Systemic Blockade of TNF-α does not Improve Insulin Resistance in Humans

The purpose of this study was to determine whether long-term modulation of inflammatory activity by tumor necrosis factor (TNF)-alpha inhibitors has some influence on insulin resistance (IR). 16 active rheumatoid arthritis (RA) patients without CV risk factors treated with anti-TNF-alpha agents were included in this study. RA activity by disease activity score 28, IR by HOMA2-IR, body composition by impedance analysis, physical activity by accelerometry, abdominal fat distribution by magnetic resonance imaging, and serum level of key adipokines by ELISA were measured at baseline and during a 1-year follow-up period. Patient body mass index increased significantly (26.94 +/- 3.88 vs. 28.06 +/- 4.57 kg/m(2), p = 0.02) after 1 year of treatment. Body composition, in terms of fat and fat-free mass, remained unchanged except for a significant elevation in body cell mass (25.50 +/- 4.60 vs. 26.60 +/- 3.17 kg, p = 0.02). Basal levels of IR in the RA patients included in this study were significantly higher than healthy controls (1.6 +/- 0.8 vs. 1.11 +/- 0.56, p = 0.011) but did not change during the follow-up. Nor did basal concentrations of adiponectin, visfatin, leptin, ghrelin, resistin, and apelin in response to anti-TNF-alpha treatment; only retinol-binding protein 4, showed a significant increase (51.7 +/- 32.7 vs. 64.9 +/- 28.4 mu g/ml, p = 0.03) at the end of the study. IR, adiposity distribution, and serum levels of most adipokines are not significantly affected by long-term inhibition of TNF-alpha in RA patients. Our data suggest that although systemic blockade of TNF-alpha exerts an anticachectic effect in RA patients, it does not seem to play a major role in IR.