REFERENCES

1. Yeni-Komshian H, Carantoni M, Abbasi F, Reaven GM. Relationship between several surrogate estimates of insulin resistance and quantification of insulin-mediated glucose disposal in 490 healthy, nondiabetic volunteers. Diabetes Care 23:171-175, 2000.

2.. Lillioja S, Mott DM, Spraul M, et al. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin dependent diabetes mellitus N Engl J Med 329:1988-1992, 1993.

3. Warram JH, Martin BC, Krowlewski As, et al. Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the off-spring of the diabetic parents. Ann Intern Med 113:909,1990.

4. Reaven GM. Role of insulin resistance in human disease. Diabetes 37:1595-1607, 1988

5. Executive summary of the third report of he national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 285:2846-2497,2002

6. Reaven GM.The insulin resistance syndrome. Curr Atheroscler Rep 2003; 5; 364-371.

7. Bernstein RJ, Davis BM, Olefsky JM, Reaven GM. Hepatic insulin responsiveness in patients with endogenous hypertriglyceridemia. Diabetologia 1978; 14:249-253.

8. Skott P, Vaag A, Bruum NE, Hother-Nielsen O, Gall M-A, Beck-Nielsen H,Parving H-H. Effect of insulin on renal sodium handling in hyperinsulinemic type 2 (non-insulin-dependent) diabetic patients with peripheral insulin resistance. Diabetologia 1991; 34:275-281.

9. Facchini FS, Riccardo A, Stoohs A, Reaven GM. Enhanced sympathetic nervous system activity- the linchpin between insulin resistance, hyperinsulinemia, and heart rate. Am J Hypertens 1996; 9:1013-1017.

10. Reaven GM. The kidney: An unwilling accomplice in Syndrome X. Am Journal of Kidney Diseases 1997; 30: 928-931.

11. Swislocki ALM, Chen Y-DI, Golay A, Chang MO, Reaven GM. Insulin suppression of plasma-free fatty acid concentration in normal individuals and patients with type 2 (non-insulin-dependent) diabetes. Diabetologia 1987; 30:622-626.

12. Abbasi F, McLaughlin T, Lamendola C, Reaven GM. The relationship between glucose disposal in response to physiological hyperinsulinemia and basal glucose and free fatty acid concentrations in healthy volunteers. J Clin Endocrinol Metab 2000; 85:1251-1254.

13. Facchini F, Chen YD-I, Hollenbeck C, Reaven GM. Relationship between resistance to insulin-mediated glucose uptake, urinary uric acid clearance, and plasma uric acid concentration. JAMA 1991; 266:3008-3011.

14. Facchini FS, DoNascimento C, Reaven GM, Yip JW, Ni PX, Humphreys MH. Blood pressure, sodium intake, insulin resistance, and urinary nitrate excretion. Hypertension 1999; 33:1008-1012

15. Dunaiff A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997; 18:774-800.

16. Sanyal AJ, Campbell-Sargent C, Mirashi F, Rizzo WB, Contos MJ, Sterling RK, et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001; 120:1183-1192

17. Tuan C-Y, Abbasi F, Lamendola C, McLaughlin T, Reaven G. Usefulness of plasma glucose and insulin concentrations in identifying patients with insulin resistance. Am J Cardiol 2003; 92: 606-610.

18. Reaven GM, Lerner R., Stern M, Farquhar JW. Role of insulin in endogenous hypertriglyceridemia. J. Clin. Invest. 46:1756-1767, 1967

19. Olefsky JM, Farquhar JW, Reaven GM. Reappraisal of the role of insulin in hypertriglyceridemia. Am J Med 1974; 57:551-560.

20. Laws A, Reaven GM. Evidence for an independent relationship between insulin resistance and fasting plasma HDL-cholesterol, triglyceride and insulin concentrations. J Int Med 1992; 231:25-30. .

21. Jeppesen J, Hollenbeck CB, Zhou M-Y, Coulston AM, Jones C, Chen, Y-DI, Reaven GM. Relation between insulin resistance, hyperinsulinemia, postheparin plasma lipoprotein lipase activity, and postprandial lipemia. Arterioscler Thromb Vasc Biol 1995; 15: 320-324l.

22. Abbasi F, McLaughlin T, Lamendola C, Yeni-Komshian H, Tanaka A, Wang T, Nakajima K, Reaven GM. Fasting remnant lipoprotein cholesterol and triglyceride concentrations are elevated in nondiabetic, insulin-resistant, female volunteers. J Clin Endocrinol Metab 1999; 84:3903-3906.

23. Reaven GM, Chen Y-DI, Jeppesen J, Maheux P, Krauss RM. Insulin resistance and hyperinsulinemia in individuals with small, dense, low density lipoprotein particles. J Clin Invest 1993; 92:141-146.

24. Ross R. The pathogenesis of atherosclerosis. N Engl J Med 1986; 314:488-500,

25. Chen N-G, Abbasi F, Lamendola C, McLaughlin T., Cooke JP, Tsao PS, Reaven GM. Mononuclear cell adherence to cultured endothelium is enhanced by hypertension and insulin resistance in healthy nondiabetic volunteers. Circulation 1999; 100:940-943.

26. Chen N-G, Holmes M, Reaven GM. Relationship between insulin resistance, soluble adhesion molecules, and mononuclear cell binding in healthy volunteers. J Clin Endocrinol Metab 1999; 84:3485-3489.

27. Stuhlinger MC, Abbasi F, Chu JW, Lamendola C, McLaughlin TL, Cooke JP, Reaven GM, Tsao PS. Relationship between insulin resistance and an endogenous nitiric oxide synthase inhibitor. JAMA 2002; 287:1420-1426.

28. Baron A. Vascular reactivity. Am J Cardiol 1999; 84:25J-27J.

29. Juhan-Vague I, Thompson SG, Jeppesen J, on behalf of the ECAT Angina Pectoris Study Group. Involvement of the hemostatic system in the insulin resistance syndrome. Arterioscler Thromb 1993; 13:1865-1873, 1993.

30. Meigs JB, Mittelmann MA, Nathan DM, et al. Hyperinsulinemia, hyperglycemia, and impaired hemostasis. The Framingham Offspring Study. JAMA 2000; 283:221-228.

31. Abbasi, F, McLaughlin, T, Lamendola, C, Lipinska, I, Tofler, G, Reaven, GM. Comparison of plasminogen activator inhibitor-1 concentration in insulin-resistant versus insulin-sensitive healthy women. Arterioscler Thromb Vasc Biol 1999; 19: 2818-2822.

32. Reaven GM, Lithell H, Landsberg L. Hypertension and associated metabolic abnormalities--the role of insulin resistance and the sympathoadrenal system. N Engl J Med 1996; 334:374-381.

33. Pyorala K. Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease; results from two population studies in Finland. Diabetes Care 1979; 2:131-141.

34. Ducimetiere P, Eschwege E, Papoz L, et al. Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population. Diabetologia 1980; 19:205-211.

35. Després J-P, Lamarche B, Mauriége P, et al. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996; 334:952-957.

36. Yip J, Facchini FS, Reaven GM. Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease. J Clin Endocrinol Metab 1998; 83:2773-2776.

37. Facchini FS, Hua N, Abbasi F, Reaven GM. Insulin resistance as a predictor of age-related diseases. J Clin Endocrinol Metab 2001; 86:3574-3578.

38. Facchini F, Hollenbeck CB, ChenYN, Chen Y-DI, Reaven GM. Demonstration of a relationship between white blood cell count, insulin resistance, and several risk factors for coronary heart disease in women. J Int Med 1992; 232:267-272.

39. McLaughlin T, Abbasi F, Lamendola C, Liang L, Reaven G, Schaaf P, Reaven P. Differentiation between obesity and insulin resistance in the association with C-reactive protein. Circulation 2002; 106:2908-2912.

40. McLaughlin T, Allison G, Abbasi F, Lamendola C, Reaven G. Prevalence of insulin resistance and associated cardiovascular disease risk factors among normal weight, overweight, and obese individuals. Metabolism 2004; 53: 495-499.

41. Vgontzas AN, Bixler EO, Chrousos GP. Metabolic disturbances in obesity versus sleep apnea: the importance of visceral obesity and insulin resistance. J Int Med 2003; 254; 32-44.

42. Himsworth HP.The syndrome of diabetes mellitus and its causes. Lancet 1949; 1, 465-473

43. Shen S-W, Reaven GM, Farquhar JW. Comparison of impedance to insulin mediated glucose uptake in normal and diabetic subjects. J Clin Invest 1970; 49:2151-2160.

44. Ginsberg H, Kimmerling G, Olefsky JM, Reaven GM. Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia. J Clin Invest 1975; 55:454-461.

45. Reaven GM.The Fourth Musketeer--from Alexander Dumas to Claude Bernard. Diabetologia 1995; 38:3-13.

46. Ferrannini E, Buzzigoli G, Bonadona R. Insulin resistance in essential hypertension. N Engl J Med 317 1987; 317: 350-357.

47. Shen D-C, Shieh S-M, Fuh M, Wu D-A, Chen Y-DI, Reaven GM. Resistance to insulin-stimulated glucose uptake in patients with hypertension. J Clin Endocrinol Metab 1988; 66:580-583.

48. Swislocki ALM, Hoffman BB, Reaven GM. Insulin resistance, glucose intolerance and hyperinsulinemia in patients with hypertension. Am J Hypertens 1989; 2:419-423

49. Ferrari P, Weidmann P, Shaw S, Giachino D, Riesen W, Allemann Y, Heynen G. Altered insulin sensitivity, hyperinsulinemia and dyslipidemia in individuals with a hypertensive parent. Am J Med 1991; 91:589-596.

50. Facchini F, Chen Y-DI, Clinkingbeard C, Jeppesen J, Reaven GM. Insulin resistance, hyperinsulinemia, and dyslipidemia in nonobese individuals with a family history of hypertension. Am J Hypertens 1992; 5:694-699.

51. Allemann Y, Horber FF, Colombo M, Ferrari P, Shaw S, Jaeger P, Weidman P. Insulin sensitivity and body fat distribution in normotensive offspring of hypertensive parents. Lancet 1993; 341:327-331.

52. Skarfors ET, Lithell HO, Selinus I. Risk factors for the development of hypertension: a 10-year longitudinal study in middle-aged men. J Hypertension 1991; 9:217-223.

53. Lissner L, Bengtsson C, Lapidus L, Kristjansson K, Wedel H. Fasting insulin in relation to subsequent blood pressure changes and hypertension in women. Hypertension 1992; 20:797-801.

54. Taittonen L, Uhari M, Nuutinen M, Turtinen J, Pokka T, Akerblom HK. Insulin and blood pressure among healthy children. Am J Hypertens 1996; 9:193-199.

55. Raitakari OT, Porkka KVK, Rönnemaa T, Knip M, Uhari M, Akerblom HK. Viikari JSA. The role of insulin in clustering of serum lipids and blood pressure in children and adolescents. Diabetologia 1995; 38:1042-1050.

56. Zavaroni I, Mazza S, Dall’Aglio E, Gasparini P, Passeri M, Reaven GM. Prevalence of hyperinsulinaemia in patients with high blood pressure. J Intern Med 1992; 231:235-240.

57. Sheuh WH-H, Jeng C-Y, Shieh S-M, Fuh MM, Shen DD, Chen Y-DI, Reaven GM. Insulin resistance and abnormal electrocardiograms in patients with high blood pressure Am J Hypertens 5: 444-448, 1992.

58. Jeppesen J, Hein HO, Suadicani P, Gynterberg F. Low triglycerides-high high-density lipoprotein cholesterol and risk of ischemic heart disease. Arch Int Med 2001; 361-366.

59. Sharma AM, Schorr U, Distler A. Insulin resistance in young salt-sensitive normotensive subjects. Hypertension 1993; 21:273-279.

60. Zavaroni I, Coruzzi P, Bonini L, Mossini GL, Musiari L, Gasparini P, Fantuzzi M, Reaven GM. Association between salt sensitivity and insulin concentrations in patients with hypertension. Am J Hypertens 1995; 8:855-858.

61. Troisi RJ, Weiss ST, Parker DR, Sparrow D, Young JB, Landsberg L. Relation of obesity, insulin, and sympathetic nervous system activity. Hypertension 17: 669-677, 1991.

62. O’Hare JA, Minaker KL, Meneilly GS, Rowe JW, Palotta JA, Young JB. Effect of insulin on plasma norepinephrine and 3,4 dihydroxyphenylalanine in obese men. Metabolism 1989; 38:322-329.

63. Nestler JE, Jakuboficz J, Evans WS, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Eng J Med 1998; 338:1876-1880.

64. Reaven GM. Effect of metformin on various aspects of glucose, insulin and lipid metabolism in patients with non-insulin-dependent diabetes mellitus with varying degrees of hyperglycemia. Diab/Metab Rev 1995; 11:S97-S108.

65. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in the polycystic ovary syndrome. Diabetes 1989; 38:1165-1174.

66. Dixon JB, Bhathal PS, O’Brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 2001; 121: 91-100.

67. Seppala-Lindros A, Vehkavaara S, Hakinen AM, Gotto Takashi, Westerbacka J, Soviharvi A, Halavaara J, Yki-Jarvinen H. Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 2002; 87: 3023-3028.

68. Argiles JM, Lopez-Soriano. Insulin and cancer. Int J Oncol 2001; 18:683-687.

69. Bruning PF, Bonfret JMG, Van Nooyrd PAH, Hart AA, De Jong-Bakker M, Noojen WJ. Insulin resistance and breast cancer risk. Int J Cancer 1992; 52:511-516.

70. DelGiudice ME, Fantus IG, Ezzat S, McKeown-Eyssen G, Page D, et al. Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Research and Treatment 1998; 111-120.

71. Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madamas Y, et al. Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol 2001; 20:42-51.

72. Goodwin PJ, Boyd NF, Hanna W, Hartwick W, Murray D, Qizilbash A, et al. Elevated levels of plasma triglycerides are associated with premenopausal breast cancer risk. Nutr Cancer 1997; 27:284-292.

73. Glicksman AS, Myers WPL, Rawson RW. Diabetes mellitus and carbohydrate metabolism inpatients with cancer. Med Clin N Amer 1956; 40: 887-900.

74. Goodwin PJ, Boyd NF. Body size and breast cancer prognosis. A critical review. Breast Cancer Res Treat 1990; 16: 205-214.

75 La Vecchia C, Negri E, Decarli A, Frabceschi S. Diabetes mellitus and colorectal cancer risk. Cancer Epidemol Biomarkers Prev 1997; 6:1007-1110.

76. Will JC, Galuska DA, Vinicor F, Calle EE. Colorectal cancer: another complication of diabetes mellitus? Am J Epidemiol 1998; 147: 816-825.

77. Hu FB, Manson JE, Hunter D, Colditz GA, Michaels KB, Speizer FE, et al. Prospective study of diabetes mellitus (type 2) and risk of colorectal cancer in women. J Natl Cancer Inst 1999; 91: 542-547.

78.. Andersson SO, Wolk A, Bergstrom R, Adami HO, Engholm G, Englund A, et al. Body size and prostate cancer: a 20-year follow-up study among 135006 Swedish construction workers. J Natl Cancer Inst 1997; 89: 386-389.

79. Rodriguez C, Patel AV, Calle EE, Jacobs EJ, Chao A, Thun MJ. Body mass index, height, and prostate cancer mortality in two large cohorts of adult men in the United States. Cancer Epidemiol Biomarkers Prev 2001; 10: 345-353.

80. Moyad MA. Is obesity a risk factor for prostate cancer, and does it even matter? A hypothesis and different perspective. Urology 2002; 59:(Suppl 4A) 41-50.

81. Copeland GP, Leinster SJ, Davis JC, Hipkin LJ. Insulin resistance in patients

with colorectal cancer. Br J Surg 1987; 74: 1031-1035.

82. Kaaks R, Toniolo P, Akhmedkhanov A, Lukanova A. Biessy C, Dechaud H, et al. Serum C-peptide, insulin-like growth factor (IGF)-I binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst 2000; 92: 1592-1600.

83. Hsing AW, Chua S Jr, Gao YT, Gentzcheim E, Chang L, Deng J, et al. Prostate cancer risk and serum levels of insulin and leptin: a population-based study. J Natl Cancer Inst 2001; 93: 783-789.

84. Lehrer S, Diamond EJ, Stagger S, Stone NN, Stock RG. Serum insulin level, disease stage, prostate specific antigen (PSA) and Gleason score in prostate cancer. Br J Cancer 2002; 23: 726-728,

85. Balkau B, Kahn HS, Courbon D, Eschwege E, Ducimetiere P. Hyperinsulinemia predicts fatal liver cancer but is inversely associated with fatal cancer as some other sites: the Paris Prospective Study. Diabetes Care 2001; 24: 843-849.

86. Liao Y, Kwon S, Shaughnessy S, Wallace P, Hutto A, Jenkins AJ, Klein RL, Garvey WT. Critical evaluation of adult treatment panel III criteria in identifying insulin resistance with dyslipidemia. Diabetes Care 2004; 27: 1011-1020. 87. Reaven G. The metabolic syndrome or the insulin resistance syndrome? Different names, different concepts, and different goals. Endocrinol Metab Clin N Am 2004; 33: 283-303.

88. Kim SH, Reaven GM. The metabolic syndrome: one step forward, two steps back. Diabetes & Vascular Disease Research 2004; 1: 68-76.

89. Cheal KL, Abbasi F, Lamendola C, McLaughlin T, Reaven GM, Ford ES. Relationship to insulin resistance of the Adult Treatment Panel III diagnostic criteria for identification of the metabolic syndrome. Diabetes 2004; 53: 1195-1200.

90. Stern MP, Williams K, Gonzalez-Villalpando C, Hunt KJ, Haffner SM. Does the metabolic syndrome improve identification of individuals at risk of type 2 diabetes and/or cardiovascular disease? Diabetes Care 2004; 27; 2676-2681.

91. Bogardus C, Lillioja S, Mot, DM, Hollenbeck C, Reaven GM. Relationship between degree of obesity and in vivo insulin action in man. Am J Physiol 1985; 248 (Endocrinol Metab 11) :E286-E291