Adiponectin Is Associated With Vascular Function Independent of Insulin Sensitivity

Adiponectin Is Associated With Vascular Function Independent of Insulin Sensitivity José-Manuel Fernández-Real , MD, PHD 1 , Antoni Castro , MD, PHD 1 , Gabriel Vázquez , MD 1 , Roser Casamitjana , PHD 2 , Abel López-Bermejo , MD, PHD 1 , Georgina Peñarroja , MD 1 and Wifredo Ricart , MD 1 1 Unitat de Diabetologia, Endocrinologia i Nutricio and Servei de Medicina Interna, University Hospital of Girona “Dr. Josep Trueta,” Girona, Spain 2 Hormonal Laboratory, Hospital Clinic, Barcelona, Spain Address correspondence and reprint requests to J.-M. Fernández-Real, MD, PhD, Unit of Diabetes, Endocrinology, and Nutrition, Hospital de Girona “Dr. Josep Trueta,” Ctra. França s/n, 17007 Girona, Spain. E-mail: uden.jmfernandezreal{at}htrueta.scs.es Abstract OBJECTIVE —Adiponectin has been proposed to play important roles in the regulation of energy homeostasis and insulin sensitivity. In experimental studies, adiponectin has also been found to inhibit vascular smooth muscle cell proliferation. Decreased adiponectin levels have been described in patients with coronary artery disease, and circulating adiponectin predicts cardiovascular death in patients with renal failure. Because adiponectin appears to influence both insulin sensitivity and vessel wall physiology, we examined insulin sensitivity and vascular function in relation with circulating adiponectin. RESEARCH DESIGN AND METHODS —We studied brachial artery vascular reactivity (high-resolution external ultrasound) and insulin sensitivity (minimal model) in 68 healthy subjects. Brachial artery vascular reactivity was also determined in 52 patients with altered glucose tolerance: 30 subjects with impaired fasting glucose (IFG) or glucose intolerance (GIT) and 22 patients with type 2 diabetes. RESULTS —Circulating adiponectin concentration was significantly associated with insulin sensitivity ( r = 0.29, P = 0.02) and with fasting serum triglycerides ( r = −0.29, P = 0.02) in healthy subjects. In the latter, adiponectin levels were positively associated with arterial vasodilation in response to nitroglycerin (endothelium-independent vasodilation [EIVD], r = 0.41, P = 0.002) but not with flux-induced, endothelium-dependent vasodilation (EDVD) ( r = 0.007, P = NS). In contrast, EIVD was not significantly associated with adiponectin in subjects with IFG, GIT, or type 2 diabetes ( r ≤ 0.10, P = NS). In a multiple linear regression analysis to predict EIVD in healthy subjects, age ( P = 0.012), sex ( P = 0.042), and adip