Piemonti Lorenzo, Calori Giliola, Mercalli Alessia, Lattuada Guido, Monti Paolo, Garancini Maria Paola, Costantino Federica, Ruotolo Giacomo, Luzi Livio, Perseghin Gianluca
Surgical Department, Istituto Scientifico H San Raffaele, Milan, Italy.
Diabetes Care. 2003 Oct;26(10):2883-9. doi: 10.2337/diacare.26.10.2883.
Leptin and tumor necrosis factor (TNF)-alpha 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.
In this study, fasting plasma leptin, soluble TNF-alpha receptor 2 (TNF-alpha-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.
At baseline, leptin and TNF-alpha-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).
In middle-aged women, MCP-1/CCL2, leptin, and TNF-alpha-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-alpha-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.
瘦素和肿瘤坏死因子（TNF）-α与胰岛素抵抗及心血管疾病相关。体外研究表明，这些作用可能通过单核细胞趋化蛋白（MCP）-1/CCL2的过量产生介导，MCP-1/CCL2是一种参与动脉粥样硬化发病机制的趋化因子。
在本研究中，对207名中年女性（年龄61±12岁，体重指数30.1±6.6kg/m²）进行空腹血浆瘦素、可溶性TNF-α受体2（TNF-α-R2）和MCP-1/CCL2浓度测定，其中包括53例2型糖尿病患者、42例糖耐量受损患者和112例糖耐量正常者，以横断面评估它们与动脉粥样硬化标志物的关系，并纵向随访7年，观察其循环水平是否与心血管疾病（CVD）死亡率相关。
在基线时，各组间瘦素和TNF-α-R2无差异；同时，2型糖尿病患者的MCP-1/CCL2升高（P<0.05）。所有指标均与动脉粥样硬化的生化风险标志物显著相关。单因素分析显示，年龄、空腹胰岛素、瘦素和MCP-1/CCL2与7年时的CVD死亡率相关。进行多因素分析时，只有年龄、瘦素和胰岛素与CVD死亡率保持独立相关，瘦素显示出保护作用（风险比0.88；P<0.02）。
在中年女性中，MCP-1/CCL2、瘦素和TNF-α-R2均与动脉粥样硬化的生化风险标志物相关。与非糖尿病女性相比，MCP-1/CCL2浓度是2型糖尿病患者中唯一升高的指标，也是单因素分析中7年随访期后与CVD死亡风险增加相关的唯一指标。多因素分析中，MCP-1/CCL2和TNF-α-R2均与CVD死亡率无关，数据检查显示，在单因素和多因素分析中，瘦素均与保护作用相关。
