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| {{Insulin resistance}} | | {{Insulin resistance}} |
| {{CMG}} | | {{CMG}} {{AE}} {{DD}} |
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| ==Investigation== | | == [[Insulin resistance overview|Overview]] == |
| ===Fasting Insulin Levels===
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| A fasting serum insulin level of greater than the upper limit of normal for the assay used (approximately 60pmol/L) is considered evidence of insulin resistance.
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| ===Glucose tolerance testing (GTT)=== | | == [[Insulin resistance historical perspective|Historical Perspective]] == |
| During a [[glucose tolerance test]], which may be used to diagnose diabetes mellitus, a fasted patient takes a 75 gram oral dose of glucose. Blood glucose levels are then measured over the following 2 hours.
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| Interpretation is based on WHO guidelines, but [[glycemia]] greater than or equal to 11.1mmol/L at 2 hours or greater than or equal to 7.0mmol/L fasting is diagnostic for diabetes mellitus.
| | == [[Insulin resistance pathophysiology|Pathophysiology]] == |
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| OGTT can 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 (after the meal) peak in insulin production. Extension of the testing (for several more hours) may reveal a [[hypoglycemia|hypoglycemic]] "dip", which is a result of an overshoot in insulin production after the failure of the physiologic postprandial insulin response.
| | == [[Insulin resistance causes|Causes]] == |
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| ===Measuring Insulin Resistance=== | | == [[Insulin resistance differential diagnosis|Differentiating Insulin Resistance from other Diseases]] == |
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| '''Hyperinsulinemic euglycemic clamp'''
| | == [[Insulin resistance epidemiology and demographics|Epidemiology and Demographics]] == |
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| 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 |author=DeFronzo R, Tobin J, Andres R |title=Glucose clamp technique: a method for quantifying insulin secretion and resistance |journal=Am J Physiol |volume=237 |issue=3 |pages=E214-23 |year=1979 |pmid=382871}}</ref> 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 is commonly referred to in diabetes literature as the GINF value.
| | == [[Insulin resistance risk factors|Risk Factors]] == |
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| The procedure takes about 2 hours. Through a [[peripheral vein]], [[insulin]] is infused at 10-120 mU per m2 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 mmol/l. The rate of glucose infusion is determined by checking the [[blood sugar]] levels every 5-10 minutes. Low dose insulin infusions are more useful for assessing the response of the liver whereas high dose insulin infusions are useful for assessing peripheral (i.e. muscle and fat) insulin action.
| | == [[Insulin resistance screening|Screening]] == |
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| The rate of glucose infusion during the last 30 minutes of the test determines insulin sensitivity. If high levels (7.5 mg/min or higher) are required, the patient is insulin-sensitive. Very low levels (4.0 mg/min or lower) indicate that the body is resistant to insulin action. Levels between 4.0 and 7.5 mg/min are not definitive and suggest "impaired glucose tolerance," an early sign of insulin resistance.
| | == [[Insulin resistance natural history, complications and prognosis|Natural History, Complications, and Prognosis]] == |
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| This basic technique can be significantly enhanced by the use of glucose tracers. Glucose can be labeled with either stable or radioactive atoms. Commonly used tracers are 3-3H glucose (radioactive), 6,6 2H-glucose (stable) and 1-13C Glucose (stable). Prior to beginning the hyperinsulinemic period, a 3h tracer infusion enables one to determine the basal rate of glucose production. During the clamp, the plasma tracer concentrations enable the calculation of whole body insulin stimulated glucose metabolism as well as the production of glucose by the body (i.e. endogenous glucose production).
| | == Diagnosis == |
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| '''Modified Insulin Suppression Test'''
| | [[Insulin resistance history and symptoms|History and Symptoms]] | [[Insulin resistance physical examination|Physical Examination]] | [[Insulin resistance laboratory findings|Laboratory Findings]] | [[Insulin resistance CT|CT]] | [[Insulin resistance MRI|MRI]] | [[Insulin resistance ultrasound|Ultrasound]] | [[Insulin resistance other imaging findings|Other Imaging Findings]] | [[Insulin resistance other diagnostic studies|Other Diagnostic Studies]] |
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| 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.
| | == Treatment == |
| | [[Insulin resistance medical therapy|Medical Therapy]] | [[Insulin resistance surgery|Surgery]] | [[Insulin resistance primary prevention|Primary Prevention]] | [[Insulin resistance secondary prevention|Secondary Prevention]] | [[Insulin resistance cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Insulin resistance future or investigational therapies|Future or Investigational Therapies]] |
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| Patients initially receive 25mcg of sandostatin in 5ml of normal saline over 3-5 min IV as an initial bolus and then will be infused continuously with an intravenous infusion of somatostatin (0.27microgm/m2/min) to suppress endogenous insulin and glucose secretion. Insulin and 20% glucose is then infused at rates of 32 and 267mg/m2/min, respectively. Blood glucose is checked at zero, 30, 60, 90 and 120 minutes and then every 10 minutes for the last 1/2 hour of the test. These last 4 values are averaged to determine the steady state plasma glucose level. Subjects with an SSPG greater than 150mg/dl are considered to be insulin resistant.
| | == Case Studies == |
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| ===Alternatives===
| | [[Insulin resistance case study one|Case #1]] |
| 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), and a more recent method is the QUICKI (quantitative insulin sensitivity check index). Both employ [[fasting]] [[insulin]] and [[glucose]] levels to calculate insulin resistance, and both correllate reasonably with the results of clamping studies. Wallace ''et al'' point out that QUICKI is the logarithm of the value from one of the HOMA equations.<ref name=Wallace_2004>{{cite journal |author=Wallace T, Levy J, Matthews D |title=Use and abuse of HOMA modeling |journal=Diabetes Care |volume=27 |issue=6 |pages=1487-95 |year=2004 |pmid=15161807}}</ref>
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| ==Causes of insulin resistance== | | ==Related Chapters== |
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| The cause of the vast majority of cases of insulin resistance remains unknown. However, insulin resistance might be caused by a high carbohydrate diet. Some physicians also believe that [[glucosamine]] (often prescribed for joint problems) may cause insulin resistance.
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| ==Associated Conditions==
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| Several associated conditions include
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| * Abnormally Sedentary Lifestyle, whether the result of the effects of [[aging]] on the body or lack of physical exercise (both of which can also produce [[obesity]])
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| * [[Haemochromatosis]]
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| * [[Polycystic ovarian syndrome]] (PCOS)
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| * [[Hypercortisolism]] (e.g. [[steroid]] use or [[Cushing's disease]])
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| * [[Medication|Drugs]] (e.g. [[rifampicin]], [[isoniazid]], [[olanzapine]], [[risperidone]], [[progestogen]]s, many antiretrovirals, possibly [[alcohol]], [[methadone]])
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| * Genetic causes
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| **[[Insulin receptor]] mutations (Donohue Syndrome)
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| **[[LMNA]] mutations (Familial Partial Lipodystrophy)
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| Insulin resistance may also be caused by the damage of liver cells which result in defect of insulin receptors in hepatocytes.
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| ==Therapy==
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| The primary treatment for insulin resistance is [[exercise]] and [[weight loss]]. In some individuals, a low [[glycemic index]] or a low carbohydrate diet may also help. Fasting might also help. Both [[metformin]] and the [[thiazolidinedione]]s improve insulin resistance, but are only approved therapies for type 2 diabetes, not insulin resistance, per se. By contrast, [[Growth hormone treatment|growth hormone replacement therapy]] may be associated with increased insulin resistance.<ref name=Bramnert_2003>{{cite journal | author=Bramnert M, Segerlantz M, Laurila E, Daugaard JR, Manhem P, Groop L | title=Growth hormone replacement therapy induces insulin resistance by activating the glucose-fatty acid cycle | journal=THE JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM| year=2003| volume=88 | issue=4 | pages=1455-1463 | url=http://jcem.endojournals.org/cgi/content/full/88/4/1455 | id=PMID 12679422}}</ref>
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| The ''Diabetes Prevention Program'' showed that exercise and diet were nearly twice as effective as [[metformin]] at reducing the risk of progressing to type 2 diabetes.<ref name=Knowler_2002>{{cite journal | author=Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group | title=Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin | journal=[[New England Journal of Medicine]]| year=2002 | volume=346 | issue=6 | pages=393-403 | url=http://content.nejm.org/cgi/content/abstract/346/6/393 | id=PMID 11832527}}</ref>
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| Some types of [[Monounsaturated fat|Monounsaturated fatty acids]] and saturated fats appear to promote insulin resistance, whereas some types of [[Polyunsaturated fat|polyunsaturated fatty acids]] (omega 3) can increase insulin sensitivity.<ref name=Lovejoy_2002>{{cite journal | author=Lovejoy, JC | title=The influence of dietary fat on insulin resistance | journal=Current Diabetes Reports | year=2002 | volume=2 | issue=5 | pages= 435–440 | id=PMID 12643169}}</ref><ref name=Fukuchi_2004>{{cite journal | author=Fukuchi S | title=Role of Fatty Acid Composition in the Development of Metabolic Disorders in Sucrose-Induced Obese Rats | journal=Experimental Biology and Medicine | year=2004 | volume=229 | issue=6 | pages= 486–493 | url=http://www.ebmonline.org/cgi/content/full/229/6/486 | id=PMID 15169967}}</ref><ref name=Storlien_1996>{{cite journal | author=Storlien LH | title=Dietary fats and insulin action | journal=Diabetologica | year=1996 | volume=39 | issue=6 | pages=621–631 | id=PMID 8781757}}</ref>
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| There are scientific studies showing that [[chromium picolinate]] can increase insulin sensitivity, especially in type 2 diabetics, but other studies show no effect. The results are controversial.
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| Naturopathic approaches to insulin resistance have been advocated including supplementation of vanadium, bitter melon (momordica) and [[Gymnema sylvestre]].<ref name=Harinantenaina_2006>{{cite journal | author=Harinantenaina L | title=Momordica charantia constituents and antidiabetic screening of the isolated major compounds | journal=Chemical & Pharmaceutical Bulletin (Tokyo) | year=2006 | volume=54 | issue=7 | pages= 1017–21 | url=http://www.jstage.jst.go.jp/article/cpb/54/7/54_1017/_article | id=PMID 16819222}}</ref>
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| ==History==
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| The concept that insulin resistance may be the underlying cause of [[diabetes mellitus]] type 2 was first advanced by Sir [[Harold Percival Himsworth]] of the University College Hospital Medical Center in London in 1936.<ref name=Himsworth_1936>{{cite journal | author = Himsworth HP | title = Diabetes mellitus: its differentiation into insulin-sensitive and insulin-insensitive types | journal = Lancet | year = 1936 | volume = 1 | pages = 127–130 | url= }}</ref>
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| ==References==
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| {{Reflist|2}}
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| ==See also==
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| * [[Chronic Somogyi rebound]] | | * [[Chronic Somogyi rebound]] |
| | | * [[Metabolic syndrome]] |
| ==External links==
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| * [http://www.insulinresistancecouncil.org The National Insulin Resistance Council] | |
| * [http://search.dmoz.org/cgi-bin/search?search=Insulin+resistance Insulin resistance] at the [[Open Directory Project]]
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| * [http://www.online-diabetes-information.com/insulin/insulin-resistance/ Insulin Resistance Information]
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| * [http://www.healthynerd.com/2006/08/02/bitter-melon-prickly-pear-cactus-reduce-glucose-levels-of-type-2-diabetics/ Bitter Melon, Prickly Pear Cactus, Address Insulin Resistance]
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| {{clr}}
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| [[Category:Diabetes]]
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| [[Category:Cardiology]]
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| [[Category:Endocrinology]]
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| [[de:Insulinresistenz]]
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| [[ja:インスリン抵抗性]]
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| [[pl:Insulinooporność]]
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| [[pt:Regulagem da glicemia]]
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| [[fi:Insuliiniresistenssi]]
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| [[tr:İnsülin direnci]]
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| [[zh:胰岛素抵抗]] | |
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