Endothelial dysfunction in diabetes: Pathogenesis, significance, and treatment

Review of Diabetic Studies

Volumn 10, Issue 2-3, 2013, Pages 133-156

  Hamilton, Sandra J ^a   Watts, Gerald F ^b  

^a UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^b UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

Author keywords

Dyslipoproteinemia; Lipoprotein; Type 2 diabetes; Vascular disease

Indexed keywords

ASCORBIC ACID; ATORVASTATIN; CERIVASTATIN; CIPROFIBRATE; COLESEVELAM; DALCETRAPIB; DOCOSAHEXAENOIC ACID; ENDOTHELIAL NITRIC OXIDE SYNTHASE; ENDOTHELIN 1; FENOFIBRATE; FISH OIL; GEMFIBROZIL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ICOSAPENTAENOIC ACID; INSULIN SENSITIZING AGENT; IRBESARTAN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MIPOMERSEN; MONOUNSATURATED FATTY ACID; NICOTINIC ACID; NITRIC OXIDE; OLIVE OIL; OMEGA 3 FATTY ACID; PLACEBO; PROBUCOL; RAMIPRIL; ROSUVASTATIN; SIMVASTATIN; UBIDECARENONE; UNINDEXED DRUG;

ABDOMINAL OBESITY; AEROBIC EXERCISE; CARDIOVASCULAR RISK; DIET RESTRICTION; DIET SUPPLEMENTATION; DRUG SUBSTITUTION; DYSLIPIDEMIA; DYSLIPOPROTEINEMIA; ENDOTHELIAL DYSFUNCTION; HUMAN; HYPERGLYCEMIA; HYPERTENSION; INFLAMMATION; INSULIN RESISTANCE; LIFESTYLE MODIFICATION; LIPOTOXICITY; LOW DRUG DOSE; META ANALYSIS (TOPIC); MICROALBUMINURIA; NON INSULIN DEPENDENT DIABETES MELLITUS; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; PATHOGENESIS; PHYSICAL ACTIVITY; PREDICTIVE VALUE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SMOKING; VASODILATATION; WEIGHT REDUCTION;

ANIMALS; DIABETES MELLITUS, TYPE 2; DIABETIC ANGIOPATHIES; ENDOTHELIUM, VASCULAR; HUMANS; HYPOLIPIDEMIC AGENTS;

EID: 84891781043     PISSN: 16136071     EISSN: 16140575     Source Type: Journal    
DOI: 10.1900/RDS.2013.10.133     Document Type: Review

References (241)

1. Haffner S, 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.
2. Kim J, Koh KK, Quon MJ. The Union of Vascular and Metabolic Actions of Insulin in Sickness and in Health. Arterioscler Thromb Vasc Biol 2005. 25(5):889-891.
3. Almdal TD, Scharling HM, Jensen JS, Vestergaard HD. The Independent Effect of Type 2 Diabetes Mellitus on Ischemic Heart Disease, Stroke, and Death: A Population-Based Study of 13,000 Men and Women With 20 Years of Follow-up. Arch Intern Med 2004. 164(13):1422-1426.
4. Woodman RJ, Chew GT, Watts GF. Mechanisms, significance and treatment of vascular dysfunction in type 2 diabetes mellitus: focus on lipid-regulating therapy. Drugs 2005. 65(1):31-74.
5. Watts GF, Playford DA. Dyslipoproteinaemia and hyperoxidative stress in the pathogenesis of endothelial dysfunction in non-insulin dependent diabetes mellitus: an hypothesis. Atherosclerosis 1998. 141(1):17-30.
6. Kim J, Montagnani M, Koh KK, Quon MJ. Reciprocal Relationships Between Insulin Resistance and Endothelial Dysfunction: Molecular and Pathophysiological Mechanisms. Circulation 2006. 113(15):1888-1904.
7. Nesto R. C-reactive protein, its role in inflammation, Type 2 diabetes and cardiovascular disease, and the effects of insulin-sensitizing treatment with thiazolidinediones. Diabet Med 2004. 21(8):810-817.
8. Dandona P, Aljada A, Chaudhuri A. Endothelial Dysfunction, Inflammation and Diabetes. Rev Endocr Metabol Disord 2004. 5:189-197.
9. Versari D, Daghini E, Virdis A. Endothelium-dependent contractions and endothelial dysfunction in human hypertension. Br J Pharmacol 2009. 157:527-536.
10. Leiter LA, Lewanczuk RZ. Of the renin-angiotensin system and reactive oxygen species: type 2 diabetes and angiotensin II inhibition. Am J Hypertens 2005. 18(1):121-128.
11. Widlansky ME, Gokce N, Keaney JF Jr, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol 2003. 42(7):1149-1160.
12. Hamilton SJ, Chew GT, Watts GF. Therapeutic regulation of endothelial dysfunction in type 2 diabetes mellitus. Diabetes Vasc Dis Res 2007. 4(2):89-102.
13. Esper R, Nordaby R, Vilarino J, Paragano A, Cacharron J, Machado R. Endothelial dysfunction: a comprehensive appraisal. Cardiovas Diabetol 2006. 5(1):4.
14. Vita JA, Keaney JF. Endothelial function: a barometer for cardiovascular risk? Circulation 2002. 106(6):640-642.
15. Levine TB, Levine AB. The endothelium and nitric oxide. Metabolic syndrome and cardiovascular disease 2006. 1st edition, pp 173-210.
16. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: A report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002. 39(2):257-265.
17. Pyke KE, Tschakovsky ME. The relationship between shear stress and flow-mediated dilatation: implications for the assessment of endothelial function. J Physiol 2005. 568(2):357-369.
18. Al-Qaisi M, Kharbanda RK, Mittal TK, Donald AE. Measurement of endothelial funciton and its clinical utility for cardiovascular risk. Vasc Health and Risk Manag 2008. 4(3):647-652.
19. Higashi Y, Sasaki S, Nakagawa K, Matsuura H, Kajiyama G, Oshima T. A noninvasive measurement of reactive hyperemia that can be used to assess resistance artery endothelial function in humans. Am J Cardiol 2001. 87(1):121-125.
20. Benjamin N, Calver A, Collier J, Robinson B, Vallance P, Webb D. Measuring Forearm Blood Flow and Interpreting the Responses to Drugs and Mediators. Hypertension 1995. 25(5):918-923.
21. Rubinshtein R, Kuvin JT, Soffler M, Lennon R, Lavi S, Nelson R, Pumper G, Lerman L, Lerman A. Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Euro Heart J 2010. 31(9):1142-1148.
22. Fitch KV, Stavrou E, Looby SE, Hemphill L, Jaff MR, Grinspoon SK. Associations of cardiovascular risk factors with two surrogate markers of subclinical atherosclerosis: Endothelial function and carotid intima media thickness. Atherosclerosis. 2011. 217(2):437-440.
23. Kato MD, Shiode MD, Yamagata MD, Matsuura MD, Kajiyama MD. Coronary Segmental Responses to Acetylcholine and Bradykinin in Patients With Atherosclerotic Risk Factors. Am J Cardiol 1997. 80(6):751-755.
24. Stehouwer CD, Stroes ES, Hackeng WH, Mulder PG, Den Ottolander GJ. von Willebrand factor and development of diabetic nephropathy in IDDM. Diabetes 1991. 40(8):971-976.
25. Jensen T, Bjerre-Knudsen J, Feldt-Rasmussen B, Deckert T. Features of endothelial dysfunction in early diabetic nephropathy. Lancet 1989. 1(8636):461-463.
26. Gearing AJH, Newman W. Circulating adhesion molecules in disease. Immunol Today. 1993. 14(10):506-512.
27. Albertini JP, Valensi P, Lormeau B, Aurousseau M, Ferriere F, Attali J, Gattegno L. Elevated concentrations of soluble E-selectin and vascular cell adhesion molecule-1 in NIDDM. Effect of intensive insulin treatment. Diabetes Care 1998. 21(6):1008.
28. Hwang SJ, Ballantyne CM, Sharrett AR, Smilth L, Davis C, Gotto A, Boerwinkle E. Circulating adhesion molecules VCAM-1, ICAM-1, and e-selectin in carotid atherosclerosis and incident coronary heart disease cases: The Atherosclerosis Risk In Communities (ARIC) Study. Circulation 1997. 96(12):4219-4225.
29. Thorand B, Baumert J, Chambless L, Meisinger C, Kolb H, Doring A, Lowel H, Koenig W, MONICA/KORA Study Group. Elevated markers of endothelial dysfunction predict type 2 diabetes mellitus in middle-aged men and women from the general population. Arterioscler Thromb Vasc Biol 2006. 26(2):398-405.
30. 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(11):1865.
31. Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T. Circulating Endothelial Progenitor Cells, Vascular Function, and Cardiovascular Risk. N Engl J Med 2003. 348(7):593-600.
32. Giannotti G, Doerries C, Mocharla PS, Mueller MF, Bahlmann FH, Horyath T, Jiang H, Sorrention SA, Steenken N, Manes C, et al. Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Prehypertension: Relation to Endothelial Dysfunction. Hypertension 2010. 55(6):1389-1397.
33. Curtis AM, Zhang L, Medenilla E, Gui M, Wilkinson P, Hu E, Giri J, Doraiswamy V, Gunda S, Burgert M, et al. Relationship of microparticles to progenitor cells as a measure of vascular health in a diabetic population. Cytometry B Clin Cytom 2010. 78B(5):329-337.
34. Avogaro A, Albiero M, Menegazzo L, de Kreutzenberg S, Fadini GP. Endothelial Dysfunction in Diabetes. Diabetes Care 2011. 34(Supplement 2):S285-S290.
35. Nozaki T, Sugiyama S, Koga H, Sugamura K, Ohba K, Matsuzawa, Sumida H, Matsui K, Jinnouchi H, Ogawa H. Significance of a multiple biomarkers strategy including endothelial dysfunction to improve risk stratification for cardiovascular events in patients at high risk for coronary heart disease. J Am Coll Cardiol 2009. 54(7):601-608.
36. Landmesser U, Merten R, Spiekermann S, Buttner K, Drexler H, Hornig B. Vascular extracellular superoxide dismutase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. Circulation 2000. 101(19):2264-2270.
37. Ingelsson E, Syvänen A, Lind L. Endotheliumdependent vasodilation in conduit and resistance vessels in relation to the endothelial nitric oxide synthase gene. J Hum Hypertens 2008. 22(8):569-578.
38. Russo G, Leopold JA, Loscalzo J. Vasoactive substances: Nitric oxide and endothelial dysfunction in atherosclerosis. Vascul Pharmacol 2002. 38(5):259-269.
39. Chew GT, Watts GF. Coenzyme Q10 and diabetic endotheliopathy: oxidative stress and the 'recoupling hypothesis'. QJM 2004. 97(8):537-548.
40. Alp NJ, Channon KM. Regulation of Endothelial Nitric Oxide Synthase by Tetrahydrobiopterin in Vascular Disease. Arterioscler Thromb Vasc Biol 2004. 24(3):413-420.
41. Katusic ZS. Vascular endothelial dysfunction: does tetrahydrobiopterin play a role? Am J Physiol Heart Circ Physiol 2001. 281(3):H981-H986.
42. Chan SY, Mancini GB, Kuramoto L, Schulzer M, Frohlich J, Ignaszewski A. The prognostic importance of endothelial dysfunction and carotid atheromaburden in patients with coronary artery disease. J Am Coll Cardiol 2003. 42(6):1037-1043.
43. Papaioannou GI, Kasapis C, Seip RL, Grey NJ, Katten D, Wackers FJ, Inzucchi SE, Engel S, Taylor A, Young LH, et al. Value of peripheral vascular endothelial function in the detection of relative myocardial ischemia in asymptomatic type 2 diabetic patients who underwent myocardial perfusion imaging. J Nucl Cardiol 2006. 13(3):362-368.
44. Muiesan ML, Salvetti M, Paini A, Monteduro C, Galbassini G, Poisa P, Porteri E, Agabiti-Rosei C, Paderno V, Belotti E, et al. Prognostic role of flow-mediated dilatation of the brachial artery in hypertensive patients. J Hypertens 2008. 26(8):1612-1618.
45. Rossi R, Nuzzo A, Origliani G, Modena MG. Prognostic role of flow-mediated dilation and cardiac risk factors in post-menopausal women. J Am Coll Cardiol 2008. 51(10):997-1002.
46. Yeboah JM, Folsom AR, Burke GL, Johnson C, Polak JF, Post W, Lima JA, Crouse JR, Herrington DM. Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: The Multi-Ethnic Study of Atherosclerosis. Circulation 2009. 120(6):502-509.
47. Kitta Y, Obata Je, Nakamura T, Hirano M, Kodama Y, Fujioka D, Saito Y, Kawabata K, Sano K, Kobayashi T, et al. Persistent impairment of endothelial vasomotor function has a negative impact on outcome in patients with coronary artery disease. J Am Coll Cardiol 2009. 53(4):323-330.
48. Al Suwaidi J, Hamasaki S, Higano ST, Nishimura RA, Holmes DR Jr, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 2000. 101(9):948-954.
49. Schachinger VM, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse longterm outcome of coronary heart disease. Circulation 2000. 101(16):1899-1906.
50. Halcox JP, Schenke WH, Zalos GR, Mincemoyer R, Prasad A, Waclawiw, MA, Nour KR, Quyyumi AA. Prognostic value of coronary vascular endothelial dysfunction. Circulation 2002. 106(6):653-658.
51. Nitenberg A, Valensi P, Sachs R, Cosson E, Attali JR, Antony I. Prognostic value of epicardial coronary artery constriction to the cold pressor test in type 2 diabetic patients with angiographically normal coronary arteries and no other major coronary risk factors. Diabetes Care 2004. 27(1):208-215.
52. Nitenberg A, Pham I, Antony I, Valensi P, Attali JR, Chemla D. Cardiovascular outcome of patients with abnormal coronary vasomotion and normal coronary arteriography is worse in type 2 diabetes mellitus than in arterial hypertension: A 10 year follow-up study. Atherosclerosis 2005. 183(1):113-120.
53. Perticone F, Ceravolo R, Pujia A, Ventura G, Iacopino S, Scozzafava A, Ferraro A, Chello M, Mastroroberto P, Verdecchia P, Schillaci G. Prognostic Significance of Endothelial Dysfunction in Hypertensive Patients. Circulation 2001. 104(2):191-196.
54. Lind L, Berglund L, Larsson A, Sundstrom J. Endothelial function in resistance and conduit arteries and 5-year risk of cardiovascular disease. Circulation 2011. 123(14):1545-1551.
55. Inaba Y, Chen J, Bergmann S. Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis. Int J Cardiovasc Imaging 2010. 26(6):631-640.
56. Green DJ, Jones H, Thijssen D, Cable NT, Atkinson G. Flow-mediated dilation and cardiovascular event prediction: does nitric oxide matter? Hypertension 2011. 57(3):363-369.
57. McVeigh GE, Brennan GM, Johnston GD, McDermott BJ, McGrath LT, Henry WR, Andrews JW, Hayes JR. Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulindependent) diabetes mellitus. Diabetologia 1992. 35(8):771-776.
58. Watts GF, O'Brien SF, Silvester W, Millar JA. Impaired endothelium-dependent and independent dilatation of forearm resistance arteries in men with diet-treated noninsulin-dependent diabetes: role of dyslipidaemia. Clin.Sci.(Lond) 1996. 91(5):567-573.
59. 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(3):567-574.
60. Enderle MD, Benda N, Schmuelling RM, Haering HU, Pfohl M. Preserved endothelial function in IDDM patients, but not in NIDDM patients, compared with healthy subjects. Diabetes Care 1998. 21(2):271-277.
61. Henry RMA, Ferreira I, Kostense PJ, Dekker JM, Nijpels G, Heine RJ, Kamp O, Bouter LM, Stehouwer CD. Type 2 diabetes is associated with impaired endothelium-dependent, flow-mediated dilation, but impaired glucose metabolism is not: The Hoorn Study. Atherosclerosis 2004. 174(1):49-56.
62. Nitenberg A, Valensi P, Sachs R, Dali M, Aptecar E, Attali JR. Impairment of coronary vascular reserve and ACh-induced coronary vasodilation in diabetic patients with angiographically normal coronary arteries and normal left ventricular systolic function. Diabetes 1993. 42(7):1017-1025.
63. Prior JO, Quinones MJ, Hernandez-Pampaloni M, Facta AD, Schindler TH, Sayre JW, Hsueh WA, Schelbert HR. Coronary Circulatory Dysfunction in Insulin Resistance, Impaired Glucose Tolerance, and Type 2 Diabetes Mellitus. Circulation 2005. 111(18):2291-2298.
64. Guerci B, Kearney-Schwartz A, Bohme P, Zannad F, Drouin P. Endothelial dysfunction and type 2 diabetes. Part 1: physiology and methods for exploring the endothelial function. Diabetes Metab 2001. 27(4 Pt 1):425-434.
65. Papaioannou GI, Seip RL, Grey NJ, Katten D, Taylor A, Inzucchi SE, Young LH, Chyun DA, Davey JA, Wackers FJ, et al. Brachial artery reactivity in asymptomatic patients with type 2 diabetes mellitus and microalbuminuria (from the Detection of Ischemia in Asymptomatic Diabetics-Brachial Artery Reactivity study). Am J Cardiol 2004. 94(3):294-299.
66. Tabit C, Chung W, Hamburg N, Vita J. Endothelial dysfunction in diabetes mellitus: Molecular mechanisms and clinical implications. Rev Endocr Metab Disord 2010. 11(1):61-74.
67. Iiyama K, Nagano M, Yo Y, Nagano N, Kamide K, Higaki J, Mikami H, Ogihara. Impaired endothelial function with essential hypertension assessed by ultrasonography. Am Heart J 1996. 132(4):779-782.
68. Arcaro G, Zamboni M, Rossi L, Turcato E, Covi G, Armellini F, Bosello O, Lechi A. Body fat distribution predicts the degree of endothelial dysfunction in uncomplicated obesity. Int J Obes 1999. 23(9):936.
69. Cleland SJ, Petrie JR, Small M, Elliott HL, Connell JM. Insulin Action Is Associated With Endothelial Function in Hypertension and Type 2 Diabetes. Hypertension 2000. 35(1):507-511.
70. Petrie JR, Ueda S, Webb DJ, Elliott HL, Connell JM. Endothelial nitric oxide production and insulin sensitivity: a physiological link with implications for pathogenesis of cardiovascular disease. Circulation 1996. 93(7):1331-1333.
71. Nappo F, Esposito K, Cioffi M, Giugliano G, Molinari AM, Paolisso G, Marfella R, Giuglano D. Postprandial endothelial activation in healthy subjects and in type 2 diabetic patients: role of fat and carbohydrate meals. J Am Coll Cardiol 2002. 39(7):1145-1150.
72. Anderson RA, Evans ML, Ellis GR, Graham J, Morris K, Jackson SK, Lewis MJ, Rees A, Frenneaux MP. The relationships between postprandial lipaemia, endothelial function and oxidative stress in healthy individuals and patients with type 2 diabetes. Atherosclerosis 2001. 154(2):475-483.
73. Anderson RA, Jones CJ, Goodfellow J. Is the fatty meal a trigger for acute coronary syndromes. Atherosclerosi. 2001. 159(1):9-15.
74. Kawano H, Motoyama T, Hirashima O, Hirai N, Miyao Y, Sakamoto T, Kugiyama K, Ogawa H, Yasue H. Hyperglycemia rapidly suppresses flow-mediated endotheliumdependent vasodilation of brachial artery. J Am Coll Cardiol 1999. 34(1):146-154.
75. Shige H, Ishikawa T, Suzukawa M, Ito T, Nakajima K, Higashi K, Ayaroi M, Tabata S, Ohsuzu F, Nakamura H. Endothelium-dependent flow-mediated vasodilation in the postprandial state in type 2 diabetes mellitus. Am J Cardiol 1999. 84(10):1272-1274.
76. Haller H. Postprandial glucose and vascular disease. Diabet.Med 1997. 14 Suppl 3:S50-S56.
77. Lin KY, Ito AM, Asagami TM, Tsao PS, Adimoolam S, Kimoto M, Tsuji H, Reaven G, Cooke J. Impaired Nitric Oxide Synthase Pathway in Diabetes Mellitus: Role of Asymmetric Dimethylarginine and Dimethylarginine Dimethylaminohydrolase. Circulation 2002. 106(8):987-992.
78. Davignon J. Beneficial Cardiovascular Pleiotropic Effects of Statins. Circulation 2004. 109(23 Suppl 1):1-39.
79. Chan DC, Watts GF, Ng TW, Yamashita S, Barrett PH. Effect of weight loss on markers of triglyceride-rich lipoprotein metabolism in the metabolic syndrome. Eur J Clin Invest 2008. 38(10):743-751.
80. Ng TW, Watts GF, Barrett PH, Rye KA, Chan DC. Effect of weight loss on LDL and HDL kinetics in the metabolic syndrome: associations with changes in plasma retinolbinding protein-4 and adiponectin levels. Diabetes Care 2007. 30(11):2945-2950.
81. Watts GF, Chan DC. Mechanisms for therapeutic correction of dyslipidaemia in insulin resistance and diabetes. Atheroscler Suppl 2010. 11(1):61-64.
82. Chan DC, Watts GF. Dyslipidaemia in the metabolic syndrome and type 2 diabetes: pathogenesis, priorities, pharmacotherapies. Expert Opin Pharmacother 2011. 12(1):13-30.
83. Wing R, Look Ahead Research Group. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: fouryear results of the Look AHEAD Trial. Arch Intern Med 2010. 170(17):1566-1575.
84. Alam S, Stolinski M, Pentecost C, Boroujerdi MA, Jones RH, Sonksen PH, Umpleby AM. The effect of a six-month exercise program on very low-density lipoprotein apolipoprotein B secretion in type 2 diabetes. J Clin Endocrinol Metab 2004. 89(2):688-694.
85. Phillips SA, Jurva JW, Syed AQ, Kulinski JP, Pleuss J, Hoffmann RG, Gutterman DD. Benefit of low-fat over low-carbohydrate diet on endothelial health in obesity. Hypertension 2008. 51(2):376-382.
86. Pierce GL, Beske SD, Lawson BR, Southall KL, Benay FJ, Donato AJ, Seals DR. Weight loss alone improves conduit and resistance artery endothelial function in young and older overweight/obese adults. Hypertension 2008. 52(1):72-79.
87. Ades PA, Savage PD, Lischke S, Toth MJ, Harvey-Berino J, Bunn JY, Ludlow M, Schneider DJ. The effect of weight loss and exercise training on flow-mediated dilatation in coronary heart disease: a randomized trial. Chest 2011. 140(6):1420-1427.
88. Bigornia SJ, Mott MM, Hess DT, Apovian CM, McDonnell ME, Duess MA, Kluge MA, Fiscale AJ, Vita JA, Gokce N. Long-term successful weight loss improves vascular endothelial function in severely obese individuals. Obesity (Silver Spring) 2010. 18(4):754-759.
89. Varady KA, Bhutani S, Klempel MC, Phillips SA. Improvements in vascular health by a low-fat diet, but not a high-fat diet, are mediated by changes in adipocyte biology. Nutr J 2011. 10:8.
90. Camarillo-Romero E, Dominguez-Garcia MV, Amaya-Chavez A, Camarillo-Romero M, Talavera-Pina J, Huitron-Bravo G, Majluf-Cruz A. Effects of a physical activity program on markers of endothelial dysfunction, oxidative stress, and metabolic status in adolescents with metabolic syndrome. ISRN Endocrinol 2012. 2012:970629.
91. Hamdy O, Ledbury S, Mullooly C, Jarema C, Porter S, Ovalle K, Moussa A, Caselli A, Caballero AE, Economides PA, et al. Lifestyle Modification Improves Endothelial Function in Obese Subjects With the Insulin Resistance Syndrome. Diabetes Care 2003. 26(7):2119-2125.
92. Maiorana A, O'Driscoll G, Cheetham C, Dembo L, Stanton K, Goodman C, Taylor R, Green D. The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes. J Am Coll Cardiol 2001. 38(3):860-866.
93. Kwon HR, Min KW, Ahn HJ, Seok HG, Lee JH, Park GS, Han KA. Effects of aerobic exercise vs. resistance training on endothelial function in women with type 2 diabetes mellitus. Diabetes Metab J 2011. 35(4):364-373.
94. Green DJ, Walsh JH, Maiorana A, Best MJ, Taylor RR, O'Driscoll JG. Exercise-induced improvement in endothelial dysfunction is not mediated by changes in CV risk factors: pooled analysis of diverse patient populations. Am J Physiol - Heart Circ Physiol 2003. 285(6):H2679-H2687.
95. Green DJ, Maiorana A, O'Driscoll G, Taylor R. Effect of exercise training on endothelium-derived nitric oxide function in humans. J Physiol 2004. 561(1):1-25.
96. Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease: An update. J Am Coll Cardiol 2004. 43(10):1731-1737.
97. Haire-Joshu D, Glasgow RE, Tibbs TL. Smoking and Diabetes. Diabetes Care 2004. 27:S74.
98. Celermajer DS, Sorensen KE, Georgakopoulos D, Bull C, Thomas O, Robinaon J, Deanfield JE. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation 1993. 88(5):2149-2155.
99. Celermajer DS, Adams MR, Clarkson P, Robinson J, McCredie R, Donald A, Deanfield JE. Passive smoking and impaired endothelium-dependent arterial dilatation in healthy young adults. N Engl J Med 1996. 334(3):150-154.
100. Poredos P, Orehek M, Tratnik E. Smoking is associated with dose-related increase of intima-media thickness and endothelial dysfunction. Angiology 1999. 50(3):201-208.
101. Johnson HM, Gossett LK, Piper ME, Aeschlimann SE, Korcarz CE, Baker TB, Fiore MC, Stein JH. Effects of Smoking and Smoking Cessation on Endothelial Function: 1-Year Outcomes From a Randomized Clinical Trial. J Am Coll Cardiol 2010. 55(18):1988-1995.
102. Collins R, Armitage J, Parish S, Sleigh P, Peto R. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003. 361:2005-2016.
103. Stroes ES, Koomans HA, de Bruin TW, Rabelink TJ. Vascular function in the forearm of hypercholesterolaemic patients off and on lipid-lowering medication. Lancet 1995. 346:467-471.
104. O'Driscoll G, Green D, Taylor R. Simvastatin, an HMG-Coenzyme A Reductase Inhibitor, Improves Endothelial Function Within 1 Month. Circulation 1997. 95(5):1126-1131.
105. van de Ree MA, Huisman MV, de Man FH, van der Vijver JC, Meinders AE, Blauw GJ. Impaired endothelium-dependent vasodilation in type 2 diabetes mellitus and the lack of effect of simvastatin. Cardiovasc.Res 2001. 52(2):299-305.
106. van Etten RW, de Koning EJ, Honing ML, Stroes ES, Gaillard CA, Rabelink TJ. Intensive lipid lowering by statin therapy does not improve vasoreactivity in patients with type 2 diabetes. Arterioscler Thromb Vasc Biol 2002. 22(5):799-804.
107. Sheu WH, Juang BL, Chen YT, Lee WJ. Endothelial dysfunction is not reversed by simvastatin treatment in type 2 diabetic patients with hypercholesterolemia. Diabetes Care 1999. 22(7):1224-1225.
108. Sheu WH, Chen YT, Lee WJ. Improvement in endothelial dysfunction with LDL cholesterol level <80 mg/dl in type 2 diabetic patients. Diabetes Care 2001. 24(8):1499-1501.
109. Ceriello A, Assaloni R, Da Ros R, Maier A, Piconi L, Quagliaro L, Esposito K, Giugilano D. Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic patients. Circulation 2005. 111(19):2518-2524.
110. Tsunekawa T, Hayashi T, Kano H, Sumi D, Matsui-Hirai H, Thakur NK, Egashira K, Iguchi A. Cerivastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, improves endothelial function in elderly diabetic patients within 3 days. Circulation 2001. 104(4):376-379.
111. Tan KC, Chow WS, Tam SC, Ai VH, Lam CH, Lam KS. Atorvastatin lowers C-reactive protein and improves endothelium-dependent vasodilation in type 2 diabetes mellitus. J Clin Endocrinol Metab 2002. 87(2):563-568.
112. Ceriello A, Taboga C, Tonutti L, Quagliaro L, Piconi L, Bais B, Da Ros R, Motz E. Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation 2002. 106(10):1211-1218.
113. Adel A, Abdel-Salam Z, Nammas W. Low-dose statin therapy improves endothelial function in type 2 diabetic patients with normal serum total cholesterol: a randomized placebo-controlled study. J Clin Hypertens 2010. 12(10):820-825.
114. Dalla N, Passaro A, Zamboni PF, Calzoni F, Fellin R, Solini A. Atorvastatin improves metabolic control and endothelial function in type 2 diabetic patients: a placebocontrolled study. J Endocrinol Invest 2003. 26(1):73-78.
115. Rawlings R, Nohria A, Liu PY, Donnelly J, Creager MA, Ganz P, Selwyn A, Liao JK. Comparison of effects of rosuvastatin (10 mg) versus atorvastatin (40 mg) on rho kinase activity in Caucasian men with a previous atherosclerotic event. Am J Cardiol 2009. 103(4):437-441.
116. Brunetti ND, Maulucci G, Casavecchia GP, Distaso C, De Gennaro L, Pellegrino PL, Di Biase M. Improvement in endothelium dysfunction in diabetics treated with statins: a randomized comparison of atorvastatin 20 mg versus rosuvastatin 10 mg. J Interv Cardiol 2007. 20(6):481-487.
117. Economides PA, Caselli A, Tiani E, Khaodhiar L, Horton ES, Veves A. The effects of atorvastatin on endothelial function in diabetic patients and subjects at risk for type 2 diabetes. J Clin Endocrinol Metab 2004. 89(2):740-747.
118. Beishuizen ED, Tamsma JT, Jukema JW, van de Ree MA, van der Vijver JC, Meinders AE, Huisman MV. The effect of statin therapy on endothelial function in type 2 diabetes without manifest cardiovascular disease. Diabetes Care 2005. 28(7):1668-1674.
119. van Venrooij FV, van de Ree MA, Bots ML, Stolk RP, Huisman MV, Banga JD. Aggressive lipid lowering does not improve endothelial function in type 2 diabetes: the Diabetes Atorvastatin Lipid Intervention (DALI) Study: a randomized, double-blind, placebo-controlled trial. Diabetes Care 2002. 25(7):1211-1216.
120. Balletshofer BM, Goebbel S, Rittig K, Enderle M, Schmolzer I, Wascher TC, Ferenc Pap A, Westermeier T, Petzinna D, Matthaei S, Haring HU. Intense cholesterol-lowering therapy with a HMG-CoA reductase inhibitor does not improve nitric oxide dependent endothelial function in type 2 diabetes. Exp Clin Endocrinol Diabetes 2005. 6:324-330.
121. Tantikosoom W, Thinkhamrop B, Kiatchusakul S, Jarernsiripornkul N, Srinakarin J, Ojongpian S. Randomized trial of atorvastatin in improving endothelial function in diabetics without prior coronary disease and having average cholesterol level. J Med Assoc Thai 2005. 88(3):399-406.
122. Tousoulis D, Antoniades C, Vasiliadou C, Kourtellaris P, Koniari K, Marinou K, Charakida M, Ntarladimas I, Siasos G, Stefanadis C. Effects of atorvastatin and vitamin C on forearm hyperaemic blood flow, asymmentrical dimethylarginine levels and the inflammatory process in patients with type 2 diabetes mellitus. Heart 2007. 93(2):244-246.
123. Tran D, Lowy A, Howes JB, Howes LG. Effects of cerivastatin on forearm vascular responses, blood pressure responsiveness and ambulatory blood pressure in type 2 diabetic men. Diabetes Obes Metab 2005. 7(3):273-281.
124. Chan D. Regulation of proprotein convertase subtilisin/kexin type 9: therapeutical perspectives. Atherosclerosis 2011. 217(1):77-79.
125. Goldberg R. Improving glycemic and cholesterol control through an integrated approach incorporating colesevelam - a clinical perspective. Diabetes Metab Syndr Obes 2009. 2:11-21.
126. Jialal I, Abby SL, Misir S, Nagendran S. Concomitant reduction in low-density lipoprotein cholesterol and glycated hemoglobin with colesevelam hydrochloride in patients with type 2 diabetes: a pooled analysis. Metab Syndr Relat Disord 2009. 7(3):255-258.
127. Fonseca VA, Handelsman Y, Staels B. Colesevelam lowers glucose and lipid levels in type 2 diabetes: the clinical evidence. Diabetes Obes Metab 2010. 12(5):384-392.
128. Fonseca VA, Rosenstock J, Wang AC, Truitt KE, Jones MR. Colesevelam HCl improves glycemic control and reduces LDL cholesterol in patients with inadequately controlled type 2 diabetes on sulfonylurea-based therapy. Diabetes Care 2008. 31(8):1479-1484.
129. Kastelein JJ, Wedel MK, Baker BF, Su J, Bradley J, Yu R, Chuang E, Graham M, Crooke R. Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B. Circulation 2006. 114(16):1729-1735.
130. Akdim F, Visser ME, Tribble DL, Baker BF, Stroes ES, Yu R, Flaim JD, Su J, Stein EA, Kastelein JJ. Effect of mipomersen, an apolipoprotein B synthesis inhibitor, on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia. Am J Cardiol 2010. 105(10):1413-1419.
131. Raal FJ, Santos RD, Blom DJ, Marais AD, Charng M, Cromwell WC, Lachmann RH, Gaudet D, Tan JL, Chasan-Taber S, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebocontrolled trial. Lancet. 2010. 375(9719):998-1006.
132. Bell DA, Hooper AJ, Burnett JR. Mipomersen, an antisense apolipoprotein B synthesis inhibitor. Expert Opin Investig Drugs 2011. 20(2):265-272.
133. Bell DA, Hooper AJ, Watts GF, Burnett JR. Mipomersen and other therapies for the treatment of severe familial hypercholesterolemia. Vasc Health Risk Manag 2012. 8:651-659.
134. Jun M, Foote C, Lv J, Neal B, Patel A, Nicholls SJ, Grobbee DE, Cass A, Chalmers J, Perkovic V. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 2010. 375(9729):1875-1884.
135. Jun M, Zhu B, Tonelli M, Jardine MJ, Patel A, Neal B, Liyanage T, Keech A, Cass A, Perkovic V. Effects of fibrates in kidney disease: a systematic review and metaanalysis. J Am Coll Cardiol 2012. 60(20):2061-2071.
136. Malik J, Melenovsky V, Wichterle D, Haas T, Simek J, Ceska R, Hradec J. Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial--FAT). Cardiovasc Res 2001. 52(2):290-298.
137. Koh KK, Han SH, Quon MJ, Yeal Ahn J, Shin EK. Beneficial Effects of Fenofibrate to Improve Endothelial Dysfunction and Raise Adiponectin Levels in Patients With Primary Hypertriglyceridemia. Diabetes Care 2005. 28(6):1419-1424.
138. Playford DA, Watts GF, Best JD, Burke V. Effect of fenofibrate on brachial artery flow-mediated dilatation in type 2 diabetes mellitus. Am J Cardiol 2002. 90(11):1254-1257.
139. Playford DA, Watts GF, Croft KD, Burke V. Combined effect of coenzyme Q10 and fenofibrate on forearm microcirculatory function in type 2 diabetes. Atherosclerosis 2003. 168(1):169-179.
140. Chew GT, Watts GF, Davis TM, Stuckey BG, Beilin LJ, Thompson PL, Burke B, Currie PJ. Hemodynamic effects of fenofibrate and coenzyme Q10 in type 2 diabetic subjects with left ventricular diastolic dysfunction. Diabetes Care 2008. 31(8):1502-1509.
141. Evans M, Anderson RA, Graham J, Ellis GR, Morris K, Davies S, Jackson SK, Lewis MJ, Frenneaux MP, Rees A. Ciprofibrate Therapy Improves Endothelial Function and Reduces Postprandial Lipemia and Oxidative Stress in Type 2 Diabetes Mellitus. Circulation 2000. 101(15):1773-1779.
142. Avogaro A, Miola M, Favaro A, Gottardo L, Pacini G, Manzato E, Zambon S, Sacerdoti D, de Kreutzenberg S, Piliego T, et al. Gemfibrozil improves insulin sensitivity and flow-mediated vasodilatation in type 2 diabetic patients. Eur J Clin Invest 2001. 31(7):603-609.
143. Fegan PG, Shore AC, Mawson D, Tooke JE, MacLeod KM. Microvascular endothelial function in subjects with Type 2 diabetes and the effect of lipid-lowering therapy. Diabet Med 2005. 22(12):1670-1676.
144. Hiukka A, Westerbacka J, Leinonen ES, Watanabe H, wiklund O, Hulten LM, Salonen JT, Tuomainen TP, Yki-Jarvinen H, Keech AC, Taskinen MR. Long-term effects of fenofibrate on carotid intima-media thickness and augmentation index in subjects with type 2 diabetes mellitus. J Am Coll Cardiol 2008. 52(25):2190-2197.
145. Keech AC, Mitchell P, Summanen PA, O'Day J, Davis TM, Moffitt MS, Taskinen MR, Simes RJ, Tse D, Williamson E, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 2007. 370(9600):1687-1697.
146. Davis T, Ting R, Best J, Donoghoe M, Drury P, Sullivan D, Jenkins A, O'Connell R, Whiting M, Glasziou P, et al. Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. Diabetologia 2011. 54(2):280-290.
147. Ismail-Beigi F, Craven T, Banerji MA, Basile J, Calles J, Cohen RM, Cuddihy R, Cushman WC, Genuth S, Grimm RH, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet 2010. 376(9739):419-430.
148. Chew E, Ambrosius W, Davis M, Danis R, Gangaputra S, Greven C, Hubbard L, Esser BA, Lovato JF, Perdue LH, et al. for the ACCORD Study Group and ACCORD Eye Study Group. Effects of Medical Therapies on Retinopathy Progression in Type 2 Diabetes. N Engl J Med 2010. 363(3):233-244.
149. Vosper H. Niacin: a re-emerging pharmaceutical for the treatment of dyslipidaemia. Br J Pharmacol 2009. 158 429-441.
150. Benjo AM, Maranhao RC, Coimbra SR, Andrade AC, Favarato D, Molina MS, Brandizzi LI, da Luz PL. Accumulation of chylomicron remnants and impaired vascular reactivity occur in subjects with isolated low HDL cholesterol: Effects of niacin treatment. Atherosclerosis 2006. 187(1):116-122.
151. Thoenes M, Oguchi A, Nagamia S, Vaccari CS, Hammoud R, Umpierrez GE, Khan BV. The effects of extended-release niacin on carotid intimal media thickness, endothelial function and inflammatory markers in patients with the metabolic syndrome. Int J Clin Pract 2007. 61(11):1942-1948.
152. Mori TA, Woodman RJ. The independent effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors in humans. Curr Opin Clin Nutr Metab Care. 2006. 9(2):95-104.
153. McVeigh GE, Brennan GM, Johnston GD, McDermott BJ, McGrath LT, Henry WR, Andrews JW, Hayes JR. Dietary fish oil augments nitric oxide production or release in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1993. V36(1):33-38.
154. Woodman RJ, Mori TA, Burke V, Puddey IB, Barden A, Watts GF, Beilin LJ. Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. Atherosclerosis 2003. 166(1):85-93.
155. Wong CY, Yiu KH, Li SW, Lee S, Tam S, Lau CP, Tse HF. Fish-oil supplement has neutral effects on vascular and metabolic function but improves renal function in patients with Type 2 diabetes mellitus. Diabet Med 2010. 27(1):54-60.
156. Stirban A, Nandrean S, Gotting C, Tamler R, Pop A, Negrean M, Gawlowski T, Stratmann B, Tschoepe D. Effects of n-3 fatty acids on macro- and microvascular function in subjects with type 2 diabetes mellitus. Am J Clin Nutr 2010. 91(3):808-813.
157. West SG, Hecker KD, Mustad VA, Nicholson S, Schoemer SL, Wagner P, Hiderliter AL, Ulbrecht J, Ruey P, Kris-Etherton PM. Acute effects of monounsaturated fatty acids with and without omega-3 fatty acids on vascular reactivity in individuals with type 2 diabetes. Diabetologia 2005. 48(1):113-122.
158. Hilpert KF, West SG, Kris-Etherton PM, Hecker KD, Simpson NM, Alaupovic P. Postprandial effect of n-3 polyunsaturated fatty acids on apolipoprotein B-containing lipoproteins and vascular reactivity in type 2 diabetes. Am J Clin Nutr 2007. 85(2):369-376.
159. Mori TA, Watts GF, Burke V, Hilme E, Puddey IB, Beilin LJ. Differential effects of eicosapentaenoic acid and docosahexaenoic acid on vascular reactivity of the forearm microcirculation in hyperlipidemic, overweight men. Circulation 2000. 102(11):1264-1269.
160. Parthasarathy S, Young SG, Witztum JL, Pittman RC. Probucol inhibits oxidative modification of low density lipoprotein. J Clin Invest 1986. 77:641-644.
161. Yokoi H, Daida H, Kuwabara Y, Nishikawa H, Takatsu F, Tomihara H, Nakata Y, Kutsumi Y, Ohshima S, Nishiyama S, et al. Effectiveness of an antioxidant in preventing restenosis after percutaneous transluminal coronary angioplasty: the Probucol Angioplasty Restenosis Trial. J Am Coll Cardiol 1997. 30(4):855-862.
162. Sawayama Y, Shimizu C, Maeda N, Tatsukawa M, Kinukawa N, Koyanagi S, Kashiwagi S, Hayashi J. Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia: Fukuoka atherosclerosis trial (FAST). J Am Coll Cardiol 2002. 39(4):610-616.
163. Endo K, Miyashita Y, Sasaki H, Ebisumo M, Ohira M, Saiki A, Koide N, Oyama T, Takeyoshi M, Shirai K. Probucol and atorvastatin decrease urinary 8-hydroxy-2'deoxyguanosine in patients with diabetes and hypercholesterolemia. J Atheroscler Thromb 2006. 13(1):68-75.
164. Evans M, Anderson RA, Smith JC, Khan N, Graham JM, thomas AW, Morris K, Deely D, Frenneaux MP, Davies JS, Rees A. Effects of insulin lispro and chronic vitamin C therapy on postprandial lipaemia, oxidative stress and endothelial function in patients with type 2 diabetes mellitus. Eur J Clin Invest 2003. 33(3):231-238.
165. Gaenzer H, Neumayr G, Marschang P, Strum W, Lechleitner M, Foger B, Kirchmair R, Patsch J. Effect of insulin therapy on endothelium-dependent dilation in type 2 diabetes mellitus. Am J Cardiol 2002. 89(4):431-434.
166. Rask-Madsen C, Ihlemann N, Krarup T, Christiansen E, Kober L, Kistorp CN, Torp-Pedersen C. Insulin therapy improves insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease. Diabetes 2001. 50(11):2611-2618.
167. Vehkavaara S, Yki-Jarvinen H. 3.5 years of insulin therapy with insulin glargine improves in vivo endothelial function in type 2 diabetes. Arterioscler Thromb Vasc Biol 2004. 24(2):325-330.
168. Vehkavaara S, Makimattila S, Schlenzka A, Vakkilainen J, Westerbacka J, Yki-Jarvinen H. Insulin therapy improves endothelial function in type 2 diabetes. Arterioscler Thromb Vasc Biol 2000.20(2):545-550.
169. Rask-Madsen C, King GL. Mechanisms of disease: endothelial dysfunction in insulin resistance and diabetes. Nat Clin Pract Endocrinol Metab 2007. 3(1):46-56.
170. Sundaresan P, Lykos D, Daher A, Diamond T, Morris R, Howes LG. Comparative effects of glibenclamide and metformin on ambulatory blood pressure and cardiovascular reactivity in NIDDM. Diabetes Care 1997. 20(5):692-697.
171. Williams S, Abbott D, Morfis L, Manwaring P, Diamond T, Howes LG. Effects of glibenclamide on blood pressure and cardiovascular responsiveness in non-insulin dependent diabetes mellitus. J Hypertens 1998. 16(5):705-711.
172. Spallarossa P, Schiavo M, Rossettin P, Cordone S, Olivotti L, Cordera R, Brunelli C. Sulfonylurea treatment of type 2 diabetic patients does not reduce the vasodilator response to ischemia. Diabetes Care 2001. 24(4):738-742.
173. Wascher TC, Boes U. Forearm vascular reactivity is differentially influenced by gliclazide and glibenclamide in chronically treated type 2 diabetic patients. Clin Physiol Funct Imaging 2005. 25(1):40-46.
174. Abbink EJ, Pickkers P, Van Rosendaal AJ, Lutterman JA, Tack CJ, Russel FG, Smits P. Vascular effects of glibenclamide vs. glimepiride and metformin in Type 2 diabetic patients. Diabet Med 2002. 19(2):136-143.
175. Manzella D, Grella R, Abbatecola AM, Paolisso G. Repaglinide administration improves brachial reactivity in type 2 diabetic patients. Diabetes Care 2005. 28(2):366-371.
176. Schmoelzer I, Wascjer TC. Effect of repaglinide on endothelial dysfunction during a glucose tolerance test in subjects with impaired glucose tolerance. Cardiovasc Diabetol 2006. 5(9):4.
177. Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol 2001. 37(5):1344-1350.
178. Machado HA, Vieira M, Cunha MR, Correia MR, Fukui RT, dos Santos RF, Rocha DM, Wajchengerg BL, Lage SG, da Silva ME. Metformin, but not glimepiride, improves carotid artery diameter and blood flow in patients with type 2 diabetes mellitus. Clinics (Sao Paulo) 2012. 67(7):711-717.
179. Natali A, Baldeweg S, Toschi E, Capaldo B, Barbaro D, Gastaldelli A, Yudkin JS, Ferrannini E. Vascular effects of improving metabolic control with metformin or rosiglitazone in type 2 diabetes. Diabetes Care 2004. 27(6):1349-1357.
180. Gervois P, Fruchart JC, Staels B. Drug Insight: mechanisms of action and therapeutic applications for agonists of peroxisome proliferator-activated receptors. Nat Clin Pract Endocrinol Metab 2007. 3(2):145-156.
181. Caballero AE, Saouaf R, Lim SC, Hamdy O, AbouElenin K, O'Connor C, Logerfo FW, Horton ES, Veves A. The effects of troglitazone, an insulin-sensitizing agent, on the endothelial function in early and late type 2 diabetes: A placebo-controlled randomized clinical trial. Metabolism 2003. 52(2):173-180.
182. Suzuki M, Takamisawa I, Yoshimasa Y, Harano Y. Association between insulin resistance and endothelial dysfunction in type 2 diabetes and the effects of pioglitazone. Diabetes Res Clin 2007. 76(1):12-17.
183. Martens FM, Visseren FL, de Koning EJ, Rabelink TJ. Short-term pioglitazone treatment improves vascular function irrespective of metabolic changes in patients with type 2 diabetes. J Cardiovasc. Pharmacol 2005. 46(6):773-778.
184. Pistrosch F, Passauer J, Fischer S, Fuecker K, Hanefeld M, Gross P. In type 2 diabetes, rosiglitazone therapy for insulin resistance ameliorates endothelial dysfunction independent of glucose control. Diabetes Care 2004. 27(2):484-490.
185. Shimabukuro M, Higa N, Chinen I, Yamakawa K, Takasu N. Effects of a single administration of acarbose on postprandial glucose excursion and endothelial dysfunction in type 2 diabetic patients: a randomized crossover study. J Clin Endocrinol Metab 2006. 91(3):837-842.
186. Forst T, Weber MM, Pfutzner A. Cardiovascular benefits of GLP-1-based therapies in patients with diabetes mellitus type 2: effects on endothelial and vascular dysfunction beyond glycemic control. Exp Diabetes Res 2012. 2012:635472.
187. Koska JM, Schwartz EP, Mullin MB, Schwenke DP, Reaven PM. Improvement of postprandial endothelial function after a single dose of exenatide in individuals with impaired glucose tolerance and recent-onset type 2 diabetes. Diabetes Care 2010. 33(5):1028-1030.
188. Nystrom T, Gutniak MK, Zhang Q, Zhang F, Holst JJ, Ahren B, Sjoholm A. Effects of glucagon-like peptide1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab 2004. 287(6):E1209-E1215.
189. van Poppel PC, Netea MG, Smits P, Tack CJ. Vildagliptin improves endothelium-dependent vasodilatation in type 2 diabetes. Diabetes Care 2011. 34(9):2072-2077.
190. Hoogwerf BJ, Doshi KB, Diab D. Pramlintide, the synthetic analogue of amylin: physiology, pathophysiology, and effects on glycemic control, body weight, and selected biomarkers of vascular risk. Vasc Health and Risk Manag 2008. 4(2):355-362.
191. Ryan G, Briscoe TA, Jobe L. Review of pramlintide as adjunctive therapy in treatment of type 1 and type 2 diabetes. Drug Des Devel Ther 2008. 2:203-214.
192. Wysham C, Lush C, Zhang B, Maier H, Wilhelm K. Effect of pramlintide as an adjunct to basal insulin on markers of cardiovascular risk in patients with type 2 diabetes. Curr Med Res Opin 2007. 24(1):79-85.
193. Hardman TC, Dubrey SW. Development and potential role of type-2 sodium-glucose transporter inhibitors for management of type 2 diabetes. Diabetes Ther 2011. 2(3):133-145.
194. Kim Y, Babu AR. Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes. Diabetes Metab Syndr Obes 2012. 5:313-327.
195. Stocker R. Molecular mechanisms underlying the antiatherosclerotic and antidiabetic effects of probucol, succinobucol, and other probucol analogues. Curr Opin Lipidol 2009. 20(3):227-235.
196. Elgebaly MM, Portik-Dobos V, Sachidanandam K, Rychly D, Malcom D, Johnson M, Ergul A. Differential effects of ETA and ETB receptor antagonism on oxidative stress in type 2 diabetes. Vascul Pharmacol 2007. 47(2-3):125-130.
197. Reriani M, Raichlin E, Prasad A, Mathew V, Pumper GM, Nelson RE, Lennon R, Rihal C, Lerman LO, Lerman A. Long-term administration of endothelin receptor antagonist improves coronary endothelial function in patients with early atherosclerosis. Circulation 2010. 122(10):958-966.
198. Lu X, Bean JS, Kassab GS, Rekhter MD. Protein kinase C inhibition ameliorates functional endothelial insulin resistance and vascular smooth muscle cell hypersensitivity to insulin in diabetic hypertensive rats. Cardiovasc Diabetol 2011. 10:48.
199. Mehta NN, Sheetz M, Price K, Comiskey L, Amrutia S, Iqbal N, Mohler ER, Reilly MP. Selective PKC beta inhibition with ruboxistaurin and endothelial function in type-2 diabetes mellitus. Cardiovasc Drugs Ther 2009. 23(1):17-24.
200. Beckman JA, Goldfine AB, Goldin A, Prsic A, Kim S, Creager MA. Inhibition of protein kinase C beta does not improve endothelial function in type 2 diabetes. J Clin Endocrinol Metab 2010. 95(8):3783-3787.
201. Colhoun PH, Betteridge PD, Durrington PP, Hitaman G, Neil HA, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller J. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004. 364(9435):685-696.
202. Shepherd J, Barter P, Carema R, Deedwania P, Fruchart J, Haffner S, Hsia J, Breazna A, Larosa J, Grundy S, et al. Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: The Treating to New Targets (TNT) study. Diabetes Care 2006. 29(6):1220-1226.
203. Kearney PM, Blackwell L, Collins R, Keech A Simes J, Peto R, Armitage J, Baigent C. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008. 371:117-125.
204. Athyros VG, Papageorgiou AA, Athyrou VV, Demitriadis DS, Kontopoulos AG. Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia. Diabetes Care 2002. 25(7):1198-1202.
205. Durrington PN, Tuomilehto J, Hamann A, Kallend D, Smith K. Rosuvastatin and fenofibrate alone and in combination in type 2 diabetes patients with combined hyperlipidaemia. Diabetes Res Clin Pract 2004. 64(2):137-151.
206. Gavish D, Leibovitz E, Shapira I, Rubinstein A. Bezafibrate and simvastatin combination therapy for diabetic dyslipidaemia: efficacy and safety. J Intern Med 2000. 247(5):563-569.
207. Derosa G, Cicero AEG, Bertone G, Piccinni MN, Ciccarelli L, Roggeri DE. Comparison of fluvastatin plus fenofibrate combination therapyand fluvastatin monotherapy in the treatment of combined hyperlipidemia,type 2 diabetes mellitus, and coronary heart disease: a 12-month, randomized, double-blind, controlled trial. Clin Ther 2004. 26(10):1599-1607.
208. Hamilton SJ, Chew GT, Davis TM, Watts GF. Fenofibrate improves endothelial function in the brachial artery and forearm resistance arterioles of statin-treated type 2 diabetic patients. Clin Sci (Lond) 2010. 118(10):607-615.
209. Muhlestein JB, May HT, Jensen JR, Horne BD, Lanman RB, Lavasani F, Wolfert RL, Pearson RR, Yannicelli HD, Anderson JL. The reduction of inflammatory biomarkers by statin, fibrate, and combination therapy among diabetic patients with mixed dyslipidemia: The DIACOR (Diabetes and Combined Lipid Therapy Regimen) Study. J Am Coll Cardiol 2006. 48(2):396-401.
210. Shepherd J, Betteridge J, Van Gaal L. Nicotinic acid in the management of dyslipidaemia associated with diabetes and metabolic syndrome: a position paper developed by a European Consensus Panel. Curr Med Res Opin 2005. 21(5):665-682.
211. Toth PP, Thakker KM, Jiang P, Padley RJ. Niacin extended-release/simvastatin combination therapy produces larger favorable changes in high-density lipoprotein particles than atorvastatin monotherapy. Vasc Health Risk Manag 2012. 8:39-44.
212. Van JT, Pan J, Wasty T, Chan E, Wu X, Charles MA. Comparison of extended-release niacin and atorvastatin monotherapies and combination treatment of the atherogenic lipid profile in diabetes mellitus. Am J Cardiol 2002. 89(11):1306-1308.
213. Brown BG, Zhao X, Chait A, Fisher LD, Cheung MC, Morse JS, Dowdy AA, Marino EK, Bolson EL, Alaupovic P. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001. 345(22):1583-1592.
214. Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA. Arterial biology for the investigation of the treatment effects of reducing cholesterol (ARBITER) 2: a doubleblind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation 2004. 110(23):3512-3517.
215. Taylor A, Lee H, Sullenberger L. The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3. Curr Med Res Opin 2006. 22(11):2243-2250.
216. Taylor AJ, Villines TC, Stanek EJ, Devine PJ, Griffen L, Miller M, Weissman NJ, Turco M. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med 2009. 361(22):2113-2122.
217. Kuvin JT, Ramet ME, Patel AR, Pandian NG, Mendelsohn ME, Karas RH. A novel mechanism for the beneficial vascular effects of high-density lipoprotein cholesterol: Enhanced vasorelaxation and increased endothelial nitric oxide synthase expression. Am Heart J 2002. 144(1):165-172.
218. Warnholtz A, Wild P, Ostad MA, Elsner V, stieber F, Schinzel R, Walter U, Peetz D, Lackner K, Blankenberg S, Munzel T. Effects of oral niacin on endothelial dysfunction in patients with coronary artery disease: Results of the randomized, double-blind, placebo-controlled INEF study. Atherosclerosis 2009. 204(1):216-221.
219. Lee JM, Robson MD, Yu LM, Shirodaria CC, Cunnington C, Kylintireas I, digby JE, Bannister T, Handa A, Wiesmann F, et al. Effects of high-dose modified-release nicotinic acid on atherosclerosis and vascular function: a randomized, placebo-controlled, magnetic resonance imaging study. J Am Coll Cardiol 2009. 54(19):1787-1794.
220. Hamilton SJ, Chew GT, Davis TM, Watts GF. Niacin improves small artery vasodilatory function and compliance in statin-treated type 2 diabetic patients. Diab Vasc Dis Res 2010. 7(4):296-299.
221. Boden WE, Probstfield JK, Anderson T, Chaitman BR, Koprowicz K, Teo K, Weintraub W, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011. 365(24):2255-2267.
222. HPS2-THRIVE Collaborative Group. HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment. Eur Heart J 2013. 34:1279-1291.
223. HPS-2 THRIVE misses primary end point: no benefit of niacin/laropiprant. http://www.theheart.org/article/1490635.do.
224. Lavigne PM, Karas RH. The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression. J Am Coll Cardiol 2013. 61(4):440-446.
225. Koh KK, Quon MJ, Han SH, Ahn JY, Jin DK, Kim JS, Kim DS, Shin EK. Vascular and metabolic effects of combined therapy with ramipril and simvastatin in patients with type 2 diabetes. Hypertension 2005. 45(6):1088-1093.
226. Martin-Ventura JL, Tunon J, Duran MC, Blanco-Colio LM, Vivanco F, Egido J. Vascular protection of dual therapy (atorvastatin-amlodipine) in hypertensive patients. J Am Soc Nephrol 2006. 17(12 Suppl 3):S189-S193.
227. Koh KK, Quon MJ, Han SH, Ahn JY, Lee Y, Shin EK. Combined therapy with ramipril and simvastatin has beneficial additive effects on tissue factor activity and prothrombin fragment 1+2 in patients with type 2 diabetes. Atherosclerosis 2007. 194(1):230-237.
228. Jukema JW, Zwinderman AH, van Boven AJ, Reiber JH, Van der Laarse A, Lie KI, Bruschke AV. Evidence for a Synergistic Effect of Calcium Channel Blockers With Lipid-Lowering Therapy in Retarding Progression of Coronary Atherosclerosis in Symptomatic Patients With Normal to Moderately Raised Cholesterol Levels. Arterioscler Thromb Vasc Biol 1996. 16(3):425-430.
229. Jukema JW, Ad JB, Aeilko HZ, Arnoud VD, Albert VG. Proposed synergistic effect of calcium channel blockers with lipid-lowering therapy in retarding progression of coronary atherosclerosis. Cardiovasc Drugs and Ther 1998. 12:111-118.
230. Fogari R, Derosa G, Lazzari P, Zoppi A, Fogari E, Rinaldi A, Mugellini A. Effect of amlodipine-atorvastatin combination on fibrinolysis in hypertensive hypercholesterolemic patients with insulin resistance. Am J Hypertens 2004. 17(9):823-827.
231. Tousoulis D, Antoniades C, Vassiliadou C, Toutouza M, Pitsavos C, Tentolouris C, Trikas A, Stefanadis C. Effects of combined administration of low dose atorvastatin and vitamin E on inflammatory markers and endothelial function in patients with heart failure. Eur J Heart Fail 2005. 7(7):1126-1132.
232. Watts GF, Castelluccio C, Rice-Evans C, Taub NA, Baum H, Quinn PJ. Plasma coenzyme Q (ubiquinone) concentrations in patients treated with simvastatin. J Clin Pathol 1993. 46(11):1055-1057.
233. Littarru GP, Langsjoen P. Coenzyme Q10 and statins: Biochemical and clinical implications. Mitochondrion 2007.7(Supplement 1):S168-S174.
234. Hamilton SJ, Chew GT, Watts GF. Coenzyme Q10 improves endothelial dysfunction in statin-treated type 2 diabetic patients. Diabetes Care 2009. 32(5):810-812.
235. Tiano L, Belardinelli R, Carnevali P, Principi F, Seddaiu G, Littarru GP. Effect of coenzyme Q10 administration on endothelial function and extracellular superoxide dismutase in patients with ischaemic heart disease: a doubleblind, randomized controlled study. Eur Heart J 2007. 28(18):2249.
236. Fleg JL, Mete M, Howard BV, Umans JG, roman MJ, Ratner RE, Silverman A, Galloway JM, Henderson JA, Weir MR, et al. Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis in type 2 diabetes: The SANDS (Stop Atherosclerosis in Native Diabetics Study) Trial. J Am Coll Cardiol 2008. 52(25):2198-2205.
237. Bosch J, Gerstein HC, Dagenais GR, Diaz R, Dyal L, Jung H, Maggiono AP, Probstfield J, Riddle MC, Ryden LE, et al. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med 2012. 367(4):309-318.
238. Clinical Trials.gov. A Study of AMR101 to evaluate its ability to reduce cardiovascular events in high risk patients with hypertriglyceridemia and on statin (REDUCE-IT). http://clinicaltrials.gov/show/NCT01492361.
239. Kastelein JJP, Duivenvoorden R, Deanfield J, do Groot E, Judema JW, Kaski J, Munzel T, Taddei S, Lehnert V, Burgess T, et al. Rationale and design of dalVESSEL: a study to assess the safety and efficacy of dalcetrapib on endothelial function using brachial artery flowmediated vasodilatation. Curr Med Res Opin 2011. 27(1):141-150.
240. Luescher TF, Taddei S, Kaski J, Jukema JW, Kallend D, Munzel t, Kastelein JJ, Deanfield JE, dal-VESSEL investigators. dal-VESSEL: Efficacy and safety of dalcetrapib in patients with or at risk of coronary heart disease - the dal-VESSEL trial. Conference abstract. http://www.escardio.org/congresses/esc-2011/congress-reports/Pages/706-3-dal-VESSEL.aspx#presenter. Accessed 13/01/12.
241. Fayad ZA, Mani V, Woodward M, Kallend D, Abt M, Burgess T, Fuster V, Ballantyne CM, Stein EA, Tardif J, et al. Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial. Lancet 2011. 378:1547-1559.