Insulin Resistance Differential Diagnoses

  • Author: Samuel T Olatunbosun, MD, FACP; Chief Editor: George T Griffing, MD   more...
 
Updated: Aug 2, 2011
 
 

Diagnostic Considerations

In an effort to clinically identify patients with insulin resistance, various organizations have developed diagnostic criteria. The most commonly used criteria in the United States are those of the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III).

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

NCEP/ATP III criteria for metabolic syndrome

NCEP/ATP III criteria for the diagnosis of the metabolic syndrome include the following (diagnosis is made when 3 or more are present):

  • Waist circumference of more than 102 cm in men or more than 88 cm in women
  • Fasting triglyceride level of 150 mg/dL or higher
  • Blood pressure level of 130/85 mm Hg or higher
  • High-density lipoprotein cholesterol (HDL-C) level of less than 40 mg/dL in men or less than 50 mg/dL in women
  • Fasting glucose level of 110 mg/dL or higher (which has been changed to 100 mg/dL to reflect revised criteria for impaired fasting glucose [IFG])

WHO criteria for metabolic syndrome

The World Health Organization (WHO) has also developed criteria for the diagnosis of the metabolic syndrome, as follows:

  • Type 2 diabetes
  • IFG level of 101-125 mg/dL
  • Impaired glucose tolerance (IGT) (glucose level of 140-199 mg/dL 2 h after administration of 75 g of glucose)
  • Glucose uptake level of less than the lowest quartile for ethnic population under hyperinsulinemic, euglycemic conditions if the fasting glucose level is normal

In addition to the aforementioned criteria, the diagnosis must also include 2 of the following:

  • Use of antihypertensive medication; blood pressure of 140 mm Hg systolic or higher, 90 mm Hg diastolic or higher, or both
  • Triglyceride level of 150 mg/dL or higher
  • HDL-C level of less than 35 mg/dL in men or less than 39 mg/dL in women
  • Body mass index (BMI) of more than 30 kg/m2, waist-to-hip ratio of more than 0.9 in men or more than 0.85 in women, or both
  • Urinary albumin excretion level of 20 mcg/min or higher or albumin-creatinine ratio of 30 mg/g or higher

AACE clinical criteria for insulin resistance syndrome

The American Association of Clinical Endocrinologists (AACE) has formulated clinical criteria for the diagnosis of insulin resistance syndrome, as follows[35] :

  • BMI of 25 kg/m2 or higher
  • Triglyceride level of 150 mg/dL or higher
  • HDL-C level of less than 40 mg/dL in men or less than 50 mg/dL in women
  • Blood pressure of 130/85 mm Hg or higher
  • Glucose level of more than 140 mg/dL 2 hours after administration of 75 g of glucose
  • Fasting glucose level of 110-126 mg/dL

Additional risk factors include the following:

Differences in diagnostic criteria

Whereas the NCEP/ATP III criteria use fasting glucose level as the only measurement of glucose tolerance, the WHO and AACE criteria include the option of performing a 2-hour oral glucose tolerance test (OGTT). The OGTT better identifies individuals at risk for endothelial damage due to hyperglycemia, because IGT has been shown to be independently associated with endothelial dysfunction and, hence, cardiovascular risk.[5]

IDF global consensus statement on metabolic syndrome

In a global consensus statement, an International Diabetes Federation (IDF) panel presented a worldwide definition of the metabolic syndrome aimed at facilitating early detection and more intensive management of the condition, with the hope of reducing the long-term risk of cardiovascular disease (CVD) and diabetes.

According to the definition by the IDF panel, the diagnostic criteria for the metabolic syndrome include central obesity (defined as waist circumference ≥94 cm in men or ≥80 cm in women in Europid persons and in ethnic-specific levels in Chinese, Japanese, and South Asian persons) together with 2 of the following:

  • Triglyceride level of 1.7 mmol/L (150 mg/dL) or higher
  • Low HDL-C level (defined as < 1.04 mmol/L [40 mg/dL] in men or < 1.29 mmol/L [50 mg/dL] in women)
  • Blood pressure of 130/85 mm Hg or higher
  • Fasting hyperglycemia (defined as glucose level ≥5.6 mmol/L [100 mg/dL]) or previous diagnosis of diabetes or IGT.

The scientific basis for the definition of the metabolic syndrome and its clinical utility have been debated.[39, 40, 41] The debate was accentuated by a joint statement from the American Diabetes Association and the European Association for the Study of Diabetes.[42]

Both sides of the debate, however, generally agree that the risk factors commonly coexist in the same patient and that insulin resistance is the major underlying mechanism. Moreover, the metabolic syndrome serves as a clinical tool to raise awareness among health care providers, thus assisting in identifying high-risk individuals.

Differential Diagnoses

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Contributor Information and Disclosures
Author

Samuel T Olatunbosun, MD, FACP  Endocrinology Department, Wilford Hall Medical Center, 59th Medical Wing, Lackland Air Force Base

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

Disclosure: Nothing to disclose.

Coauthor(s)

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, Endocrine Society, and Royal College of Physicians

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

Specialty Editor Board

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, and Society for Experimental Biology and Medicine

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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 Research, and Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD  Professor 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, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

References

  1. Ahrén B, Pacini G. Islet adaptation to insulin resistance: mechanisms and implications for intervention. Diabetes Obes Metab. Jan 2005;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. Sep 2005;8(5):529-33. [Medline].

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

  4. Kim JA, Wei Y, Sowers JR. Role of mitochondrial dysfunction in insulin resistance. Circ Res. Feb 29 2008;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. Feb 2010;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. Jan 2007;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. Jan 9 2008;582(1):97-105. [Medline]. [Full Text].

  9. Tilg H, Moschen AR. Inflammatory mechanisms in the regulation of insulin resistance. Mol Med. Mar-Apr 2008;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. Jan 2006;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. Sep 2005;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. Mar 2005;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. May 2008;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. Jun 2005;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. May 2010;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. Jul 2010;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. Jun 2007;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. Apr 2008;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). Apr 9 2010;7:27. [Medline]. [Full Text].

  21. Hug C, Lodish HF. The role of the adipocyte hormone adiponectin in cardiovascular disease. Curr Opin Pharmacol. Apr 2005;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. Aug 2006;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;Available at http://www.medscape.com/viewprogram/3942.

  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. Aug 2010;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. Feb 12 2008;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. Aug 2011;54(8):2103-12. [Medline].

  27. [Best Evidence] 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. Jun 2008;31(6):1224-9. [Medline]. [Full Text].

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

  29. 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. Mar 2010;11(2):101-6. [Medline].

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

  31. 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. Dec 2010;95(12):5189-98. [Medline].

  32. 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].

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

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

  35. 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. May-Jun 2003;9(3):237-52. [Medline].

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

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

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

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

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

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

  42. 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. Sep 2005;28(9):2289-304. [Medline].

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

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

  45. 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. Jul 1985;28(7):412-9. [Medline].

  46. 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. Jul 2000;85(7):2402-10. [Medline].

  47. 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. Jan 2008;294(1):E15-26. [Medline].

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

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

  50. 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. Nov 2010;99(11):1735-40. [Medline].

  51. 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. Jun 2008;158(6):793-801. [Medline].

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

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

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

  55. 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. May 2005;288(5):E930-4. [Medline].

  56. 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. Sep 2008;18(9):1119-25. [Medline].

  57. [Best Evidence] 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. Mar 1 2005;142(5):323-32. [Medline]. [Full Text].

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

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

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

  61. 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. Jan 2010;59(1):144-51. [Medline].

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

  63. 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. Feb 2005;90(2):729-33. [Medline].

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

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

  66. 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. May 2005;7(3):254-62. [Medline].

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

 
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