disposition index
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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.{{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 }}{{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 }} "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.{{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 }} Loss of function of the beta cells, reducing their capacity to compensate for insulin resistance, results in a lower disposition index.
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{{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 }}
- Frequently-sampled intravenous glucose tolerance testing (IVGTT or FSIGT)
- Frequently-sampled oral glucose tolerance testing (OGTT or FSOGT){{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}}{{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 }}
- Simultaneous fasting measurements of insulin and glucose in conjunction with mathematical modelling (SPINA){{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 |doi=10.1111/1753-0407.13525 |pmid=38169110|doi-access=free |pmc=11418405 }}
If clamp investigations are used the disposition index is defined as the product of the area under the insulin response curve () and the insulin sensitivity index (ISIClamp, average glucose infusion rate divided by average insulin concentration) with
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.{{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 |pages=583016 |doi=10.3389/fendo.2020.583016 |doi-access=free |pmid=33658981|pmc=7917251 }} The disposition index is then calculated as
from the first phase response of plasma insulin to the glucose injection () and the insulin sensitivity index (SI).
Based on an oral glucose tolerance test a disposition index can be calculated with
from the insulinogenic index (IGI) and the insulin sensitivity index (ISIcomposite).
The fasting-based disposition index (SPINA-DI) can be obtained from the product of the secretory capacity of pancreatic beta cells ( or SPINA-GBeta) times the insulin receptor gain ( or SPINA-GR):
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.{{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 }}{{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 }} 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.
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.{{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 }}
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 2 diabetes.{{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 }}
Disposition index can be increased by aerobic exercise, but only to the extent that insulin sensitivity is improved.{{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 }}
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.{{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}}