Chung Cecilia P, Oeser Annette, Solus Joseph F, Gebretsadik Tebeb, Shintani Ayumi, Avalos Ingrid, Sokka Tuulikki, Raggi Paolo, Pincus Theodore, Stein C Michael
Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6602, USA.
Arthritis Rheum. 2008 Jul;58(7):2105-12. doi: 10.1002/art.23600.
Insulin resistance is increased by inflammation, but the mechanisms are unclear. The present study was undertaken to test the hypothesis that decreased insulin sensitivity is differentially associated with mediators of inflammation by studying 2 chronic inflammatory diseases of different pathogenesis, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).
We measured fasting insulin, glucose, and lipid levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and coronary artery calcification in 103 patients with SLE and in 124 patients with RA. Insulin sensitivity was measured using the homeostasis model assessment (HOMA) index.
The HOMA value was higher in RA patients (median 2.05 [interquartile range (IQR) 1.05-3.54]) than in SLE patients (1.40 [0.78-2.59]) (P = 0.007). CRP and ESR did not differ significantly in RA and SLE patients. Body mass index (BMI) was significantly correlated with the HOMA index in both RA (rho = 0.20) and SLE (rho = 0.54), independently of age, sex, race, and current use of corticosteroids. In RA patients, the HOMA index was also significantly positively correlated with IL-6 (rho = 0.63), TNFalpha (rho = 0.50), CRP (rho = 0.29), ESR (rho = 0.26), coronary calcification (rho = 0.26), and Disease Activity Score in 28 joints (rho = 0.21); associations adjusted for age, sex, race, BMI, and current use of corticosteroids remained significant (P < 0.05). In SLE patients, the HOMA index was also significantly correlated with ESR (rho = 0.35) and CRP (rho = 0.25), but not with other variables. The association between the ESR and the HOMA value in patients with SLE remained significant after adjustment for confounding covariates (P = 0.008). In multivariable models, the major contributing factors to the HOMA index were the BMI in SLE patients, and IL-6 and TNFalpha levels in RA patients.
The pathogenesis of insulin resistance and its contribution to atherogenesis varies in different inflammatory settings.
炎症会增加胰岛素抵抗，但具体机制尚不清楚。本研究旨在通过研究两种不同发病机制的慢性炎症性疾病——系统性红斑狼疮（SLE）和类风湿关节炎（RA），来验证胰岛素敏感性降低与炎症介质存在差异关联这一假说。
我们测量了103例SLE患者和124例RA患者的空腹胰岛素、血糖、血脂水平、红细胞沉降率（ESR）、C反应蛋白（CRP）、白细胞介素-6（IL-6）、肿瘤坏死因子α（TNFα）以及冠状动脉钙化情况。采用稳态模型评估（HOMA）指数来测量胰岛素敏感性。
RA患者的HOMA值（中位数2.05 [四分位间距（IQR）1.05 - 3.54]）高于SLE患者（1.40 [0.78 - 2.59]）（P = 0.007）。RA和SLE患者的CRP和ESR无显著差异。体重指数（BMI）在RA（rho = 0.20）和SLE（rho = 0.54）患者中均与HOMA指数显著相关，且不受年龄、性别、种族和当前使用糖皮质激素的影响。在RA患者中，HOMA指数还与IL-6（rho = 0.63）、TNFα（rho = 0.50）、CRP（rho = 0.29）、ESR（rho = 0.26）、冠状动脉钙化（rho = 0.26）以及28个关节的疾病活动评分（rho = 0.21）显著正相关；在对年龄、性别、种族、BMI和当前使用糖皮质激素进行校正后，这些关联仍然显著（P < 0.05）。在SLE患者中，HOMA指数也与ESR（rho = 0.35）和CRP（rho = 0.25）显著相关，但与其他变量无关。在对混杂协变量进行校正后，SLE患者中ESR与HOMA值之间的关联仍然显著（P = 0.008）。在多变量模型中，SLE患者中HOMA指数的主要影响因素是BMI，而RA患者中是IL-6和TNFα水平。
在不同的炎症背景下，胰岛素抵抗的发病机制及其对动脉粥样硬化的影响各不相同。
