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Serum Interleukin-6 Correlates With Endothelial Dysfunction in Healthy Men Independently of Insulin Sensitivity

¹ Unit of Diabetes, Endocrinology, and Nutrition, Department of Internal Medicine, Hospital of Girona Dr. Josep Trueta, Girona, Spain
² CIBER Pathophysiology of Obesity (CB/06), Girona, Spain
³ Unit of Diabetes, Endocrinology and Nutrition, Hospital of Tarragona "Joan XXIII," Tarragona, Spain

Address correspondence and reprint requests to J.M. Fernández-Real, MD, PhD, Unit of Diabetes, EndocrinologyNutrition, Hospital de Girona "Dr Josep Trueta," Ctra. França s/n, 17007 Girona, Spain. E-mail: uden.jmfernandezreal{at}htrueta.scs.es

OBJECTIVE—Interleukin (IL)-6 is a proinflammatory cytokine that is implicated in the pathogenesis of atherosclerosis and insulin resistance. Both endothelial dysfunction and insulin resistance are among the earliest abnormalities that can be detected in people at risk for cardiovascular events. We aimed to evaluate whether increased serum IL-6 concentrations associated with endothelial dysfunction are independent of insulin sensitivity in apparently healthy men.

RESEARCH DESIGN AND METHODS—Association studies were performed in well-characterized nondiabetic Caucasian men (n = 99) recruited for energy balance studies. Insulin sensitivity (minimal model) and brachial vascular reactivity (high-resolution external ultrasound) were assessed. Circulating IL-6 concentrations were measured by enzyme-linked immunosorbent assay.

RESULTS—Serum IL-6 was an independent contributor to the variance of endothelium-dependent vasodilatation after adjusting for age, BMI, smoking status, LDL cholesterol, systolic blood pressure, diastolic blood pressure, and insulin sensitivity (P = 0.001). In fact, circulating IL-6 was negatively associated with endothelium-dependent vasodilatation (r = –0.247, P = 0.014) and insulin sensitivity (r = –0.262, P = 0.011) and correlated positively with age (r = 0.241, P = 0.016), BMI (r = 0.240, P = 0.017), systolic blood pressure (r = 0.299, P = 0.003), diastolic blood pressure (r = 0.295, P = 0.003), and triglycerides (r = 0.212, P = 0.035). No significant associations were observed between endothelium-independent vasodilatation and serum IL-6 concentrations.

CONCLUSIONS—Circulating IL-6 is linked to endothelial dysfunction independently of insulin sensitivity in apparently healthy men.

Abbreviations: IL, interleukin • TNF, tumor necrosis factor

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