Anti-tumour necrosis factor alpha therapy improves insulin sensitivity in normal-weight but not in obese patients with rheumatoid arthritis

Abstract

Introduction: 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 (TNF alpha), has been associated with IR, and the administration of anti-TNF alpha agents is suggested to improve insulin sensitivity. However obesity, a potent contributor to IR, may limit the beneficial effects of anti-TNF alpha medication on IR. The aim of this study is to compare the effects of anti-TNF alpha therapy on IR between normal-weight and obese patients with RA. Methods: Patients who were normal-weight with IR (N+IR) or obese with IR (O+IR) and had embarked on anti-TNF alpha 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-TNF alpha 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. Results: 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. Conclusions: Anti-TNF alpha 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.