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Insulin Resistance

  • Author: Samuel T Olatunbosun, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
Updated: Jan 30, 2015


Insulin resistance is a state in which a given concentration of insulin produces a less-than-expected biological effect. (See Pathophysiology.) Insulin resistance has also been arbitrarily defined as the requirement of 200 or more units of insulin per day to attain glycemic control and to prevent ketosis.

The syndromes of insulin resistance actually make up a broad clinical spectrum, which includes obesity, glucose intolerance, diabetes, and the metabolic syndrome, as well as an extreme insulin-resistant state. Many of these disorders are associated with various endocrine, metabolic, and genetic conditions. These syndromes may also be associated with immunological diseases and may exhibit distinct phenotypic characteristics. (See Etiology and Clinical Presentation.)

The metabolic syndrome —a state of insulin-resistance that is also known as either syndrome X or the dysmetabolic syndrome—has drawn the greatest attention because of its public health importance. (See Diagnostic Considerations.)

In clinical practice, no single laboratory test is used to diagnose insulin resistance syndrome. Diagnosis is based on clinical findings corroborated with laboratory tests. Individual patients are screened based on the presence of comorbid conditions. (See Workup.)

Treatment involves pharmacologic therapy to reduce insulin resistance, along with surgical management of underlying causes if appropriate. Comorbid conditions should be evaluated and addressed; this is generally feasible on an outpatient basis, though some patients will require admission. The metabolic syndrome requires aggressive control of cardiovascular and metabolic risk factors. Modifications of diet and activity are recommended. (See Treatment and Management.)

Go to Diabetes Mellitus, Type 1 and Diabetes Mellitus, Type 2 for complete information on these topics.



In insulin resistance, various clinical entities of this state are evident. The clinical heterogeneity can be explained, at least in part, on a biochemical basis. Insulin binds and acts mainly through the insulin receptor and also acts via the insulinlike growth factor–1 (IGF-1) receptor; cellular actions of insulin involve a wide variety of effects on postreceptor signaling pathways within target cells.

The b subunit of the insulin receptor is a tyrosine kinase, which is activated when insulin binds to the a subunit; the kinase activity autophosphorylates and mediates multiple actions of insulin. Ambient insulin levels, various physiological and disease states, and drugs regulate insulin receptor concentration or affinity.

Insulin sensitivity and secretion are reciprocally related; thus, insulin resistance results in increased insulin secretion to maintain normal glucose and lipid homeostasis.[1, 2] The mathematical relation between sensitivity and secretion is curvilinear or hyperbolic. Several mediators are thought to signal the pancreatic B cells to respond to insulin resistance; failure of the signals or of the B cells to adapt adequately in relation to insulin sensitivity results in inappropriate insulin levels, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes.

These potential signaling mediators include glucose, free fatty acids, autonomic nerves, fat-derived hormones (eg, adiponectin), and the gut hormone glucagonlike peptide 1 (GLP-1). GLP-1 is an incretin hormone that stimulates insulin secretion, causes B-cell mitosis while inhibiting apoptosis, inhibits glucagon secretion, and delays gastric emptying with overall antidiabetic effects.

The mechanisms responsible for insulin resistance syndromes include genetic or primary target cell defects, autoantibodies to insulin, and accelerated insulin degradation.[3] Given that glucose and lipid metabolism largely depend on mitochondria to generate energy in cells, mitochondrial dysfunction may play an important role in the development of insulin resistance and associated complications.[4]

Obesity, the most common cause of insulin resistance, is associated with a decreased number of receptors and with postreceptor failure to activate tyrosine kinase. While adiposity and insulin resistance are related, they are not necessarily synonymous, and each may make independent and different contributions to increasing the risk of cardiovascular disease.[5]

Leptin and ghrelin are 2 hormones that have a major influence on energy balance. Leptin is a long-term regulator of energy balance, suppressing food intake and thereby inducing weight loss, while ghrelin is a fast-acting hormone, seemingly playing a role in meal initiation. Obese subjects tend to be leptin resistant; their circulating levels of the anorexigenic hormone leptin are increased, but the levels of the orexigenic hormone ghrelin are decreased. Potential exists for both hormones as drug targets.[6]

Insulin resistance plays a major pathogenic role in the development of the metabolic syndrome, which may include any or all of the following:

Inflammation and adipocytokines probably play some role in the etiopathogenesis of metabolic syndrome.[8, 9, 10] Increased levels of the acute-phase inflammatory marker C-reactive protein (CRP) are related to insulin resistance and the metabolic syndrome, suggesting a role for chronic, low-grade inflammation.[11] In a number of prospective studies, increased levels of CRP predict the development of diabetes and cardiovascular disease.[5, 12, 13]

Reduced serum levels of adiponectin (a hormone made by fat tissue) and elevated leptin concentration are also features of conditions associated with the metabolic syndrome or cardiovascular disease.[14, 15, 16, 17]

Omentin, a novel adipokine, is a protein expressed and secreted from visceral but not subcutaneous adipose tissue that increases insulin sensitivity in adipocytes. Plasma levels of omentin-1, the major circulating isoform, are inversely correlated with body mass index (BMI), waist circumference, leptin levels, and insulin resistance syndrome and are positively correlated with adiponectin and high-density lipoprotein (HDL) levels.[18, 19, 20, 21]

Insulin resistance, the compensatory hyperinsulinemia, and other components are associated with increased risk of cardiovascular disease; endothelial dysfunction is a prominent feature of insulin resistance syndrome.[22] Type 2 diabetes is characterized by increased hepatic glucose output, increased peripheral resistance to insulin action (due to receptor and postreceptor defects), and impaired insulin secretion.[23]

In skeletal muscle, various abnormalities, including defective glucose transport, may cause insulin resistance. Glucose transporter 4 (GLUT-4) is the main insulin-responsive transporter. Insulin and IGFs are important regulators of ovarian function. Insulin resistance and hyperinsulinemia are thought to be responsible for the hyperandrogenism that is characteristic of the polycystic ovary syndrome (PCOS). Other distinct manifestations of insulin resistance syndrome or related conditions involve various organs, as well as the skin.

Two major variants of insulin receptor abnormalities associated with acanthosis nigricans have been described—the classic type A insulin resistance syndrome, which is due to an absent or dysfunctional receptor, and type B insulin resistance syndrome, which results from autoantibodies to the insulin receptor. Both syndromes are associated with hyperinsulinemia.

Hypoglycemia may still occur in some individuals with insulin resistance syndrome because of an agonist effect of autoantibodies on the insulin receptor. In some patients with insulin-binding antibodies, hypoglycemia may occur when insulin dissociates from the antibodies several hours after a meal.

Insulin resistance may also develop in some type 1 diabetic patients; in a recent study, Uruska et al found that an independent relationship existed between insulin resistance and the risk of microangiopathy in 81 patients with diabetes type 1 who began receiving intensive insulin therapy right after their diagnosis.[24] The authors determined that insulin resistance indicators, including waist circumference, waist-to-hip ratio, and triglyceride levels, were greater in cohort members with microangiopathy than in those without it. In addition, the estimated glucose disposal rate was lower in the microangiopathy patients than in the others.



Insulin resistance results from inherited and acquired influences. Hereditary causes include mutations of insulin receptor, glucose transporter, and signaling proteins, although the common forms are largely unidentified. Acquired causes include physical inactivity, diet, medications, hyperglycemia (glucose toxicity), increased free fatty acids, and the aging process.[25]

Classification of prereceptor, receptor, and postreceptor causes

The underlying causes of insulin-resistant states may also be categorized according to whether their primary effect is before, at, or after the insulin receptor (see below).

Prereceptor causes of insulin resistance include the following:

  • Abnormal insulin (mutations)
  • Anti-insulin antibodies

Receptor causes include the following:

  • Decreased number of receptors (mainly, failure to activate tyrosine kinase)
  • Reduced binding of insulin
  • Insulin receptor mutations
  • Insulin receptor–blocking antibodies

Postreceptor causes include the following:

  • Defective signal transduction
  • Mutations of GLUT4 (In theory, these mutations could cause insulin resistance, but polymorphisms in the GLUT4 gene are rare.)

Combinations of causes are common. For example, obesity, the most common cause of insulin resistance, is associated mainly with postreceptor abnormality but is also associated with a decreased number of insulin receptors.

Other conditions that are categorized as receptor or postreceptor insulin-resistant states include the following:

  • Type A syndrome
  • Type B syndrome
  • Leprechaunism
  • Lipodystrophic states
  • Ataxia-telangiectasia
  • Werner syndrome
  • Rabson-Mendenhall syndrome
  • Pineal hypertrophic syndrome

Specific causes of insulin resistance

Specific conditions and agents that may cause insulin resistance include the following:

  • Aging: This may cause insulin resistance through a decreased production of GLUT-4.
  • Increased production of insulin antagonists: A number of disorders are associated with this effect, such as Cushing syndrome, acromegaly, and stress states, such as trauma, surgery, diabetes ketoacidosis, severe infection, uremia, and liver cirrhosis.
  • Medications: Agents associated with insulin resistance syndrome include glucocorticoids (Cushing syndrome), cyclosporine, niacin, and protease inhibitors. Glucocorticoid therapy is a common cause of glucose intolerance; impairment of glucose tolerance may occur even at low doses when administered long term. [26]
  • Sodium: High sodium intake has been associated with increased glucocorticoid production and insulin resistance. [27]
  • Anti-HIV therapy [28] : Protease inhibitor–associated lipodystrophy is a recognized entity. [29] Nucleoside analogues have also been implicated in the development of insulin resistance.
  • Androgen-deprivation therapy: This therapy causes severe hypogonadism with unfavorable metabolic changes. [30]
  • Insulin therapy: Low-titer immunoglobulin G (IgG) anti-insulin antibody levels are present in most patients who receive insulin. Rarely, the antibodies result in significant prereceptor insulin resistance. Patients with a history of interrupted exposure to beef insulin treatment are particularly prone to this resistance. Clinically significant resistance usually occurs in patients with preexisting, significant tissue insensitivity to insulin. Enhanced destruction of insulin at the subcutaneous injection site has also been implicated in resistance.


United States statistics

In the United States, the frequency of insulin resistance is observed to be 3% in the general population; a several-fold increase occurs in individuals with glucose intolerance.

International statistics

A quarter of the world’s adults are considered to have the metabolic syndrome.[31, 32] Worldwide, early studies indicated a more significant association between insulin resistance and the various components of the metabolic syndrome in white persons than in members of other ethnic groups. Prevalence rates of insulin resistance syndrome reported for white populations ranged from 3-16%; a rate of less than 2% was reported among Japanese populations.

Subsequent findings, however, have suggested a similar relationship in many minority populations. Nevertheless, available systematic data apply mainly to white populations. Marked variations exist in methodologies and diagnostic criteria.

Age distribution for insulin resistance

Type A insulin resistance typically occurs in younger patients, while type B insulin resistance occurs more often in older women. Women with polycystic ovary syndrome (PCOS) usually present in their mid-20s. Many rare disorders of insulin resistance present in early life (eg, leprechaunism [first year of life], lipodystrophic states [ages 6-9 y until early puberty]).

The strongest relationship between insulin resistance and cardiovascular risk factors is observed in middle-aged persons rather than in older individuals, although cardiovascular morbidity and mortality increase with age.

Despite the growing obesity epidemic and insulin resistance in children, no clear diagnostic criteria and surrogate markers have been identified. An international consensus group recommended against screening children for insulin resistance in children based on existing methodology and criteria.[33]

Sex distribution for insulin resistance

The metabolic syndrome is more evident in middle-aged men. Women tend to assume increased cardiovascular risk after menopause. PCOS is a disease limited to women. Type A and type B syndromes are typically found in women but can occur in men. Hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN) syndrome has also been proposed as an alternative to type A in describing females with congenital forms of insulin resistance and acanthosis nigricans with ovarian hyperandrogenism but no other phenotypic changes such as growth retardation or lipodystrophy.

Prevalence of insulin resistance by race

Insulin resistance syndrome is found in all races. The degree of clustering of the risk variables of the metabolic syndrome is generally considered to be higher among whites. However, prevalence rates of the various components of the metabolic syndrome tend to be higher among nonwhite populations.[34]

Acanthosis nigricans, a common physical sign of insulin resistance syndrome, occurs in all ethnic groups, but the prevalence is higher in Hispanics and blacks than it is in whites.



Prognosis depends on the type of insulin resistance syndrome. The prognosis is guarded in regard to many of the disorders related to insulin resistance syndrome early in life. For instance, in leprechaunism, the clinical course is often characterized by growth retardation, abnormal glucose homeostasis (especially occurrence of hypoglycemia), and fatality within the first year of life. In other conditions, progression of insulin resistance and manifestation of related disorders continue into adulthood.

In the metabolic syndrome, the prognosis is often affected by the number and severity of comorbid conditions and by the institution of appropriate therapy. People with the metabolic syndrome are twice as likely to die from, and 3 times as likely to have, a myocardial infarction (MI) or stroke than are with people without the syndrome. They also have a 5-fold increased risk of developing type 2 diabetes.

Insulin resistance is a common basis for development of glucose intolerance, including diabetes and coronary artery disease (CAD).

Diabetes mellitus is the sixth leading cause of death by disease and the seventh leading cause of death in the United States. Globally, up to 80% of the 200 million people with diabetes will die of cardiovascular disease. Diabetes is the leading cause of end-stage renal disease and blindness in the United States. Individuals with diabetes have a much higher risk of heart disease and a higher risk of stroke; they also have a high risk of neuropathy and gangrene. Diabetes is also associated with acute metabolic complications.

CAD is the leading cause of death in the United States and in most developed countries. Coronary artery disease is responsible for 500,000 deaths annually in the United States. Nearly 1.5 million MIs, approximately one third of which are fatal, occur annually. The total annual economic cost of CAD in the United States is nearly $60 billion.

Mortality and morbidity related to other conditions associated with insulin resistance include the following:

The availability of newer modalities of treatment specifically targeted at primary and secondary prevention of complications has improved survival and quality of life significantly in patients with insulin resistance syndrome. However, morbidity and mortality rates are still considerable in the general population.


Patient Education

Educate patients who have insulin resistance on the nature of the disease, treatment, risk of complications, and primary and/or secondary preventive measures, including adoption of a healthier lifestyle. Educate family members on various issues related to the management and screening of persons at risk.

For patient education information, see the Diabetes Center.

Contributor Information and Disclosures

Samuel T Olatunbosun, MD, FACP, FACE Endocrinology Service, SAMMC/59th Medical Wing and Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine

Samuel T Olatunbosun, MD, FACP, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, Endocrine Society, American College of Physicians-American Society of Internal Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Don S Schalch, MD Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics

Don S Schalch, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

David S Schade, MD Chief, Division of Endocrinology and Metabolism, Professor, Department of Internal Medicine, University of New Mexico School of Medicine and Health Sciences Center

David S Schade, MD is a member of the following medical societies: American College of Physicians, American Diabetes Association, American Federation for Medical Research, Endocrine Society, New Mexico Medical Society, New York Academy of Sciences, Society for Experimental Biology and Medicine

Disclosure: Nothing to disclose.


Samuel Dagogo-Jack, MD, MBBS, MSc, FRCP Professor of Medicine, Program Director, Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center

Samuel Dagogo-Jack, MD, MBBS, MSc, FRCP is a member of the following medical societies: American College of Physicians, American Diabetes Association, American Federation for Medical Research, Royal College of Physicians, and The Endocrine Society

Disclosure: Eli Lilly None Speaking and teaching; GlaxoSmithKline None Speaking and teaching; Merck None Speaking and teaching

  1. Ahrén B, Pacini G. Islet adaptation to insulin resistance: mechanisms and implications for intervention. Diabetes Obes Metab. 2005 Jan. 7(1):2-8. [Medline].

  2. Mari A, Ahrén B, Pacini G. Assessment of insulin secretion in relation to insulin resistance. Curr Opin Clin Nutr Metab Care. 2005 Sep. 8(5):529-33. [Medline].

  3. Reaven GM. Pathophysiology of insulin resistance in human disease. Physiol Rev. 1995 Jul. 75(3):473-86. [Medline].

  4. Kim JA, Wei Y, Sowers JR. Role of mitochondrial dysfunction in insulin resistance. Circ Res. 2008 Feb 29. 102(4):401-14. [Medline]. [Full Text].

  5. Lee SH, Park SA, Ko SH, Yim HW, Ahn YB, Yoon KH, et al. Insulin resistance and inflammation may have an additional role in the link between cystatin C and cardiovascular disease in type 2 diabetes mellitus patients. Metabolism. 2010 Feb. 59(2):241-6. [Medline].

  6. Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007 Jan. 8(1):21-34. [Medline].

  7. Reaven G, Abbasi F, McLaughlin T. Obesity, insulin resistance, and cardiovascular disease. Recent Prog Horm Res. 2004. 59:207-23. [Medline].

  8. de Luca C, Olefsky JM. Inflammation and insulin resistance. FEBS Lett. 2008 Jan 9. 582(1):97-105. [Medline]. [Full Text].

  9. Tilg H, Moschen AR. Inflammatory mechanisms in the regulation of insulin resistance. Mol Med. 2008 Mar-Apr. 14(3-4):222-31. [Medline]. [Full Text].

  10. Grant PJ. Inflammatory, atherothrombotic aspects of type 2 diabetes. Curr Med Res Opin. 2005. 21 Suppl 1:S5-12. [Medline].

  11. Florez H, Castillo-Florez S, Mendez A, Casanova-Romero P, Larreal-Urdaneta C, Lee D, et al. C-reactive protein is elevated in obese patients with the metabolic syndrome. Diabetes Res Clin Pract. 2006 Jan. 71(1):92-100. [Medline].

  12. Laaksonen DE, Niskanen L, Nyyssönen K, Punnonen K, Tuomainen TP, Salonen JT. C-reactive protein in the prediction of cardiovascular and overall mortality in middle-aged men: a population-based cohort study. Eur Heart J. 2005 Sep. 26(17):1783-9. [Medline].

  13. Rifai N. High-sensitivity C-reactive protein: a useful marker for cardiovascular disease risk prediction and the metabolic syndrome. Clin Chem. 2005 Mar. 51(3):504-5. [Medline].

  14. Semple RK, Cochran EK, Soos MA, Burling KA, Savage DB, Gorden P, et al. Plasma adiponectin as a marker of insulin receptor dysfunction: clinical utility in severe insulin resistance. Diabetes Care. 2008 May. 31(5):977-9. [Medline].

  15. Brabant G, Müller G, Horn R, Anderwald C, Roden M, Nave H. Hepatic leptin signaling in obesity. FASEB J. 2005 Jun. 19(8):1048-50. [Medline].

  16. Fuke Y, Fujita T, Satomura A, Wada Y, Matsumoto K. Alterations of insulin resistance and the serum adiponectin level in patients with type 2 diabetes mellitus under the usual antihypertensive dosage of telmisartan treatment. Diabetes Technol Ther. 2010 May. 12(5):393-8. [Medline].

  17. Meilleur KG, Doumatey A, Huang H, Charles B, Chen G, Zhou J, et al. Circulating adiponectin is associated with obesity and serum lipids in West Africans. J Clin Endocrinol Metab. 2010 Jul. 95(7):3517-21. [Medline]. [Full Text].

  18. de Souza Batista CM, Yang RZ, Lee MJ, Glynn NM, Yu DZ, Pray J, et al. Omentin plasma levels and gene expression are decreased in obesity. Diabetes. 2007 Jun. 56(6):1655-61. [Medline].

  19. Tan BK, Adya R, Farhatullah S, Lewandowski KC, O'Hare P, Lehnert H, et al. Omentin-1, a novel adipokine, is decreased in overweight insulin-resistant women with polycystic ovary syndrome: ex vivo and in vivo regulation of omentin-1 by insulin and glucose. Diabetes. 2008 Apr. 57(4):801-8. [Medline].

  20. Moreno-Navarrete JM, Catalán V, Ortega F, Gómez-Ambrosi J, Ricart W, Frühbeck G, et al. Circulating omentin concentration increases after weight loss. Nutr Metab (Lond). 2010 Apr 9. 7:27. [Medline]. [Full Text].

  21. Hug C, Lodish HF. The role of the adipocyte hormone adiponectin in cardiovascular disease. Curr Opin Pharmacol. 2005 Apr. 5(2):129-34. [Medline].

  22. Diamant M, Tushuizen ME. The metabolic syndrome and endothelial dysfunction: common highway to type 2 diabetes and CVD. Curr Diab Rep. 2006 Aug. 6(4):279-86. [Medline].

  23. Dushay J, Abrahamson MJ. Insulin resistance and type 2 diabetes: a comprehensive review. Medscape Today [serial online]. Apr 8 2005. [Full Text].

  24. Uruska A, Araszkiewicz A, Zozulinska-Ziolkiewicz D, Uruski P, Wierusz-Wysocka B. Insulin resistance is associated with microangiopathy in type 1 diabetic patients treated with intensive insulin therapy from the onset of disease. Exp Clin Endocrinol Diabetes. 2010 Aug. 118(8):478-84. [Medline].

  25. Lutsey PL, Steffen LM, Stevens J. Dietary intake and the development of the metabolic syndrome: the Atherosclerosis Risk in Communities study. Circulation. 2008 Feb 12. 117(6):754-61. [Medline].

  26. van Raalte DH, Brands M, van der Zijl NJ, et al. Low-dose glucocorticoid treatment affects multiple aspects of intermediary metabolism in healthy humans: a randomised controlled trial. Diabetologia. 2011 Aug. 54(8):2103-12. [Medline].

  27. Baudrand R, Campino C, Carvajal CA, Olivieri O, Guidi G, Faccini G, et al. High sodium intake is associated with increased glucocorticoid production, insulin resistance and metabolic syndrome. Clin Endocrinol (Oxf). 2014 May. 80(5):677-84. [Medline].

  28. De Wit S, Sabin CA, Weber R, Worm SW, Reiss P, Cazanave C, et al. Incidence and risk factors for new-onset diabetes in HIV-infected patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. Diabetes Care. 2008 Jun. 31(6):1224-9. [Medline]. [Full Text].

  29. Wierzbicki AS, Purdon SD, Hardman TC, Kulasegaram R, Peters BS. HIV lipodystrophy and its metabolic consequences: implications for clinical practice. Curr Med Res Opin. 2008 Mar. 24(3):609-24. [Medline].

  30. Yu IC, Lin HY, Sparks JD, Yeh S, Chang C. Androgen receptor roles in insulin resistance and obesity in males: the linkage of androgen-deprivation therapy to metabolic syndrome. Diabetes. 2014 Oct. 63(10):3180-8. [Medline]. [Full Text].

  31. Moadab MH, Kelishadi R, Hashemipour M, Amini M, Poursafa P. The prevalence of impaired fasting glucose and type 2 diabetes in a population-based sample of overweight/obese children in the Middle East. Pediatr Diabetes. 2010 Mar. 11(2):101-6. [Medline].

  32. Sarti C, Gallagher J. The metabolic syndrome: prevalence, CHD risk, and treatment. J Diabetes Complications. 2006 Mar-Apr. 20(2):121-32. [Medline].

  33. Levy-Marchal C, Arslanian S, Cutfield W, Sinaiko A, Druet C, Marcovecchio ML, et al. Insulin resistance in children: consensus, perspective, and future directions. J Clin Endocrinol Metab. 2010 Dec. 95(12):5189-98. [Medline].

  34. Beck-Nielsen H. General characteristics of the insulin resistance syndrome: prevalence and heritability. European Group for the study of Insulin Resistance (EGIR). Drugs. 1999. 58 Suppl 1:7-10; discussion 75-82. [Medline].

  35. Hirschler V, Ruiz A, Romero T, Dalamon R, Molinari C. Comparison of different anthropometric indices for identifying insulin resistance in schoolchildren. Diabetes Technol Ther. 2009 Sep. 11(9):615-21. [Medline].

  36. Savino A, Pelliccia P, Chiarelli F, Mohn A. Obesity-related renal injury in childhood. Horm Res Paediatr. 2010. 73(5):303-11. [Medline].

  37. Einhorn D, Reaven GM, Cobin RH, Ford E, Ganda OP, Handelsman Y, et al. American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract. 2003 May-Jun. 9(3):237-52. [Medline].

  38. American Association of Clinical Endocrinologists Position Statement on Metabolic and Cardiovascular Consequences of Polycystic Ovary Syndrome. Endocr Pract. 2005 Mar-Apr. 11(2):126-34. [Medline].

  39. Essah PA, Nestler JE. The metabolic syndrome in polycystic ovary syndrome. J Endocrinol Invest. 2006 Mar. 29(3):270-80. [Medline].

  40. Pasquali R, Patton L, Pagotto U, Gambineri A. Metabolic alterations and cardiovascular risk factors in the polycystic ovary syndrome. Minerva Ginecol. 2005 Feb. 57(1):79-85. [Medline].

  41. Cheng AY, Leiter LA. Metabolic syndrome under fire: weighing in on the truth. Can J Cardiol. 2006 Apr. 22(5):379-82. [Medline]. [Full Text].

  42. Daskalopoulou SS, Athyros VG, Kolovou GD, Anagnostopoulou KK, Mikhailidis DP. Definitions of metabolic syndrome: Where are we now?. Curr Vasc Pharmacol. 2006 Jul. 4(3):185-97. [Medline].

  43. Reaven GM. The metabolic syndrome: is this diagnosis necessary?. Am J Clin Nutr. 2006 Jun. 83(6):1237-47. [Medline].

  44. Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2005 Sep. 28(9):2289-304. [Medline].

  45. De Taeye B, Smith LH, Vaughan DE. Plasminogen activator inhibitor-1: a common denominator in obesity, diabetes and cardiovascular disease. Curr Opin Pharmacol. 2005 Apr. 5(2):149-54. [Medline].

  46. Sjöholm A, Nyström T. Endothelial inflammation in insulin resistance. Lancet. 2005 Feb 12-18. 365(9459):610-2. [Medline].

  47. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985 Jul. 28(7):412-9. [Medline].

  48. Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000 Jul. 85(7):2402-10. [Medline].

  49. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 2008 Jan. 294(1):E15-26. [Medline].

  50. Antuna-Puente B, Faraj M, Karelis AD, et al. HOMA or QUICKI: is it useful to test the reproducibility of formulas?. Diabetes Metab. 2008 Jun. 34(3):294-6. [Medline].

  51. Vaccaro O, Masulli M, Cuomo V, et al. Comparative evaluation of simple indices of insulin resistance. Metabolism. 2004 Dec. 53(12):1522-6. [Medline].

  52. Rossner SM, Neovius M, Mattsson A, Marcus C, Norgren S. HOMA-IR and QUICKI: decide on a general standard instead of making further comparisons. Acta Paediatr. 2010 Nov. 99(11):1735-40. [Medline].

  53. Sobngwi E, Kengne AP, Echouffo-Tcheugui JB, Choukem S, Sobngwi-Tambekou J, Balti EV, et al. Fasting insulin sensitivity indices are not better than routine clinical variables at predicting insulin sensitivity among Black Africans: a clamp study in sub-Saharan Africans. BMC Endocr Disord. 2014 Aug 9. 14:65. [Medline]. [Full Text].

  54. Jensterle M, Janez A, Mlinar B, Marc J, Prezelj J, Pfeifer M. Impact of metformin and rosiglitazone treatment on glucose transporter 4 mRNA expression in women with polycystic ovary syndrome. Eur J Endocrinol. 2008 Jun. 158(6):793-801. [Medline].

  55. Salpeter SR, Buckley NS, Kahn JA, Salpeter EE. Meta-analysis: metformin treatment in persons at risk for diabetes mellitus. Am J Med. 2008 Feb. 121(2):149-157.e2. [Medline].

  56. Quinn CE, Hamilton PK, Lockhart CJ, McVeigh GE. Thiazolidinediones: effects on insulin resistance and the cardiovascular system. Br J Pharmacol. 2008 Feb. 153(4):636-45. [Medline]. [Full Text].

  57. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007 Jun 14. 356(24):2457-71. [Medline].

  58. Rasouli N, Raue U, Miles LM, Lu T, Di Gregorio GB, Elbein SC, et al. Pioglitazone improves insulin sensitivity through reduction in muscle lipid and redistribution of lipid into adipose tissue. Am J Physiol Endocrinol Metab. 2005 May. 288(5):E930-4. [Medline].

  59. Lee WJ, Lee YC, Ser KH, Chen JC, Chen SC. Improvement of insulin resistance after obesity surgery: a comparison of gastric banding and bypass procedures. Obes Surg. 2008 Sep. 18(9):1119-25. [Medline].

  60. Herman WH, Hoerger TJ, Brandle M, Hicks K, Sorensen S, Zhang P, et al. The cost-effectiveness of lifestyle modification or metformin in preventing type 2 diabetes in adults with impaired glucose tolerance. Ann Intern Med. 2005 Mar 1. 142(5):323-32. [Medline]. [Full Text].

  61. Pritchett AM, Foreyt JP, Mann DL. Treatment of the metabolic syndrome: the impact of lifestyle modification. Curr Atheroscler Rep. 2005 Mar. 7(2):95-102. [Medline].

  62. Hawley JA. Exercise as a therapeutic intervention for the prevention and treatment of insulin resistance. Diabetes Metab Res Rev. 2004 Sep-Oct. 20(5):383-93. [Medline].

  63. Hawley JA, Lessard SJ. Exercise training-induced improvements in insulin action. Acta Physiol (Oxf). 2008 Jan. 192(1):127-35. [Medline].

  64. Shih KC, Janckila AJ, Kwok CF, Ho LT, Chou YC, Chao TY. Effects of exercise on insulin sensitivity, inflammatory cytokines, and serum tartrate-resistant acid phosphatase 5a in obese Chinese male adolescents. Metabolism. 2010 Jan. 59(1):144-51. [Medline].

  65. Ioannides-Demos LL, Proietto J, McNeil JJ. Pharmacotherapy for obesity. Drugs. 2005. 65(10):1391-418. [Medline].

  66. Jayagopal V, Kilpatrick ES, Holding S, Jennings PE, Atkin SL. Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome. J Clin Endocrinol Metab. 2005 Feb. 90(2):729-33. [Medline].

  67. Kiortsis DN, Filippatos TD, Elisaf MS. The effects of orlistat on metabolic parameters and other cardiovascular risk factors. Diabetes Metab. 2005 Feb. 31(1):15-22. [Medline].

  68. Sjöström L. Analysis of the XENDOS study (Xenical in the Prevention of Diabetes in Obese Subjects). Endocr Pract. 2006 Jan-Feb. 12 Suppl 1:31-3. [Medline].

  69. Swinburn BA, Carey D, Hills AP, Hooper M, Marks S, Proietto J, et al. Effect of orlistat on cardiovascular disease risk in obese adults. Diabetes Obes Metab. 2005 May. 7(3):254-62. [Medline].

  70. Fauci AS, Braunwald E, Kasper DL, et al. Harrison’s Principles of Internal Medicine. 17th ed. New York, NY: New York, NY; 2008.

  71. Kolterman OG, Buse JB, Fineman MS, Gaines E, Heintz S, Bicsak TA, et al. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab. 2003 Jul. 88(7):3082-9. [Medline].

  72. Sarkar G, Alattar M, Brown RJ, Quon MJ, Harlan DM, Rother KI. Exenatide treatment for 6 months improves insulin sensitivity in adults with type 1 diabetes. Diabetes Care. 2014 Mar. 37(3):666-70. [Medline]. [Full Text].

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