CLINICAL STUDY: ENDOTHELIAL FUNCTION
Oral glucose loading acutely attenuates endothelium-dependent vasodilation in healthy adults without diabetes: an effect prevented by vitamins C and E
Lawrence M. Title, MD*,
Peter M. Cummings, BA, MSc ,
Karen Giddens* and
Bassam A. Nassar, MB, PhD, BCh
* Division of Cardiology, Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia, Canada
Department of Pathology and Laboratory Medicine at the Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia, Canada
Manuscript received February 2, 2000;
revised manuscript received May 25, 2000,
accepted July 13, 2000.
Reprint requests and correspondence to: Dr. Lawrence Title, Queen Elizabeth II Health Sciences Center, Division of Cardiology, 6896-1796 Summer St., Halifax, Nova Scotia, Canada B3H 3A7 ltitle{at}is.dal.ca
OBJECTIVES
The goal of this study was to determine whether postprandial hyperglycemia, induced by oral glucose loading, attenuates endothelial function in healthy subjects without diabetes and whether coadministration of vitamins C and E could prevent these postprandial changes.
BACKGROUND
Epidemiologic evidence suggests that postprandial hyperglycemia, below diabetic levels, is a risk factor for cardiovascular disease. Postprandial hyperglycemia may promote atherosclerosis through endothelial dysfunction and oxidative stress.
METHODS
We evaluated the acute effects of oral glucose loading (75 g), alone and with vitamins C (2 g) and E (800 IU), on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery, in a randomized, double-blind, placebo-controlled, crossover study of 10 healthy volunteers. Changes in the levels of markers of oxidative stress (plasma malondialdehyde and erythrocyte glutathione, glutathione peroxidase and superoxide dismutase) were also assessed.
RESULTS
Increases in plasma glucose and insulin after glucose loading were unaffected by vitamin coadministration. With glucose loading alone, FMD fell from 6.5 ± 2.2 at baseline to 5.4 ± 1.7, 3.7 ± 2.1*, 4.1 ± 3.5* and 5.7 ± 1.9% at 1, 2, 3 and 4 h (*p < 0.05 vs. 0 h). In contrast, FMD did not change significantly after glucose plus vitamins (6.4 ± 1.3, 7.6 ± 1.8, 7.9 ± 2.7, 6.9 ± 2.3, 6.9 ± 1.9% at 0, 1, 2, 3 and 4 h). By two-way repeated measures analysis of variance we found a significant interaction between vitamin treatment and time (p = 0.0003), indicating that vitamins prevented the glucose-induced attenuation of FMD. Oxidative stress markers did not significantly change with glucose loading alone or with vitamins.
CONCLUSIONS
Oral glucose loading causes an acute, transient decrease of FMD in healthy subjects without diabetes, which is prevented by vitamins C and E.
|
Abbreviations and Acronyms
| | ANOVA | = analysis of variance | | FMD | = flow-mediated dilation | | IGT | = impaired glucose tolerance | | IRCM | = Institut de recherches cliniques de Montréal | | NO | = nitric oxide | | SOD | = superoxide dismutase |
|
This article has been cited by other articles:

|
 |

|
 |
 
T. Lavi, A. Karasik, N. Koren-Morag, H. Kanety, M. S. Feinberg, and M. Shechter
The acute effect of various glycemic index dietary carbohydrates on endothelial function in nondiabetic overweight and obese subjects.
J. Am. Coll. Cardiol.,
June 16, 2009;
53(24):
2283 - 2287.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. P Weiss, H. Arif, D. T Villareal, E. Marzetti, and J. O Holloszy
Endothelial function after high-sugar-food ingestion improves with endurance exercise performed on the previous day
Am. J. Clinical Nutrition,
July 1, 2008;
88(1):
51 - 57.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. Faridi, V. Y. Njike, S. Dutta, A. Ali, and D. L Katz
Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial
Am. J. Clinical Nutrition,
July 1, 2008;
88(1):
58 - 63.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. O. Stirban and D. Tschoepe
Cardiovascular Complications in Diabetes: Targets and interventions
Diabetes Care,
February 1, 2008;
31(Supplement_2):
S215 - S221.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Toth, A. Racz, J. Toth, P. M. Kaminski, M. S. Wolin, Z. Bagi, and A. Koller
Contribution of polyol pathway to arteriolar dysfunction in hyperglycemia. Role of oxidative stress, reduced NO, and enhanced PGH2/TXA2 mediation
Am J Physiol Heart Circ Physiol,
November 1, 2007;
293(5):
H3096 - H3104.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Zheng, M. Patel, R. Cable, L. Young, and S. D. Katz
Insulin Sensitivity, Vascular Function, and Iron Stores in Voluntary Blood Donors
Diabetes Care,
October 1, 2007;
30(10):
2685 - 2689.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X.-Y. Zheng and L. Liu
Remnant-like lipoprotein particles impair endothelial function: direct and indirect effects on nitric oxide synthase
J. Lipid Res.,
August 1, 2007;
48(8):
1673 - 1680.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Muniyappa, M. Montagnani, K. K. Koh, and M. J. Quon
Cardiovascular Actions of Insulin
Endocr. Rev.,
August 1, 2007;
28(5):
463 - 491.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Hovorka, J. Kremen, J. Blaha, M. Matias, K. Anderlova, L. Bosanska, T. Roubicek, M. E. Wilinska, L. J. Chassin, S. Svacina, et al.
Blood Glucose Control by a Model Predictive Control Algorithm with Variable Sampling Rate Versus a Routine Glucose Management Protocol in Cardiac Surgery Patients: A Randomized Controlled Trial
J. Clin. Endocrinol. Metab.,
August 1, 2007;
92(8):
2960 - 2964.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. H. McNulty, M. A. Tulli, B. J. Robertson, V. Lendel, L. A. Harach, S. Scott, and J. P. Boehmer
Effect of simulated postprandial hyperglycemia on coronary blood flow in cardiac transplant recipients
Am J Physiol Heart Circ Physiol,
July 1, 2007;
293(1):
H103 - H108.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Mariotti, J. F. Huneau, I. Szezepanski, K. J. Petzke, Y. Aggoun, D. Tome, and D. Bonnet
Meal Amino Acids with Varied Levels of Arginine do Not Affect Postprandial Vascular Endothelial Function in Healthy Young Men
J. Nutr.,
June 1, 2007;
137(6):
1383 - 1389.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. A. Phillips
Effects of low-carbohydrate diet on vascular health: more than just weight loss
Am J Physiol Heart Circ Physiol,
May 1, 2007;
292(5):
H2037 - H2039.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Nakagawa, W. Sato, O. Glushakova, M. Heinig, T. Clarke, M. Campbell-Thompson, Y. Yuzawa, M. A. Atkinson, R. J. Johnson, and B. Croker
Diabetic Endothelial Nitric Oxide Synthase Knockout Mice Develop Advanced Diabetic Nephropathy
J. Am. Soc. Nephrol.,
February 1, 2007;
18(2):
539 - 550.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. E. J. Lott, C. Hogeman, M. Herr, R. Gabbay, and L. I. Sinoway
Effects of an oral glucose tolerance test on the myogenic response in healthy individuals
Am J Physiol Heart Circ Physiol,
January 1, 2007;
292(1):
H304 - H310.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. J. A. Jenkins, C. W. C. Kendall, A. R. Josse, S. Salvatore, F. Brighenti, L. S. A. Augustin, P. R. Ellis, E. Vidgen, and A. V. Rao
Almonds Decrease Postprandial Glycemia, Insulinemia, and Oxidative Damage in Healthy Individuals
J. Nutr.,
December 1, 2006;
136(12):
2987 - 2992.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Barsheshet, M. Garty, E. Grossman, A. Sandach, B. S. Lewis, S. Gottlieb, A. Shotan, S. Behar, A. Caspi, R. Schwartz, et al.
Admission Blood Glucose Level and Mortality Among Hospitalized Nondiabetic Patients With Heart Failure.
Arch Intern Med,
August 14, 2006;
166(15):
1613 - 1619.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Silvestro, V. Schiano, R. Bucur, G. Brevetti, F. Scopacasa, and M. Chiariello
Effect of Propionylcarnitine on Changes in Endothelial Function and Plasma Levels of Adhesion Molecules Induced by Acute Exercise in Patients with Intermittent Claudication
Angiology,
March 1, 2006;
57(2):
145 - 154.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Nieuwdorp, T. W. van Haeften, M. C.L.G. Gouverneur, H. L. Mooij, M. H.P. van Lieshout, M. Levi, J. C.M. Meijers, F. Holleman, J. B.L. Hoekstra, H. Vink, et al.
Loss of Endothelial Glycocalyx During Acute Hyperglycemia Coincides With Endothelial Dysfunction and Coagulation Activation In Vivo
Diabetes,
February 1, 2006;
55(2):
480 - 486.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. S. Naik, L. Xiang, and R. L. Hester
Enhanced role for RhoA-associated kinase in adrenergic-mediated vasoconstriction in gracilis arteries from obese Zucker rats
Am J Physiol Regulatory Integrative Comp Physiol,
January 1, 2006;
290(1):
R154 - R161.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Manuel-y-Keenoy, A. Van Campenhout, P. Aerts, J. Vertommen, P. Abrams, L. F. Van Gaal, C. Van Gils, and I. H. De Leeuw
Time Course of Oxidative Stress Status in the Postprandial and Postabsorptive States in Type 1 Diabetes Mellitus: Relationship to Glucose and Lipid Changes
J. Am. Coll. Nutr.,
December 1, 2005;
24(6):
474 - 485.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. M. Ladeia, C. Ladeia-Frota, L. Pinho, E. Stefanelli, and L. Adan
Endothelial Dysfunction Is Correlated With Microalbuminuria in Children With Short-Duration Type 1 Diabetes
Diabetes Care,
August 1, 2005;
28(8):
2048 - 2050.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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
Circulation,
July 12, 2005;
112(2):
179 - 184.
[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. L. Moens, I. Goovaerts, M. J. Claeys, and C. J. Vrints
Flow-Mediated Vasodilation: A Diagnostic Instrument, or an Experimental Tool?
Chest,
June 1, 2005;
127(6):
2254 - 2263.
[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]
|
 |
|

|
 |

|
 |
 
C. K. Roberts and R. J. Barnard
Effects of exercise and diet on chronic disease
J Appl Physiol,
January 1, 2005;
98(1):
3 - 30.
[Abstract]
[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]
|
 |
|

|
 |

|
 |
 
P. A. Economides, L. Khaodhiar, A. Caselli, A. E. Caballero, H. Keenan, S.-E. Bursell, G. L. King, M. T. Johnstone, E. S. Horton, and A. Veves
The Effect of Vitamin E on Endothelial Function of Micro- and Macrocirculation and Left Ventricular Function in Type 1 and Type 2 Diabetic Patients
Diabetes,
January 1, 2005;
54(1):
204 - 211.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. L. Katz, M. A. Evans, W. Chan, H. Nawaz, B. P. Comerford, M. L. Hoxley, V. Y. Njike, and P. M. Sarrel
Oats, Antioxidants and Endothelial Function in Overweight, Dyslipidemic Adults
J. Am. Coll. Nutr.,
October 1, 2004;
23(5):
397 - 403.
[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]
|
 |
|

|
 |

|
 |
 
M. J. Jarvisalo, M. Raitakari, J. O. Toikka, A. Putto-Laurila, R. Rontu, S. Laine, T. Lehtimaki, T. Ronnemaa, J. Viikari, and O. T. Raitakari
Endothelial Dysfunction and Increased Arterial Intima-Media Thickness in Children With Type 1 Diabetes
Circulation,
April 13, 2004;
109(14):
1750 - 1755.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. S. Reed, N. Charkoudian, A. Vella, P. Shah, R. A. Rizza, and M. J. Joyner
Forearm vascular control during acute hyperglycemia in healthy humans
Am J Physiol Endocrinol Metab,
March 1, 2004;
286(3):
E472 - E480.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
V. Fonseca, C. Desouza, S. Asnani, and I. Jialal
Nontraditional Risk Factors for Cardiovascular Disease in Diabetes
Endocr. Rev.,
February 1, 2004;
25(1):
153 - 175.
[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]
|
 |
|

|
 |

|
 |
 
F. Khan, F. C Green, J S. Forsyth, S. A Greene, A. D Morris, and J. J F Belch
Impaired microvascular function in normal children: effects of adiposity and poor glucose handling
J. Physiol.,
September 1, 2003;
551(2):
705 - 711.
[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]
|
 |
|

|
 |

|
 |
 
L. Li, T. Sawamura, and G. Renier
Glucose Enhances Endothelial LOX-1 Expression: Role for LOX-1 in Glucose-Induced Human Monocyte Adhesion to Endothelium
Diabetes,
July 1, 2003;
52(7):
1843 - 1850.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. E. Gerich
Clinical Significance, Pathogenesis, and Management of Postprandial Hyperglycemia
Arch Intern Med,
June 9, 2003;
163(11):
1306 - 1316.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. J. H. H. M. van Oostrom, T. P. Sijmonsma, C. Verseyden, E. H. J. M. Jansen, E. J. P. de Koning, T. J. Rabelink, and M. Castro Cabezas
Postprandial recruitment of neutrophils may contribute to endothelial dysfunction
J. Lipid Res.,
March 1, 2003;
44(3):
576 - 583.
[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]
|
 |
|

|
 |

|
 |
 
C. K. Roberts, N. D. Vaziri, and R. J. Barnard
Effect of Diet and Exercise Intervention on Blood Pressure, Insulin, Oxidative Stress, and Nitric Oxide Availability
Circulation,
November 12, 2002;
106(20):
2530 - 2532.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Charkoudian, A. Vella, A. S. Reed, C. T. Minson, P. Shah, R. A. Rizza, and M. J. Joyner
Cutaneous vascular function during acute hyperglycemia in healthy young adults
J Appl Physiol,
October 1, 2002;
93(4):
1243 - 1250.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. A. Kingwell, M. Formosa, M. Muhlmann, S. J. Bradley, and G. K. McConell
Nitric Oxide Synthase Inhibition Reduces Glucose Uptake During Exercise in Individuals With Type 2 Diabetes More Than in Control Subjects
Diabetes,
August 1, 2002;
51(8):
2572 - 2580.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. S. Ludwig
The Glycemic Index: Physiological Mechanisms Relating to Obesity, Diabetes, and Cardiovascular Disease
JAMA,
May 8, 2002;
287(18):
2414 - 2423.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. A van de Ree, M. V Huisman, F. H de Man, J. C van der Vijver, A.E. Meinders, and G. J Blauw
Impaired endothelium-dependent vasodilation in type 2 diabetes mellitus and the lack of effect of simvastatin
Cardiovasc Res,
November 1, 2001;
52(2):
299 - 305.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|