Endothelial dysfunction in obesity and insulin resistance: A road to diabetes and heart disease

Obesity Research

Volumn 11, Issue 11, 2003, Pages 1278-1289

  Caballero, A Enrique ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Diabetes; Endothelium; Inflammation; Insulin resistance; Prediabetes

Indexed keywords

HEART DISEASE; HUMAN; INSULIN RESISTANCE; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PATHOPHYSIOLOGY; REVIEW; VASCULAR ENDOTHELIUM; WEIGHT REDUCTION;

DIABETES MELLITUS, TYPE 2; ENDOTHELIUM, VASCULAR; HEART DISEASES; HUMANS; INSULIN RESISTANCE; OBESITY; WEIGHT LOSS;

EID: 1542545604     PISSN: 10717323     EISSN: None     Source Type: Journal    
DOI: 10.1038/oby.2003.174     Document Type: Review

References (90)

1. Flegal KM, Carroll MD, Ogeden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999-2000. JAMA. 2000;288:1723-7.
2. Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL. Overweight and obesity in the United States: prevalence and trends, 1960-1994. Int J Obes Relat Metab Disord. 1998;22:39-47.
3. Pi-Sunyer FX. The obesity epidemic: pathophysiology and consequences of obesity. Obes Res. 2002;10(Suppl 2):97S-104S.
4. Bergman RN, Mittelman SD. Central role of the adipocyte in insulin resistance. J Basic Clin Physiol Pharmacol. 1998;9:205-21.
5. Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003;423:762-9.
6. Aldhahi W, Hamdy O. Adipokines, inflammation and the endothelium in diabetes. Curr Diab Rep. 2003;3:293-8.
7. Sobel BE. Coronary artery disease and fibrinolysis: from the blood to the vessel wall. Thromb Haemost. 1999;82(Suppl 1):8-13.
8. Reaven GM. Role of insulin resistance in human disease (syndrome X): an expanded definition. Annu Rev Med. 1993;44:121-31.
9. Ross R. Atherosclerosis - an inflammatory disease. N Engl J Med. 1999;340:115-26.
10. Steinberg HO, Chaker H, Learning R, Johnson A, Brechtel G, Baron A. Obesity/insulin resistance is associated with endothelial dysfunction. J Clin Invest. 1996;97:2601-10.
11. Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest. 2000;106:473-81.
12. Haffner SM. Pre-diabetes, insulin resistance, inflammation and CVD risk. Diabetes Res Clinc Pract. 2003;61(Suppl 1):S9-S18.
13. Goran MI, Ball GD, Cruz ML. Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents. J Clin Endocrinol Metab. 2003;88:1417-27.
14. Gerich JE. Contributions of insulin-resistance and insulin-secretory defects to the pathogenesis of type 2 diabetes mellitus. Mayo Clin Proc. 2003;78:411-3.
15. Caballero AE. Diabetes in Minority Populations. In: Joslin Diabetes Textbook. (in press).
16. Quyyumi AA. Endothelial function in health and disease: new insights into the genesis of cardiovascular disease. Am J Med. 1998;105:32S-39S.
17. Mano T, Masuyama T, Yamamoto K, et al. Endothelial dysfunction in the early stage of atherosclerosis precedes appearance of intimal lesions assessable with intravascular ultrasound. Am Heart J. 1996;131:231-8.
18. Tooke JE. Microvascular function in human diabetes: a physiologic perspective. Diabetes. 1995;44:721-6.
19. Calles-Escandon J, Cipolla M. Diabetes and endothelial dysfunction: a clinical perspective. Endocrine Rev. 2001;22:36-52.
20. Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340:1111-5.
21. Saouaf R, Arora S, Smakowski P, Caballero AE, Veves A. Reactive hyperemic response of the brachial artery: comparison of proximal and distal occlusion. Acad Radiol. 1998;5:556-60.
22. Correti MC, Anderson TJ, Benjamin EJ, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow mediated vasodilation of the brachial artery. J Am Coll Cardial. 2002;39:257-65.
23. Schachinger V, Britten MB, Zeiber AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation. 2000;101:1899-906.
24. Williams SB, Cusco JA, Roddy MA, Johnstone MT, Creager MA. Impaired nitric-oxide mediated vasodilation in patients with non-insulin dependent diabetes mellitus. J Am Coll Cardiol. 1996;27:567-74.
25. Lim SC, Caballero AE, Smakowski P, LoGerfo FW, Horton ES, Veves A. Soluble intercellular adhesion molecule, vascular cell adhesion molecule, and impaired microvascular reactivity are early markers of vasculopathy in type 2 diabetic individuals without microalbuminuria. Diabetes Care. 1999;22:1865-70.
26. King GL, Wakasaki H. Theoretical mechanisms by which hyperglycemia and insulin resistance could cause cardiovascular diseases in diabetes. Diabetes Care. 1999;22(Suppl 3):C31-7.
27. Arora S, Veves A, Caballero AE, Smakowski P, LoGerfo F. Estrogen improves endothelial function. J Vasc Surg. 1998;27:1141-7.
28. Steinberg HO, Paradisi G, Cronin J, et al. Type II diabetes abrogates sex differences in endothelial function in premenopausal women. Circulation. 2000;101:2040-6.
29. Lim SC, Caballero AE, Arora S, et al. The effect of hormonal replacement therapy on the vascular reactivity and endothelial function of healthy individuals and individuals with type 2 diabetes. J Clin Endo Metab. 1999;84:4159-64.
30. Tounian P, Aggoun Y, Dubern B, et al. Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study. Lancet. 2001;358:1400-4.
31. Caballero AE, Arora S, Saouaf R, et al. Micro and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes. Diabetes. 1999;48:1856-62.
32. Balletshofer BM, Rittig K, Enderle MD, et al. Endothelial dysfunction is detectable in young normotensive first-degree relatives of subjects with type 2 diabetes in association with insulin resistance. Circulation. 2000;101:1780-4.
33. Chen NG, Homes M, Reaven GM. Relationship between insulin resistance, soluble adhesion molecules, and mononuclear cell binding in healthy volunteers. J Clin Endocrinol Metab. 1999;84:3485-9.
34. Anastasiou E, Leakakis JP, Alevizaki M, et al. Impaired endothelium-dependent vasodilatation in women with previous gestational diabetes. Diabetes Care. 1998;21:2111-5.
35. Ferri C, Desideri G, Baldoncini R, et al. Early activation of vascular endothelium in nonobese, nondiabetic essential hypertensive patients with multiple metabolic abnormalities. Diabetes. 1998;47:660-7.
36. Lundman P, Eriksson MJ, Silveira A, et al. Relation of hypertriglyceridemia to plasma concentrations of biochemical markers of inflammation and endothelial activation (C-reactive protein, interleukin-6, soluble adhesion molecules, von Willebrand factor, and endothelin-1). Am J Cardiol. 2003;91:1128-31.
37. Paradisi G, Steinberg HO, Hempfling A, et al. Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation. 2001;103:1410-5.
38. Griffin ME, Marcucci MJ, Cline SW, et al. Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes. 1999;48:1270-4.
39. Hotamisligil GS. The role of TNF-alpha and TNF receptors in obesity and insulin resistance. J Intern Med. 1999;245:621-5.
40. Kim YB, Uotani S, Perroz DD, Flier JS, Kahn BB. In vivo administration of leptin activates signal transduction directly in insulin sensitive tissues: overlapping but distinct pathways from insulin. Endocrinology. 2000;141:2328-39.
41. Shimabukuro M, Koyama K, Chen G, et al. Direct antidiabetic effects of leptin through triglyceride depletion of tissues. Proc Natl Acad Sci USA. 1997;94:4637-41.
42. Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes. Nature. 2001;409:307-12.
43. Nagaev I, Smith U. Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle. Biochem Biophys Res Commun. 2001;285:561-4.
44. Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7:941-6.
45. Steinberg HO, Baron AD. Vascular function, insulin resistance and fatty acids. Diabetologia. 2002;45:623-34.
46. Winkler G, Lakatos P, Salamon F, et al. Elevated serum TNF-alpha level as a link between endothelial dysfunction and insulin resistance in normotensive obese patients. Diabet Med. 1999;16:207-11.
47. Lembo G, Vecchione C, Fratta L, et al. Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes. 2000;49:293-7.
48. Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis. 2002;148:209-14.
49. Yudkin SJ, 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;19:972-8.
50. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105:1135-43.
51. Depres JP, Lamarche M, Mauriege P, et al. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med. 1996;334:952-7.
52. Howard G, O'Leary DH, Zaccaro D, et al. Insulin sensitivity and atherosclerosis. Circulation. 1996;93:1809-17.
53. Kuboki K, Jiang ZY, Takahara N, et al. Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells in vivo: a specific vascular action of insulin. Circulation. 2000;101:676-81.
54. Montagnani M, Quon MJ. Insulin action in vascular endothelium: potential mechanisms linking insulin resistance with hypertension. Diabetes Obes Metab. 2000;2:285-92.
55. Cusi K, Maezono K, Osman A, et al. Insulin resistance differentially affects the PI-3-kinase and MAP kinase mediated signaling in human muscle. J Clin Invest. 2000;105:311-20.
56. Hsueh WA, Law RE. Insulin signaling in the arterial wall. Am J Cardiol. 1999;84:21J-24J.
57. Jiang ZY, Lin YW, Clemont A, et al. Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats. J Clin Invest. 1999;104:447-57.
58. Arcaro G, Cretti A, Balzano S, et al. Insulin causes endothelial dysfunction in humans: sites and mechanisms. Circulation. 2002;105:576-82.
59. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases. The role of oxidant stress. Circ Res. 2000;87:840-4.
60. Folli F, Saad JMJ, Velloso L, et al. Crosstalk between insulin and angiotensin II signaling systems. Exp Clin Endocrinol Diabetes. 1999;107:133-9.
61. Piatti P, Monti LD, Galli L, et al. Relationship between endothelin-1 concentrations and metabolic alterations typical of the insulin resistance syndrome. Metabolism. 2000;49:748-52.
62. Miyamoto Y, Saito Y, Kajiyama N, et al. Endothelial nitric oxide synthase gene is positively associated with essential hypertension. Hypertension. 1998;32:3-8.
63. Pinkney JH, Stehower CD, Coppack SW, Judkin JS. Endothelial dysfunction: cause of the insulin resistance syndrome. Diabetes. 1997;46:S9-13.
64. Utriainen T, Makimattila S, Virkamaki A, Bergholm R, Yki-Jarvinen H. Dissociation between insulin sensitivity of glucose uptake and endothelial function in normal subjects. Diabetologia. 1996;39:1477-82.
65. Natali A, Taddei S, Quinones A, et al. Insulin sensitivity, vascular reactivity, and clamp-induced vasodilation in essential hypertension. Circulation. 1997;96:849-55.
66. 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;83:2907-10.
67. Ziccardi P, Nappo F, Giugliano C, et al. Reduction of inflammatory cytokine concentrations and improvement of endothelial function in obese women after weight loss over one year. Circulation. 2002;105:804-9.
68. Balkestein EJ, van Aggel-Leijssen DP, van Baak MA, Struijker-Boudier HA, Van Bortel LM. The effect of weight loss with or without exercise training on large artery compliance in healthy obese men. J Hypertens. 1999;17:1831-5.
69. Sciacqua Q, Candigliota M, Ceravolo R, et al. Weight loss in combination with physical activity improves endothelial dysfunction in human obesity. Diabetes Care. 2003;26:1673-8.
70. Hamdy O, Ledbury S, Mullooly C, et al. Lifestyle modification improves endothelial function in obese subjects with the insulin resistance syndrome. Diabetes Care. 2003;26:2119-25.
71. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle modification or metformin. N Engl J Med. 2002;346:393-403.
72. Kahn CR, Chen L, Cohen SE. Unraveling the mechanism of action of thiazolidinediones. J Clin Invest. 2000;106:1305-7.
73. Law RE, Goetz S, Xi XP, et al. Expression and function of PPAR-γ in rat and human vascular smooth muscle cells. Circulation. 2000;101:1311-8.
74. Marx N, Schonbeck U, Lazar MA, Libby P, Plutzky J. Peroxisome proliferator-activated receptor gamma activators inhibit gene expression and migration in human vascular smooth muscle cells. Circ Res. 1998;83:1097-103.
75. Hsueh WA, Jackson S, Law RE. Control of vascular cell proliferation and migration by PPAR-γ. A new approach to the macrovascular complications of diabetes. Diabetes Care. 2001;24:392-7.
76. Parulkar AA, Pendergrass ML, Granda-Ayala R, Lee TR, Fonseca VA. Nonhypoglycemic effects of thiazolidinediones. Ann Intern Med. 2001;134:61-71.
77. kB by troglitazone: evidence for an anti-inflamamatory effect and potential antiatherosclerotic effect in the obese. J Clin Endocrinol Metab. 2001;86:1306-12.
78. Caballero AE, Saouaf R, Lim SC, et al. The effects of troglitazone on the endothelial function of the micro-and macrocirculation in patients with early and late type 2 diabetes. Metabolism. 2003;52:173-80.
79. Koshiyama H, Shimono D, Kuwamura N, Minamikawa J, Nakamura Y. Inhibitory effect of pioglitazone on carotid arterial wall thickness in type 2 diabetes. J Clin Endocrinol Metab. 2001;86:3452-6.
80. Ishibashi M, Egashira K, Hiasa K, et al. Anti-inflammatory and anti-atherosclerotic effects of pioglitazone. Hypertension. 2002;40:687-93.
81. Haffner SM, Greenberg AS, Weston WM, Chen H, Williams K, Freed MI. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation. 2002;106:679-84.
82. Martens FM, Visseren FL, Lemay J, de Koning EJ, Rabelink TJ. Metabolic and additional vascular effects of thiazolidinediones. Drugs. 2002;62:1463-80.
83. Nakamura T, Ushiyama C, Osada S, Hara M, Shimada N, Koide H. Pioglitazone reduces urinary podocyte excretion in type 2 diabetes patients with microalbuminuria. Metabolism. 2001;50:1193-6.
84. Bakris G, Viberti G, Weston WM, Heise M, Porter LE, Freed MI. Rosiglitazone reduces urinary albumin excretion in type II diabetes. J Hum Hypertens. 2003;17:7-12.
85. 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;352:854-65.
86. Johnson JA, Majumdar SR, Simpson SH, Toth EL. Decreased mortality associated with the use of metformin compared with sulfonylurea monotherapy in type 2 diabetes. Diabetes Care. 2002;25:2244-8.
87. Grant P. The effects of high- and medium-dose metformin therapy on cardiovascular risk factors in patients with type 2 diabetes. Diabetes Care. 1996;19:64-6.
88. Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol. 2001;37:1344-50.
89. Charles MA, Morange P, Eschwege E, Andre P, Vague P, Juhan-Vague I. Effect of weight change and metformin on fibrinolysis and the von Willebrand factor in obese nondiabetic subjects. The BIGPRO1 Study. Diabetes Care. 1998;21:1967-72.
90. Caballero AE, Delgado A, Naranjo A, et al. Metformin improves markers of endothelial activation but not markers of inflammation in subjects with impaired glucose tolerance. Diabetes. 2003;52(Suppl 1):A20.