Disposition index

Last updated

Hyberbolic 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 Glucoregulatory hyperbola.png
Hyberbolic 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

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. [3] [4] "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. [5] Loss of function of the beta cells, reducing their capacity to compensate for insulin resistance, results in a lower disposition index. [3]

Contents

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:

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

. [6]

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. [10] 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). [10]

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). [7] [8]

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):

. [9]

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. [11] [12] 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. [9]

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. [13] 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. [14]

Disposition index can be increased by aerobic exercise, but only to the extent that insulin sensitivity is improved. [15]

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. [16]

See also

Related Research Articles

Insulin resistance (IR) is a pathological condition in which cells in insulin-sensitive tissues in the body fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia.

<span class="mw-page-title-main">Beta cell</span> Type of cell found in pancreatic islets

Beta cells (β-cells) are specialized endocrine cells located within the pancreatic islets of Langerhans responsible for the production and release of insulin and amylin. Constituting ~50–70% of cells in human islets, beta cells play a vital role in maintaining blood glucose levels. Problems with beta cells can lead to disorders such as diabetes.

<span class="mw-page-title-main">Glucose tolerance test</span> Medical test of how quickly glucose is cleared from the blood

The glucose tolerance 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. The test is usually used to test for diabetes, insulin resistance, impaired beta cell function, 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. 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.

<span class="mw-page-title-main">Hyperglycemia</span> Too much blood sugar, usually because of diabetes

Hyperglycemia or hyperglycaemia is a condition where unusually high amount of glucose is present in blood. It is defined as blood glucose level exceeding 6.9 mmol/L after fasting for 8 hours and 10 mmol/L 2 hours after eating.

<span class="mw-page-title-main">Type 2 diabetes</span> Form of diabetes mellitus

Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, fatigue and unexplained weight loss. Other symptoms include increased hunger, having a sensation of pins and needles, and sores (wounds) that heal slowly. Symptoms often develop slowly. Long-term complications from high blood sugar include heart disease, stroke, diabetic retinopathy, which can result in blindness, kidney failure, and poor blood flow in the lower-limbs, which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.

<span class="mw-page-title-main">Pancreatic islets</span> Regions of the pancreas

The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1–2% of the pancreas volume and receive 10–15% of its blood flow. The pancreatic islets are arranged in density routes throughout the human pancreas, and are important in the metabolism of glucose.

<span class="mw-page-title-main">Gestational diabetes</span> Exercise and Obesity Management During Pregnancy

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, obesity increases the rate of pre-eclampsia, cesarean sections, and embryo macrosomia, as well as gestational diabetes. Babies born to individuals with poorly treated gestational diabetes are at increased risk of macrosomia, of having hypoglycemia after birth, and of jaundice. If untreated, diabetes can also result in stillbirth. Long term, children are at higher risk of being overweight and of developing type 2 diabetes.

<span class="mw-page-title-main">Hyperinsulinemia</span> Abnormal increase in insulin in the bloodstream relative to glucose

Hyperinsulinemia is a condition in which there are excess levels of insulin circulating in the blood relative to the level of glucose. While it is often mistaken for diabetes or hyperglycaemia, hyperinsulinemia can result from a variety of metabolic diseases and conditions, as well as non-nutritive sugars in the diet. While hyperinsulinemia is often seen in people with early stage type 2 diabetes mellitus, it is not the cause of the condition and is only one symptom of the disease. Type 1 diabetes only occurs when pancreatic beta-cell function is impaired. Hyperinsulinemia can be seen in a variety of conditions including diabetes mellitus type 2, in neonates and in drug-induced hyperinsulinemia. It can also occur in congenital hyperinsulinism, including nesidioblastosis.

Steroid-induced diabetes is characterized as an unusual rise in blood sugar that is linked to the use of glucocorticoids in a patient who may or may not have had diabetes in the past.

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.

<span class="mw-page-title-main">Blood sugar regulation</span> Hormones regulating blood sugar levels

Blood sugar regulation is the process by which the levels of blood sugar, the common name for glucose dissolved in blood plasma, are maintained by the body within a narrow range.

<span class="mw-page-title-main">Glucagon-like peptide-1 receptor</span> Receptor activated by peptide hormone GLP-1

The glucagon-like peptide-1 receptor (GLP1R) is a G protein-coupled receptor (GPCR) found on beta cells of the pancreas and on neurons of the brain. It is involved in the control of blood sugar level by enhancing insulin secretion. In humans it is synthesised by the gene GLP1R, which is present on chromosome 6. It is a member of the glucagon receptor family of GPCRs. GLP1R is composed of two domains, one extracellular (ECD) that binds the C-terminal helix of GLP-1, and one transmembrane (TMD) domain that binds the N-terminal region of GLP-1. In the TMD domain there is a fulcrum of polar residues that regulates the biased signaling of the receptor while the transmembrane helical boundaries and extracellular surface are a trigger for biased agonism.

<span class="mw-page-title-main">Forkhead box protein O1</span> Protein

Forkhead box protein O1 (FOXO1), also known as forkhead in rhabdomyosarcoma (FKHR), is a protein that in humans is encoded by the FOXO1 gene. FOXO1 is a transcription factor that plays important roles in regulation of gluconeogenesis and glycogenolysis by insulin signaling, and is also central to the decision for a preadipocyte to commit to adipogenesis. It is primarily regulated through phosphorylation on multiple residues; its transcriptional activity is dependent on its phosphorylation state.

MODY 3 or HNF1A-MODY is a form of maturity-onset diabetes of the young. It is caused by mutations of the HNF1-alpha gene, a homeobox gene on human chromosome 12. This is the most common type of MODY in populations with European ancestry, accounting for about 70% of all cases in Europe. HNF1α is a transcription factor that is thought to control a regulatory network important for differentiation of beta cells. Mutations of this gene lead to reduced beta cell mass or impaired function. MODY 1 and MODY 3 diabetes are clinically similar. About 70% of people develop this type of diabetes by age 25 years, but it occurs at much later ages in a few. This type of diabetes can often be treated with sulfonylureas with excellent results for decades. However, the loss of insulin secretory capacity is slowly progressive and most eventually need insulin.

Glucose clamp technique is a method for quantifying insulin secretion and resistance. It is used to measure either how well an individual metabolizes glucose or how sensitive an individual is to insulin.

Ketosis-prone diabetes (KPD) is an intermediate form of diabetes that has some characteristics of type 1 and some of type 2 diabetes. Type 1 diabetes involves autoimmune destruction of pancreatic beta cells which create insulin. This occurs earlier in a person's life, leading to patients being insulin dependent, and the lack of natural insulin makes patients prone to a condition called diabetic ketoacidosis (DKA). Type 2 diabetes is different in that it is usually caused by insulin resistance in the body in older patients leading to beta cell burnout over time, and is not prone to DKA. KPD is a condition that involves DKA like type 1, but occurs later in life and can regain beta cell function like type 2 diabetes. However, it is distinct from latent autoimmune diabetes of adults (LADA), a form of type 1 sometimes referred to as type 1.5 that does not occur with DKA. There are also distinctions to be made between KPD and LADA as patients who exhibit KPD symptoms can regain beta cell function similar to type 2 diabetics whereas LADA will not exhibit this reclamation of beta cell function.

The Metabolic Score for Insulin Resistance (METS-IR) is a metabolic index developed with the aim to quantify peripheral insulin sensitivity in humans; it was first described under the name METS-IR by Bello-Chavolla et al. in 2018. It was developed by the Metabolic Research Disease Unit at the Instituto Nacional de Ciencias Médicas Salvador Zubirán and validated against the euglycemic hyperinsulinemic clamp and the frequently-sampled intravenous glucose tolerance test in Mexican population. It is a non-insulin-based alternative to insulin-based methods to quantify peripheral insulin sensitivity and an alternative to SPINA Carb, the Homeostatic Model Assessment (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). METS-IR is currently validated for its use to assess cardio-metabolic risk in Latino population.

SPINA-GR is a calculated biomarker for insulin sensitivity. It represents insulin receptor gain.

SPINA-GBeta is a calculated biomarker for pancreatic beta cell function. It represents the maximum amount of insulin that beta cells can produce per time-unit.

Pancreatic beta cell function is one of the preconditions of euglycaemia, i.e. normal blood sugar regulation. It is defined as insulin secretory capacity, i.e. the maximum amount of insulin to be produced by beta cells in a given unit of time.

References

  1. 1 2 Cobelli C, Toffolo GM, Dalla Man C, Campioni M, Denti P, Caumo A, Butler P, Rizza R (July 2007). "Assessment of beta-cell function in humans, simultaneously with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests". American Journal of Physiology. Endocrinology and Metabolism. 293 (1): E1–E15. doi:10.1152/ajpendo.00421.2006. PMID   17341552.
  2. ↑ Hannon TS, Kahn SE, Utzschneider KM, Buchanan TA, Nadeau KJ, Zeitler PS, Ehrmann DA, Arslanian SA, Caprio S, Edelstein SL, Savage PJ, Mather KJ, RISE C (January 2018). "Review of methods for measuring β-cell function: Design considerations from the Restoring Insulin Secretion (RISE) Consortium". Diabetes, Obesity & Metabolism. 20 (1): 14–24. doi:10.1111/dom.13005. PMC   6095472 . PMID   28493515.
  3. 1 2 Bergman RN, Ader M, Huecking K, Van Citters G (2002). "Accurate assessment of beta-cell function: the hyperbolic correction". Diabetes . 51 (Supp 1): S212–S220. doi: 10.2337/diabetes.51.2007.s212 . PMID   11815482.
  4. ↑ Ferrannini E, Mari A (May 2004). "Beta cell function and its relation to insulin action in humans: a critical appraisal". Diabetologia. 47 (5): 943–56. doi: 10.1007/s00125-004-1381-z . PMID   15105990.
  5. ↑ Defronzo RA (2009). "Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus". Diabetes . 58 (4): 773–795. doi:10.2337/db09-9028. PMC   2661582 . PMID   19336687.
  6. 1 2 Shah SS, Ramirez CE, Powers AC, Yu C, Shibao CA, Luther JM (June 2016). "Hyperglycemic clamp-derived disposition index is negatively associated with metabolic syndrome severity in obese subjects". Metabolism: Clinical and Experimental. 65 (6): 835–42. doi:10.1016/j.metabol.2016.02.011. PMC   4867079 . PMID   27173462.
  7. 1 2 Matsuda M, DeFronzo RA (September 1999). "Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp". Diabetes Care. 22 (9): 1462–70. doi:10.2337/diacare.22.9.1462. PMID   10480510.
  8. 1 2 DeFronzo RA, Matsuda M (July 2010). "Reduced time points to calculate the composite index". Diabetes Care. 33 (7): e93. doi: 10.2337/dc10-0646 . PMID   20587713.
  9. 1 2 3 Dietrich JW, Abood A, Dasgupta R, Anoop S, Jebasingh FK, Spurgeon R, Thomas N, Boehm BO (2 January 2024). "A novel simple disposition index (SPINA-DI) from fasting insulin and glucose concentration as a robust measure of carbohydrate homeostasis". Journal of Diabetes . 16 (9). doi: 10.1111/1753-0407.13525 . PMC   11418405 . PMID   38169110.
  10. 1 2 Bergman RN (2020). "Origins and History of the Minimal Model of Glucose Regulation". Frontiers in Endocrinology. 11: 583016. doi: 10.3389/fendo.2020.583016 . PMC   7917251 . PMID   33658981.
  11. ↑ Retnakaran R, Qi Y, Goran MI, Hamilton JK (December 2009). "Evaluation of proposed oral disposition index measures in relation to the actual disposition index". Diabetic Medicine. 26 (12): 1198–203. doi:10.1111/j.1464-5491.2009.02841.x. PMID   20002470. S2CID   9477335.
  12. ↑ Sjaarda LG, Bacha F, Lee S, Tfayli H, Andreatta E, Arslanian S (July 2012). "Oral disposition index in obese youth from normal to prediabetes to diabetes: relationship to clamp disposition index". The Journal of Pediatrics. 161 (1): 51–7. doi:10.1016/j.jpeds.2011.12.050. PMC   3366166 . PMID   22325254.
  13. ↑ Lorenzo C, Wagenknecht LE, Rewers MJ, Karter AJ, Bergman RN, Hanley AJ, Haffner SM (2011). "Disposition index, glucose effectiveness, and conversion to type 2 diabetes: the Insulin Resistance Atherosclerosis Study (IRAS)". Diabetes Care . 33 (9): 2098–2103. doi:10.2337/dc10-0165. PMC   2928371 . PMID   20805282.
  14. ↑ Goldfine AB, Bouche C, Parker RA, Kim C, Kerivan A, Soeldner JS, Martin BC, Warram JH, Kahn CR (2003). "Insulin resistance is a poor predictor of type 2 diabetes in individuals with no family history of disease". Proceedings of the National Academy of Sciences of the United States of America . 100 (5): 2724–2729. Bibcode:2003PNAS..100.2724G. doi: 10.1073/pnas.0438009100 . PMC   151408 . PMID   12591951.
  15. ↑ Solomon TP, Malin SK, Karstoft K, Kashyap SR, Haus JM, Kirwan JP (2013). "Pancreatic β-cell function is a stronger predictor of changes in glycemic control after an aerobic exercise intervention than insulin sensitivity". The Journal of Clinical Endocrinology and Metabolism . 98 (10): 4176–4186. doi:10.1210/jc.2013-2232. PMC   3790622 . PMID   23966244.
  16. ↑ Dietrich JW (2024). "P4-Endokrinologie – Kybernetische Perspektiven eines neuen Ansatzes" (PDF). Leibniz Online. 54. doi:10.53201/LEIBNIZONLINE54.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.