Division of Rheumatology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-2681, USA.
Lupus. 2013 Jan;22(1):26-33. doi: 10.1177/0961203312462756. Epub 2012 Oct 11.
Free fatty acids (FFAs) are implicated in the pathogenesis of insulin resistance and atherosclerosis. Inflammatory cytokines promote lipolysis and increase FFAs, a cause of endothelial dysfunction and increased atherosclerosis risk. We hypothesized that increased inflammation is associated with increased FFAs, resulting in insulin resistance and atherosclerosis in patients with systemic lupus erythematosus (SLE). We measured clinical variables, serum FFAs, homeostasis model assessment for insulin resistance (HOMA), inflammatory cytokines, markers of endothelial activation, cholesterol concentrations and coronary artery calcium in 156 patients with SLE and 90 controls. We compared FFAs in patients with SLE and controls using Wilcoxon rank sum tests and further tested for the independent association between FFAs and disease status with adjustment for age, race and sex using multivariable regression models. We assessed the relationship between FFAs and continuous variables of interest using Spearman correlation and multivariable regression analysis. Levels of FFAs were higher in patients with SLE than controls (0.55 mmol/l (0.37-0.71) vs 0.44 mmol/l (0.32-0.60), P = 0.02). Levels of FFAs remained significantly higher among patients with SLE after adjustment for age, race and sex (P = 0.03) but not after further adjustment for body mass index (P = 0.13). FFA levels did not differ according to the usage of current immunosuppressive medications in univariate and adjusted analysis (all P > 0.05). Among patients with SLE, concentrations of FFAs were higher among those with metabolic syndrome compared to those without (0.66 mmol/l (0.46-0.81) vs 0.52 mmol/l (0.35-0.66), P < 0.001). FFAs were positively correlated with insulin resistance (HOMA) (rho = 0.23, P = 0.004, P adjusted = 0.006) and triglyceride levels (rho = 0.22, P = 0.01, P adjusted = 0.004). FFAs were not associated with inflammatory cytokines (IL-6, TNF-α) (all P > 0.05) but were positively associated with levels of E-selectin (rho = 0.33, P = < 0.001, P adjusted = 0.001) and ICAM-1 (rho = 0.35, P < 0.001, P adjusted = 0.001). FFAs were correlated with coronary artery calcium score (rho = 0.20, P = 0.01) but this was attenuated after adjustment for age, race and sex (P = 0.33). From our study we concluded that FFAs are elevated in patients with SLE, particularly those with metabolic syndrome. FFAs in patients with SLE are not associated with markers of generalized inflammation but are associated with insulin resistance and markers of endothelial activation.
游离脂肪酸（FFAs）与胰岛素抵抗和动脉粥样硬化的发病机制有关。炎症细胞因子促进脂肪分解并增加 FFAs，导致内皮功能障碍和动脉粥样硬化风险增加。我们假设炎症增加与 FFAs 增加有关，导致系统性红斑狼疮（SLE）患者的胰岛素抵抗和动脉粥样硬化。我们测量了 156 例 SLE 患者和 90 例对照者的临床变量、血清 FFAs、胰岛素抵抗的稳态模型评估（HOMA）、炎症细胞因子、内皮激活标志物、胆固醇浓度和冠状动脉钙。我们使用 Wilcoxon 秩和检验比较了 SLE 患者和对照组的 FFAs，并使用多变量回归模型进一步测试了 FFAs 与疾病状态之间的独立关联，调整了年龄、种族和性别。我们使用 Spearman 相关和多变量回归分析评估了 FFAs 与感兴趣的连续变量之间的关系。SLE 患者的 FFAs 水平高于对照组（0.55mmol/L（0.37-0.71）比 0.44mmol/L（0.32-0.60），P=0.02）。在校正年龄、种族和性别后，SLE 患者的 FFAs 水平仍然显著升高（P=0.03），但在校正体重指数后则没有（P=0.13）。在单变量和调整分析中，FFAs 水平不因当前免疫抑制药物的使用而有所不同（所有 P>0.05）。在 SLE 患者中，与无代谢综合征的患者相比，有代谢综合征的患者的 FFAs 水平更高（0.66mmol/L（0.46-0.81）比 0.52mmol/L（0.35-0.66），P<0.001）。FFAs 与胰岛素抵抗（HOMA）呈正相关（rho=0.23，P=0.004，P 调整=0.006）和甘油三酯水平（rho=0.22，P=0.01，P 调整=0.004）。FFAs 与炎症细胞因子（IL-6、TNF-α）无关（所有 P>0.05），但与 E-选择素水平呈正相关（rho=0.33，P<0.001，P 调整=0.001）和 ICAM-1（rho=0.35，P<0.001，P 调整=0.001）。FFAs 与冠状动脉钙评分呈正相关（rho=0.20，P=0.01），但在校正年龄、种族和性别后减弱（P=0.33）。从我们的研究中我们得出结论，SLE 患者的 FFAs 升高，特别是有代谢综合征的患者。SLE 患者的 FFAs 与全身炎症标志物无关，但与胰岛素抵抗和内皮激活标志物有关。
