Tumor Necrosis Factor Inhibitors May Improve Glycemic Control in Patients Rheumatoid Arthritis and Concomitant Type 2 Diabetes Mellitus

Abstract

Insulin resistance is a key feature of obesity, metabolic syndrome, and Type 2 Diabetes Mellitus (T2DM). Inflammation and insulin resistance are closely linked with each other. I. Tumor necrosis factor-α (TNF-α) has been found to impair the insulin sensitivity and promote insulin resistance through multiple actions on the insulin sensitive tissues. Inflammatory cyto-kines such as TNF, Interleukin (IL)-6, IL-1 and IL-8 may inhibit insulin signaling.1 Hotamisligil et al2 did the pioneering work in 1993 confirming the link between TNF-α and insulin resis-tance in mice. Animal studies have confirmed that the TNF-α interferes with phosphorylation cascades of the insulin receptor beta subunit and insulin receptor substrate-1, thereby alter-ing the transmembrane signaling that is essential for insulin action in various insulin sensitive tissues.3-5 Also TNF-α causes depletion of GLUT 4, the insulin sensitive glucose transporter in adipocytes and muscles.2,6,7 A intravenous administration of a recombinant TNF-α receptor antibody resulted in improvement in insulin sensitivity2 and dramatic reductions in plasma in-sulin, glucose, and non-esterified fatty acid levels5 in obese, as compared with lean rats.