HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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 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 Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Natali, A. Articles by Ferrannini, E. Search for Related Content PubMed PubMed Citation Articles by Natali, A. Articles by Ferrannini, E. Social Bookmarking                What's this?

Clustering of Insulin Resistance With Vascular Dysfunction and Low-Grade Inflammation in Type 2 Diabetes

¹ Department of Internal Medicine and CNR Institute of Clinical Physiology, University of Pisa, Pisa, Italy
² Department of Medicine, University College London, London, U.K
³ Department of Internal Medicine and Cardiovascular Sciences, "Federico II" University, Naples, Italy

Address correspondence and reprint requests to Dr. Andrea Natali, Department of Internal Medicine and CNR Institute of Clinical Physiology, University of Pisa, Via Roma, 67, 56100 Pisa, Italy. E-mail: anatali{at}ifc.cnr.it

Abbreviations: Ach, acetylcholine; EGP, endogenous glucose production; ELISA, enzyme-linked immunosorbent assay; FBF, forearm blood flow; FFA, free fatty acid; hs-CRP, high-sensitivity C-reactive protein; IL, interleukin; L-NMMA, L-monomethyl-N-arginine; PAI, plasminogen activator inhibitor; SNP, sodium nitroprusside; TNF, tumor necrosis factor; tPA, tissue plasminogen activator; vWF, von Willebrand factor

Vascular dysfunction, low-grade inflammation, insulin resistance, and impaired fibrinolysis have each been reported to be present in type 2 diabetes, but their relationships, and the role of obesity, have not been investigated. We measured insulin sensitivity (euglycemic clamp), forearm blood flow responses to graded local acetylcholine (Ach) and sodium nitroprusside (SNP) infusions, plasma concentrations of tumor necrosis factor (TNF)-, interleukin (IL)-6, von Willebrand factor (vWF), plasminogen activator inhibitor (PAI)-1, tissue plasminogen activator (tPA), and high-sensitivity C-reactive protein (hs-CRP) in 81 diabetic patients. When patients were stratified by insulin resistance, more severe insulin resistance was associated (P < 0.05) with overweight, central fat distribution, hypertension, and dyslipidemia (with similar sex distribution, age, fasting plasma glucose, and HbA_1c). With regard to vascular function, both endothelium-dependent (Ach) (–22, –40, and –52%; P < 0.0001) and -independent (SNP) (–3, –7, and –27%; P < 0.02) vasodilatation were progressively reduced across insulin resistance tertiles. In multivariate analysis, inflammatory markers (IL-6, hs-CRP, and TNF-) were independently associated with insulin resistance and fasting glycemia, fibrinolytic markers PAI-1 and tPA with insulin resistance and central fat distribution, and vascular indexes (vWF, Ach, and SNP vasodilation) with insulin resistance and obesity or cytokines (TNF- or IL-6). In type 2 diabetes, insulin resistance is associated with vascular dysfunction/damage, impaired fibrinolysis, and low-grade inflammation independently of obesity and poor glycemic control.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. M. Ivey, A. S. Ryan, C. E. Hafer-Macko, A. P. Goldberg, and R. F. Macko Treadmill Aerobic Training Improves Glucose Tolerance and Indices of Insulin Sensitivity in Disabled Stroke Survivors: A Preliminary Report Stroke, October 1, 2007; 38(10): 2752 - 2758. [Abstract] [Full Text] [PDF]

				M. G. Flynn, B. K. McFarlin, and M. M. Markofski State of the Art Reviews: The Anti-Inflammatory Actions of Exercise Training American Journal of Lifestyle Medicine, May 1, 2007; 1(3): 220 - 235. [Abstract] [PDF]

				E. Esteve, A. Castro, A. Lopez-Bermejo, J. Vendrell, W. Ricart, and J.-M. Fernandez-Real Serum Interleukin-6 Correlates With Endothelial Dysfunction in Healthy Men Independently of Insulin Sensitivity Diabetes Care, April 1, 2007; 30(4): 939 - 945. [Abstract] [Full Text] [PDF]

				J. V. Silha, B.L. G. Nyomba, W. D. Leslie, and L. J. Murphy Ethnicity, Insulin Resistance, and Inflammatory Adipokines in Women at High and Low Risk for Vascular Disease Diabetes Care, February 1, 2007; 30(2): 286 - 291. [Abstract] [Full Text] [PDF]

				A. E. Pontiroli, P. Pizzocri, R. Paroni, and F. Folli Sympathetic Overactivity, Endothelial Dysfunction, Inflammation, and Metabolic Abnormalities Cluster in Grade III (World Health Organization) Obesity: Reversal through sustained weight loss obtained with laparoscopic adjustable gastric banding Diabetes Care, December 1, 2006; 29(12): 2735 - 2738. [Full Text] [PDF]