From the Vascular Medicine and Atherosclerosis Unit of the Cardiovascular
Division, Brigham and Women's Hospital (S.B.W., F.K.T., H.H.T., M.-A.
R., M.A.C.) and the Endocrine Division of the Brigham and Women's
Hospital and the Joslin Diabetes Center (A.B.G., D.C.S.), Harvard Medical
School, Boston, Mass.
Correspondence to Mark A. Creager, MD, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115. E-mail macreager{at}bics.bwh.harvard.edu
Background—Endothelial
function is impaired in patients with diabetes mellitus. However, the
factors contributing to this defect are currently unknown.
Hyperglycemia attenuates endothelium-dependent
relaxation in normal rabbit arteries in vitro and rat arterioles in
vivo. Accordingly, this study examined the effect of acute
hyperglycemia on endothelium-dependent vasodilation in
nondiabetic humans in vivo.
Methods and Results—Endothelium-dependent
vasodilation was assessed through brachial artery infusion of
methacholine chloride both before and during 6 hours of local
hyperglycemia (300 mg/dL) achieved by intra-arterial
infusion of 50% dextrose. Forearm blood flow was determined by
plethysmography. In a group of 10 subjects, there was a trend toward
attenuated methacholine-mediated vasodilation during hyperglycemia
compared with euglycemia (P=.07 by ANOVA; maximal
response, 13.3±2.8 versus 14.7±1.5 mL ·
min-1 · 100 mL-1, respectively). In
these subjects, the systemic serum insulin levels increased
significantly during the dextrose infusion (P<.001). To
eliminate the confounding vasoactive effects of insulin, the protocol
was repeated during systemic infusion of octreotide (30 ng ·
kg-1 · min-1) to inhibit pancreatic
secretion of insulin. In these subjects (n=10), hyperglycemia
significantly attenuated the forearm blood flow response to
methacholine (P<.01 by ANOVA; maximal response,
16.9±2.5 before versus 12.7±1.8 mL · min-1
· 100 mL-1 during hyperglycemia). Methacholine-mediated
vasodilation was not attenuated by an equimolar infusion of mannitol
(P>.40), nor did hyperglycemia reduce
endothelium-independent vasodilation to
verapamil (P>.50).
Conclusions—Acute hyperglycemia impairs
endothelium-dependent vasodilation in healthy humans in
vivo. This finding suggests that elevated glucose may contribute to the
endothelial dysfunction observed in patients with
diabetes mellitus.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Acute Hyperglycemia Attenuates Endothelium-Dependent Vasodilation in Humans In Vivo
Key Words: diabetes mellitus • endothelium-derived factors • vasodilation • glucose • nitric oxide
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R. Ferrara, G. Guardigli, and R. Ferrari Myocardial metabolism: the diabetic heart Eur. Heart J. Suppl., January 1, 2003; 5(suppl_B): B15 - B18. [Abstract] [PDF]
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N. N. Wahab, E. A. Cowden, N. J. Pearce, M. J. Gardner, H. Merry, J. L. Cox, and ICONS Investigators Is blood glucose an independent predictor of mortality in acute myocardial infarction in the thrombolytic era? J. Am. Coll. Cardiol., November 20, 2002; 40(10): 1748 - 1754. [Abstract] [Full Text] [PDF]
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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]
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 S. Dickinson, S. Colagiuri, E. Faramus, P. Petocz, and J. C. Brand-Miller Postprandial Hyperglycemia and Insulin Sensitivity Differ among Lean Young Adults of Different Ethnicities J. Nutr., September 1, 2002; 132(9): 2574 - 2579. [Abstract] [Full Text] [PDF]
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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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J. L. Carson, P. M. Scholz, A. Y. Chen, E. D. Peterson, J. Gold, and S. H. Schneider Diabetes mellitus increases short-term mortality and morbidity in patients undergoing coronary artery bypass graft surgery J. Am. Coll. Cardiol., August 7, 2002; 40(3): 418 - 423. [Abstract] [Full Text] [PDF]
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M. G. Modena, L. Bonetti, F. Coppi, F. Bursi, and R. Rossi Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women J. Am. Coll. Cardiol., August 7, 2002; 40(3): 505 - 510. [Abstract] [Full Text] [PDF]
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C. Desouza, A. Parulkar, D. Lumpkin, D. Akers, and V. A. Fonseca Acute and Prolonged Effects of Sildenafil on Brachial Artery Flow-Mediated Dilatation in Type 2 Diabetes Diabetes Care, August 1, 2002; 25(8): 1336 - 1339. [Abstract] [Full Text] [PDF]
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L. S. Hermann and N. Wiernsperger Impaired glucose tolerance and metformin: clinical and mechanistic aspects The British Journal of Diabetes & Vascular Disease, May 1, 2002; 2(3): 177 - 183. [Abstract] [PDF]
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R. W. van Etten, E. J.P. de Koning, M. L. Honing, E. S. Stroes, C. A. Gaillard, and T. J. Rabelink Intensive Lipid Lowering by Statin Therapy Does Not Improve Vasoreactivity in Patients With Type 2 Diabetes Arterioscler. Thromb. Vasc. Biol., May 1, 2002; 22(5): 799 - 804. [Abstract] [Full Text] [PDF]
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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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I. B. Wilkinson, I. R. Hall, H. MacCallum, I. S. Mackenzie, C. M. McEniery, B. J. van der Arend, Y.-E. Shu, L. S. MacKay, D. J. Webb, and J. R. Cockcroft Pulse-Wave Analysis: Clinical Evaluation of a Noninvasive, Widely Applicable Method for Assessing Endothelial Function Arterioscler. Thromb. Vasc. Biol., January 1, 2002; 22(1): 147 - 152. [Abstract] [Full Text] [PDF]
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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. [Full Text] [PDF]
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E. Bonora, F. Calcaterra, S. Lombardi, N. Bonfante, G. Formentini, R. C. Bonadonna, and M. Muggeo Plasma Glucose Levels Throughout the Day and HbA1c Interrelationships in Type 2 Diabetes: Implications for treatment and monitoring of metabolic control Diabetes Care, December 1, 2001; 24(12): 2023 - 2029. [Abstract] [Full Text] [PDF]
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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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C. Rask-Madsen, N. Ihlemann, T. Krarup, E. Christiansen, L. Kober, C. Nervil Kistorp, and C. Torp-Pedersen Insulin Therapy Improves Insulin-Stimulated Endothelial Function in Patients With Type 2 Diabetes and Ischemic Heart Disease Diabetes, November 1, 2001; 50(11): 2611 - 2618. [Abstract] [Full Text] [PDF]
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J. R. Kersten, W. G. Toller, J. P. Tessmer, P. S. Pagel, and D. C. Warltier Hyperglycemia reduces coronary collateral blood flow through a nitric oxide-mediated mechanism Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H2097 - H2104. [Abstract] [Full Text] [PDF]
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R. Marfella, F. Nappo, M. A. Marfella, and D. Giugliano Acute Hyperglycemia and Autonomic Function Diabetes Care, November 1, 2001; 24(11): 2016 - 2017. [Full Text] [PDF]
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 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]
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S. J. Duffy, E. S. Biegelsen, M. Holbrook, J. D. Russell, N. Gokce, J. F. Keaney Jr, and J. A. Vita Iron Chelation Improves Endothelial Function in Patients With Coronary Artery Disease Circulation, June 12, 2001; 103(23): 2799 - 2804. [Abstract] [Full Text] [PDF]
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K. L. Goh, A. C. Shore, M. Quinn, and J. E. Tooke Impaired Microvascular Vasodilatory Function in 3-Month-Old Infants of Low Birth Weight Diabetes Care, June 1, 2001; 24(6): 1102 - 1107. [Abstract] [Full Text]
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G. Booth, T. J. Stalker, A. M. Lefer, and R. Scalia Elevated ambient glucose induces acute inflammatory events in the microvasculature: effects of insulin Am J Physiol Endocrinol Metab, June 1, 2001; 280(6): E848 - E856. [Abstract] [Full Text] [PDF]
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M. Zanetti, J.'I. Sato, Z. S. Katusic, and T. O'Brien Gene transfer of superoxide dismutase isoforms reverses endothelial dysfunction in diabetic rabbit aorta Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2516 - H2523. [Abstract] [Full Text] [PDF]
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K. J. Mather, S. Verma, and T. J. Anderson Improved endothelial function with metformin in type 2 diabetes mellitus J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1344 - 1350. [Abstract] [Full Text] [PDF]
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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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H. G. Bohlen and G. P. Nase Arteriolar nitric oxide concentration is decreased during hyperglycemia-induced {beta}II PKC activation Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H621 - H627. [Abstract] [Full Text] [PDF]
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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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T. Hammoud, J.-F. Tanguay, and M. G. Bourassa Management of coronary artery disease: therapeutic options in patients with diabetes J. Am. Coll. Cardiol., August 1, 2000; 36(2): 355 - 365. [Abstract] [Full Text] [PDF]
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M. J. Mullen, D. Wright, A. E. Donald, S. Thorne, H. Thomson, and J. E. Deanfield Atorvastatin but not L-arginine improves endothelial function in type I diabetes mellitus: a double-blind study J. Am. Coll. Cardiol., August 1, 2000; 36(2): 410 - 416. [Abstract] [Full Text] [PDF]
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