 |pmid=22325254|pmc=3366166 }}</ref> In direct comparison, the SPINA-based disposition index (SPINA-DI) had higher discriminatory power for the diagnosis of diabetes than the OGTT-based disposition index according to Matsuda and DeFronzo.<ref name="Dietrich_2024"/>

== Clinical implications ==

Disposition index is used as a measure of beta cell function and the ability of the body to dispose of a glucose load. Thus a lowering of disposition index predicts the conversion of insulin resistance to diabetes mellitus type 2.<ref name="pmid20805282">{{cite journal | vauthors=Lorenzo C, Wagenknecht LE, Rewers MJ, Karter AJ, Bergman RN, Hanley AJ, Haffner SM | title=Disposition index, glucose effectiveness, and conversion to type 2 diabetes: the Insulin Resistance Atherosclerosis Study (IRAS) | journal= Diabetes Care | volume=33 | issue=9 | pages=2098–2103 | year=2011 | doi= 10.2337/dc10-0165| pmid = 20805282 | pmc=2928371 }}</ref> Disposition index, but not insulin resistance, can predict type 2 diabetes in persons with normal blood glucose levels, but who do not have a family history (genetic predisposition) to type&nbsp;2 diabetes.<ref name="pmid12591951">{{cite journal | vauthors=Goldfine AB, Bouche C, Parker RA, Kim C, Kerivan A, Soeldner JS, Martin BC, Warram JH, Kahn CR | title=Insulin resistance is a poor predictor of type 2 diabetes in individuals with no family history of disease | journal= Proceedings of the National Academy of Sciences of the United States of America | volume=100 | issue=5 | pages=2724–2729 | year=2003 | doi= 10.1073/pnas.0438009100| pmid = 12591951 | pmc=151408 | bibcode=2003PNAS..100.2724G | doi-access=free }}</ref>

Disposition index can be increased by aerobic exercise, but only to the extent that insulin sensitivity is improved.<ref name="pmid23966244">{{cite journal | vauthors=Solomon TP, Malin SK, Karstoft K, Kashyap SR, Haus JM, Kirwan JP | title=Pancreatic β-cell function is a stronger predictor of changes in glycemic control after an aerobic exercise intervention than insulin sensitivity | journal= The Journal of Clinical Endocrinology and Metabolism | volume=98 | issue=10 | pages=4176–4186 | year=2013 | doi= 10.1210/jc.2013-2232 | pmc=3790622 | pmid = 23966244 }}</ref>

The static disposition index (SPINA-DI) declines with increasing adherence to mediterranean diet. This may result from increased use of other macronutrients for the provision of energy and a reduction in the chronic stimulus for dynamical compensation with consecutive insulin hypersecretion<ref>{{cite journal |last1=Herrera-Carrasco |first1=Karin |last2=Puche-Juarez |first2=Maria |last3=Toledano |first3=Juan Manuel |last4=Ocaña-Peinado |first4=Francisco Manuel |last5=Ochoa |first5=Julio J. |last6=Diaz-Castro |first6=Javier |last7=Moreno-Fernandez |first7=Jorge |title=Combined Effects of Mediterranean Diet Adherence and Physical Activity on Metabolic Homeostasis and Beta-Cell Function in Male Adolescents |journal=Nutrients |date=30 April 2026 |volume=18 |issue=9 |pages=1453 |doi=10.3390/nu18091453 |doi-access=free |hdl=10481/113206 |hdl-access=free }}</ref>.

The disposition index is reduced in several chronic conditions including cystic fibrosis,<ref>{{cite journal |last1=Nielsen |first1=BU |last2=Mathiesen |first2=IHM |last3=Krogh-Madsen |first3=R |last4=Katzenstein |first4=TL |last5=Pressler |first5=T |last6=Shaw |first6=JAM |last7=Rickels |first7=MR |last8=Almdal |first8=TP |last9=Faurholt-Jepsen |first9=D |last10=Stefanovski |first10=D |title=Insulin sensitivity, disposition index and insulin clearance in cystic fibrosis: a cross-sectional study. |journal=Diabetologia |date=October 2024 |volume=67 |issue=10 |pages=2188–2198 |doi=10.1007/s00125-024-06220-6 |pmid=39093413|pmc=11447061 }}</ref> reduced PCSK9 expression<ref>{{cite journal |last1=Cyr |first1=Y |last2=Lamantia |first2=V |last3=Bissonnette |first3=S |last4=Burnette |first4=M |last5=Besse-Patin |first5=A |last6=Demers |first6=A |last7=Wabitsch |first7=M |last8=Chrétien |first8=M |last9=Mayer |first9=G |last10=Estall |first10=JL |last11=Saleh |first11=M |last12=Faraj |first12=M |title=Lower plasma PCSK9 in normocholesterolemic subjects is associated with upregulated adipose tissue surface-expression of LDLR and CD36 and NLRP3 inflammasome. |journal=Physiological Reports |date=February 2021 |volume=9 |issue=3 |article-number=e14721 |doi=10.14814/phy2.14721 |pmid=33527668|pmc=7851436 }}</ref> and inflammatory diseases, e.g. hidradenitis suppurativa (acne inversa).<ref>{{cite journal |last1=Abu Rached |first1=N |last2=Dietrich |first2=JW |last3=Ocker |first3=L |last4=Stockfleth |first4=E |last5=Haven |first5=Y |last6=Myszkowski |first6=D |last7=Bechara |first7=FG |title=Endotyping Insulin-Glucose Homeostasis in Hidradenitis Suppurativa: The Impact of Diabetes Mellitus and Inflammation. |journal=Journal of Clinical Medicine |date=21 March 2025 |volume=14 |issue=7 |page=2145 |doi=10.3390/jcm14072145 |doi-access=free |pmid=40217596|pmc=11990022 }}</ref>

== Predictive aspects == In a longitudinal evaluation of the NHANES study, a large sample of the general US population, over 10 years, a reduced static disposition index (SPINA-DI) significantly predicted all-cause mortality.<ref>{{cite journal |last1=Dietrich |first1=Johannes W. |title=P4-Endokrinologie – Kybernetische Perspektiven eines neuen Ansatzes |journal=Leibniz Online |date=2024 |volume=54 |doi=10.53201/LEIBNIZONLINE54 |url=https://leibnizsozietaet.de/wp-content/uploads/2024/12/03_03_Kybernetik-2024_DietrichLeibniz-Online-Fachbeitrag.pdf |language=de}}</ref>

== See also == * SPINA-GBeta * SPINA-GR

==References== {{reflist}}

{{Diabetes}}

Category:Diabetes-related tests Category:Static endocrine function tests