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

Abstract

The purpose of this study was to determine whether long-term modulation of inflammatory activity by tumor necrosis factor (TNF)-α inhibitors has some influence on insulin resistance (IR). 16 active rheumatoid arthritis (RA) patients without CV risk factors treated with anti-TNF-α 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/m2, 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-α treatment; only retinol-binding protein 4, showed a significant increase (51.7 ± 32.7 vs. 64.9 ± 28.4 μg/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-α in RA patients. Our data suggest that although systemic blockade of TNF-α exerts an anticachectic effect in RA patients, it does not seem to play a major role in IR.

Improvement in insulin resistance is greater when infliximab is added to methotrexate during intensive treatment of early rheumatoid arthritis—results from the IDEA study

“…Similar magnitudes of change have been reported previously [13]. The effect of therapy on HOMA-IR has been less well studied [40], with most reporting the effect of TNFi alone, involving small established RA cohorts [19,20] or short-term follow-up [18]. Our study provides valuable longer-term data.…”

“…DMARDS appear to reduce TC/HDL-C [13,14], however, metaanalyses report conflicting results [15,16], suggesting a complex relationship. IR can be improved with DMARDs in established RA [17], but the effect of TNFi is unclear [18][19][20][21][22][23][24]. The limited data on NT-proBNP suggest improvement with TNFi [25].…”

TNF-α in the cardiovascular system: from physiology to therapy

“…While some studies reported improved insulin sensitivity in infliximab-treated patients with rheumatoid arthritis, 185,186 other authors found that insulin resistance was not alleviated by antagonism of TNF-α. 187 Gonzalez-Gay et al 188 suggested that the effects may depend on the degree and severity of insulin resistance before the start of therapy, whereby the beneficial effect is observed in patients with the most severe disease.…”

Visfatin: a new player in rheumatic diseases

“…RA in humans has been associated with impaired insulin sensitivity and glucose tolerance [31]. High serum visfatin has adiponectin [20].…”