Stavropoulos-Kalinoglou Antonios, Metsios Giorgos S, Panoulas Vasileios F, Nightingale Peter, Koutedakis Yiannis, Kitas George D
Arthritis Res Ther. 2012 Jul 5;14(4):R160. doi: 10.1186/ar3900.
Insulin resistance (IR), a risk factor for the development of cardiovascular disease, is common among patients with rheumatoid arthritis (RA). Inflammation, and especially tumour necrosis factor alpha (TNFα), has been associated with IR, and the administration of anti-TNFα agents is suggested to improve insulin sensitivity. However obesity, a potent contributor to IR, may limit the beneficial effects of anti-TNFα medication on IR. The aim of this study is to compare the effects of anti-TNFα therapy on IR between normal-weight and obese patients with RA.
Patients who were normal-weight with IR (N+IR) or obese with IR (O+IR) and had embarked on anti-TNFα treatment, participated. Assessments included body mass index (BMI), insulin sensitivity (Homeostasis Model Assessment of insulin resistance, HOMA and the Quantitative Insulin sensitivity Check Index, QUICKI), and RA disease characteristics before and following six months of anti-TNFα treatment. Their results were compared to matched (for age, gender, BMI, disease duration and smoking status) normal-weight patients without IR (N-IR) and obese without IR (N-IR), respectively. In total, 32 patients were assessed for this study, with 8 in each group.
Following six months of treatment, disease activity was significantly reduced in all groups (P < 0.05) to a similar extent (P for differences between groups > 0.05 in all cases). In the total population, changes in HOMA (mean reduction at 6 m = -0.2 ± 0.1; P = 0.088) and QUICKI (mean increase at 6 m = 0.03 ± 0.022; P = 0.092) after treatment were not statistically significant, though a trend towards improvement was observed. However, N+IR patients showed a significant decrease in HOMA (mean reduction at 6 m = -0.54 ± 0.2; P = 0.002) and increase in QUICKI (mean increase at 6 m = 0.046 ± 0.02; P = 0.011). These changes were significantly different compared to the other groups (P < 0.05 in all cases). Multivariable analyses showed that the change in Erythrocyte Sedimentation Rate (ESR), and the change in C-Reactive Protein (CRP) associated with the improvement in HOMA (ESR: F₁₋₇ = 5.143, P = 0.019; CRP: F₁₋₇ = 3.122, P = 0.022) and QUICKI (ESR: F₁₋₇ = 3.814, P = 0.021; CRP: F₁₋₇ = 2.67; P = 0.041) only in the N+IR group.
Anti-TNFα therapy, through controlling inflammation, seems to improve insulin sensitivity in normal-weight RA patients with insulin resistance, but is not sufficient to achieving the same beneficial effect in obese RA patients with insulin resistance.
胰岛素抵抗（IR）是心血管疾病发生的一个危险因素，在类风湿关节炎（RA）患者中很常见。炎症，尤其是肿瘤坏死因子α（TNFα），与IR有关，有人提出使用抗TNFα药物可改善胰岛素敏感性。然而，肥胖是导致IR的一个重要因素，可能会限制抗TNFα药物对IR的有益作用。本研究的目的是比较抗TNFα治疗对体重正常和肥胖的RA患者IR的影响。
纳入体重正常且有IR（N+IR）或肥胖且有IR（O+IR）并开始接受抗TNFα治疗的患者。评估指标包括体重指数（BMI）、胰岛素敏感性（胰岛素抵抗稳态模型评估，HOMA以及定量胰岛素敏感性检查指数，QUICKI），以及抗TNFα治疗6个月前后的RA疾病特征。他们的结果分别与年龄、性别、BMI、病程和吸烟状况相匹配的体重正常无IR（N-IR）和肥胖无IR（O-IR）患者进行比较。本研究共评估了32例患者，每组8例。
治疗6个月后，所有组的疾病活动度均显著降低（P<0.05），且降低程度相似（所有情况下组间差异P>0.05）。在总体人群中，治疗后HOMA（6个月时平均降低=-0.2±0.1；P=0.088）和QUICKI（6个月时平均升高=0.03±0.022；P=0.092）的变化无统计学意义，尽管观察到有改善趋势。然而，N+IR组患者的HOMA显著降低（6个月时平均降低=-0.54±0.2；P=0.002），QUICKI升高（6个月时平均升高=0.046±0.02；P=0.011）。与其他组相比，这些变化有显著差异（所有情况下P<0.05）。多变量分析显示，红细胞沉降率（ESR）的变化以及C反应蛋白（CRP）的变化与HOMA（ESR：F₁₋₇=5.143，P=0.019；CRP：F₁₋₇=3.122，P=0.022）和QUICKI（ESR：F₁₋₇=3.814，P=0.021；CRP：F₁₋₇=2.67；P=0.041）的改善仅在N+IR组相关。
抗TNFα治疗通过控制炎症，似乎可改善体重正常且有胰岛素抵抗的RA患者的胰岛素敏感性，但不足以在肥胖且有胰岛素抵抗的RA患者中产生同样的有益效果。
