Cardiovascular effects of the thiazolidinediones

Diabetes/Metabolism Research and Reviews

Volumn 22, Issue 2, 2006, Pages 88-97

  Qayyum, Rehan ^a,b   Schulman, Peter ^a  

^a UNIVERSITY OF CONNECTICUT HEALTH CENTER   (United States)

^b NONE   (United States)

Author keywords

Atherosclerosis; Congestive heart failure; Hypertension; Pioglitazone; Rosiglitazone

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ANTIDIABETIC AGENT; GLIBENCLAMIDE; INSULIN; METFORMIN; ORAL ANTIDIABETIC AGENT; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PIOGLITAZONE; PLACEBO; ROSIGLITAZONE; SULFONYLUREA; TRANSCRIPTION FACTOR; TROGLITAZONE;

ATHEROGENESIS; BLOOD PRESSURE REGULATION; CARDIOVASCULAR DISEASE; CARDIOVASCULAR EFFECT; CHRONIC DRUG ADMINISTRATION; CLINICAL TRIAL; CONGESTIVE HEART FAILURE; CORONARY ARTERY ATHEROSCLEROSIS; DIABETIC HYPERTENSION; DISEASE EXACERBATION; DRUG POTENTIATION; DRUG RECEPTOR BINDING; EVIDENCE BASED MEDICINE; FLUID RETENTION; FOOT EDEMA; GENE EXPRESSION REGULATION; HEART ARRHYTHMIA; HEART FAILURE; HEART LEFT VENTRICLE HYPERTROPHY; HEART LEFT VENTRICLE MASS; HEART MUSCLE ISCHEMIA; HEART PROARRHYTHMIA; HEART PROTECTION; HUMAN; HYPERTENSION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PERIPHERAL EDEMA; PHARMACOGENETICS; PRIORITY JOURNAL; REPERFUSION INJURY; REVIEW; SIDE EFFECT; TISSUE DISTRIBUTION;

ATHEROSCLEROSIS; DIABETES MELLITUS, TYPE 2; DIABETIC ANGIOPATHIES; HEART FAILURE, CONGESTIVE; HUMANS; HYPERTENSION; HYPOGLYCEMIC AGENTS; MYOCARDIAL ISCHEMIA; RISK FACTORS; THIAZOLIDINEDIONES; VENTRICULAR FUNCTION, LEFT;

EID: 33644981038     PISSN: 15207552     EISSN: 15207560     Source Type: Journal    
DOI: 10.1002/dmrr.596     Document Type: Review

References (107)

1. De Backer G, Ambrosioni E, Borch-Johnsen K, et al. European Society of Cardiology Committee for Practice Guidelines. European guidelines on cardiovascular disease prevention in clinical practice: third joint task force of European and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of eight societies and by invited experts). Eur J Cardiovasc Prev Rehabil 2003; 10(Suppl. 1): S1-S78.
2. American Heart Association. Heart Disease and Stroke Statistics - 2005 Update. American Heart Association: Dallas, TX, 2005; ©2005, American Heart Association.
3. Haffner SM. Coronary heart disease in patients with diabetes. N Engl J Med 2000; 342: 1040-1042.
4. Haffner SM, Mykkanen L, Festa A, Burke JP, Stern MP. Insulin-resistant prediabetic subjects have more atherogenic risk factors than insulin-sensitive prediabetic subjects: implications for preventing coronary heart disease during the prediabetic state. Circulation 2000; 101: 975-980.
5. Haffner SM, Miettinen H, Gaskill SP, Stern MP. Decreased insulin secretion and increased insulin resistance are independently related to the 7-year risk of NIDDM in Mexican-Americans. Diabetes 1995; 44: 1386-1391.
6. Spiegelman BM. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes 1998; 47: 507-514.
7. Barbier O, Torra IP, Duguay Y, et al. Pleiotropic actions of peroxisome proliferator-activated receptors in lipid metabolism and atherosclerosis. Arterioscler Thromb Vasc Biol 2002; 22: 717-726. doi:10.1161/01.ATV.0000015598.86369.04.
8. Carretero OA, Oparil S. Essential hypertension. Part I: definition and etiology. Circulation 2000; 101: 329-335.
9. Ferrannini E, Natali A, Capaldo B, Lehtovirta M, Jacob S, Yki-Järvinen H, European Group for the Study of Insulin Resistance (EGIR). Insulin resistance, hyperinsulinemia, and blood pressure: role of age and obesity. Hypertension 1997; 30: 1144-1149.
10. Natali A, Baldeweg S, Toschi E, et al. Vascular effects of improving metabolic control with metformin or rosiglitazone in type 2 diabetes. Diabetes Care 2004; 27: 1349-1357.
11. Diep QN, El Mabrouk M, Cohn JS, et al. Structure, endothelial function, cell growth, and inflammation in blood vessels of angiotensin II-infused rats: role of peroxisome proliferator-activated receptor-gamma. Circulation 2002; 105: 2296-2302. doi:10.1161/01.CIR.0000016049.86468.23.
12. Wu L, Wang R, De Champlain J, Wilson TW. Beneficial and deleterious effects of rosiglitazone on hypertension development in spontaneously hypertensive rats. Am J Hypertens 2004; 17: 749-756. doi:10.1016/ j.amjhyper.2004.04.010.
13. St John Sutton M, Rendell M, Dandona P, et al. A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type 2 diabetes. Diabetes Care 2002; 25: 2058-2064.
14. Sung BH, Izzo JL Jr, Dandona P, Wilson ME. Vasodilatory effects of troglitazone improve blood pressure at rest and during mental stress in type 2 diabetes mellitus. Hypertension 1999; 34: 83-88.
15. Raji A, Seely EW, Bekins SA, Williams GH, Simonson DC. Rosiglitazone improves insulin sensitivity and lowers blood pressure in hypertensive patients. Diabetes Care 2003; 26: 172-178.
16. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322: 1561-1566.
17. Ilercil A, Devereux RB, Roman MJ, et al. Relationship of impaired glucose tolerance to left ventricular structure and function: The Strong Heart Study. Am Heart J 2001; 141: 992-998.
18. Lind L, Andersson PE, Andren B, Hanni A, Lithell HO. Left ventricular hypertrophy in hypertension is associated with the insulin resistance metabolic syndrome. J Hypertens 1995; 13: 433-438.
19. Sundstrom J, Lind L, Nystrom N, et al. Left ventricular concentric remodeling rather than left ventricular hypertrophy is related to the insulin resistance syndrome in elderly men. Circulation 2000; 101: 2595-2600.
20. Yamamoto K, Ohki R, Lee RT, Ikeda U, Shimada K. Peroxisome proliferator-activated receptor gamma activators inhibit cardiac hypertrophy in cardiac myocytes. Circulation 2001; 104: 1670-1675.
21. Asakawa M, Takano H, Nagai T, et al. Peroxisome proliferator activated receptor-γ plays a critical role in inhibition of cardiac hypertrophy in vitro and in vivo. Circulation 2002; 105: 1240-1246. doi:10.1161/ hc1002.105225.
22. Sakai S, Miyauchi T, Irukayama-Tomobe Y, Ogata T, Goto K, Yamaguchi I. Peroxisome proliferator-activated receptor-γ activators inhibit endothelin-1-related cardiac hypertrophy in rats. Clin Sci (Lond) 2002; 103: 16S-20S.
23. Takano H, Nagai T, Asakawa M, et al. Peroxisome proliferator-activated receptor activators inhibit lipopolysaccharide-induced tumor necrosis factor-alpha expression in neonatal rat cardiac myocytes. Circ Res 2002; 87: 596-602.
24. Ghazzi MN, Perez JE, Antonucci TK, et al., The Troglitazone Study Group. Cardiac and glycemic benefits of troglitazone treatment in NIDDM. Diabetes 1997; 46: 433-439.
25. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation 2002; 106: 3143-3421.
26. Ayyobi AF, Brunzell JD. Lipoprotein distribution in the metabolic syndrome, type 2 diabetes mellitus, and familial combined hyperlipidemia. Am J Cardiol 2003; 92: 27J-33J. doi:10.1016/ S0002-9149(03)00613-1.
27. Florkowski CM. Management of co-existing diabetes mellitus and dyslipidemia: defining the role of thiazolidinediones. Am J Cardiovasc Drugs 2002; 2: 15-21.
28. Fonseca VA. Management of diabetes mellitus and insulin resistance in patients with cardiovascular disease. Am J Cardiol 2003; 92: 50J-60J. doi:10.1016/S0002-9149(03)00616-7.
29. Kopp HP, Kopp CW, Festa A, 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: 1042-1047. doi:10.1161/01.ATV.0000073313.16135.21.
30. Varo N, Vicent D, Libby P, et al. Elevated plasma levels of the atherogenic mediator soluble CD40 ligand in diabetic patients. A novel target of thiazolidinediones. Circulation 2003; 107: 2664-2669. doi:10.1161/01.CIR.0000074043.46437.44.
31. Takata Y, Kitami Y, Yang ZH, Nakamura M, Okura T, Hiwada K. Vascular inflammation is negatively autoregulated by interaction between CCAAT/ enhancer-binding protein-delta and peroxisome proliferator-activated receptor-gamma. Circ Res 2002; 91: 427-433. doi:10.1161/ 01.RES.0000031271 20771.4F.
32. Ridker PM, Rifai N, Pfeffer M, Sacks F, Lepage S, Braunwald E. Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation 2000; 101: 2149-2153.
33. Marx N, Imhof A, Froehlich J, et al. Effect of rosiglitazone treatment on soluble CD40L in patients with type 2 diabetes and coronary artery disease. Circulation 2003; 107: 1954-1957. doi:10.1161/ 01.CIR.0000069272.06194.91.
34. Schonbeck U, Varo N, Libby P, Buring J, Ridker PM. Soluble CD40L and cardiovascular risk in women. Circulation 2001; 104: 2266-2268.
35. Eckel RH, Wassef M, Chait A, et al. Prevention conference VI: diabetes and cardiovascular disease. Writing Group II: pathogenesis of atherosclerosis in diabetes. Circulation 2002; 105: e138-e143.
36. Glass CK. Antiatherogenic effects of thiazolidinediones? Arterioscler Thromb Vasc Biol 2001; 21: 295-296.
37. Wang N, Verna L, Chen NG. et al. Constitutive activation of peroxisome proliferator-activated receptor-gamma suppresses pro-inflammatory adhesion molecules in human vascular endothelial cells. J Biol Chem 2002; 277: 34176-34181. doi:10.1074/jbc.M203436200.
38. Delerive P, Martin-Nizard F, Chinetti G, et al. Peroxisome proliferator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway. Circ Res 1999; 85: 394-402.
39. Hannan KM, Dilley RJ, de Dios ST, Little PJ. Troglitazone stimulates repair of the endothelium and inhibits neointimal formation in denuded rat aorta. Arterioscler Thromb Vasc Biol 2003; 23: 762-768. doi:10.1161/ 01.ATV.0000069210.46539.0D.
40. Murao K, Imachi H, Momoi A, et al. Thiazolidinedione inhibits the production of monocyte chemoattractant protein-1 in cytokine-treated human vascular endothelial cells. FEBS Lett 1999; 454: 27-30.
41. Kwak BR, Myit S, Mulhaupt F, et al. PPARgamma but not PPARalpha ligands are potent repressors of major histocompatibility complex class II induction in atheroma-associated cells. Circ Res 2002; 90: 356-362. doi:10.1161/hh0302.104924.
42. Calnek DS, Mazzella L, Roser S, Roman J, Hart CM. Peroxisome proliferator-activated receptor gamma ligands increase release of nitric oxide from endothelial cells. Arterioscler Thromb Vasc Biol 2003; 23: 52-57. doi:10.1161/01.ATV.0000044461.01844.C9.
43. Bishop-Bailey D, Hla T. Endothelial cell apoptosis induced by the peroxisome proliferator-activated receptor (PPAR) ligand 15-deoxy-Delta12, 14-prostaglandin J2. J Biol Chem 1999; 274: 17 042-17 048.
44. Xin X, Yang S, Kowalski J, Gerritsen ME. Peroxisome proliferator-activated receptor gamma-ligands are potent inhibitors of angiogenesis in vitro and in vivo. J Biol Chem 1999; 274: 9116-9121.
45. Walker AB, Chattington PD, Buckingham RE, Williams G. The thiazolidinedione rosiglitazone (BRL-49653) lowers blood pressure and protects against impairment of endothelial function in Zucker fatty rats. Diabetes 1999; 48: 1448-1453.
46. Garg R, Kumbkarni Y, Aljada A, et al. Troglitazone reduces reactive oxygen species generation by leukocytes and lipid peroxidation and improves flow-mediated vasodilatation in obese subjects. Hypertension 2000; 36: 430-435.
47. Paradisi G, Steinberg HO, Shepard MK, Hook G, Baron AD. Troglitazone therapy improves endothelial function to near normal levels in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003; 88: 576-580.
48. Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med 1999; 340: 115-126.
49. Han KH, Chang MK, Boullier A, et al. Oxidized LDL reduces monocyte CCR2 expression through pathways involving peroxisome proliferator-activated receptor gamma. J Clin Invest 2000; 106: 793-802.
50. Jiang C, Ting AT, Seed B. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 1998; 391: 82-86.
51. Tontonoz P, Nagy L, Alvarez JG, Thomazy VA, Evans RM. PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 1998; 93: 241-252.
52. Febbraio M, Podrez EA, Smith JD, et al. Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J Clin Invest 2000; 105: 1049-1056.
53. Ibrahimi A, Bonen A, Blinn WD, et al. Muscle-specific overexpression of FAT/CD36 enhances fatty acid oxidation by contracting muscle, reduces plasma triglycerides and fatty acids, and increases plasma glucose and insulin. J Biol Chem 1999; 274: 26 761-26 766.
54. Law RE, Goetze S, Xi XP, et al. Expression and function of PPARgamma in rat and human vascular smooth muscle cells. Circulation 2000; 101: 1311-1318.
55. Law RE, Meehan WP, Xi XP, et al. Troglitazone inhibits vascular smooth muscle cell growth and intimal hyperplasia. J Clin Invest 1996; 98: 1897-1905.
56. Dubey RK, Zhang HY, Reddy SR, Boegehold MA, Kotchen TA. Pioglitazone attenuates hypertension and inhibits growth of renal arteriolar smooth muscle in rats. Am J Physiol 1993; 265: R726-R732.
57. Phillips JW, Barringhaus KG, Sanders JM, et al. Rosiglitazone reduces the accelerated neointima formation after arterial injury in a mouse injury model of type 2 diabetes. Circulation 2003; 108: 1994-1999. doi:10.1161/01.CIR.0000092886.52404.50.
58. Bruemmer D, Yin F, Liu J, et al. Regulation of the growth arrest and DNA damage-inducible gene 45 (GADD45) by peroxisome proliferator-activated receptor gamma in vascular smooth muscle cells. Circ Res 2003; 93: e38-e47. doi:10.1161/01.RES.0000088344.15288.E6.
59. Aizawa Y, Kawabe J, Hasebe N, Takehara N, Kikuchi K. Pioglitazone enhances cytokine-induced apoptosis in vascular smooth muscle cells and reduces intimal hyperplasia. Circulation 2001; 104: 455-460.
60. Galis ZS, Muszynski M, Sukhova GK, et al. Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. Circ Res 1994; 75: 181-189.
61. Silva JA, Escobar A, Collins TJ, Ramee SR, White CJ. Unstable angina. A comparison of angioscopic findings between diabetic and nondiabetic patients. Circulation 1995; 92: 1731-1736.
62. Marx N, Froehlich J, Siam L, et al. Antidiabetic PPAR gamma-activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2003; 23: 283-288. doi:10.1161/01.ATV.0000054195.35121.5E.
63. Game BA, Xu M, Lopes-Virella MF, Huang Y. Regulation of MMP-1 expression in vascular endothelial cells by insulin sensitizing thiazolidinediones. Atherosclerosis 2003; 169: 235-243. doi:10.1016/S0021-9150(03)00165-5.
64. Lyon CJ, Hsueh WA. Effect of plasminogen activator inhibitor-1 in diabetes mellitus and cardiovascular disease. Am J Med 2003; 115: 62S-68S. doi:10.1016/j.amjmed.2003.08.014.
65. Thogersen AM, Jansson JH, Boman K, et al. High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor. Circulation 1998; 98: 2241-2247.
66. Zirlik A, Leugers A, Lohrmann J, et al. Direct attenuation of plasminogen activator inhibitor type-1 expression in human adipose tissue by thiazolidinediones. Thromb Haemost 2004; 91: 674-682.
67. Nordt TK, Peter K, Bode C, Sobel BE. Differential regulation by troglitazone of plasminogen activator inhibitor type 1 in human hepatic and vascular cells. J Clin Endocrinol Metab 2000; 85: 1563-1568.
68. Lehmann ED, Hopkins KD, Rawesh A, et al. Relation between number of cardiovascular risk factors/events and noninvasive Doppler ultrasound assessments of aortic compliance. Hypertension 1998; 32: 565-569.
69. Boutouyrie P, Tropeano AI, Asmar R, et al. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study. Hypertension 2002; 39: 10-15.
70. Satoh N, Ogawa Y, Usui T, et al. Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect. Diabetes Care 2003; 26: 2493-2499.
71. Shargorodsky M, Wainstein G, Gavish E, Leibovitz Z, Matas D, Zimlichman R. Treatment with rosiglitazone reduces hyperinsulinemia and improves arterial elasticity in patients with type 2 diabetes mellitus. Am J Hypertens 2003; 16: 617-622.
72. Hodis HN, Mack WJ, LaBree L, et al. The role of carotid arterial intima-media thickness in predicting clinical coronary events. Ann Intern Med 1998; 128: 262-269.
73. Minamikawa J, Tanaka S, Yamauchi M, Inoue D, Koshiyama H. Potent inhibitory effect of troglitazone on carotid arterial wall thickness in type 2 diabetes. J Clin Endocrinol Metab 1998; 83: 1818-1820.
74. 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: 3452-3456.
75. Takagi T, Yamamuro A, Tamita K, et al. Pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus: an intravascular ultrasound scanning study. Am Heart J 2003; 146: E5. doi:10.1016/S0002-8703(03)00146-7.
76. Yue Tl TL, Chen J, Bao W, et al. In vivo myocardial protection from ischemia/reperfusion injury by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. Circulation 2001; 104: 2588-2594.
77. Wayman NS, Hattori Y, McDonald MC, et al. Ligands of the peroxisome proliferator-activated receptors (PPAR-γ and PPAR-α) reduce myocardial infarct size. FASEB J 2002; 16: 1027-1040.
78. Ito H, Nakano A, Kinoshita M, Matsumori A. Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates myocardial ischemia/reperfusion injury in a rat model. Lab Invest 2003; 83: 1715-1721.
79. Khandoudi N, Delerive P, Berrebi-Bertrand I, Buckingham RE, Staels B, Bril A. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma, inhibits the jun nh(2)-terminal kinase/activating protein 1 pathway and protects the heart from ischemia/reperfusion injury. Diabetes 2002; 51: 1507-1514.
80. Zhu P, Lu L, Xu Y, Schwartz GG. Troglitazone improves recovery of left ventricular function after regional ischemia in pigs. Circulation 2000; 101: 1165-1171.
81. Xu Y, Lu L, Greyson C, et al. Deleterious effects of acute treatment with a peroxisome proliferator-activated receptor-γ activator in myocardial ischemia and reperfusion in pigs. Diabetes 2003; 52: 1187-1194.
82. Kelly DP. PPARs of the heart: three is a crowd. Circ Res 2003; 92: 482-484.
83. Narula J, Haider N, Virmani R, et al. Apoptosis in myocytes in end-stage heart failure. N Engl J Med 1996; 335: 1182-1189.
84. Li Y, Cohen R. Caspase inhibitors and myocardial apoptosis. Int Anesthesiol Clin 2005; 43: 77-89.
85. Liu HR, Tao L, Gao E, et al. Anti-apoptotic effects of rosiglitazone in hypercholesterolemic rabbits subjected to myocardial ischemia and reperfusion. Cardiovasc Res 2004; 62(1): 135-144.
86. Murray DR, Freeman GL. Proinflammatory cytokines: predictors of a failing heart? Circulation 2003; 107: 1460-1462.
87. Shiomi T, Tsutsui H, Hayashidani S, et al. Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation 2002; 106: 3126-3132. doi:10.1161/ 01.CIR.0000039346.31538.2C.
88. Frantz S, Hu K, Widder J, et al. Peroxisome proliferator activated-receptor agonism and left ventricular remodeling in mice with chronic myocardial infarction. Br J Pharmacol 2004; 141: 9-14. doi: 10.1038/sj.bjp.0705585.
89. Nesto RW, Bell D, Bonow RO, American Heart Association; American Diabetes Association. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Circulation 2003; 108: 2941-2948.
90. Delea TE, Edelsberg JS, Hagiwara M, Oster G, Phillips LS. Use of thiazolidinediones and risk of heart failure in people with type 2 diabetes: a retrospective cohort study. Diabetes Care 2003; 26: 2983-2989.
91. Masoudi FA, Inzucchi SE, Wang Y, Havranek EP, Foody JM, Krumholz HM. Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study. Circulation 2005; 111(5): 583-590.
92. Charbonnel B, Dormandy J, Erdmann E, Massi-Benedetti M, Skene A, PROactive Study Group. The prospective pioglitazone clinical trial in macrovascular events (PROactive): can pioglitazone reduce cardiovascular events in diabetes? Study design and baseline characteristics of 5238 patients. Diabetes Care 2004; 27: 1647-1653.
93. Fullert S, Schneider F, Haak E, et al. Effects of pioglitazone in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study. J Clin Endocrinol Metab 2002; 87: 5503-5506.
94. Yosefy C, Magen E, Kiselevich A, et al. Rosiglitazone improves, while Glibenclamide worsens blood pressure control in treated hypertensive diabetic and dyslipidemic subjects via modulation of insulin resistance and sympathetic activity. J Cardiovasc Pharmacol 2004; 44: 215-222.
95. Patel J, Anderson RJ, Rappaport EB. Rosiglitazone monotherapy improves glycaemic control in patients with type 2 diabetes: a twelve-week, randomized, placebo-controlled study. Diabetes Obes Metab 1999; 1: 165-172. doi:10.1046/j.1463-1326.1999.00020.x.
96. Lebovitz HE, Dole JF, Patwardhan R, Rappaport EB, Freed MI, Rosiglitazone Clinical Trials Study Group. Rosiglitazone monotherapy is effective in patients with type 2 diabetes. J Clin Endocrinol Metab 2001; 86: 280-288.
97. Barnett AH, Grant PJ, Hitman GA, Indo-Asian Trial Investigators. Rosiglitazone in Type 2 diabetes mellitus: an evaluation in British Indo-Asian patients. Diabet Med 2003; 20: 387-393. doi:10.1046/ j.1464-5491.2003.00925.x.
98. Kipnes MS, Krosnick A, Rendell MS, Egan JW, Mathisen AL, Schneider RL. Pioglitazone hydrochloride in combination with sulfonylurea therapy improves glycemic control in patients with type 2 diabetes mellitus: a randomized, placebo-controlled study. Am J Med 2001; 111: 10-17. doi:10.1016/S0002-9343(01)00713-6.
99. Herz M, Johns D, Reviriego J, et al. A randomized, double-blind, placebo-controlled, clinical trial of the effects of pioglitazone on glycemic control and dyslipidemia in oral antihyperglycemic medication-naive patients with type 2 diabetes mellitus. Clin Ther 2003; 25: 1074-1095. doi:10.1016/S0149-2918(03)80068-1.
100. Einhorn D, Rendell M, Rosenzweig J, Egan JW, Mathisen AL, Schneider RL, The Pioglitazone 027 Study Group. Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, placebo-controlled study. Clin Ther 2000; 22: 1395-1409. doi:10.1016/S0149-2918(00)83039-8.
101. 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: 679-684. doi:10.1161/01.CIR.0000025403.20953.23.
102. Wang TD, Chen WJ, Lin JW, Chen MF, Lee YT. Effects of rosiglitazone on endothelial function, C-reactive protein, and components of the metabolic syndrome in nondiabetic patients with the metabolic syndrome. Am J Cardiol 2004; 93: 362-365. doi:10.1016/j.amjcard. 2003.10.022.
103. Sidhu JS, Cowan D, Kaski JC. The effects of rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, on markers of endothelial cell activation, C-reactive protein, and fibrinogen levels in non-diabetic coronary artery disease patients. J Am Coll Cardiol 2003; 42: 1757-1763. doi:10.1016/j.jacc.2003.04.001.
104. Ghanim H, Garg R, Aljada A, et al. Suppression of nuclear factor-kappaB and stimulation of inhibitor kappaB by troglitazone: evidence for an anti-inflammatory effect and a potential antiatherosclerotic effect in the obese. J Clin Endocrinol Metab 2001; 86: 1306-1312.
105. Mohanty P, Aljada A, Ghanim H, et al. Evidence for a potent antiinflammatory effect of rosiglitazone. J Clin Endocrinol Metab 2004; 89: 2728-2735.
106. Choi D, Kim SK, Choi SH, et al. Preventative effects of rosiglitazone on restenosis after coronary stent implantation in patients with type 2 diabetes. Diabetes Care 2004; 27: 2654-2660.
107. Xiang AH, Peters RK, Kjos SL, et al. Effect of thiazolidinedione treatment on progression of subclinical atherosclerosis in premenopausal women at high risk for type 2 diabetes. J Clin Endocrinol Metab 2005; 90: 1986-1991.