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.
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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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51(11):
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8 - 14.
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|
|
|
|
|
|
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|
|
|
|
|
|
|
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27(11):
2456 - 2462.
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|
|
|
|
|
|
|
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293(5):
H3096 - H3104.
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|
|
|
|
|
|
|
J. Uribarri, A. Stirban, D. Sander, W. Cai, M. Negrean, C. E. Buenting, T. Koschinsky, and H. Vlassara
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30(10):
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|
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|
|
|
|
|
H. Zheng, M. Patel, R. Cable, L. Young, and S. D. Katz
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30(10):
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|
|
|
|
|
|
|
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293(1):
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|
|
|
|
|
|
|
P. H. McNulty, M. A. Tulli, B. J. Robertson, V. Lendel, L. A. Harach, S. Scott, and J. P. Boehmer
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293(1):
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|
|
|
|
|
|
|
S. W. Zarich and R. W. Nesto
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May 8, 2007;
115(18):
e436 - e439.
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|
|
|
|
|
|
|
J. A. Beckman, A. B. Goldfine, A. Dunaif, M. Gerhard-Herman, and M. A. Creager
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30(5):
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|
|
|
|
|
|
|
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292(1):
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|
|
|
|
|
|
|
S. Yasuda, S. Miyazaki, M. Kanda, Y. Goto, M. Suzuki, Y. Harano, and H. Nonogi
Intensive treatment of risk factors in patients with type-2 diabetes mellitus is associated with improvement of endothelial function coupled with a reduction in the levels of plasma asymmetric dimethylarginine and endogenous inhibitor of nitric oxide synthase
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27(10):
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|
|
|
|
|
|
|
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91(3):
837 - 842.
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|
|
|
|
|
|
|
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Enhanced role for RhoA-associated kinase in adrenergic-mediated vasoconstriction in gracilis arteries from obese Zucker rats
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January 1, 2006;
290(1):
R154 - R161.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
R. Scognamiglio, C. Negut, S. V. De Kreutzenberg, A. Tiengo, and A. Avogaro
Postprandial Myocardial Perfusion in Healthy Subjects and in Type 2 Diabetic Patients
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July 12, 2005;
112(2):
179 - 184.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
E. D. Beishuizen, J. T. Tamsma, J. W. Jukema, M. A. van de Ree, J. C. M. van der Vijver, A. E. Meinders, and M. V. Huisman
The Effect of Statin Therapy on Endothelial Function in Type 2 Diabetes Without Manifest Cardiovascular Disease
Diabetes Care,
July 1, 2005;
28(7):
1668 - 1674.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Capaldo, M. Galderisi, A. A. Turco, A. D'Errico, S. Turco, A. A. Rivellese, G. de Simone, O. de Divitiis, and G. Riccardi
Acute Hyperglycemia Does Not Affect the Reactivity of Coronary Microcirculation in Humans
J. Clin. Endocrinol. Metab.,
July 1, 2005;
90(7):
3871 - 3876.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ceriello, R. Assaloni, R. Da Ros, A. Maier, L. Piconi, L. Quagliaro, K. Esposito, and D. Giugliano
Effect of Atorvastatin and Irbesartan, Alone and in Combination, on Postprandial Endothelial Dysfunction, Oxidative Stress, and Inflammation in Type 2 Diabetic Patients
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May 17, 2005;
111(19):
2518 - 2524.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. T. McMahon, J. Plutzky, E. Daher, T. Bhattacharyya, G. Grunberger, and M. F. DiCarli
Effect of a Peroxisome Proliferator-Activated Receptor-{gamma} Agonist on Myocardial Blood Flow in Type 2 Diabetes
Diabetes Care,
May 1, 2005;
28(5):
1145 - 1150.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Bots, J. Westerink, T. J. Rabelink, and E. J.P. de Koning
Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response
Eur. Heart J.,
February 2, 2005;
26(4):
363 - 368.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Kaufmann and P. G. Camici
Myocardial Blood Flow Measurement by PET: Technical Aspects and Clinical Applications
J. Nucl. Med.,
January 1, 2005;
46(1):
75 - 88.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ceriello
Postprandial Hyperglycemia and Diabetes Complications: Is It Time to Treat?
Diabetes,
January 1, 2005;
54(1):
1 - 7.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M E Tushuizen, M Diamant, and R J Heine
Postprandial dysmetabolism and cardiovascular disease in type 2 diabetes
Postgrad. Med. J.,
January 1, 2005;
81(951):
1 - 6.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Mullan, C. N. Ennis, H. J. P. Fee, I. S. Young, and D. R. McCance
Protective effects of ascorbic acid on arterial hemodynamics during acute hyperglycemia
Am J Physiol Heart Circ Physiol,
September 1, 2004;
287(3):
H1262 - H1268.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Bagi, E. Toth, A. Koller, and G. Kaley
Microvascular dysfunction after transient high glucose is caused by superoxide-dependent reduction in the bioavailability of NO and BH4
Am J Physiol Heart Circ Physiol,
August 1, 2004;
287(2):
H626 - H633.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. M. Maggi, S. Raselli, L. Grigore, L. Redaelli, S. Fantappie, and A. L. Catapano
Lipoprotein Remnants and Endothelial Dysfunction in the Postprandial Phase
J. Clin. Endocrinol. Metab.,
June 1, 2004;
89(6):
2946 - 2950.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Otto, A. Svatikova, R. B. d. M. Barretto, S. Santos, M. Hoffmann, B. Khandheria, and V. Somers
Early Morning Attenuation of Endothelial Function in Healthy Humans
Circulation,
June 1, 2004;
109(21):
2507 - 2510.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Stranders, M. Diamant, R. E. van Gelder, H. J. Spruijt, J. W. R. Twisk, R. J. Heine, and F. C. Visser
Admission Blood Glucose Level as Risk Indicator of Death After Myocardial Infarction in Patients With and Without Diabetes Mellitus
Arch Intern Med,
May 10, 2004;
164(9):
982 - 988.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ceriello and E. Motz
Is Oxidative Stress the Pathogenic Mechanism Underlying Insulin Resistance, Diabetes, and Cardiovascular Disease? The Common Soil Hypothesis Revisited
Arterioscler. Thromb. Vasc. Biol.,
May 1, 2004;
24(5):
816 - 823.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Hanefeld, J. L. Chiasson, C. Koehler, E. Henkel, F. Schaper, and T. Temelkova-Kurktschiev
Acarbose Slows Progression of Intima-Media Thickness of the Carotid Arteries in Subjects With Impaired Glucose Tolerance
Stroke,
May 1, 2004;
35(5):
1073 - 1078.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. N. Thomas, P. Chook, M. Qiao, X. S. Huang, H. C. Leong, D. S. Celermajer, and K. S. Woo
Deleterious Impact of "High Normal" Glucose Levels and Other Metabolic Syndrome Components on Arterial Endothelial Function and Intima-Media Thickness in Apparently Healthy Chinese Subjects: The CATHAY Study
Arterioscler. Thromb. Vasc. Biol.,
April 1, 2004;
24(4):
739 - 743.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Clement, S. S. Braithwaite, M. F. Magee, A. Ahmann, E. P. Smith, R. G. Schafer, and I. B. Hirsch
Management of Diabetes and Hyperglycemia in Hospitals
Diabetes Care,
February 1, 2004;
27(2):
553 - 591.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Raitakari, T. Ilvonen, M. Ahotupa, T. Lehtimaki, A. Harmoinen, P. Suominen, J. Elo, J. Hartiala, and O. T. Raitakari
Weight Reduction With Very-Low-Caloric Diet and Endothelial Function in Overweight Adults: Role of Plasma Glucose
Arterioscler. Thromb. Vasc. Biol.,
January 1, 2004;
24(1):
124 - 128.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Singleton, A. G. Smith, J. W. Russell, and E. L. Feldman
Microvascular Complications of Impaired Glucose Tolerance
Diabetes,
December 1, 2003;
52(12):
2867 - 2873.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-L. Chiasson, R. G. Josse, R. Gomis, M. Hanefeld, A. Karasik, and M. Laakso
Acarbose Treatment and the Risk of Cardiovascular Disease and Hypertension in Patients With Impaired Glucose Tolerance: The STOP-NIDDM Trial
JAMA,
July 23, 2003;
290(4):
486 - 494.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Ihlemann, C. Rask-Madsen, A. Perner, H. Dominguez, T. Hermann, L. Kober, and C. Torp-Pedersen
Tetrahydrobiopterin restores endothelial dysfunction induced by an oral glucose challenge in healthy subjects
Am J Physiol Heart Circ Physiol,
July 11, 2003;
285(2):
H875 - H882.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. T. Bloomgarden
Inflammation and Insulin Resistance
Diabetes Care,
June 1, 2003;
26(6):
1922 - 1926.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Ceriello
New Insights on Oxidative Stress and Diabetic Complications May Lead to a "Causal" Antioxidant Therapy
Diabetes Care,
May 1, 2003;
26(5):
1589 - 1596.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. F. Di Carli, J. Janisse, G. Grunberger, and J. Ager
Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes
J. Am. Coll. Cardiol.,
April 16, 2003;
41(8):
1387 - 1393.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Kingwell, M. Formosa, M. Muhlmann, S. J. Bradley, and G. K. McConell
Type 2 Diabetic Individuals Have Impaired Leg Blood Flow Responses to Exercise: Role of endothelium-dependent vasodilation
Diabetes Care,
March 1, 2003;
26(3):
899 - 904.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Schiekofer, M. Andrassy, J. Chen, G. Rudofsky, J. Schneider, T. Wendt, N. Stefan, P. Humpert, A. Fritsche, M. Stumvoll, et al.
Acute Hyperglycemia Causes Intracellular Formation of CML and Activation of ras, p42/44 MAPK, and Nuclear Factor {kappa}B in PBMCs
Diabetes,
March 1, 2003;
52(3):
621 - 633.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-i. Koide, K. Kugiyama, S. Sugiyama, S.-i. Nakamura, H. Fukushima, O. Honda, M. Yoshimura, and H. Ogawa
Association of polymorphism in glutamate-cysteine ligase catalytic subunit gene with coronary vasomotor dysfunction and myocardial infarction
J. Am. Coll. Cardiol.,
February 19, 2003;
41(4):
539 - 545.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J Woodman, T. A Mori, V. Burke, I. B Puddey, G. F Watts, and L. J Beilin
Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension
Am. J. Clinical Nutrition,
November 1, 2002;
76(5):
1007 - 1015.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
