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© 2003 by the American Diabetes Association, Inc.
Pathophysiology/Complications |
Fasting Plasma Leptin, Tumor Necrosis Factor-
Receptor 2, and Monocyte Chemoattracting Protein 1 Concentration in a Population of Glucose-Tolerant and Glucose-Intolerant Women
Impact on cardiovascular mortality
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
OBJECTIVE—Leptin and tumor necrosis factor (TNF)-
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- receptor 2 (TNF--R2), and MCP-1/CCL2 concentrations were measured in 207 middle-aged women (age 61 ± 12 years, BMI 30.1 ± 6.6 kg/m2), 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--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 CVD mortality, with leptin showing a protective effect (hazard ratio 0.88; P < 0.02).
CONCLUSIONS—In middle-aged women, MCP-1/CCL2, leptin, and TNF--R2 were all related to biochemical risk markers of atherosclerosis. MCP-1/CCL2 concentration was the only one to be increased in type 2 diabetes with respect to nondiabetic women and the only one to be associated with increased risk of CVD mortality after a 7-year follow-up period in the univariate analysis. In the multivariate analysis, neither MCP-1/CCL2 nor TNF--R2 was associated with CVD mortality, and inspection of the data showed that leptin, in both the univariate and multivariate analysis, was associated with a protective effect.
Abbreviations: ALP, alkaline phosphatase • ALT, alanine transaminase • AST, aspartate transaminase • CVD, cardiovascular disease • 
GT, -glutamyl transferase • IGT, impaired glucose tolerance • NGT, normal glucose tolerance • MCP, monocyte chemoattracting protein • QUICKI, quantitative insulin sensitivity check index • TNF, tumor necrosis factor • TNF--R2, TNF- receptor 2
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