Fasting Plasma Leptin, Tumor Necrosis Factor-α Receptor 2, and Monocyte Chemoattracting Protein 1 Concentration in a Population of Glucose-Tolerant and Glucose-Intolerant Women

Fasting Plasma Leptin, Tumor Necrosis Factor-α Receptor 2, and Monocyte Chemoattracting Protein 1 Concentration in a Population of Glucose-Tolerant and Glucose-Intolerant Women Impact on cardiovascular mortality Lorenzo Piemonti , MD 1 , Giliola Calori , MD 2 , Alessia Mercalli , PHD 1 , Guido Lattuada , PHD 3 , Paolo Monti , PHD 1 , Maria Paola Garancini , MD 2 , Federica Costantino 3 , Giacomo Ruotolo , MD 3 , Livio Luzi , MD 3 4 5 and Gianluca Perseghin , MD 3 4 1 Laboratory of Experimental Surgery, Surgical Department, Istituto Scientifico H San Raffaele, Milan, Italy 2 Epidemiology Unit, Istituto Scientifico H San Raffaele, Milan, Italy 3 Section of Nutrition/Metabolism, Istituto Scientifico H San Raffaele, Milan, Italy 4 Unit of Clinical Spectroscopy, Istituto Scientifico H San Raffaele, Milan, Italy 5 Faculty of Exercise Sciences, Università degli Studi di Milano, Milan, Italy Address correspondence and reprint requests to Gianluca Perseghin, MD, Internal Medicine, Section of Nutrition/Metabolism/Unit of Clinical Spectroscopy, Istituto Scientifico H San Raffaele, via Olgettina 60, 20132, Milan, Italy. E-mail: perseghin.gianluca{at}hsr.it Abstract OBJECTIVE —Leptin and tumor necrosis factor (TNF)-α are associated with insulin resistance and cardiovascular disease. In vitro studies suggested that these effects may be mediated via overproduction of monocyte chemoattracting protein (MCP)-1/CCL2, which is a chemokine involved in the pathogenesis of atherosclerosis. RESEARCH DESIGN AND METHODS —In this study, fasting plasma leptin, soluble TNF-α receptor 2 (TNF-α-R2), and MCP-1/CCL2 concentrations were measured in 207 middle-aged women (age 61 ± 12 years, BMI 30.1 ± 6.6 kg/m 2 ), including 53 patients with type 2 diabetes, 42 with impaired glucose tolerance, and 112 with normal glucose tolerance, to assess cross-sectionally their relationship with markers of atherosclerosis and, longitudinally over 7 years, whether their circulating levels were associated with cardiovascular disease (CVD) mortality. RESULTS —At baseline, leptin and TNF-α-R2 were not different among groups; meanwhile, MCP-1/CCL2 was increased in type 2 diabetes ( P < 0.05). All showed significant associations with biochemical risk markers of atherosclerosis. In a univariate analysis, age, fasting insulin, leptin, and MCP-1/CCL2 were associated with CVD mortality at 7 years. When a multivariate analysis was performed, only age, leptin, and insulin retained an independent association with CV