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Insulin Resistance and the Pathogenesis of Cardiovascular Disease

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Insulin Resistance

Part of the book series: Contemporary Endocrinology ((COE))

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The prevalence of diabetes has considerably increased over the past few decades, and is predicted to reach 4.4% worldwide by 2030 (1). Hyperglycemia in diabetes is due to a combination of decreased tissue sensitivity to insulin, increased hepatic production of glucose, and impaired insulin secretion by the pancreas. Insulin resistance (IR) is a state that requires increased concentrations of insulin to achieve its desired biological effect and is tightly linked to excess white adipose tissue and obesity (2). In the early stages of IR, hyperinsulinemia takes place through additional insulin production by the pancreas, to compensate for “decreased insulin activity”, thereby keeping the blood glucose within the normal range. Without intervention to restore normal insulin sensitivity, the pancreas eventually loses its capacity to produce extra insulin (secondary β-cell failure) and the ensuing hyperglycemia results in the development of type 2 diabetes (T2DM).

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References

  1. Wild S, Roglic G, Green A, Sicree R, King H. Prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27 (5): 1047–1053

    PubMed  Google Scholar 

  2. Cefalu WT. I nsulin resistance: cellular and clinical concepts. E xp Biol Med (Maywood) 2001; 226 (1): 13–26

    CAS  Google Scholar 

  3. Chan JM, Rimm EB, Colditz GA, Stampfer MJ, Willett WC. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 1994; 17 (9): 961–969

    PubMed  CAS  Google Scholar 

  4. Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 1995; 122 (7): 481–486

    PubMed  CAS  Google Scholar 

  5. Lee JM, Okumura MJ, Davis MM, Herman WH, Gurney JG. Prevalence and determinants of insulin resistance among US adolescents: a population-based study. Diabetes Care 2006; 29 (11): 2427–2432

    PubMed  Google Scholar 

  6. Rappaport EB, Usher DC. Obesity, insulin resistance, and type 2 diabetes in children and adolescents. Pediatr Ann 2006; 35 (11): 822–826

    PubMed  Google Scholar 

  7. Vivian E M. T ype 2 diabetes in children and adolescents–the next epidemic? Curr Med Res Opin 2006; 22 (2): 297–306

    PubMed  Google Scholar 

  8. Himsworth HP. Mechanisms of diabetes mellitus. L ancet 1939; 65: 171–175

    Google Scholar 

  9. Reaven G, Calciano A, Cody R, Lucas C, Miller R. Carbohydrate intolerance and hyperlipemia in patients with myocardial infarction without known diabetes mellitus. J Clin Endocrinol Metab 1963; 23: 1013–1023

    PubMed  CAS  Google Scholar 

  10. Kannel WB, McGee DL. Diabetes and cardiovascular ascular disease. T he Framingham study. JAMA 1979; 241 (19): 2035–2038

    CAS  Google Scholar 

  11. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339 (4): 229–234

    PubMed  CAS  Google Scholar 

  12. Schnell O, Standl E. Impaired glucose tolerance, diabetes, and cardiovascular disease. Endocr Pract 2006; 12 (Suppl 1): 16–19

    PubMed  Google Scholar 

  13. Norhammar A, Tenerz A, Nilsson G, Hamsten A, Efendic S, Ryden L et al. Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study. Lancet 2002; 359 (9324): 2140–2144

    PubMed  CAS  Google Scholar 

  14. Sorof JM, Lai D, Turner J, Poffenbarger T, Portman RJ. Overweight, ethnicity, and the prevalence of hypertension in school-aged children. Pediatrics 2004; 113 (3 Pt 1): 475–482

    PubMed  Google Scholar 

  15. Desideri G, De Simone M, Iughetti L, Rosato T, Iezzi ML, Marinucci MC et al. Early activation of vascular endothelial cells and platelets in obese children. J Clin Endocrinol Metab 2005; 90 (6): 3145–3152

    PubMed  CAS  Google Scholar 

  16. Nigro J, Osman N, Dart AM, Little PJ. Insulin resistance and atherosclerosis. Endocr Rev 2006; 27 (3): 242–259

    PubMed  CAS  Google Scholar 

  17. Reaven G. All obese individuals are not created equal: insulin resistance is the major determinant of cardiovascular disease in overweight/obese individuals. Diab Vasc Dis Res 2005; 2 (3): 105–112

    PubMed  Google Scholar 

  18. Li S, Chen W, Srinivasan SR, Bond MG, Tang R, Urbina EM et al. Childhood cardiovascular risk factors and carotid vascular changes in adulthood: the Bogalusa Heart Study. JAMA 2003; 290 (17): 2271–2276

    PubMed  CAS  Google Scholar 

  19. Tzou WS, Douglas PS, Srinivasan SR, Bond MG, Tang R, Chen W et al. Increased subclinical atherosclerosis in young adults with metabolic syndrome: the Bogalusa Heart Study. J Am Coll Cardiol 2005; 46 (3): 457–463

    PubMed  CAS  Google Scholar 

  20. Ross R. Atherosclerosis–an inflammatory disease. N Engl J Med 1999; 340 (2): 115–126

    PubMed  CAS  Google Scholar 

  21. Endo T, Imaizumi T, Tagawa T, Shiramoto M, Ando S, Takeshita A. Role of nitric oxide in exercise-induced vasodilation of the forearm. Circulation 1994; 90 (6): 2886–2890

    PubMed  CAS  Google Scholar 

  22. Quyyumi AA, Dakak N, Andrews NP, Gilligan DM, Panza JA, Cannon RO, III Contribution of nitric oxide to metabolic coronary vasodilation in the human heart. Circulation 1995; 92 (3): 320–326

    PubMed  CAS  Google Scholar 

  23. Clapp BR, Hingorani AD, Kharbanda RK, Mohamed-Ali V, Stephens JW, Vallance P et al. Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress. Cardiovasc Res 2004; 64 (1): 172–178

    PubMed  CAS  Google Scholar 

  24. Kataoka C, Egashira K, Inoue S, Takemoto M, Ni W, Koyanagi M et al. Important role of Rho-kinase in the pathogenesis of cardiovascular inflammation and remodeling induced by long-term blockade of nitric oxide synthesis in rats. Hypertension 2002; 39 (2): 245–250

    PubMed  CAS  Google Scholar 

  25. Bohl KS, West JL. Nitric oxide-generating polymers reduce platelet adhesion and smooth muscle cell proliferation. Biomaterials 2000; 21 (22): 2273–2278

    PubMed  CAS  Google Scholar 

  26. Tanner FC, Meier P, Greutert H, Champion C, Nabel EG, Luscher TF. Nitric oxide modulates expression of cell cycle regulatory proteins: a cytostatic strategy for inhibition of human vascular smooth muscle cell proliferation. Circulation 2000; 101 (16): 1982–1989

    PubMed  CAS  Google Scholar 

  27. Kenagy RD, Clowes AW. Blockade of smooth muscle cell migration and proliferation in baboon aortic explants by interleukin-1beta and tumor necrosis factor-alpha is nitric oxidedependent and nitric oxide-independent. J Vasc Res 2000; 37 (5): 381–389

    PubMed  CAS  Google Scholar 

  28. Cornwell TL, Arnold E, Boerth NJ, Lincoln TM. I nhibition of smooth muscle cell growth by nitric oxide and activation of cAMP-dependent protein kinase by cGMP. Am J Physiol 1994; 267 (5 Pt 1): C1405–C1413

    PubMed  CAS  Google Scholar 

  29. Monastyrskaya E, Folarin N, Malyshev I, Green C, Andreeva L. Application of the nitric oxide donor SNAP to cardiomyocytes in culture provides protection against oxidative stress. Nitric Oxide 2002; 7 (2): 127–131

    PubMed  CAS  Google Scholar 

  30. Schafer A, Wiesmann F, Neubauer S, Eigenthaler M, Bauersachs J, Channon KM. Rapid regulation of platelet activation in vivo by nitric oxide. Circulation 2004; 109 (15): 1819–1822

    PubMed  Google Scholar 

  31. Kalinowski L, Matys T, Chabielska E, Buczko W, Malinski T. Angiotensin II AT1 receptor antagonists inhibit platelet adhesion and aggregation by nitric oxide release. Hypertension 2002; 40 (4): 521–527

    PubMed  CAS  Google Scholar 

  32. Schachinger V, Britten MB, Zeiher AM. P rognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 2000; 101 (16): 1899–1906

    PubMed  CAS  Google Scholar 

  33. Bugiardini R, Manfrini O, Pizzi C, Fontana F, Morgagni G. Endothelial function predicts future development of coronary artery disease: a study of women with chest pain and normal coronary angiograms. Circulation 2004; 109 (21): 2518–2523

    PubMed  Google Scholar 

  34. Williams IL, Wheatcroft SB, Shah AM, Kearney MT. Obesity, atherosclerosis and the vascular endothelium: mechanisms of reduced nitric oxide bioavailability in obese humans. Int J Obes Relat Metab Disord 2002; 26 (6): 754–764

    PubMed  CAS  Google Scholar 

  35. Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest 1996; 97 (11): 2601–2610

    PubMed  CAS  Google Scholar 

  36. Laine H, Yki-Jarvinen H, Kirvela O, Tolvanen T, Raitakari M, Solin O et al. Insulin resistance of glucose uptake in skeletal muscle cannot be ameliorated by enhancing endotheliumdependent blood flow in obesity. J Clin Invest 1998; 101 (5): 1156–1162

    PubMed  CAS  Google Scholar 

  37. Arcaro G, Zamboni M, Rossi L, Turcato E, Covi G, Armellini F et al. Body fat distribution predicts the degree of endothelial dysfunction in uncomplicated obesity. Int J Obes Relat Metab Disord 1999; 23 (9): 936–942

    PubMed  CAS  Google Scholar 

  38. Tack CJ, Ong MK, Lutterman JA, Smits P. Insulin-induced vasodilatation and endothelial function in obesity/insulin resistance. Effects of troglitazone. Diabetologia 1998; 41 (5): 569–576

    PubMed  CAS  Google Scholar 

  39. Westerbacka J, Vehkavaara S, Bergholm R, Wilkinson I, Cockcroft J, Yki-Jarvinen H. Marked resistance of the ability of insulin to decrease arterial stiffness characterizes human obesity. Diabetes 1999; 48 (4): 821–827

    PubMed  CAS  Google Scholar 

  40. Williams IL, Chowienczyk PJ, Wheatcroft SB, Patel AG, Sherwood RA, Momin A et al. Endothelial function and weight loss in obese humans. Obes Surg 2005; 15 (7): 1055–1060

    PubMed  Google Scholar 

  41. Williams IL, Chowienczyk PJ, Wheatcroft SB, Patel A, Sherwood R, Momin A et al. Effect of fat distribution on endothelial-dependent and endothelial-independent vasodilatation in healthy humans. Diabetes Obes Metab 2006; 8 (3): 296–301

    PubMed  CAS  Google Scholar 

  42. Murphy C, Kanaganayagam GS, Jiang B, Chowienczyk PJ, Zbinden R, Saha M et al. Vascular dysfunction and reduced circulating endothelial progenitor cells in young healthy UK South Asian men. Arterioscler Thromb Vasc Biol 2007

    Google Scholar 

  43. Urbich C, Dimmeler S. Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 2004; 95 (4): 343–353

    PubMed  CAS  Google Scholar 

  44. Winters B, Mo Z, Brooks-Asplund E, Kim S, Shoukas A, Li D et al. Reduction of obesity, as induced by leptin, reverses endothelial dysfunction in obese (Lep(ob)) mice. J Appl Physiol 2000; 89 (6): 2382–2390

    PubMed  CAS  Google Scholar 

  45. Zecchin HG, Bezerra RM, Carvalheira JB, Carvalho-Filho MA, Metze K, Franchini KG et al. Insulin signalling pathways in aorta and muscle from two animal models of insulin resistance–the obese middle-aged and the spontaneously hypertensive rats. Diabetologia 2003; 46 (4): 479–491

    PubMed  CAS  Google Scholar 

  46. Noronha BT, Li JM, Wheatcroft SB, Shah AM, Kearney MT. Inducible nitric oxide synthase has divergent effects on vascular and metabolic function in obesity. Diabetes 2005; 54 (4): 1082–1089

    PubMed  CAS  Google Scholar 

  47. Kuboki K, Jiang ZY, Takahara N, Ha SW, Igarashi M, Yamauchi T et al. Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo: a specific vascular action of insulin. Circulation 2000; 101 (6): 676–681

    PubMed  CAS  Google Scholar 

  48. Woodman CR, Price EM, Laughlin MH. Shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries. J Appl Physiol 2004

    Google Scholar 

  49. Yoshizumi M, Perrella MA, Burnett JC, Jr., Lee ME. Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life. Circ Res 1993; 73 (1): 205–209

    PubMed  CAS  Google Scholar 

  50. Wheatcroft SB, Kearney MT, Shah AM, Grieve DJ, Williams IL, Miell JP et al. Vascular endothelial function and blood pressure homeostasis in mice overexpressing IGF binding protein-1. Diabetes 2003; 52 (8): 2075–2082

    PubMed  CAS  Google Scholar 

  51. Flavahan NA. Atherosclerosis or lipoprotein-induced endothelial dysfunction. Potential mechanisms underlying reduction in EDRF/nitric oxide activity. Circulation 1992; 85 (5): 1927–1938

    PubMed  CAS  Google Scholar 

  52. Duncan ER, Li J-M, Wheatcroft SB, Shah AM, Kearney MT. Insulin resistance is a substrate for accelerated endothelial dysfunction in middle age–studies in mice heterozygous for knockout of the insulin receptor gene (IR). Circulation 2005; 112 (II): 314

    Google Scholar 

  53. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 1999; 399 (6736): 601–605

    PubMed  CAS  Google Scholar 

  54. Wheatcroft SB, Shah AM, Li JM, Duncan E, Noronha BT, Crossey PA et al. Preserved glucoregulation but attenuation of the vascular actions of insulin in mice heterozygous for knockout of the insulin receptor. Diabetes 2004; 53 (10): 2645–2652

    PubMed  CAS  Google Scholar 

  55. Cai H, Harrison DG. E ndothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 2000; 87 (10): 840–844

    PubMed  CAS  Google Scholar 

  56. Guzik TJ, West NE, Black E, McDonald D, Ratnatunga C, Pillai R et al. Vascular superoxide production by NAD(P)H oxidase: association with endothelial dysfunction and clinical risk factors. Circ Res 2000; 86 (9): E85–E90

    PubMed  CAS  Google Scholar 

  57. Harrison DG. Cellular and molecular mechanisms of endothelial cell dysfunction. J Clin Invest 1997; 100 (9): 2153–2157

    PubMed  CAS  Google Scholar 

  58. Li JM, Shah AM. Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology. Am J Physiol Regul Integr Comp Physiol 2004; 287 (5): R1014–R1030

    PubMed  CAS  Google Scholar 

  59. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004; 114 (12): 1752–1761

    PubMed  CAS  Google Scholar 

  60. Alp NJ, Channon KM. Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease. Arterioscler Thromb Vasc Biol 2004; 24 (3): 413–420

    PubMed  CAS  Google Scholar 

  61. Shinozaki K, Nishio Y, Okamura T, Yoshida Y, Maegawa H, Kojima H et al. Oral administration of tetrahydrobiopterin prevents endothelial dysfunction and vascular oxidative stress in the aortas of insulin-resistant rats. Circ Res 2000; 87 (7): 566–573

    PubMed  CAS  Google Scholar 

  62. Ishii M, Shimizu S, Nagai T, Shiota K, Kiuchi Y, Yamamoto T. Stimulation of tetrahydrobiopterin synthesis induced by insulin: possible involvement of phosphatidylinositol 3-kinase. Int J Biochem Cell Biol 2001; 33 (1): 65–73

    PubMed  CAS  Google Scholar 

  63. Alp NJ, Mussa S, Khoo J, Cai S, Guzik T, Jefferson A et al. Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I overexpression. J Clin Invest 2003; 112 (5): 725–735

    PubMed  CAS  Google Scholar 

  64. Hansson GK, Libby P, Schonbeck U, Yan ZQ. Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ Res 2002; 91 (4): 281–291

    PubMed  CAS  Google Scholar 

  65. Corti R, Hutter R, Badimon JJ, Fuster V. Evolving concepts in the triad of atherosclerosis, inflammation and thrombosis. J Thromb Thrombolysis 2004; 17 (1): 35–44

    PubMed  CAS  Google Scholar 

  66. Newby AC. Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol Rev 2005; 85 (1): 1–31

    PubMed  CAS  Google Scholar 

  67. Schonbeck U, Libby P. CD40 signaling and plaque instability. Circ Res 2001; 89 (12): 1092–1103

    PubMed  CAS  Google Scholar 

  68. Lutgens E, Daemen MJ. CD40–CD40L interactions in atherosclerosis. Trends Cardiovasc Med 2002; 12 (1): 27–32

    PubMed  CAS  Google Scholar 

  69. Danese S, Fiocchi C. Platelet activation and the CD40/CD40 ligand pathway: mechanisms and implications for human disease. Crit Rev Immunol 2005; 25 (2): 103–121

    PubMed  CAS  Google Scholar 

  70. Vishnevetsky D, Kiyanista VA, Gandhi PJ. CD40 ligand: a novel target in the fight against cardiovascular disease. Ann Pharmacother 2004; 38 (9): 1500–1508

    PubMed  CAS  Google Scholar 

  71. Aukrust P, Muller F, Ueland T, Berget T, Aaser E, Brunsvig A et al. Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina. Possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes. Circulation 1999; 100 (6): 614–620

    PubMed  CAS  Google Scholar 

  72. Varo N, de Lemos JA, L ibby P, Morrow DA, Murphy SA, Nuzzo R et al. Soluble CD40L: risk prediction after acute coronary syndromes. Circulation 2003; 108 (9): 1049–1052

    PubMed  CAS  Google Scholar 

  73. Schernthaner GH, Kopp HP, Krzyzanowska K, Kriwanek S, Koppensteiner R, Schernthaner G. Soluble CD40L in patients with morbid obesity: significant reduction after bariatric surgery. Eur J Clin Invest 2006; 36 (6): 395–401

    PubMed  CAS  Google Scholar 

  74. Desideri G, Ferri C. Effects of obesity and weight loss on soluble CD40L levels. JAMA 2003; 289 (14): 1781–1782

    PubMed  Google Scholar 

  75. Madamanchi NR, Hakim ZS, Runge MS. Oxidative stress in atherogenesis and arterial thrombosis: the disconnect between cellular studies and clinical outcomes. J Thromb Haemost 2005; 3 (2): 254–267

    PubMed  CAS  Google Scholar 

  76. Singh U, Jialal I. Oxidative stress and atherosclerosis. Pathophysiology 2006; 13 (3): 129–142

    PubMed  CAS  Google Scholar 

  77. Urakawa H, Katsuki A, Sumida Y, Gabazza EC, Murashima S, Morioka K et al. Oxidative stress is associated with adiposity and insulin resistance in men. J Clin Endocrinol Metab 2003; 88 (10): 4673–4676

    PubMed  CAS  Google Scholar 

  78. Delbosc S, Paizanis E, Magous R, Araiz C, Dimo T, Cristol JP et al. Involvement of oxidative stress and NADPH oxidase activation in the development of cardiovascular complications in a model of insulin resistance, the fructose-fed rat. Atherosclerosis 2005; 179 (1): 43–49

    PubMed  CAS  Google Scholar 

  79. Hansen LL, Ikeda Y, Olsen GS, Busch AK, Mosthaf L. Insulin signaling is inhibited by micromolar concentrations of H(2)O(2). Evidence for a role of H(2)O(2) in tumor necrosis factor alpha-mediated insulin resistance. J Biol Chem 1999; 274 (35): 25078–25084

    PubMed  CAS  Google Scholar 

  80. Tuomisto TT, Riekkinen MS, Viita H, Levonen AL, Yla-Herttuala S. Analysis of gene and protein expression during monocyte-macrophage differentiation and cholesterol loading–cDNA and protein array study. Atherosclerosis 2005; 180 (2): 283–291

    PubMed  CAS  Google Scholar 

  81. Nicholson AC, Han J, Febbraio M, Silversterin RL, Hajjar DP. Role of CD36, the macrophage class B scavenger receptor, in atherosclerosis. Ann N Y Acad Sci 2001; 947: 224–228

    PubMed  CAS  Google Scholar 

  82. Sampson MJ, Davies IR, Braschi S, Ivory K, Hughes DA. Increased expression of a scavenger receptor (CD36) in monocytes from subjects with Type 2 diabetes. Atherosclerosis 2003; 167 (1): 129–134

    PubMed  CAS  Google Scholar 

  83. Griffin E, Re A, Hamel N, Fu C, Bush H, McCaffrey T et al. A link between diabetes and atherosclerosis: Glucose regulates expression of CD36 at the level of translation. Nat Med 2001; 7 (7): 840–846

    PubMed  CAS  Google Scholar 

  84. Handberg A, Levin K, Hojlund K, Beck-Nielsen H. Identification of the oxidized low-density lipoprotein scavenger receptor CD36 in plasma: a novel marker of insulin resistance. Circulation 2006; 114 (11): 1169–1176

    PubMed  CAS  Google Scholar 

  85. Rosenson RS, Koenig W. Utility of inflammatory markers in the management of coronary artery disease. Am J Cardiol 2003; 92 (1A): 10i–18i

    PubMed  Google Scholar 

  86. Ajjan RA, Grant PJ, Futers TS, Brown JM, Cymbalista CM, oothby M et al. Complement C3 and C-reactive protein levels in patients with stable coronary artery disease. Thromb Haemost 2005; 94: 1048–1054

    PubMed  CAS  Google Scholar 

  87. Reynolds GD, Vance RP. C-reactive protein immunohistochemical localization in normal and atherosclerotic human aortas. Arch Pathol Lab Med 1987; 111 (3): 265–269

    PubMed  CAS  Google Scholar 

  88. Torzewski M, Rist C, Mortensen RF, Zwaka TP, Bienek M, Waltenberger J et al. C-reactive protein in the arterial intima: role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis. Arterioscler Thromb Vasc Biol 2000; 20 (9): 2094–2099

    PubMed  CAS  Google Scholar 

  89. Libby P, Ridker PM. Inflammation and atherosclerosis: role of C-reactive protein in risk assessment. Am J Med 2004; 1166: 9S–16S

    Google Scholar 

  90. Yasojima K, Schwab C, McGeer EG, McGeer P L. C omplement components, but not complement inhibitors, are upregulated in atherosclerotic plaques. Arterioscler Thromb Vasc Biol 2001; 21 (7): 1214–1219

    PubMed  CAS  Google Scholar 

  91. Muscari A, Bozzoli C, Puddu GM, Sangiorgi Z, Dormi A, Rovinetti C et al. Association of serum C3 levels with the risk of myocardial infarction. Am J Med 1995; 98 (4): 357–364

    PubMed  CAS  Google Scholar 

  92. Buono C, Come CE, W itztum JL, Maguire GF, Connelly PW, Carroll M et al. Influence of C3 deficiency on atherosclerosis. Circulation 2002; 105 (25): 3025–3031

    PubMed  CAS  Google Scholar 

  93. Schwarzenberg SJ, Sinaiko AR. 2006; Obesity and inflammation in children. Paediatr Respir Rev 7 (4): 239–246

    PubMed  Google Scholar 

  94. Ebstein W. Z ur therapie des Diabetes mellitus, insbesondere ü ber die Anwendung des salicylsauren Natron bei demselben. Berliner Klinische Wochenschrift 1876; 13: 337–340

    Google Scholar 

  95. Hotamisligil GS, Shargill NS, Spiegelman BM. A dipose expression of tumor necrosis factoralpha: direct role in obesity-linked insulin resistance. Science 1993; 259 (5091): 87–91

    PubMed  CAS  Google Scholar 

  96. Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB. The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J Clin Invest 1995; 95 (5): 2111–2119

    PubMed  CAS  Google Scholar 

  97. Dandona P, Weinstock R, Thusu K, Abdel-Rahman E, Aljada A, Wadden T. Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab 1998; 83 (8): 2907–2910

    PubMed  CAS  Google Scholar 

  98. Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 1999; 19 (4): 972–978

    PubMed  CAS  Google Scholar 

  99. Pickup JC, Mattock MB, Chusney GD, Burt D. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 1997; 40 (11): 1286–1292

    PubMed  CAS  Google Scholar 

  100. Blankenberg S, Rupprecht HJ, Bickel C, P eetz D, Hafner G, Tiret L et al. Circulating cell adhesion molecules and death in patients with coronary artery disease. Circulation 2001; 104 (12): 1336–1342

    PubMed  CAS  Google Scholar 

  101. Fasching P, Waldhausl W, Wagner OF. Elevated circulating adhesion molecules in NIDDM–potential mediators in diabetic macroangiopathy. Diabetologia 1996; 39 (10): 1242–1244

    PubMed  CAS  Google Scholar 

  102. Esposito K, Nappo F, Giugliano F, Di Palo C, Ciotola M, Barbieri M et al. Cytokine milieutends toward inflammation in type 2 diabetes. Diabetes Care 2003; 26 (5): 1647

    PubMed  Google Scholar 

  103. Chen H. Cellular inflammatory responses: novel insights for obesity and insulin resistance. Pharmacol Res 2006; 53 (6): 469–477

    PubMed  CAS  Google Scholar 

  104. Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res 2005; 96 (9): 939–949

    PubMed  CAS  Google Scholar 

  105. Bastard JP, Jardel C, Bruckert E, Blondy P, Capeau J, Laville M et al. Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. J Clin Endocrinol Metab 2000; 85 (9): 3338–3342

    PubMed  CAS  Google Scholar 

  106. Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 2003; 289 (14): 1799–1804

    PubMed  CAS  Google Scholar 

  107. Kopp HP, Kopp CW, Festa A, Krzyzanowska K, Kriwanek S, Minar E et al. Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol 2003; 23 (6): 1042–1047

    PubMed  CAS  Google Scholar 

  108. Sharma AM, Staels B. Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and adipose tissue–understanding obesity-related changes in regulation of lipid and glucose metabolism. J Clin Endocrinol Metab 2006

    Google Scholar 

  109. Hotamisligil GS. Inflammatory pathways and insulin action. Int J Obes Relat Metab Disord 2003; 27 (Suppl 3): S53–S55

    PubMed  CAS  Google Scholar 

  110. Ronti T, Lupattelli G, Mannarino E. The endocrine function of adipose tissue: an update. Clin Endocrinol (Oxf) 2006; 64 (4): 355–365

    CAS  Google Scholar 

  111. Lee SW, Song KE, Shin DS, Ahn SM, Ha ES, Kim DJ et al. Alterations in peripheral blood levels of TIMP-1, MMP-2, and MMP-9 in patients with type-2 diabetes. Diabetes Res Clin Pract 2005; 69 (2): 175–179

    PubMed  CAS  Google Scholar 

  112. Yamauchi T, Kamon J, Waki H, Imai Y, Shimozawa N, Hioki K et al. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem 2003; 278 (4): 2461–2468

    PubMed  CAS  Google Scholar 

  113. Kubota N, Yamauchi T, Tobe K, Kadowaki T. Adiponectin-dependent and-independent pathways in insulin-sensitizing and antidiabetic actions of thiazolidinediones. Diabetes 2006; 55 (Suppl 2): S32–S38

    CAS  Google Scholar 

  114. Trujillo ME, Scherer PE. Adiponectin–journey from an adipocyte secretory protein to biomarker of the metabolic syndrome. J Intern Med 2005; 257 (2): 167–175

    PubMed  CAS  Google Scholar 

  115. Park JY, Gavrilova O, Gorden P. The clinical utility of leptin therapy in metabolic dysfunction. Minerva Endocrinol 2006; 31 (2): 125–131

    PubMed  CAS  Google Scholar 

  116. Bakker AH, Dielen FM, Van Greve JW, Adam JA, Buurman WA. Preadipocyte number in omentali and subcutaneous adipose tissue of obese individuals. Obes Res 2004; 12 (3): 488–498

    PubMed  Google Scholar 

  117. Matarese G, La Cava A, Sanna V, Lord GM, Lechler RI, Fontana S et al. Balancing susceptibility to infection and autoimmunity: a role for leptin? Trends Immunol 2002; 23 (4): 182–187

    PubMed  CAS  Google Scholar 

  118. Bodary PF, Westrick RJ, Wickenheiser KJ, Shen Y, Eitzman DT. Effect of leptin on arterial thrombosis following vascular injury in mice. JAMA 2002; 287 (13): 1706–1709

    PubMed  CAS  Google Scholar 

  119. Miller GE, Freedland KE, Carney RM, Stetler CA, Banks WA. Pathways linking depression, adiposity, and inflammatory markers in healthy young adults. Brain Behav Immun 2003; 17 (4): 276–285

    PubMed  CAS  Google Scholar 

  120. Wallerstedt SM, Eriksson AL, Niklason A, Ohlsson C, Hedner T. Serum leptin and myocardial infarction in hypertension. Blood Press 2004; 13 (4): 243–246

    PubMed  CAS  Google Scholar 

  121. Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004; 291 (14): 1730–1737

    PubMed  CAS  Google Scholar 

  122. Nemerson Y, Repke D. Tissue factor accelerates the activation of coagulation factor VII: the role of a bifunctional coagulation cofactor. Thromb Res 1985; 40 (3): 351–358

    PubMed  CAS  Google Scholar 

  123. Kazama Y, Hamamoto T, Foster DC, Kisiel W. Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation. J Biol Chem 1995; 270 (1): 66–72

    PubMed  CAS  Google Scholar 

  124. Bouma BN, Mosnier LO. Thrombin activatable fibrinolysis inhibitor (TAFI) at the interface between coagulation and fibrinolysis. Pathophysiol Haemost Thromb 2003; 33 (5–6): 375–381

    PubMed  Google Scholar 

  125. Norris LA. Blood coagulation. Best Pract Res Clin Obstet Gynaecol 2003; 17 (3): 369–383

    PubMed  Google Scholar 

  126. Medved L, Nieuwenhuizen W. Molecular mechanisms of initiation of fibrinolysis by fibrin. Thromb Haemost 2003; 89 (3): 409–419

    PubMed  CAS  Google Scholar 

  127. Collen D, Lijnen HR. Basic and clinical aspects of fibrinolysis and thrombolysis. Blood 1991; 78 (12): 3114–3124

    PubMed  CAS  Google Scholar 

  128. Suefuji H, Ogawa H, Yasue H, Kaikita K, Soejima H, Motoyama T et al. Increased plasma tissue factor levels in acute myocardial infarction. Am Heart J 1997; 134 (2 Pt 1): 253–259

    PubMed  CAS  Google Scholar 

  129. Soejima H, Ogawa H, Yasue H, Kaikita K, Nishiyama K, Misumi K et al. Heightened tissue factor associated with tissue factor pathway inhibitor and prognosis in patients with unstable angina. Circulation 1999; 99 (22): 2908–2913

    PubMed  CAS  Google Scholar 

  130. Meade TW, North WR, Chakrabarti R, Stirling Y, Haines AP, Thompson SG et al. Haemostatic function and cardiovascular death: early results of a prospective study. Lancet 1980; 1 (8177): 1050–1054

    PubMed  CAS  Google Scholar 

  131. Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA 1998; 279 (18): 1477–1482

    PubMed  CAS  Google Scholar 

  132. Lowe GD, Yarnell JW, Sweetnam PM, Rumley A, Thomas HF, Elwood PC. Fibrin D-dimer, tissue plasminogen activator, plasminogen activator inhibitor, and the risk of major ischaemic heart disease in the Caerphilly Study. Thromb Haemost 1998; 79 (1): 129–133

    PubMed  CAS  Google Scholar 

  133. Cushman M, Lemaitre RN, Kuller LH, Psaty BM, Macy EM, Sharrett AR et al. Fibrinolytic activation markers predict myocardial infarction in the elderly. The Cardiovascular Health Study. Arterioscler Thromb Vasc Biol 1999; 19 (3): 493–498

    PubMed  CAS  Google Scholar 

  134. Saigo M, Abe S, Ogawa M, Yamashita T, Biro S, Minagoe S et al. Imbalance of plasminogen activator inhibitor-I/ tissue plasminogen activator and tissue factor/tissue factor pathway inhibitor in young Japanese men with myocardial infarction. Thromb Haemost 2001; 86 (5): 1197–1203

    PubMed  CAS  Google Scholar 

  135. Juhan-Vague I, Pyke SD, Alessi MC, Jespersen J, Haverkate F, Thompson SG. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities. Circulation 1996; 94 (9): 2057–2063

    PubMed  CAS  Google Scholar 

  136. Fatah K, Silveira A, Tornvall P, Karpe F, Blomback M, Hamsten A. Proneness to formation of tight and rigid fibrin gel structures in men with myocardial infarction at a young age. Thromb Haemost 1996; 76 (4): 535–540

    PubMed  CAS  Google Scholar 

  137. 137. Dunn EJ, Philippou H, Ariens R, Grant PJ. Molecular mechanisms involved in the resistance of fibrin to clot lysis by plasmin in subjects with type 2 diabetes mellitus. Diabetologia 2006; 49 (5): 1071–1080

    PubMed  CAS  Google Scholar 

  138. Behague I, Poirier O, Nicaud V, Evans A, Arveiler D, Luc G et al. Beta fibrinogen gene polymorphisms are associated with plasma fibrinogen and coronary artery disease in patients with myocardial infarction. The ECTIM Study. Etude Cas-Temoins sur l ’ Infarctus du Myocarde. Circulation 1996; 93 (3): 440–449

    PubMed  CAS  Google Scholar 

  139. Lim BC, Ariens RA, Carter AM, Weisel JW, Grant PJ. Genetic regulation of fibrin structure and function: complex gene-environment interactions may modulate vascular risk. Lancet 2003; 361 (9367): 1424–1431

    PubMed  CAS  Google Scholar 

  140. Trip MD, Cats VM, van Capelle FJ, Vreeken J. Platelet hyperreactivity and prognosis in survivors of myocardial infarction. N Engl J Med 1990; 322 (22): 1549–1554

    PubMed  CAS  Google Scholar 

  141. Keating FK, Whitaker DA, Kabbani SS, Ricci MA, Sobel BE, Schneider DJ. Relation of augmented platelet reactivity to the magnitude of distribution of atherosclerosis. Am J Cardiol 2004; 94 (6): 725–728

    PubMed  Google Scholar 

  142. Endler G, Klimesch A, Sunder-Plassmann H, Schillinger M, Exner M, Mannhalter C et al. Mean platelet volume is an independent risk factor for myocardial infarction but not for coronary artery disease. Br J Haematol 2002; 117 (2): 399–404

    PubMed  Google Scholar 

  143. Sambola A, Osende J, Hathcock J, Degen M, Nemerson Y, Fuster V et al. Role of risk factors in the modulation of tissue factor activity and blood thrombogenicity. Circulation 2003; 107 (7): 973–977

    PubMed  CAS  Google Scholar 

  144. Dunn EJ, Ariens RA. Fibrinogen and fibrin clot structure in diabetes. Herz 2004; 29 (5): 470–479

    PubMed  Google Scholar 

  145. Mansfield MW, Stickland MH, Grant PJ. PAI-1 concentrations in first-degree relatives of patients with non-insulin-dependent diabetes: metabolic and genetic associations. Thromb Haemost 1997; 77 (2): 357–361

    PubMed  CAS  Google Scholar 

  146. Landin K, Tengborn L, Smith U. Elevated fibrinogen and plasminogen activator inhibitor (PAI-1) in hypertension are related to metabolic risk factors for cardiovascular disease. J Intern Med 1990; 227 (4): 273–278

    PubMed  CAS  Google Scholar 

  147. Hoekstra T, Geleijnse JM, Schouten EG, Kluft C. Plasminogen activator inhibitor-type 1: its plasma determinants and relation with cardiovascular risk. Thromb Haemost 2004; 91 (5): 861–872

    PubMed  CAS  Google Scholar 

  148. Hammer MR, John PN, Flynn MD, Bellingham AJ, Leslie RD. Glycated fibrinogen: a new index of short-term diabetic control. Ann Clin Biochem 1989; 26 (Pt 1): 58–62

    PubMed  Google Scholar 

  149. Dunn EJ, Ariens RA, Grant PJ. The influence of type 2 diabetes on fibrin structure and function. Diabetologia 2005; 48 (6): 1198–1206

    PubMed  CAS  Google Scholar 

  150. Anfossi G, Mularoni EM, Burzacca S, Ponziani MC, Massucco P, Mattiello L et al. Platelet resistance to nitrates in obesity and obese NIDDM, and normal platelet sensitivity to both insulin and nitrates in lean NIDDM. Diabetes Care 1998; 21 (1): 121–126

    PubMed  CAS  Google Scholar 

  151. Trovati M, Anfossi G. Influence of insulin and of insulin resistance on platelet and vascular smooth muscle cell function. J Diabetes Complications 2002; 16 (1): 35–40

    PubMed  Google Scholar 

  152. Westerbacka J, Yki-Jarvinen H, Turpeinen A, Rissanen A, Vehkavaara S, Syrjala M et al. Inhibition of platelet-collagen interaction: an in vivo action of insulin abolished by insulin resistance in obesity. Arterioscler Thromb Vasc Biol 2002; 22 (1): 167–172

    PubMed  CAS  Google Scholar 

  153. 153. Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes (1). N Engl J Med 1992; 326 (4): 242–250

    PubMed  CAS  Google Scholar 

  154. Davi G, Guagnano MT, Ciabattoni G, Basili S, Falco A, Marinopiccoli M et al. Platelet activation in obese women: role of inflammation and oxidant stress. JAMA 2002; 288 (16): 2008–2014

    PubMed  CAS  Google Scholar 

  155. Baldi S, Natali A, Buzzigoli G, Galvan AQ, Sironi AM, Ferrannini E. In vivo effect of insulin on intracellular calcium concentrations: relation to insulin resistance. Metabolism 1996; 45 (11): 1402–1407

    PubMed  CAS  Google Scholar 

  156. Ishibashi K, Kageyama S, Sakurai T, Murakawa Y, Aihara K, Yokota K et al. Inhibitory effects of insulin on intracellular calcium and aggregatory response of platelets are impaired in hypertensive subjects with insulin resistance. Hypertens Res 1997; 20 (3): 225–231

    PubMed  CAS  Google Scholar 

  157. Tschoepe D, Roesen P, Esser J, Schwippert B, Nieuwenhuis HK, Kehrel B et al. Large platelets circulate in an activated state in diabetes mellitus. Semin Thromb Hemost 1991; 17 (4): 433–438

    PubMed  CAS  Google Scholar 

  158. Cipollone F, Ciabattoni G, Patrignani P, Pasquale M, Di Gregorio D, Bucciarelli T et al. Oxidant stress and aspirin-insensitive thromboxane biosynthesis in severe unstable angina. Circulation 2000; 102 (9): 1007–1013

    PubMed  CAS  Google Scholar 

  159. Davi G, Guagnano MT, Ciabattoni G, Basili S, Falco A, Marinopiccoli M et al. Platelet activation in obese women: role of inflammation and oxidant stress. JAMA 2002; 288 (16): 2008–2014

    PubMed  CAS  Google Scholar 

  160. Blann AD. Assessment of endothelial dysfunction: focus on atherothrombotic disease. Pathophysiol Haemost Thromb 2003; 33 (5–6): 256–261

    PubMed  Google Scholar 

  161. Anderson TJ. Nitric oxide, atherosclerosis and the clinical relevance of endothelial dysfunction. Heart Fail Rev 2003; 8 (1): 71–86

    PubMed  Google Scholar 

  162. Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation 2004; 109 (23 Suppl 1): III27–III32

    PubMed  Google Scholar 

  163. Chyu KY, Shah PK. The role of inflammation in plaque disruption and thrombosis. Rev Cardiovasc Med 2001; 2 (2): 82–91

    PubMed  CAS  Google Scholar 

  164. Rosenson RS, Koenig W. Utility of inflammatory markers in the management of coronary artery disease. Am J Cardiol 2003; 92 (1A): 10i–18i

    PubMed  Google Scholar 

  165. Tousoulis D, Davies G, Stefanadis C, Toutouzas P, Ambrose JA. Inflammatory and thrombotic mechanisms in coronary atherosclerosis. Heart 2003; 89 (9): 993–997

    PubMed  CAS  Google Scholar 

  166. Fukudome K, Esmon CT. Identification, cloning, and regulation of a novel endothelial cell protein C/activated protein C receptor. J Biol Chem 1994; 269 (42): 26486–26491

    PubMed  CAS  Google Scholar 

  167. Archipoff G, Beretz A, Freyssinet JM, Klein-Soyer C, Brisson C, Cazenave JP. Heterogeneous regulation of constitutive thrombomodulin or inducible tissue-factor activities on the surface of human saphenous-vein endothelial cells in culture following stimulation by interleukin-1, tumour necrosis factor, thrombin or phorbol ester. Biochem J 1991; 273 (Pt 3): 679–684

    PubMed  CAS  Google Scholar 

  168. Tousoulis D, Davies G, Stefanadis C, Toutouzas P, Ambrose JA. Inflammatory and thrombotic mechanisms in coronary atherosclerosis. Heart 2003; 89 (9): 993–997

    PubMed  CAS  Google Scholar 

  169. Gawaz M. Role of platelets in coronary thrombosis and reperfusion of ischemic myocardium. Cardiovasc Res 2004; 61 (3): 498–511

    PubMed  CAS  Google Scholar 

  170. Sturn DH, Kaneider NC, Feistritzer C, Djanani A, Fukudome K, Wiedermann CJ. Expression and function of the endothelial protein C receptor in human neutrophils. Blood 2003; 102 (4): 1499–1505

    PubMed  CAS  Google Scholar 

  171. Conway EM, Van de WM, Pollefeyt S, Jurk K, Aken H, Van Vriese A De et al. The lectinlike domain of thrombomodulin confers protection from neutrophil-mediated tissue damage by suppressing adhesion molecule expression via nuclear factor kappaB and mitogen-activated protein kinase pathways. J Exp Med 2002; 196 (5): 565–577

    PubMed  CAS  Google Scholar 

  172. Lamounier-Zepter V, Ehrhart-Bornstein M, Bornstein SR. Insulin resistance in hypertension and cardiovascular disease. Best Pract Res Clin Endocrinol Metab 2006; 20 (3): 355–367

    PubMed  CAS  Google Scholar 

  173. Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Targher G et al. Prevalence of insulin resistance in metabolic disorders: the Bruneck Study. Diabetes 1998; 47 (10): 1643–1649

    PubMed  CAS  Google Scholar 

  174. Hannon TS, Bacha F, Lee SJ, Janosky J, Arslanian SA. Use of markers of dyslipidemia to identify overweight youth with insulin resistance. Pediatr Diabetes 2006; 7 (5): 260–266

    PubMed  Google Scholar 

  175. Basi S, Lewis JB. Microalbuminuria as a target to improve cardiovascular and renal outcomes. Am J Kidney Dis 2006; 47 (6): 927–946

    PubMed  CAS  Google Scholar 

  176. De Cosmo S, Minenna A, Ludovico O, Mastroianno S, DiG iorgio A, Pirro L et al. Increased urinary albumin excretion, insulin resistance, and related cardiovascular risk factors in patients with type 2 diabetes: evidence of a sex-specific association. Diabetes Care 2005; 28 (4): 910–915

    PubMed  CAS  Google Scholar 

  177. Parvanova AI, Trevisan R, Iliev IP, Dimitrov BD, Vedovato M, Tiengo A et al. Insulin resistance and microalbuminuria: a cross-sectional, case-control study of 158 patients with type 2 diabetes and different degrees of urinary albumin excretion. Diabetes 2006; 55 (5): 1456–1462

    PubMed  CAS  Google Scholar 

  178. Baron AD, Steinberg HO. Endothelial function, insulin sensitivity, and hypertension. Circulation 1997; 96 (3): 725–726

    PubMed  CAS  Google Scholar 

  179. Catalano C, Muscelli E, Quinones GA, Baldi S, Masoni A, Gibb I et al. Effect of insulin on systemic and renal handling of albumin in nondiabetic and NIDDM subjects. Diabetes 1997; 46 (5): 868–875

    PubMed  CAS  Google Scholar 

  180. Cohen AJ, McCarthy DM, Stoff JS. D irect hemodynamic effect of insulin in the isolated perfused kidney. Am J Physiol 1989; 257 (4 Pt 2): F580–F585

    PubMed  CAS  Google Scholar 

  181. Ajjan RA, Grant PJ. C ardiovascular disease prevention in patients with type 2 diabetes: the role of oral anti-diabetic agents. Diab Vasc Dis Res 2006; 3 (3): 147–158

    PubMed  Google Scholar 

  182. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346 (6): 393–403

    PubMed  CAS  Google Scholar 

  183. Buchanan TA, Xiang AH, Peters RK, Kjos SL, Marroquin A, Goico J et al. Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk hispanic women. Diabetes 2002; 51 (9): 2796–2803

    PubMed  CAS  Google Scholar 

  184. Xiang AH, Peters RK, Kjos SL, Marroquin A, Goico J, Ochoa C et al. Effect of pioglitazone on pancreatic beta-cell function and diabetes risk in Hispanic women with prior gestational diabetes. Diabetes 2006; 55 (2): 517–522

    PubMed  CAS  Google Scholar 

  185. Gerstein HC, Yusuf S, Bosch J, Pogue J, Sheridan P, Dinccag N et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006; 368 (9541): 1096–1105

    PubMed  CAS  Google Scholar 

  186. Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L. X ENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004; 27 (1): 155–161

    PubMed  CAS  Google Scholar 

  187. UK Prospective Diabetes Study (UKPDS) Group Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352 (9131): 854–865

    Google Scholar 

  188. Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial in MacroVascular Events): a randomised controlled trial. Lancet 2005; 366 (9493): 1279–1289

    PubMed  CAS  Google Scholar 

  189. Chu NV, Kong AP, Kim DD, Armstrong D, Baxi S, Deutsch R et al. Differential effects of metformin and troglitazone on cardiovascular risk factors in patients with type 2 diabetes. Diabetes Care 2002; 25 (3): 542–549

    PubMed  CAS  Google Scholar 

  190. Carter AM, Bennett CE, Bostock JA, Grant PJ. Metformin reduces C-reactive protein but not complement factor C3 in overweight patients with Type 2 diabetes mellitus. Diabet Med 2005; 22 (9): 1282–1284

    PubMed  CAS  Google Scholar 

  191. Rosen P, Wiernsperger NF. Metformin delays the manifestation of diabetes and vascular dysfunction in Goto–Kakizaki rats by reduction of mitochondrial oxidative stress. Diabetes Metab Res Rev 2006; 22 (4): 323–330

    PubMed  Google Scholar 

  192. Fanghanel G, Silva U, Sanchez-Reyes L, Sisson D, Sotres D, Torres EM. Effects of metformin on fibrinogen levels in obese patients with type 2 diabetes. Rev Invest Clin 1998; 50 (5): 389–394

    PubMed  CAS  Google Scholar 

  193. Grant PJ. Beneficial effects of metformin on haemostasis and vascular function in man. Diabetes Metab 2003; 29 (4 Pt 2): 6S44–6S52

    PubMed  CAS  Google Scholar 

  194. Vitale C, Mercuro G, Cornoldi A, Fini M, Volterrani M, Rosano GM. Metformin improves endothelial function in patients with metabolic syndrome. J Intern Med 2005; 258 (3): 250–256

    PubMed  CAS  Google Scholar 

  195. Sidhu JS, Cowan D, Tooze JA, Kaski JC. Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reduces circulating platelet activity in patients without diabetes mellitus who have coronary artery disease. Am Heart J 2004; 147 (6): e25

    PubMed  Google Scholar 

  196. Berenson GS. Childhood risk factors predict adult risk associated with subclinical cardiovascular disease. The Bogalusa Heart Study. Am J Cardiol 2002; 90 (10C): 3L–7L

    PubMed  Google Scholar 

  197. Berenson GS, Srinivasan SR, Hunter SM, Nicklas TA, Freedman DS, Shear CL et al. Risk factors in early life as predictors of adult heart disease: the Bogalusa Heart Study. Am J Med Sci 1989; 298 (3): 141–151

    PubMed  CAS  Google Scholar 

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  1. Academic Unit of Molecular Vascular Medicine, Leeds Institute of Genetics Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, UK

    Ramzi Ajjan MRCP, MMed.Sci, PhD, Mark T. Kearney FRCP, PhD & Peter J. Grant FRCP, MD

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  1. Ramzi Ajjan MRCP, MMed.Sci, PhD
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  1. Department of Pediatrics, University of Colorado Denver, Aurora, CO, 80045, USA

    Philip Scott Zeitler  & Kristen J. Nadeau  & 

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Ajjan, R., Kearney, M.T., Grant, P.J. (2008). Insulin Resistance and the Pathogenesis of Cardiovascular Disease. In: Zeitler, P.S., Nadeau, K.J. (eds) Insulin Resistance. Contemporary Endocrinology. Humana Press. https://doi.org/10.1007/978-1-59745-192-5_11

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