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J Am Coll Cardiol, 1999; 34:146-154
© 1999 by the American College of Cardiology Foundation
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CLINICAL STUDIES

Hyperglycemia rapidly suppresses flow-mediated endothelium- dependent vasodilation of brachial artery

Hiroaki Kawano, MDa, Takeshi Motoyama, MDa, Osamu Hirashima, MDa, Nobutaka Hirai, MDa, Yuji Miyao, MDa, Tomohiro Sakamoto, MDa, Kiyotaka Kugiyama, MDa, Hisao Ogawa, MDa and Hirofumi Yasue, MDa

a Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Kumamoto, Japan

Manuscript received November 9, 1998; revised manuscript received February 19, 1999, accepted March 24, 1999.

Reprint requests and correspondence: Dr. Hirofumi Yasue, Department of Cardiovascular Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto City 860-8556, Japan
yasue{at}gpo.kumamoto-u.ac.jp

OBJECTIVES

We examined whether endothelial dysfunction occurs when acute hyperglycemia is induced by oral glucose loading.

BACKGROUND

Endothelial dysfunction has been shown to occur in patients with diabetes mellitus (DM), and chronic hyperglycemia is implicated as a cause of endothelial dysfunction. However, in many patients with Type 2 DM and in those with impaired glucose tolerance (IGT), fasting blood glucose may be within normal limits, and hyperglycemia occurred only post-prandially.

METHODS

With ultrasound technique, we measured flow-mediated endothelium-dependent vasodilation during oral glucose tolerance test in 58 subjects: (17 patients with normal glucose tolerance [NGT], 24 with IGT, and 17 with type 2 DM). In addition, we measured the levels of thiobarbituric acid reactive substances (TBARS) and nitrite/nitrate.

RESULTS

Flow-mediated vasodilation decreased after glucose loading (NGT: 7.53 ± 0.40, 4.24 ± 0.28 and 6.35 ± 0.40, in fasting, at 1- and 2-h, respectively, IGT: 6.50 ± 0.48, 1.40 ± 0.41** and 4.00 ± 0.47*, respectively; DM: 4.77 ± 0.37, 1.35 ± 0.38** and 1.29 ± 0.29%**, respectively; *p < 0.01 vs. fasting, **p < 0.005 vs. fasting). The TBARS concentration increased in parallel with plasma glucose level in each group (NGT: 1.43 ± 0.07, 2.03 ± 0.12 and 1.80 ± 0.12, respectively; IGT: 1.65 ± 0.11, 2.46 ± 0.12** and 1.94 ± 0.08*, respectively; DM: 1.73 ± 0.07, 2.34 ± 0.08** and 2.47 ± 0.09** nmol/ml, respectively; *p < 0.05 vs. fasting, **p < 0.01 vs. fasting). Glucose loading did not change nitrite/nitrate concentration in any of the groups.

CONCLUSIONS

Hyperglycemia in response to oral glucose loading rapidly suppresses endothelium-dependent vasodilation, probably through increased production of oxygen-derived free radicals. These findings strongly suggest that prolonged and repeated post-prandial hyperglycemia may play an important role in the development and progression of atherosclerosis.

Abbreviations and Acronyms
  ANOVA = analysis of variance
  DM = diabetes mellitus
  FMD = flow-mediated dilation
  HDL = high-density lipoprotein
  IGT = impaired glucose tolerance
  LDL = low-density lipoprotein
  NGT = normal glucose tolerance
  NO = nitric oxide
  OGTT = oral glucose tolerance test
  TBARS = thiobarbituric acid reactive substances




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Diabetes CareHome page
G. Paradisi, A. Biaggi, S. Ferrazzani, S. De Carolis, and A. Caruso
Abnormal Carbohydrate Metabolism During Pregnancy : Association with endothelial dysfunction
Diabetes Care, March 1, 2002; 25(3): 560 - 564.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
M. Kelm
Flow-mediated dilatation in human circulation: diagnostic and therapeutic aspects
Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H1 - H5.
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J Am Coll CardiolHome page
K. K. Koh, M. H. Kang, D. K. Jin, S.-K. Lee, J. Y. Ahn, H. Y. Hwang, S. H. Yang, D. S. Kim, T. H. Ahn, and E. K. Shin
Vascular effects of estrogen in type II diabetic postmenopausal women
J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1409 - 1415.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
M. Imamura, S. Biro, T. Kihara, S. Yoshifuku, K. Takasaki, Y. Otsuji, S. Minagoe, Y. Toyama, and C. Tei
Repeated thermal therapy improves impaired vascular endothelial function in patients with coronary risk factors
J. Am. Coll. Cardiol., October 1, 2001; 38(4): 1083 - 1088.
[Abstract] [Full Text] [PDF]


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CirculationHome page
C. Iribarren, A. J. Karter, A. S. Go, A. Ferrara, J. Y. Liu, S. Sidney, and J. V. Selby
Glycemic Control and Heart Failure Among Adult Patients With Diabetes
Circulation, June 5, 2001; 103(22): 2668 - 2673.
[Abstract] [Full Text] [PDF]


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CirculationHome page
J. A. Beckman, A. B. Goldfine, M. B. Gordon, and M. A. Creager
Ascorbate Restores Endothelium-Dependent Vasodilation Impaired by Acute Hyperglycemia in Humans
Circulation, March 27, 2001; 103(12): 1618 - 1623.
[Abstract] [Full Text] [PDF]


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CirculationHome page
M. Naghavi, Z. Barlas, S. Siadaty, S. Naguib, M. Madjid, and W. Casscells
Association of Influenza Vaccination and Reduced Risk of Recurrent Myocardial Infarction
Circulation, December 19, 2000; 102(25): 3039 - 3045.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
L. M. Title, P. M. Cummings, K. Giddens, and B. A. Nassar
Oral glucose loading acutely attenuates endothelium-dependent vasodilation in healthy adults without diabetes: an effect prevented by vitamins C and E
J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2185 - 2191.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
H. Tomiyama, Y. Kimura, R. Okazaki, T. Kushiro, M. Abe, Y. Kuwabara, H. Yoshida, S. Kuwata, T. Kinouchi, and N. Doba
Close Relationship of Abnormal Glucose Tolerance With Endothelial Dysfunction in Hypertension
Hypertension, August 1, 2000; 36(2): 245 - 249.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
J. A. Beckman, A. B. Goldfine, M. B. Gordon, L. A. Garrett, and M. A. Creager
Inhibition of Protein Kinase C{beta} Prevents Impaired Endothelium-Dependent Vasodilation Caused by Hyperglycemia in Humans
Circ. Res., January 11, 2002; 90(1): 107 - 111.
[Abstract] [Full Text] [PDF]



 
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