This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Calles-Escandon, J. Articles by Cipolla, M. Search for Related Content PubMed PubMed Citation Articles by Calles-Escandon, J. Articles by Cipolla, M.

Diabetes and Endothelial Dysfunction: A Clinical Perspective

Departments of Internal Medicine (J.C.-E.) and Obstetrics and Gynecology (M.C.), College of Medicine, University of Vermont, Burlington, Vermont 05401

The main etiology for mortality and a great percent of morbidity in patients with diabetes mellitus is atherosclerosis. A hypothesis for the initial lesion of atherosclerosis is endothelial dysfunction, defined pragmatically as changes in the concentration of the chemical messengers produced by the endothelial cell and/or by blunting of the nitric oxide-dependent vasodilatory response to acetylcholine or hyperemia. Endothelial dysfunction has been documented in patients with diabetes and in individuals with insulin resistance or at high risk for developing type 2 diabetes. Factors associated with endothelial dysfunction in diabetes include activation of protein kinase C, overexpression of growth factors and/or cytokines, and oxidative stress. Several therapeutic interventions have been tested in clinical trials aimed at improving endothelial function in patients with diabetes. Insulin sensitizers may have a beneficial effect in the short term, but the virtual absence of trials with cardiovascular end-points preclude any definitive conclusion. Two trials offer optimism that treatment with ACE inhibitors may have a positive impact on the progression of atherosclerosis. Although widely used, the effect of hypolipidemic agents on endothelial function in diabetes is not clear. The role of antioxidant therapy is controversial. No data have been published regarding the effects of hormonal replacement therapy on endothelial dysfunction in postmenopausal women with type 2 diabetes.

This article has been cited by other articles:

				J. Galle, E. Schwedhelm, S. Pinnetti, R. H. Boger, C. Wanner, and on behalf of the VIVALDI investigators Antiproteinuric effects of angiotensin receptor blockers: telmisartan versus valsartan in hypertensive patients with type 2 diabetes mellitus and overt nephropathy Nephrol. Dial. Transplant., May 1, 2008; (2008) gfn230v1. [Abstract] [Full Text] [PDF]

				K. Lehle, J. G. Preuner, A. Vogt, L. Rupprecht, A. Keyser, R. Kobuch, C. Schmid, and D. E. Birnbaum Endothelial cell dysfunction after coronary artery bypass grafting with extracorporeal circulation in patients with type 2 diabetes mellitus Eur. J. Cardiothorac. Surg., October 1, 2007; 32(4): 611 - 616. [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]

				A. Miyazaki-Akita, T. Hayashi, Q. F. Ding, H. Shiraishi, T. Nomura, Y. Hattori, and A. Iguchi 17beta-Estradiol Antagonizes the Down-Regulation of Endothelial Nitric-Oxide Synthase and GTP Cyclohydrolase I by High Glucose: Relevance to Postmenopausal Diabetic Cardiovascular Disease J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 591 - 598. [Abstract] [Full Text] [PDF]

				P. Pacher, J. S. Beckman, and L. Liaudet Nitric Oxide and Peroxynitrite in Health and Disease Physiol Rev, January 1, 2007; 87(1): 315 - 424. [Abstract] [Full Text] [PDF]

				E. CHARMANDARI and G. P CHROUSOS Metabolic Syndrome Manifestations in Classic Congenital Adrenal Hyperplasia: Do They Predispose to Atherosclerotic Cardiovascular Disease and Secondary Polycystic Ovary Syndrome? Ann. N.Y. Acad. Sci., November 1, 2006; 1083(1): 37 - 53. [Abstract] [Full Text] [PDF]

				K. Nobe, M. Miyatake, T. Sone, and K. Honda High-Glucose-Altered Endothelial Cell Function Involves Both Disruption of Cell-to-Cell Connection and Enhancement of Force Development J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 530 - 539. [Abstract] [Full Text] [PDF]

				F. Homo-Delarche, S. Calderari, J.-C. Irminger, M.-N. Gangnerau, J. Coulaud, K. Rickenbach, M. Dolz, P. Halban, B. Portha, and P. Serradas Islet Inflammation and Fibrosis in a Spontaneous Model of Type 2 Diabetes, the GK Rat Diabetes, June 1, 2006; 55(6): 1625 - 1633. [Abstract] [Full Text] [PDF]

				R. Yamamoto and Y. Aso Synergistic Association of Metabolic Syndrome and Overt Nephropathy With Elevated Asymmetric Dimethylarginine in Serum and Impaired Cutaneous Microvasodilation in Patients With Type 2 Diabetes Diabetes Care, April 1, 2006; 29(4): 928 - 930. [Full Text] [PDF]

				S. Lim, C. J. Jin, M. Kim, S. S. Chung, H. S. Park, I. K. Lee, C. T. Lee, Y. M. Cho, H. K. Lee, and K. S. Park PPAR{gamma} Gene Transfer Sustains Apoptosis, Inhibits Vascular Smooth Muscle Cell Proliferation, and Reduces Neointima Formation After Balloon Injury in Rats Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 808 - 813. [Abstract] [Full Text] [PDF]

				T. K. Thethi, N. O. Asafu-Adjaye, and V. A. Fonseca Erectile Dysfunction Clin. Diabetes, July 1, 2005; 23(3): 105 - 113. [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]

				P. Fiorina, C. Gremizzi, P. Maffi, R. Caldara, D. Tavano, L. Monti, C. Socci, F. Folli, F. Fazio, E. Astorri, et al. Islet Transplantation Is Associated With an Improvement of Cardiovascular Function in Type 1 Diabetic Kidney Transplant Patients Diabetes Care, June 1, 2005; 28(6): 1358 - 1365. [Abstract] [Full Text] [PDF]

				F. Maingrette and G. Renier Linoleic Acid Increases Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Expression in Human Aortic Endothelial Cells Diabetes, May 1, 2005; 54(5): 1506 - 1513. [Abstract] [Full Text] [PDF]

				R. H Boger, E. Schwedhelm, R. Maas, S. Quispe-Bravo, and C. Skamira ADMA and oxidative stress may relate to the progression of renal disease: rationale and design of the VIVALDI study Vascular Medicine, May 1, 2005; 10(2_suppl): S97 - S102. [Abstract] [PDF]

				M. Suleiman, H. Hammerman, M. Boulos, M. R. Kapeliovich, A. Suleiman, Y. Agmon, W. Markiewicz, and D. Aronson Fasting Glucose Is an Important Independent Risk Factor for 30-Day Mortality in Patients With Acute Myocardial Infarction: A Prospective Study Circulation, February 15, 2005; 111(6): 754 - 760. [Abstract] [Full Text] [PDF]

				T. Nystrom, M. K. Gutniak, Q. Zhang, F. Zhang, J. J. Holst, B. Ahren, and A. Sjoholm Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1209 - E1215. [Abstract] [Full Text] [PDF]

				E. Aburawi, P. Liuba, E. Pesonen, S. Yla-Herttuala, and S. Sjoblad Acute Respiratory Viral Infections Aggravate Arterial Endothelial Dysfunction in Children With Type 1 Diabetes Diabetes Care, November 1, 2004; 27(11): 2733 - 2735. [Full Text] [PDF]

				S Jesmin, C N Mowa, I Sakuma, N Matsuda, H Togashi, M Yoshioka, Y Hattori, and A Kitabatake Aromatase is abundantly expressed by neonatal rat penis but downregulated in adulthood J. Mol. Endocrinol., October 1, 2004; 33(2): 343 - 359. [Abstract] [Full Text] [PDF]

				H. S. Lim, R. J. MacFadyen, and G. Y. H. Lip Diabetes Mellitus, the Renin-Angiotensin-Aldosterone System, and the Heart Arch Intern Med, September 13, 2004; 164(16): 1737 - 1748. [Abstract] [Full Text] [PDF]

				Z. Y. Fang, J. B. Prins, and T. H. Marwick Diabetic Cardiomyopathy: Evidence, Mechanisms, and Therapeutic Implications Endocr. Rev., August 1, 2004; 25(4): 543 - 567. [Abstract] [Full Text] [PDF]

				M. J. Quinones, M. Hernandez-Pampaloni, H. Schelbert, I. Bulnes-Enriquez, X. Jimenez, G. Hernandez, R. De La Rosa, Y. Chon, H. Yang, S. B. Nicholas, et al. Coronary Vasomotor Abnormalities in Insulin-Resistant Individuals Ann Intern Med, May 4, 2004; 140(9): 700 - 708. [Abstract] [Full Text] [PDF]

				M.H. Tayebjee, G.Y.H. Lip, and R.J. MacFadyen Collateralization and the response to obstruction of epicardial coronary arteries QJM, May 1, 2004; 97(5): 259 - 272. [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. Federici, A. Pandolfi, E. A. De Filippis, G. Pellegrini, R. Menghini, D. Lauro, M. Cardellini, M. Romano, G. Sesti, R. Lauro, et al. G972R IRS-1 Variant Impairs Insulin Regulation of Endothelial Nitric Oxide Synthase in Cultured Human Endothelial Cells Circulation, January 27, 2004; 109(3): 399 - 405. [Abstract] [Full Text] [PDF]

				E. T. Fossel Improvement of Temperature and Flow in Feet of Subjects with Diabetes With Use of a Transdermal Preparation of L-Arginine: A pilot study Diabetes Care, January 1, 2004; 27(1): 284 - 285. [Full Text] [PDF]

				D. Tousoulis, C. Antoniades, C. Tountas, E. Bosinakou, M. Kotsopoulou, P. Toutouzas, and C. Stefanadis Vitamin C Affects Thrombosis/ Fibrinolysis System and Reactive Hyperemia in Patients With Type 2 Diabetes and Coronary Artery Disease Diabetes Care, October 1, 2003; 26(10): 2749 - 2753. [Abstract] [Full Text] [PDF]

				D. K. Plante and J. L. Nadler Diabetes and Vascular Disease Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2003; 7(3): 295 - 310. [Abstract] [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]

				E. W. Seely and C. G. Solomon Insulin Resistance and Its Potential Role in Pregnancy-Induced Hypertension J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2393 - 2398. [Abstract] [Full Text] [PDF]

				A. Faggiano, R. Pivonello, S. Spiezia, M. C. De Martino, M. Filippella, C. Di Somma, G. Lombardi, and A. Colao Cardiovascular Risk Factors and Common Carotid Artery Caliber and Stiffness in Patients with Cushing's Disease during Active Disease and 1 Year after Disease Remission J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2527 - 2533. [Abstract] [Full Text] [PDF]

				M. G. Clark, M. G. Wallis, E. J. Barrett, M. A. Vincent, S. M. Richards, L. H. Clerk, and S. Rattigan Blood flow and muscle metabolism: a focus on insulin action Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E241 - E258. [Abstract] [Full Text] [PDF]

				S. T. Knudsen, C. H. Foss, P. L. Poulsen, T. Bek, T. Ledet, C. E. Mogensen, and L. M. Rasmussen E-selectin-inducing activity in plasma from type 2 diabetic patients with maculopathy Am J Physiol Endocrinol Metab, January 1, 2003; 284(1): E1 - E6. [Abstract] [Full Text] [PDF]

				S. Jesmin, C. N. Mowa, N. Matsuda, A.-E. Salah-Eldin, H. Togashi, I. Sakuma, Y. Hattori, and A. Kitabatake Evidence for a Potential Role of Estrogen in the Penis: Detection of Estrogen Receptor-{alpha} and -{beta} Messenger Ribonucleic Acid and Protein Endocrinology, December 1, 2002; 143(12): 4764 - 4774. [Abstract] [Full Text] [PDF]

				F. Sabatier, P. Darmon, B. Hugel, V. Combes, M. Sanmarco, J.-G. Velut, D. Arnoux, P. Charpiot, J.-M. Freyssinet, C. Oliver, et al. Type 1 And Type 2 Diabetic Patients Display Different Patterns of Cellular Microparticles Diabetes, September 1, 2002; 51(9): 2840 - 2845. [Abstract] [Full Text] [PDF]

				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]

				B.-S. Kim, J. Chen, T. Weinstein, E. Noiri, and M. S. Goligorsky VEGF Expression in Hypoxia and Hyperglycemia: Reciprocal Effect on Branching Angiogenesis in Epithelial-Endothelial Co-Cultures J. Am. Soc. Nephrol., August 1, 2002; 13(8): 2027 - 2036. [Abstract] [Full Text] [PDF]

				J. Chen, S. V. Brodsky, D. M. Goligorsky, D. J. Hampel, H. Li, S. S. Gross, and M. S. Goligorsky Glycated Collagen I Induces Premature Senescence-Like Phenotypic Changes in Endothelial Cells Circ. Res., June 28, 2002; 90(12): 1290 - 1298. [Abstract] [Full Text] [PDF]

				R. H. Eckel, M. Wassef, A. Chait, B. Sobel, E. Barrett, G. King, M. Lopes-Virella, J. Reusch, N. Ruderman, G. Steiner, et al. Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group II: Pathogenesis of Atherosclerosis in Diabetes Circulation, May 7, 2002; 105 (18): e138 - e143. [Full Text] [PDF]

				J. T. Rosenbaum Sugar Creates a Sticky Business: Round Up the Usual Suspects Am. J. Pathol., May 1, 2002; 160(5): 1547 - 1550. [Full Text] [PDF]

				J. S. Romney and R. Z. Lewanczuk Vascular Compliance Is Reduced in the Early Stages of Type 1 Diabetes Diabetes Care, December 1, 2001; 24(12): 2102 - 2106. [Abstract] [Full Text] [PDF]

				S. V. Brodsky, T. Yamamoto, T. Tada, B. Kim, J. Chen, F. Kajiya, and M. S. Goligorsky Endothelial dysfunction in ischemic acute renal failure: rescue by transplanted endothelial cells Am J Physiol Renal Physiol, June 1, 2002; 282(6): F1140 - F1149. [Abstract] [Full Text] [PDF]