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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 5 1818
Copyright © 1998 by The Endocrine Society

Rapid Communications

Potent Inhibitory Effect of Troglitazone on Carotid Arterial Wall Thickness in Type 2 Diabetes

Jun Minamikawa, Satsuki Tanaka, Mika Yamauchi, Diasuke Inoue and Hiroyuki Koshiyama

Division of Endocrinology and Metabolism, Department of Internal Medicine, Hyogo Prefectural Amagasaki Hospital, Hyogo 660-0828, Japan

Address correspondence and requests for reprints to: Dr. Hiroyuki Koshiyama, Division of Endocrinology and Metabolism, Department of Internal Medicine, Hyogo Prefectural Amagasaki Hospital, 1-1-1, Higashi-Daimotsu-cho, Amagasaki, Hyogo 660-0828, Japan.

Abstract

ABTRACT

There is increasing evidence that insulin resistance may be causally related to atherosclerosis. The measurement of common carotid arterial intimal and medial complex thickness (IMT) by B-mode ultrasound technique has been recognized as a powerful and non-invasive method to evaluate early atherosclerotic lesions. We investigated the effect of treatment with troglitazone, an insulin sensitizer, on IMT in a total of 135 Japanese subjects with type 2 diabetes. Troglitazone (400 mg daily) was administered for 6 months in 57 patients. Compared to control group (n = 78), the group given troglitazone showed a significant decrease in IMT as early as 3 months after the administration (IMT change: -0.080[SE 0.016] mm vs. control 0.027[SE 0.007] mm, P < 0.001). The decrease in IMT was also found after 6 months, although further decrease was not observed. Both HbA1c and postprandial serum triglycerides were decreased after troglitazone, but there was no statistically significant relation between a decrease in IMT and those in HbA1c or postprandial tri-glycerides. These findings indicate that troglitazone has a potent inhibitory effect on progression of early atherosclerotic lesions probably through the decreased insulin resistance in type 2 diabetes.




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D. S. Calnek, L. Mazzella, S. Roser, J. Roman, and C. M. Hart
Peroxisome Proliferator-Activated Receptor {gamma} Ligands Increase Release of Nitric Oxide From Endothelial Cells
Arterioscler Thromb Vasc Biol, January 1, 2003; 23(1): 52 - 57.
[Abstract] [Full Text] [PDF]

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 British Journal of Diabetes & Vascular DiseaseHome page
R. A Defronzo
Impaired glucose tolerance: do pharmacological therapies correct the underlying metabolic disturbance?
The British Journal of Diabetes & Vascular Disease, January 1, 2003; 3(1_suppl): S24 - S40.
[Abstract] [PDF]

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 NeurologyHome page
W. N. Kernan, S. E. Inzucchi, C. M. Viscoli, L. M. Brass, D. M. Bravata, and R. I. Horwitz
Insulin resistance and risk for stroke
Neurology, September 24, 2002; 59(6): 809 - 815.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
N. Marx
PPAR{gamma} and Vascular Inflammation: Adding Another Piece to the Puzzle
Circ. Res., September 6, 2002; 91(5): 373 - 374.
[Full Text] [PDF]

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 J Am Coll CardiolHome page
S. P. Marso
Optimizing the diabetic formulary: beyond aspirin and insulin
J. Am. Coll. Cardiol., August 21, 2002; 40(4): 652 - 661.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
P. A. Watson, C. Vinson, A. Nesterova, and J. E.-B. Reusch
Content and Activity of cAMP Response Element-Binding Protein Regulate Platelet-Derived Growth Factor Receptor-{alpha} Content in Vascular Smooth Muscles
Endocrinology, August 1, 2002; 143(8): 2922 - 2929.
[Abstract] [Full Text] [PDF]

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 Diabetes CareHome page
E. Bonora, G. Formentini, F. Calcaterra, S. Lombardi, F. Marini, L. Zenari, F. Saggiani, M. Poli, S. Perbellini, A. Raffaelli, et al.
HOMA-Estimated Insulin Resistance Is an Independent Predictor of Cardiovascular Disease in Type 2 Diabetic Subjects: Prospective data from the Verona Diabetes Complications Study
Diabetes Care, July 1, 2002; 25(7): 1135 - 1141.
[Abstract] [Full Text] [PDF]

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 Toxicol PatholHome page
C. S. Elangbam, T. A. Brodie, H. Roger Brown, J. B. Nold, T. J. Raczniak, R. D. Tyler, R. M. Lightfoot, and H. G. Wall
Vascular Effects of GI262570X (PPAR-{gamma} agonist) in the Brown Adipose Tissue of Han Wistar Rats: A Review of 1-month, 13-week, 27-week and 2-year Oral Toxicity Studies
Toxicol Pathol, June 1, 2002; 30(4): 420 - 426.
[Abstract] [PDF]

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 Arterioscler. Thromb. Vasc. Bio.Home page
O. Barbier, I. P. Torra, Y. Duguay, C. Blanquart, J.-C. Fruchart, C. Glineur, and B. Staels
Pleiotropic Actions of Peroxisome Proliferator-Activated Receptors in Lipid Metabolism and Atherosclerosis
Arterioscler Thromb Vasc Biol, May 1, 2002; 22(5): 717 - 726.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
N. Marx, B. Kehrle, K. Kohlhammer, M. Grub, W. Koenig, V. Hombach, P. Libby, and J. Plutzky
PPAR Activators as Antiinflammatory Mediators in Human T Lymphocytes: Implications for Atherosclerosis and Transplantation-Associated Arteriosclerosis
Circ. Res., April 5, 2002; 90(6): 703 - 710.
[Abstract] [Full Text] [PDF]

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 DiabetesHome page
G. J. Etgen, B. A. Oldham, W. T. Johnson, C. L. Broderick, C. R. Montrose, J. T. Brozinick, E. A. Misener, J. S. Bean, W. R. Bensch, D. A. Brooks, et al.
A Tailored Therapy for the Metabolic Syndrome : The Dual Peroxisome Proliferator-Activated Receptor-{alpha}/{gamma} Agonist LY465608 Ameliorates Insulin Resistance and Diabetic Hyperglycemia While Improving Cardiovascular Risk Factors in Preclinical Models
Diabetes, April 1, 2002; 51(4): 1083 - 1087.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. Sugawara, A. Uruno, M. Kudo, Y. Ikeda, K. Sato, Y. Taniyama, S. Ito, and K. Takeuchi
Transcription Suppression of Thromboxane Receptor Gene by Peroxisome Proliferator-activated Receptor-gamma via an Interaction with Sp1 in Vascular Smooth Muscle Cells
J. Biol. Chem., March 15, 2002; 277(12): 9676 - 9683.
[Abstract] [Full Text] [PDF]

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 Diabetes CareHome page
N. V. Chu, A. P. S. Kong, D. D. Kim, D. Armstrong, S. Baxi, R. Deutsch, M. Caulfield, S. R. Mudaliar, R. Reitz, R. R. Henry, et al.
Differential Effects of Metformin and Troglitazone on Cardiovascular Risk Factors in Patients With Type 2 Diabetes
Diabetes Care, March 1, 2002; 25(3): 542 - 549.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
B. R. Kwak, S. Myit, F. Mulhaupt, N. Veillard, N. Rufer, E. Roosnek, and F. Mach
PPAR{gamma} but not PPAR{alpha} Ligands Are Potent Repressors of Major Histocompatibility Complex Class II Induction in Atheroma-Associated Cells
Circ. Res., February 22, 2002; 90(3): 356 - 362.
[Abstract] [Full Text] [PDF]

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 J. Lipid Res.Home page
R. Walczak and P. Tontonoz
PPARadigms and PPARadoxes: expanding roles for PPAR{gamma} in the control of lipid metabolism
J. Lipid Res., February 1, 2002; 43(2): 177 - 186.
[Abstract] [Full Text] [PDF]

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 JAMAHome page
S. E. Inzucchi
Oral Antihyperglycemic Therapy for Type 2 Diabetes: Scientific Review
JAMA, January 16, 2002; 287(3): 360 - 372.
[Abstract] [Full Text] [PDF]

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 Genes Dev.Home page
M. A. Lazar
Becoming fat
Genes & Dev., January 1, 2002; 16(1): 1 - 5.
[Full Text] [PDF]

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 British Journal of Diabetes & Vascular DiseaseHome page
B. Staels
The clinical significance of PPAR{alpha} and {gamma} agonism
The British Journal of Diabetes & Vascular Disease, January 1, 2002; 2(1_suppl): S28 - S31.
[Abstract] [PDF]

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 Arterioscler. Thromb. Vasc. Bio.Home page
W. A. Hsueh and R. E. Law
PPAR{gamma} and Atherosclerosis: Effects on Cell Growth and Movement
Arterioscler Thromb Vasc Biol, December 1, 2001; 21(12): 1891 - 1895.
[Abstract] [Full Text] [PDF]

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 HeartHome page
J S Sidhu and J C Kaski
Peroxisome proliferator activated receptor {gamma}: a potential therapeutic target in the management of ischaemic heart disease
Heart, September 1, 2001; 86(3): 255 - 258.
[Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
A. Aljada, R. Garg, H. Ghanim, P. Mohanty, W. Hamouda, E. Assian, and P. Dandona
Nuclear Factor-{{kappa}}B Suppressive and Inhibitor-{{kappa}}B Stimulatory Effects of Troglitazone in Obese Patients with Type 2 Diabetes: Evidence of an Antiinflammatory Action?
J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3250 - 3256.
[Abstract] [Full Text] [PDF]

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 Diabetes CareHome page
D. Shimono, N. Kuwamura, Y. Nakamura, and H. Koshiyama
Lack of Effect of Pioglitazone on Postprandial Triglyceride Levels in Type 2 Diabetes
Diabetes Care, May 1, 2001; 24(5): 971 - 971.
[Full Text]

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 CirculationHome page
B. E. Sobel
Acceleration of Restenosis by Diabetes : Pathogenetic Implications
Circulation, March 6, 2001; 103(9): 1185 - 1187.
[Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
H. Ghanim, R. Garg, A. Aljada, P. Mohanty, Y. Kumbkarni, E. Assian, W. Hamouda, and P. Dandona
Suppression of Nuclear Factor-{{kappa}}B and Stimulation of Inhibitor {{kappa}}B by Troglitazone: Evidence for an Anti-inflammatory Effect and a Potential Antiatherosclerotic Effect in the Obese
J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1306 - 1312.
[Abstract] [Full Text]

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 Proc. Natl. Acad. Sci. USAHome page
T. Claudel, M. D. Leibowitz, C. Fiévet, A. Tailleux, B. Wagner, J. J. Repa, G. Torpier, J.-M. Lobaccaro, J. R. Paterniti, D. J. Mangelsdorf, et al.
Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor
PNAS, February 15, 2001; (2001) 41609298.
[Abstract] [Full Text]

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 Toxicol PatholHome page
C. S. Elangbam, R. D. Tyler, and R. M. Lightfoot
Peroxisome Proliferator-activated Receptors in Atherosclerosis and Inflammation--An Update
Toxicol Pathol, February 1, 2001; 29(2): 224 - 231.
[Abstract] [PDF]

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 Diabetes CareHome page
W. A. Hsueh, S. Jackson, and R. E. Law
Control of Vascular Cell Proliferation and Migration by PPAR-{gamma}: A new approach to the macrovascular complications of diabetes
Diabetes Care, February 1, 2001; 24(2): 392 - 397.
[Abstract] [Full Text]

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 ANN INTERN MEDHome page
A. A. Parulkar, M. L. Pendergrass, R. Granda-Ayala, T. R. Lee, and V. A. Fonseca
Nonhypoglycemic Effects of Thiazolidinediones
Ann Intern Med, January 2, 2001; 134(1): 61 - 71.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
R. Garg, Y. Kumbkarni, A. Aljada, P. Mohanty, H. Ghanim, W. Hamouda, and P. Dandona
Troglitazone Reduces Reactive Oxygen Species Generation by Leukocytes and Lipid Peroxidation and Improves Flow-Mediated Vasodilatation in Obese Subjects
Hypertension, September 1, 2000; 36(3): 430 - 435.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
H. Koshiyama, Y. Nakamura, S. Tanaka, and J. Minamikawa
Decrease in Carotid Intima-Media Thickness after 1-Year Therapy with Etidronate for Osteopenia Associated with Type 2 Diabetes
J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2793 - 2796.
[Abstract] [Full Text]

Home page
 CirculationHome page
V. Pasceri, H. D. Wu, J. T. Willerson, and E. T. H. Yeh
Modulation of Vascular Inflammation In Vitro and In Vivo by Peroxisome Proliferator-Activated Receptor-{gamma} Activators
Circulation, January 25, 2000; 101(3): 235 - 238.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
Y. Hattori, S. Hattori, and K. Kasai
Troglitazone Upregulates Nitric Oxide Synthesis in Vascular Smooth Muscle Cells
Hypertension, April 1, 1999; 33(4): 943 - 948.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. Claudel, M. D. Leibowitz, C. Fievet, A. Tailleux, B. Wagner, J. J. Repa, G. Torpier, J.-M. Lobaccaro, J. R. Paterniti, D. J. Mangelsdorf, et al.
Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor
PNAS, February 27, 2001; 98(5): 2610 - 2615.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
B. R. Kwak, S. Myit, F. Mulhaupt, N. Veillard, N. Rufer, E. Roosnek, and F. Mach
PPAR{gamma} but not PPAR{alpha} Ligands Are Potent Repressors of Major Histocompatibility Complex Class II Induction in Atheroma-Associated Cells
Circ. Res., February 22, 2002; 90(3): 356 - 362.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
N. Marx, B. Kehrle, K. Kohlhammer, M. Grub, W. Koenig, V. Hombach, P. Libby, and J. Plutzky
PPAR Activators as Antiinflammatory Mediators in Human T Lymphocytes: Implications for Atherosclerosis and Transplantation-Associated Arteriosclerosis
Circ. Res., April 5, 2002; 90(6): 703 - 710.
[Abstract] [Full Text] [PDF]


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