Insulin resistance

from Wikipedia, the free encyclopedia

Insulin resistance (IR) is the reduced cellular response, especially of insulin-dependent organs, to endogenous or exogenous insulin and describes a property of individual individuals . Their body cells react less to the hormone insulin than the body cells of healthy individuals. The muscles , liver and fatty tissue in particular are less sensitive to insulin. This impairs the effect of both the body's own and externally supplied (injected) insulin. Insulin resistance occurs in the metabolic syndrome and is a marker for a developing type 2 diabetes mellitus disease.

definition

The concept of insulin resistance has been around since the 1960s. It was believed that the pancreas could secrete up to 200 international units (IU) of insulin per day and defined as "severe insulin resistance" an insulin requirement of more than 200 IU over several days in order to achieve normal blood sugar levels . Although it has now been made clear that normal physiological insulin production is between 20 and 40 units per day, this old definition is still considered useful in order to delineate patients with severe, unusual insulin resistance problems.

Since 1985 the term has been given a more general meaning and describes a reduced response of the cells of the human or animal body to insulin.

Course of the day

Insulin resistance is highest in the early morning due to the nocturnal release of insulin antagonists (see dawn phenomenon ). Often there is a second, less high rise in insulin resistance in the late afternoon.

causes

Insulin resistance occurs as a phenomenon in type 2 diabetes mellitus and its preliminary stages , namely as a disturbance of the metabolism in the glucose and insulin balance of the cells and, as a result, with disturbances in the functionality of the affected organ - tissue . The cause is a constant high -carbohydrate diet and the constant overconsumption of sugar , which leads to an increased insulin level in the blood, which increases the risk of overweight and obesity and in the long run results in diabetes . The exact mechanisms that lead to insulin resistance are therefore being intensively researched , as the costs of this preliminary stage of the “ epidemic of the 21st century ” are considerable and are increasing.

Insulin resistance affects both slim and overweight type 2 diabetics, but obesity is a major risk factor . The combination of familial disposition (for obesity , for diabetes mellitus type 2 as well as for the reduced insulin sensitivity) and an oversupply of carbohydrates from the diet leads to an increased blood sugar level and increases the fatty acid synthesis of free fatty acids in the blood through oxidative decarboxylation of pyruvate in of glycolysis . This in turn increases various health risks, for example lipid metabolism disorders ( hypertriglyceridaemia ), obesity, thrombosis or arteriosclerosis of the blood vessels. This frequent excess of glucose in the blood after ingestion of carbohydrates and sugar characterizes the insulin resistance. As a reaction, there is an increased release of insulin ( hyperinsulinism ) with obesity. This leads to a downregulation of the insulin receptors on the cells, the resistance increases further. Insulin as a fat-building ( adipogenic ) factor increases fat storage (obesity) in order to get glucose out of the blood; humans continue to gain weight because the food intake of sugar and carbohydrates as the primary cause is not reduced. Insulin resistance can be recovered by minimizing carbohydrates ( low carb ), ketogenic diet or by fasting.

Other causes

Mechanisms of Insulin Resistance

Insulin resistance is increased by:

Insulin resistance

In the case of insulin resistance, there is a (compensatory) increase in insulin secretion. The first indication of insulin resistance can be increased body weight , which results from increased insulin levels in the blood, because insulin is the only hormone that builds body fat ( adipogenic effect of insulin ). All type 2 diabetics have a genetically determined tendency to insulin resistance, but this is particularly evident when they are overweight . Today it is assumed that the fat in the abdominal area in particular releases more hormonally active substances that further promote and strengthen insulin resistance.

As a measure of the abdominal fat which can abdominal circumference are measured and the body mass index (BMI), kg of starting values of 27 / m² together with a familial disposition an indication of insulin resistance.

Furthermore, the level of triglycerides can be an indication of insulin resistance. If triglyceride values ​​are above 2.44 mmol / l (or 215 mg / dl), there may be insulin resistance, especially if high fetuin A values ​​are measured at the same time .

Adiponectin

The fatty tissue hormone adiponectin is produced less by the fatty tissue of insulin-resistant people. Decreased adiponectin levels indicate insulin resistance.

Proinsulin

When insulin is made in the pancreas, a precursor molecule - the so-called proinsulin  - is first synthesized. The actual hormone insulin is only created by splitting off the so-called C-peptide . In the context of insulin resistance, more and more insulin, i.e. a disproportionate amount of proinsulin, is produced. The latter is only insufficiently broken down into insulin and can be detected as an increased proinsulin level (over 11 pmol / l) in the blood.

More insulin resistance tests

  • Sugar load test ( oral glucose tolerance test , short oGTT)
  • Fasting insulin level: In diabetics with insulin resistance, the insulin level is increased at least in the first years of type 2 diabetes, see hyperinsulinism .
  • Glucose "clamp" technique: Determination of the glucose infusion rate which is necessary for a slightly increased (e.g. 125 mg / dl or 6.9 mmol / l) but constant blood sugar value.
  • Determination of the HOMA index ( Homeostasis Model Assessment ) as a measure of insulin resistance: = fasting insulin (µU / ml) × fasting blood sugar (mmol / l) / 22.5
    • Values ​​<1: normal
    • Values> 2: indication of insulin resistance
    • Values> 2.5: Insulin resistance very likely
    • Values> 5: average value in type 2 diabetics
    • If the proinsulin level is normal, the HOMA index is a measure of the function of the β cells and is a reliable proof of insulin resistance.

therapy

In overweight type 2 diabetics, insulin resistance can be reduced in the short term by significantly reducing the energy intake (e.g. less than 4,200 kJ (1,000 kcal ) per day for a few days ) or in the long term by increasing physical activity .

A short-term increase in insulin intake to very high doses , e.g. B. also intravenously via a drug pump or subcutaneous administration ( injections into the subcutaneous fat tissue ) of normal or analog insulin (see insulin preparations ) at short intervals of a few hours "breaks" after a few days, the insulin resistance . After reaching normal blood sugar levels, a significantly lower dose of insulin is necessary for further therapy.

The influence of diets (e.g. low-fat , low-carb ) on the origin and treatment of insulin resistance is controversial.

Effective and clinically used active ingredients for reducing insulin resistance are:

history

The concept of insulin resistance as a fundamental cause of type 2 diabetes mellitus was first proposed by Wilhelm Falta and published in Vienna in 1931; the idea was confirmed in 1936 by Harold Percival Himsworth of the University College London Hospital .

literature

  • Silbernagl, Lang: Pocket Atlas of Pathophysiology . Thieme, Stuttgart 1998, ISBN 3-13-102191-8 .
  • H. Mehnert , Standl, Usadel, Häring (ed.): Diabetology in clinic and practice. 5th edition, Thieme, Stuttgart 2003, ISBN 3-13-512805-9 .
  • Richard Daikeler, Götz Use, Sylke Waibel: Diabetes. Evidence-based diagnosis and therapy. 10th edition. Kitteltaschenbuch, Sinsheim 2015, ISBN 978-3-00-050903-2 , pp. 16-19.

Web links

Wiktionary: Insulin resistance  - explanations of meanings, word origins, synonyms, translations

Remarks

  1. Richard Daikeler, idols Use, Sylke Waibel: diabetes. Evidence-based diagnosis and therapy. 10th edition. Kitteltaschenbuch, Sinsheim 2015, ISBN 978-3-00-050903-2 , pp. 16-19.
  2. ^ Diabetes epidemic out of control. Press release December 4, 2006 ( Memento of November 20, 2009 in the Internet Archive ) IDF
  3. Triglycerides on internisten-im-netz.de.
  4. Good fats, bad fats In: Pharmazeutische Zeitung . on-line.
  5. Fasting here means that, in particular, no carbohydrates or sugar are consumed for a longer period of time. Intermittent fasting extends the period of natural fasting during sleep. With fasting periods of 36 hours and more, the human body's sugar stores are depleted ( glycogen in the liver and muscle fibers) and the metabolism switches to ketosis .
  6. Insulin resistance syndrome type A. In: Orphanet (database for rare diseases).
  7. Insulin resistance syndrome type B. In: Orphanet (database for rare diseases).
  8. Anja Lütke, after SE Stern, K. Williams, E. Ferrannini et al .: Identification of Individuals With Insulin Resistance Using Routine Clinical Measurements . ( Memento of the original from April 18, 2005 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. In: Diabetes , 2005, 54, pp. 333-339 @1@ 2Template: Webachiv / IABot / www.diabetes.uni-duesseldorf.de
  9. diabetes.uni-duesseldorf.de ( Memento of the original from April 18, 2005 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Information system of the UNI Düsseldorf on diabetes mellitus from March 7, 2005 @1@ 2Template: Webachiv / IABot / www.diabetes.uni-duesseldorf.de
  10. N. Stefan, H.-U. Häring: Circulating fetuin-A and free fatty acids interact to predict insulin resistance in humans. In: Nature Medicine , 19, 2013, pp. 394-395, doi: 10.1038 / nm.3116
  11. patent-de.com
  12. Turner et al .: Insulin deficiency and insulin resistance interaction in diabetes: estimation of their relative contribution by feedback analysis from basal plasma insulin and glucose concentrations. In: Metabolism , 1979, 28, pp. 1086-1096.
  13. AS Rudenski, DR Matthews, JC Levy, RC Turner: Understanding insulin resistance: Both glucose resistance and insulin resistance are required to model human diabetes . In: Metabolism . 40, No. 9, September 1991, pp. 908-917. ISSN  0026-0495 . doi : 10.1016 / 0026-0495 (91) 90065-5 .
  14. for values ​​in mg / dl division by 405 instead of 22.5.
  15. HOMA-Index - Laborlexikon.de (accessed 2011)
  16. Richard Daikeler, idols Use, Sylke Waibel: diabetes. Evidence-based diagnosis and therapy. 2015, p. 18 f.
  17. S. Kodama et al .: Influence of fat and carbohydrate proportions on the metabolic profile in patients with type 2 diabetes: a meta-analysis . In: Diabetes Care . 2009 May, 32 (5), pp. 959-965, PMID 19407076 .
  18. G Boden, K Sargrad, C Homko, M Mozzoli, TP Stein: Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes . In: Annals of internal medicine . 142, No. 6, 2005, pp. 403-411. PMID 15767618 .
  19. W. Falta, R. Boller: Insular and insulin-resistant diabetes . In: Clinical weekly . 10, 1931, pp. 438-43. doi : 10.1007 / BF01736348 .
  20. ^ H Himsworth: Diabetes mellitus: its differentiation into insulin-sensitive and insulin insensitive types . In: The Lancet . 227, 1936, pp. 127-130. doi : 10.1016 / S0140-6736 (01) 36134-2 .