This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted 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 Hogikyan, R. V. Articles by Supiano, M. A. Search for Related Content PubMed PubMed Citation Articles by Hogikyan, R. V. Articles by Supiano, M. A.

Specific Impairment of Endothelium-Dependent Vasodilation in Subjects with Type 2 Diabetes Independent of Obesity¹

Divisions of Geriatric Medicine and Endocrinology and Metabolism, Department of Internal Medicine, and Institute of Gerontology, University of Michigan, and Michigan Diabetes Research and Training Center, and Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, Ann Arbor, Michigan 48105

Address all correspondence and requests for reprints to: Robert V. Hogikyan, M.D., Geriatric Research, Education, and Clinical Center (11G), Department of Veterans Affairs Medical Center, Ann Arbor, Michigan 48105. E-mail: hogikyan{at}umich.edu

In subjects with type 2 diabetes in whom an impaired response to an endothelial-dependent vasodilator has been characterized, the populations have also been at least moderately obese. Obesity has been characterized as an independent predictor of endothelial dysfunction in nondiabetic subjects. We hypothesized that in normotensive subjects with type 2 diabetes compared with age-matched control subjects, 1) endothelium-dependent vasodilation, as demonstrated by the forearm blood flow (FABF) response to intraarterial acetylcholine, would be decreased; 2) endothelium-independent vasodilation, as demonstrated by the FABF response to intraarterial nitroprusside, would be similar; 3) the degree of insulin resistance, as measured by the insulin sensitivity index (S_I), would predict greater impairment in the FABF response to acetylcholine; and 4) these relationships would be independent of obesity. We measured FABF by venous occlusion plethysmography during brachial arterial infusions of the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator nitroprusside in 20 control and 17 subjects with type 2 diabetes. We measured S_I using the frequently sampled iv glucose tolerance test. Among the diabetic relative to the control subjects we identified a decrease in the acetylcholine-mediated percent increase in FABF (P = 0.02). Using the absolute FABF response to acetylcholine and including adjustments for body mass index and other covariates, the overall group difference remained and was noted to be greatest in those subjects who had lower baseline FABFs. In contrast, no significant difference in the nitroprusside-mediated increase in the percent change FABF was identified between groups (P = 0.30). Finally, the degree of insulin resistance, as measured by S_I, did not independently predict greater impairment of the FABF response to acetylcholine. This study is the first to identify specific endothelial cell dysfunction that remains significant after adjustment for obesity in a population of normotensive subjects with type 2 diabetes.

This article has been cited by other articles:

				E. L. Air and B. M. Kissela Diabetes, the Metabolic Syndrome, and Ischemic Stroke: Epidemiology and possible mechanisms Diabetes Care, December 1, 2007; 30(12): 3131 - 3140. [Full Text] [PDF]

				F. Mittermayer, G. Schaller, J. Pleiner, K. Krzyzanowska, S. Kapiotis, M. Roden, and M. Wolzt Rosiglitazone Prevents Free Fatty Acid-Induced Vascular Endothelial Dysfunction J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2574 - 2580. [Abstract] [Full Text] [PDF]

				S. P. Didion, C. M. Lynch, and F. M. Faraci Cerebral vascular dysfunction in TallyHo mice: a new model of Type II diabetes Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1579 - H1583. [Abstract] [Full Text] [PDF]

				S. S. Shankar, R. V. Considine, J. C. Gorski, and H. O. Steinberg Insulin sensitivity is preserved despite disrupted endothelial function Am J Physiol Endocrinol Metab, October 1, 2006; 291(4): E691 - E696. [Abstract] [Full Text] [PDF]

				A. Natali, E. Toschi, S. Baldeweg, D. Ciociaro, S. Favilla, L. Sacca, and E. Ferrannini Clustering of insulin resistance with vascular dysfunction and low-grade inflammation in type 2 diabetes. Diabetes, April 1, 2006; 55(4): 1133 - 1140. [Abstract] [Full Text] [PDF]

				D. A. Klibansky, A. Chin, I. J. Duignan, and J. M. Edelberg Synergistic targeting with bone marrow-derived cells and PDGF improves diabetic vascular function Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1387 - H1392. [Abstract] [Full Text] [PDF]

				J. B. Meigs, C. J. O'Donnell, G. H. Tofler, E. J. Benjamin, C. S. Fox, I. Lipinska, D. M. Nathan, L. M. Sullivan, R. B. D'Agostino, and P. W.F. Wilson Hemostatic Markers of Endothelial Dysfunction and Risk of Incident Type 2 Diabetes: The Framingham Offspring Study Diabetes, February 1, 2006; 55(2): 530 - 537. [Abstract] [Full Text] [PDF]

				S. P. Didion, C. M. Lynch, G. L. Baumbach, and F. M. Faraci Impaired Endothelium-Dependent Responses and Enhanced Influence of Rho-Kinase in Cerebral Arterioles in Type II Diabetes Stroke, February 1, 2005; 36(2): 342 - 347. [Abstract] [Full Text] [PDF]

				K. J. Mather, A. Lteif, H. O. Steinberg, and A. D. Baron Interactions Between Endothelin and Nitric Oxide in the Regulation of Vascular Tone in Obesity and Diabetes Diabetes, August 1, 2004; 53(8): 2060 - 2066. [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]

				J. B. Meigs, F. B. Hu, N. Rifai, and J. E. Manson Biomarkers of Endothelial Dysfunction and Risk of Type 2 Diabetes Mellitus JAMA, April 28, 2004; 291(16): 1978 - 1986. [Abstract] [Full Text] [PDF]

				C. D. A. Stehouwer Endothelial dysfunction in diabetic nephropathy: state of the art and potential significance for non-diabetic renal disease Nephrol. Dial. Transplant., April 1, 2004; 19(4): 778 - 781. [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. 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]

				A. A Brown and F. B Hu Dietary modulation of endothelial function: implications for cardiovascular disease Am. J. Clinical Nutrition, April 1, 2001; 73(4): 673 - 686. [Abstract] [Full Text] [PDF]

				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]

				B. Hennig, M. Toborek, and C. J. McClain High-Energy Diets, Fatty Acids and Endothelial Cell Function: Implications for Atherosclerosis J. Am. Coll. Nutr., April 1, 2001; 20(2): 97 - 105. [Abstract] [Full Text] [PDF]

				J. Calles-Escandon and M. Cipolla Diabetes and Endothelial Dysfunction: A Clinical Perspective Endocr. Rev., February 1, 2001; 22(1): 36 - 52. [Abstract] [Full Text]

				D. FLISER, R. DIKOW, S. DEMUKAJ, and E. RITZ Opposing Effects of Angiotensin II on Muscle and Renal Blood Flow under Euglycemic Conditions J. Am. Soc. Nephrol., November 1, 2000; 11(11): 2001 - 2006. [Abstract] [Full Text]

				D. Perregaux, A. Chaudhuri, S. Rao, A. Airen, M. Wilson, B.-H. Sung, and P. Dandona Brachial Vascular Reactivity in Blacks Hypertension, November 1, 2000; 36(5): 866 - 871. [Abstract] [Full Text] [PDF]

				D.W. Laight, M.J. Carrier, and E.E. Anggard Antioxidants, diabetes and endothelial dysfunction Cardiovasc Res, August 18, 2000; 47(3): 457 - 464. [Abstract] [Full Text] [PDF]

				F. Brunner, G. Wolkart, S. Pfeiffer, J. C Russell, and T. C Wascher Vascular dysfunction and myocardial contractility in the JCR:LA-corpulent rat Cardiovasc Res, July 1, 2000; 47(1): 150 - 158. [Abstract] [Full Text] [PDF]

				J. M. Lash, G. P. Nase, and H. G. Bohlen Acute hyperglycemia depresses arteriolar NO formation in skeletal muscle Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1513 - H1520. [Abstract] [Full Text] [PDF]