Current Diabetes Reports

, Volume 1, Issue 2, pp 140–147 | Cite as

Management of the insulin resistance syndrome

  • Cyrus Desouza
  • Lucía Gilling
  • Vivian Fonseca


The insulin resistance syndrome (IRS) is a common disorder, which has important clinical implications. It is a cluster of cardiovascular risk factors that include obesity, hypertension, dyslipidemia, glucose intolerance, and type 2 diabetes mellitus. Lifestyle modifications and insulin sensitizers are among the several therapeutic strategies available for the treatment of the IRS. Optimal treatment will not only improve glycemic control, but may also significantly lower cardiovascular disease.


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References and Recommended Reading

  1. 1.
    American Diabetes Association: Consensus development conference on insulin resistance. Diabetes Care 1998, 21:310–314.Google Scholar
  2. 2.
    Reaven GM: Role of insulin resistance in human disease. Diabetes 1988, 37:1595–1607.PubMedCrossRefGoogle Scholar
  3. 3.
    Executive Summary of the Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) [no authors listed]. JAMA 2001, 285:2486–2497.Google Scholar
  4. 4.
    Carretero OA, Oparil S: Essential hypertension: Part I: definition and etiology. Circulation 2000, 101:329–335.PubMedGoogle Scholar
  5. 5.
    Pessin JE, Saltiel AR: Signaling pathway in insulin action: molecular targets of insulin resistance. J Clin Invest 2000, 104:165–170.Google Scholar
  6. 6.
    Shepherd PR, Kahn BB: Mechanism of disease: glucose transporter and insulin action-implication for insulin resistance and diabetes mellitus. N Engl J Med 1997, 341:248–257.CrossRefGoogle Scholar
  7. 7.
    Kahn BB, Flier JS: Obesity and insulin resistance. J Clin Invest 2000, 106:473–481.PubMedGoogle Scholar
  8. 8.
    Olefsky JM: Treatment of insulin resistance with peroxisome proliferator-activated receptor [gamma] agonists. J Clin Invest 2000, 106:467–472.PubMedGoogle Scholar
  9. 9.
    Cline G, Petersen KF, Krssak M, et al.: Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes. N Engl J Med 1999, 341:240–246. Cline et al. show that decreased stimulation of insulin-mediated muscle glycogen synthesis is predominantly the result of impaired glucose transport and not glycogen synthase activity.PubMedCrossRefGoogle Scholar
  10. 10.
    DeFronzo RA, Ferrannini E: Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991, 14:173–194.PubMedCrossRefGoogle Scholar
  11. 11.
    Abate N: Insulin resistance and obesity: the role of fat distribution pattern. Diabetes Care 1996, 19:292–294.PubMedGoogle Scholar
  12. 12.
    Boden G, Chen X, Ruiz J, et al.: Mechanisms of fatty acid-induced inhibition glucose uptake. J Clin Invest 1994, 93:2438–2446.PubMedGoogle Scholar
  13. 13.
    Steppan CM, Bailey ST, Bhat S, et al.: The hormone resistin links obesity to diabetes. Nature 2001, 409:307–312. This work described genetic material called “resistin,” expressed by adipocytes. It was found to be elated in diet-induced and genetically obese mice. PPARg is believed to regulate resistin with thiazoledinediones markedly reducing its levels. Resistin may provide a molecular link between obesity and insulin resistance.PubMedCrossRefGoogle Scholar
  14. 14.
    Panzram G: Mortality and survival in type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1987, 30:123–131.PubMedCrossRefGoogle Scholar
  15. 15.
    Després JP, Lamarche B, Mauriege P, et al.: Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996, 334:952–957. The authors show that hyperinsulinemia significantly influences ischemic heart disease even after potentially confounding factors such as body weight, blood pressure, and plasma lipoprotein concentrations have been taken into account.PubMedCrossRefGoogle Scholar
  16. 16.
    Howard G, O’Leary DH, Zaccaro D, et al., for the IRAS investigators: Insulin sensitivity and atherosclerosis. Circulation 1996, 93:1809–1817.PubMedGoogle Scholar
  17. 17.
    Steinberg HO, Chaker H, Leaming R, et al.: Obesity/insulin resistance is associated with endothelial dysfunction: implication for the syndrome of insulin resistance. J Clin Invest 1996, 97:2601–2610.PubMedGoogle Scholar
  18. 18.
    Landin K, Tengborn L, Chmielewska J, et al.: The acute effect of insulin on tissue plasminogen activator and plasminogen activator inhibitor in man. Thromb Haemost 1991, 65:130–133.PubMedGoogle Scholar
  19. 19.
    Nordt TK, Schenider DJ, Sobel BE: Augmentation of the synthesis of plasminogen activator inhibitor type-1 by precursors of insulin. A potential risk factor for vascular disease. Circulation 1994, 89:321–330.PubMedGoogle Scholar
  20. 20.
    Godsland IF, Sidhu M, Crook D, et al.: Coagulation and fibrinolytic factors, insulin resistance and the metabolic syndrome of coronary heart disease risk [abstract]. Heart 1997, 77(suppl 1):57.Google Scholar
  21. 21.
    Gaboury CL, Simonson DC, Seely EW, et al.: Relation of pressor responsiveness to angiotensin II and insulin resistance in hypertension. J Clin Invest 1994, 94:2295–2300.PubMedGoogle Scholar
  22. 22.
    Supiano MA, Hogikyan RV, Morrow LA, et al.: Hypertension and insulin resistance: role of sympathetic nervous system activity. Am J Physiol 1992, 263(5 Pt 1):E935-E942.PubMedGoogle Scholar
  23. 23.
    Steinberg HO, Brechtel G, Johnson A, et al.: Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. J Clin Invest 1994, 94:1172–1179.PubMedCrossRefGoogle Scholar
  24. 24.
    Shimamoto K, Hirata A, Fukuoka M, et al.: Insulin sensitivity and the effects of insulin on renal sodium handling and pressor systems in essential hypertension. Hypertension 1994, 23(suppl I): I–29-I-33.Google Scholar
  25. 25.
    Carr A, Samaras K, Chisholm DJ, Cooper DA: Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet 1998, 351:1881–1883. Homology between the catalytic site of HIV-1 proteins and regions of two particular proteins involved in adipocyte differentiation, inhibition of apoptosis and cleavage of fatty acids from circulating triglycerides, may account for the features of peripheral fat wasting and central adiposity, insulin resistance, and hyperlipidemia in patients treated with HIV-1 protease inhibitors.PubMedCrossRefGoogle Scholar
  26. 26.
    Dvorak RV, DeNino WF, Ades PA, Poehlmean ET: Phenotypic characteristics associated with insulin resistance in metabolically obese but mormal-weight young women. Diabetes 1999, 48:2210–2214. In a group of nonobese women (BMI < 26), with similar ages, body mass, free fat mass, and caloric intake, insulin sensitivity was found to be lower in those with higher total and visceral fat mass.PubMedCrossRefGoogle Scholar
  27. 27.
    Nestler JE: Obesity, insulin, sex, steroids and ovulation. Obes Related Metab Disord 2000, 24(suppl 2):S71-S73.Google Scholar
  28. 28.
    Dunaif A, Thomas A: Current concepts in the polycystic ovary syndrome. Annu Rev Med 2001, 52:401–419.PubMedCrossRefGoogle Scholar
  29. 29.
    Tuomilehto J, Lindstrom J, Eriksson JG, et al., for the Finnish Diabetes Prevention Study Group: Prevention of type 2 diabetes mellitus by lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001, 344:1343–1350.PubMedCrossRefGoogle Scholar
  30. 30.
    Weinstock RS, Dai H, Wadden TA: Diet and exercise in the treatment of obesity: effects of three interventions on insulin resistance: Arch Intern Med 1998, 158:2477–2483.PubMedCrossRefGoogle Scholar
  31. 31.
    Bailey CJ, Turner RC: Metformin. N Engl J Med 1996, 334:574–579.PubMedCrossRefGoogle Scholar
  32. 32.
    Defronzo RA: Pharmacological therapy for type 2 diabetes mellitus: Ann Intern Med 1999, 131:281–303.PubMedGoogle Scholar
  33. 33.
    Pioglitazone [package insert]. Indianapolis, IN: Eli Lilly and Co.; 2001.Google Scholar
  34. 34.
    Raskin P, Rappaport EB, Cole ST, et al.: Rosiglitazone short-term monotherapy lowers fasting and postprandial glucose in patients with type 2 diabetes. Diabetologia 2000, 43:278–284.PubMedCrossRefGoogle Scholar
  35. 35.
    Fonseca V, Rosenstock J, Patwardhan R, Salzman A: Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus. A randomized controlled trial. JAMA 2000, 283:1695–1702. A large clinical trial demonstrating the clinical benefits of combining insulin sensitizers.PubMedCrossRefGoogle Scholar
  36. 36.
    Rosiglitazone [package insert]. Elk Grove Village, IL: SmithKline Beecham Pharmaceuticals; 2001.Google Scholar
  37. 37.
    Parulkar A, Pendergrass M, Granda-Ayala R, et al.: Nonhypoglycemic effects of thiazolidinediones. Ann Intern Med 2001, 134:61–71. A comprehensive review of the nonhypoglycemic effects of thiazolidinediones.PubMedGoogle Scholar
  38. 38.
    Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group [no authors listed]. Lancet 1998,352:854–865.Google Scholar
  39. 39.
    Stumvoll N, Nurjhan N, Perriello G, et al.: Metabolic effects of metformin in non insulin dependant diabetes mellitus. N Engl J Med 1995, 333:541–549.CrossRefGoogle Scholar
  40. 40.
    Nagi DK, Yudkin JS: Effects of metformin on insulin resistance, risk factors for cardiovascular disease and plasminogen activator inhibitor in NIDDM subjects. A study of two ethnic groups. Diabetes Care 1993, 16:621–629.PubMedCrossRefGoogle Scholar
  41. 41.
    Grossman S, Lessem J: Mechanisms and clinical effects of thiazolidinediones. Exp Opin Invest Drugs 1997, 6:1025–1040.CrossRefGoogle Scholar
  42. 42.
    Berger A: Resistin: a new hormone that links obesity with type 2 diabetes. BMJ 2001, 322:193.CrossRefGoogle Scholar
  43. 43.
    Goldstein BJ: Rosglitazone. Int J Clin Pract 2000, 54:333–337.PubMedGoogle Scholar
  44. 44.
    Aronoff S, Rosenblatt S, Egan JW, et al.: Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes. Diabetes Care 2000, 23:1605–1611.PubMedCrossRefGoogle Scholar
  45. 45.
    Inzucchi SE, Maggs DG, Spollett GR, et al.: Efficacy and metabolic effects of metformin and troglitazone in type 2 diabetes mellitus. N Engl J Med 1998, 338:867–872. Key paper describing the different effects of metformin and thiazolidinediones on insulin resistance.PubMedCrossRefGoogle Scholar
  46. 46.
    Higashiura K, Ura N, Takada T, et al.: The effects of angiotensin- converting enzyme inhibitor and angiotensin II receptor antagonist on insulin resistance in fructose fed rats. Am J Hypertens 2000, 13:290–297.PubMedCrossRefGoogle Scholar
  47. 47.
    Paolisso G, Barbagallo M, Peterella G, et al.: Effects of sim vastatin and atorvastatin administration on insulin resistance and respiratory quotient in aged dyslipidemic non-insulin dependant diabetic patients. Atherosclerosis 2000, 150:121–127.PubMedCrossRefGoogle Scholar
  48. 48.
    Moghetti P, Catello R, Negri C, et al.: Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome. J Clin Endocrinol Metab 2000, 85:139–146.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc. 2001

Authors and Affiliations

  • Cyrus Desouza
    • 1
  • Lucía Gilling
    • 1
  • Vivian Fonseca
    • 1
  1. 1.Department of Medicine, Section of Endocrinology SL53Tulane University Health Sciences CenterNew OrleansUSA

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