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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)-\u03b1, 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 &amp;lt; 0.05) with overweight, central fat distribution, hypertension, and dyslipidemia (with similar sex distribution, age, fasting plasma glucose, and HbA1c). With regard to vascular function, both endothelium-dependent (Ach) (\u221222, \u221240, and \u221252%; P &amp;lt; 0.0001) and -independent (SNP) (\u22123, \u22127, and \u221227%; P &amp;lt; 0.02) vasodilatation were progressively reduced across insulin resistance tertiles. In multivariate analysis, inflammatory markers (IL-6, hs-CRP, and TNF-\u03b1) 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-\u03b1 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.<\/jats:p>","DOI":"10.2337\/diabetes.55.04.06.db05-1076","type":"journal-article","created":{"date-parts":[[2006,5,8]],"date-time":"2006-05-08T22:24:58Z","timestamp":1147127098000},"page":"1133-1140","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":158,"title":["Clustering of Insulin Resistance With Vascular Dysfunction and Low-Grade Inflammation in Type 2 Diabetes"],"prefix":"10.2337","volume":"55","author":[{"given":"Andrea","family":"Natali","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and CNR Institute of Clinical Physiology, University of Pisa, Pisa, Italy"}]},{"given":"Elena","family":"Toschi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and CNR Institute of Clinical Physiology, University of Pisa, Pisa, Italy"}]},{"given":"Stephanie","family":"Baldeweg","sequence":"additional","affiliation":[{"name":"Department of Medicine, University College London, London, U.K"}]},{"given":"Demetrio","family":"Ciociaro","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and CNR Institute of Clinical Physiology, University of Pisa, Pisa, Italy"}]},{"given":"Stefania","family":"Favilla","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and CNR Institute of Clinical Physiology, University of Pisa, Pisa, Italy"}]},{"given":"Luigi","family":"Sacca\u0300","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiovascular Sciences, \u201cFederico II\u201d University, Naples, Italy"}]},{"given":"Ele","family":"Ferrannini","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and CNR Institute of Clinical Physiology, University of Pisa, Pisa, Italy"}]}],"member":"1167","reference":[{"key":"2022031217132352500_R1","doi-asserted-by":"crossref","unstructured":"National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. 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