Insulin Resistance Workup

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

Approach 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. (See Clinical Presentation.) Individual patients are screened based on the presence of comorbid conditions.

Next

Lab Studies

Routine laboratory measurements in the evaluation of patients with insulin resistance syndrome include the following:

  • Plasma glucose level (fasting, random, and oral glucose tolerance test) - Diagnosis and monitoring of glucose intolerance (diabetes mellitus, impaired glucose tolerance [IGT], impaired fasting glucose [IFG])
  • Insulin resistance - May also be associated with hypoglycemia (autoimmune conditions)
  • Glycohemoglobin level – Used to assess chronic hyperglycemia
  • Fasting insulin level - A measure of the degree of insulin resistance in many patients with insulin resistance syndrome
  • Lipid profile (fasting total cholesterol, low-density lipoprotein [LDL], high-density lipoprotein [HDL], cholesterol, triglyceride) - Insulin resistance syndrome characterized by elevated LDL-B levels (small, dense, pattern B), high triglyceride levels, and reduced HDL-C levels
  • Combined use of insulin and lipid markers in atherosclerosis - Fasting insulin, apolipoprotein B, and small LDL levels are more biologically significant than are standard lipid tests. Elevations in the 3 markers increase the risk of coronary artery disease by nearly 20-fold.
  • Electrolyte levels (BUN [blood urea nitrogen], creatinine, and uric acid levels) - Hyperuricemia is common and is often considered a component of the metabolic syndrome.
  • Urinalysis - Microalbuminuria is a marker of endothelial dysfunction.
  • Homocysteine (H[e]) - An elevated level is a risk factor for atherosclerosis, which predicts macrovascular disease. levels are regulated by insulin.
  • Plasminogen activator inhibitor (PAI)-1 - An elevated level is associated with insulin resistance syndrome and is correlated with obesity, waist-to-hip ratio, hypertension, fasting and postprandial insulin levels, proinsulin levels, fasting glucose levels, and elevated triglyceride and LDL levels.[43] An increased PAI-1 level signifies impaired fibrinolysis, thus indicating increased risk of atherosclerosis.

Other laboratory studies include measurement of fibrinogen levels and testing of endothelial function. An increased fibrinogen level is a feature of insulin resistance syndrome. Endothelium plays an important role in insulin action, including in the regulation of tissue blood flow and in insulin delivery to interstitium. Endothelial dysfunction is an important component of insulin resistance syndrome and includes reduced capillary formation, reduced surface area, and abnormal reactivity of endothelium.[44]

Biochemical changes associated with endothelial dysfunction include (1) reduced nitric oxide and prostacyclin levels, (2) increased endothelin and angiotensin activity, and (3) increased local and systemic inflammation (increased C-reactive protein [CRP] levels).[11] Blood testing for CRP measurement is widely available. Smoking and abnormal lipids are major contributors to endothelial dysfunction.

In theory, insulin sensitivity can be assessed through the following methods:

  • Fasting insulin level - This provides an indirect assessment of insulin sensitivity. The limitation of this study is inaccuracy in a patient with mutant insulin in which the hormone measured by radioimmunoassay is not fully bioactive.
  • Measurement of response to direct intravenous infusion of insulin - The limitations of this measurement are a confounding factor in data interpretation and a variation in secretion of antagonist hormones in response to hypoglycemia.
  • Euglycemic insulin clamp technique - Plasma glucose levels are held constant, with variable glucose infusion. Biochemical responses that are surrogate estimates of insulin resistance, such as glucose disposal and antilipolysis, are determined. This method is considered the criterion standard.
  • The latter 2 tests are more accurate, but they are research tools and are not routinely used in clinical practice.
  • Homeostatic model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) - These are the most widely used simple indices for assessing insulin resistance in clinical research and practice. Both indices are based on fasting glucose and insulin measurements; they differ mainly in the log transformation of these variables in QUICKI.[45, 46, 47]
  • HOMA-IR is derived from the product of the insulin and glucose values divided by a constant, that is, calculated by using the following formula: fasting glucose (mg/dL) X fasting insulin (µU/mL) / 405 (for SI units: fasting glucose (mmol/L) X fasting insulin (µU/L) / 22.5). A value greater than 2 indicates insulin resistance.
  • QUICKI is derived by calculating the inverse of the sum of the logarithmically expressed values of fasting insulin and glucose: 1 /[log(fasting glucose) + log(fasting insulin)] . It measures insulin sensitivity, which is the inverse of insulin resistance. A value of less than 0.339 indicates insulin resistance.
  • They both compensate for fasting hyperglycemia, and the results for the indices correlate reasonably well with the euglycemic clamp technique. Some investigators believe that QUICKI is superior to HOMA-IR, for instance in reproducibility, but the 2 indices correlate very well.[48, 49, 50]
Previous
Next

Other Tests

Other cardiac tests include echocardiography and stress testing, depending on the presentation.

A risk-assessment calculator, based on data from the Framingham Heart Study for estimating 10-year cardiovascular risk, is available. This calculator estimates the 10-year risk for hard coronary heart disease outcomes (myocardial infarction and coronary death). The tool is designed to estimate risk in adults aged 20 years and older who do not have heart disease or diabetes.

For patients with insulin resistance without overt diabetes, the metabolic syndrome criteria for cardiovascular risk stratification are less sensitive than those of the Framingham Risk Score, which takes into account age, total cholesterol, tobacco use, HDL-C, and blood pressure, but not diabetes.

Previous
Proceed to Treatment & Management
 
 
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.

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.