on July 15, 2002
Circulation. 2002
Published online before print July 15, 2002, doi: 10.1161/01.CIR.0000025403.20953.23
Published online before print July 15, 2002, doi: 10.1161/01.CIR.0000025403.20953.23
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Submitted on March 21, 2002
From University of Texas Health Science Center at San Antonio (S.M.H., K.W.), San Antonio, Tex; Tufts-New England Medical Center (A.S.G.), Boston, Mass; and GlaxoSmithKline (W.M.W., H.C., M.I.F.), Collegeville, Philadelphia, Pa. * To whom correspondence should be addressed. E-mail: haffner{at}uthscsa.edu.
Background—Markers of systemic inflammation (eg, C-reactive protein [CRP] and interleukin-6 [IL-6]) have been proposed to be "nontraditional" risk factors for cardiovascular disease in patients with type 2 diabetes mellitus. Matrix metalloproteinase-9 (MMP-9) has been implicated in the pathogenesis of atherosclerotic plaque rupture, which raises the possibility of the use of MMP-9 levels as a marker for future myocardial infarction or unstable angina. In vitro and animal studies suggest that thiazolidinediones can reduce the expression of these markers. The purpose of this analysis was to determine whether rosiglitazone alters serum concentrations of CRP, IL-6, MMP-9, and white blood cell count (WBC) and to examine the relationship of these effects with demographic and disease variables. Methods and Results—CRP, IL-6, MMP-9, and WBC were analyzed from stored frozen serum samples obtained from patients with type 2 diabetes who completed a 26-week randomized, double-blind, placebo-controlled study. After 26 weeks of rosiglitazone treatment, the percentage reductions in mean CRP, MMP-9, and WBC levels were statistically significant compared with baseline and placebo (P<0.01). The percentage reduction in mean IL-6 was small and similar in the rosiglitazone and placebo groups. The change in each inflammatory marker from baseline to week 26 was significantly correlated (P<0.05) with each of the other markers, as well as with the homeostasis model assessment estimate of insulin resistance. Conclusions—Rosiglitazone reduces serum levels of MMP-9 and the proinflammatory marker CRP in patients with type 2 diabetes, which indicates potentially beneficial effects on overall cardiovascular risk.
Revised on May 22, 2002
Accepted on May 23, 2002
Effect of Rosiglitazone Treatment on Nontraditional Markers of Cardiovascular Disease in Patients With Type 2 Diabetes Mellitus
Steven M. Haffner MD*,
Key words: atherosclerosis • cardiovascular diseases • diabetes mellitus • inflammation • risk factors
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S. E. Inzucchi, F. A. Masoudi, Y. Wang, M. Kosiborod, J. M. Foody, J. F. Setaro, E. P. Havranek, and H. M. Krumholz Insulin-Sensitizing Antihyperglycemic Drugs and Mortality After Acute Myocardial Infarction: Insights from the National Heart Care Project Diabetes Care, July 1, 2005; 28(7): 1680 - 1689. [Abstract] [Full Text] [PDF]
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 H. Zhang, A. Zhang, D. E. Kohan, R. D. Nelson, F. J. Gonzalez, and T. Yang Collecting duct-specific deletion of peroxisome proliferator-activated receptor {gamma} blocks thiazolidinedione-induced fluid retention PNAS, June 28, 2005; 102(26): 9406 - 9411. [Abstract] [Full Text] [PDF]
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A. Pfutzner, N. Marx, G. Lubben, M. Langenfeld, D. Walcher, T. Konrad, and T. Forst Improvement of Cardiovascular Risk Markers by Pioglitazone Is Independent From Glycemic Control: Results From the Pioneer Study J. Am. Coll. Cardiol., June 21, 2005; 45(12): 1925 - 1931. [Abstract] [Full Text] [PDF]
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P. M. Ridker, D. A. Morrow, L. M. Rose, N. Rifai, C. P. Cannon, and E. Braunwald Relative Efficacy of Atorvastatin 80 mg and Pravastatin 40 mg in Achieving the Dual Goals of Low-Density Lipoprotein Cholesterol <70 mg/dl and C-Reactive Protein <2 mg/l: An Analysis of the PROVE-IT TIMI-22 Trial J. Am. Coll. Cardiol., May 17, 2005; 45(10): 1644 - 1648. [Abstract] [Full Text] [PDF]
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M.R. Langenfeld, T. Forst, C. Hohberg, P. Kann, G. Lubben, T. Konrad, S.D. Fullert, C. Sachara, and A. Pfutzner Pioglitazone Decreases Carotid Intima-Media Thickness Independently of Glycemic Control in Patients With Type 2 Diabetes Mellitus: Results From a Controlled Randomized Study Circulation, May 17, 2005; 111(19): 2525 - 2531. [Abstract] [Full Text] [PDF]
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 A. H. Berg and P. E. Scherer Adipose Tissue, Inflammation, and Cardiovascular Disease Circ. Res., May 13, 2005; 96(9): 939 - 949. [Abstract] [Full Text] [PDF]
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B. Cariou, J.-C. Fruchart, and B. Staels Review: Vascular protective effects of peroxisome proliferator-activated receptor agonists The British Journal of Diabetes & Vascular Disease, May 1, 2005; 5(3): 126 - 132. [Abstract] [PDF]
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The Diabetes Prevention Program Research Group Intensive Lifestyle Intervention or Metformin on Inflammation and Coagulation in Participants With Impaired Glucose Tolerance Diabetes, May 1, 2005; 54(5): 1566 - 1572. [Abstract] [Full Text] [PDF]
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S. B. Kritchevsky, M. Cesari, and M. Pahor Inflammatory markers and cardiovascular health in older adults Cardiovasc Res, May 1, 2005; 66(2): 265 - 275. [Abstract] [Full Text] [PDF]
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B. Kimmel and S. E. Inzucchi Oral Agents for Type 2 Diabetes: An Update Clin. Diabetes, April 1, 2005; 23(2): 64 - 76. [Abstract] [Full Text] [PDF]
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A. H. Xiang, R. K. Peters, S. L. Kjos, C. Ochoa, A. Marroquin, J. Goico, S. Tan, C. Wang, S. P. Azen, C.-r. Liu, 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., April 1, 2005; 90(4): 1986 - 1991. [Abstract] [Full Text] [PDF]
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 E. M. Stuveling, S. J. L. Bakker, H. L. Hillege, P. E. de Jong, R. O. B. Gans, and D. de Zeeuw Biochemical risk markers: a novel area for better prediction of renal risk? Nephrol. Dial. Transplant., March 1, 2005; 20(3): 497 - 508. [Full Text] [PDF]
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N. P. Kadoglou, S. S. Daskalopoulou, D. Perrea, and C. D. Liapis Matrix Metalloproteinases and Diabetic Vascular Complications Angiology, March 1, 2005; 56(2): 173 - 189. [Abstract] [PDF]
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 E. L. Schiffrin Peroxisome proliferator-activated receptors and cardiovascular remodeling Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1037 - H1043. [Abstract] [Full Text] [PDF]
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A. V. Finn, I. F. Palacios, A. Kastrati, and H. K. Gold Drug-eluting stents for diabetes mellitus: A rush to judgment? J. Am. Coll. Cardiol., February 15, 2005; 45(4): 479 - 483. [Abstract] [Full Text] [PDF]
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F. A. Masoudi, S. E. Inzucchi, Y. Wang, E. P. Havranek, J. M. Foody, and H. M. Krumholz Thiazolidinediones, Metformin, and Outcomes in Older Patients With Diabetes and Heart Failure: An Observational Study Circulation, February 8, 2005; 111(5): 583 - 590. [Abstract] [Full Text] [PDF]
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J. W Chu, F. Abbasi, C. Lamendola, T. McLaughlin, G. M Reaven, and P. S Tsao Effect of rosiglitazone treatment on circulating vascular and inflammatory markers in insulin-resistant subjects Diabetes and Vascular Disease Research, February 1, 2005; 2(1): 37 - 41. [Abstract] [PDF]
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S. S. Signorelli, G. Malaponte, M. Libra, L. D. Pino, G. Celotta, V. Bevelacqua, M. Petrina, G. S Nicotra, M. Indelicato, P. M Navolanic, et al. Plasma levels and zymographic activities of matrix metalloproteinases 2 and 9 in type II diabetics with peripheral arterial disease Vascular Medicine, February 1, 2005; 10(1): 1 - 6. [Abstract] [PDF]
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A. Tedgui The role of inflammation in atherothrombosis: implications for clinical practice Vascular Medicine, February 1, 2005; 10(1): 45 - 53. [Abstract] [PDF]
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M. Recasens, A. Lopez-Bermejo, W. Ricart, J. Vendrell, R. Casamitjana, and J. M. Fernandez-Real An Inflammation Score Is Better Associated with Basal than Stimulated Surrogate Indexes of Insulin Resistance J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 112 - 116. [Abstract] [Full Text] [PDF]
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 M. A. Crowther Pathogenesis of Atherosclerosis Hematology, January 1, 2005; 2005(1): 436 - 441. [Abstract] [Full Text] [PDF]
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W.H. W. Tang and A. M. Lincoff Diabetes, Coronary Intervention, and Platelet Glycoprotein IIb/IIIa Blockade: The Triad Revisited Circulation, December 14, 2004; 110(24): 3618 - 3620. [Full Text] [PDF]
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P. R. Moreno and V. Fuster The year in atherothrombosis J. Am. Coll. Cardiol., December 7, 2004; 44(11): 2099 - 2110. [Full Text] [PDF]
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G. Schernthaner, D. R. Matthews, B. Charbonnel, M. Hanefeld, P. Brunetti, and on Behalf of the Quarter Study Group Efficacy and Safety of Pioglitazone Versus Metformin in Patients with Type 2 Diabetes Mellitus: A Double-Blind, Randomized Trial J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6068 - 6076. [Abstract] [Full Text] [PDF]
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 A. C. Li and C. K. Glass PPAR- and LXR-dependent pathways controlling lipid metabolism and the development of atherosclerosis J. Lipid Res., December 1, 2004; 45(12): 2161 - 2173. [Abstract] [Full Text] [PDF]
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D. Choi, S.-K. Kim, S.-H. Choi, Y.-G. Ko, C.-W. Ahn, Y. Jang, S.-K. Lim, H.-C. Lee, and B.-S. Cha Preventative Effects of Rosiglitazone on Restenosis After Coronary Stent Implantation in Patients With Type 2 Diabetes Diabetes Care, November 1, 2004; 27(11): 2654 - 2660. [Abstract] [Full Text] [PDF]
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V. A. Fonseca, J. Diez, and D. B. McNamara Decreasing Restenosis Following Angioplasty: The potential of peroxisome proliferator-activated receptor {gamma} agonists Diabetes Care, November 1, 2004; 27(11): 2764 - 2766. [Full Text] [PDF]
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