Anti- and non-tumor necrosis factor-α-targeted therapies effects on insulin resistance in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis

Abstract

In addition to β-cell failure with inadequate insulin secretion, the crucial mechanism leading to establishment of diabetes mellitus (DM) is the resistance of target cells to insulin, i.e. insulin resistance (IR), indicating a requirement of beyond-normal insulin concentrations to maintain euglycemic status and an ineffective strength of transduction signaling from the receptor, downstream to the substrates of insulin action. IR is a common feature of most metabolic disorders, particularly type II DM as well as some cases of type I DM. A variety of human inflammatory disorders with increased levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β, have been reported to be associated with an increased risk of IR. Autoimmune-mediated arthritis conditions, including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), with the involvement of proinflammatory cytokines as their central pathogenesis, have been demonstrated to be associated with IR, especially during the active disease state. There is an increasing trend towards using biologic agents and small molecule-targeted drugs to treat such disorders. In this review, we focus on the effects of anti-TNF-α- and non-TNF-α-targeted therapies on IR in patients with RA, PsA and AS. Anti-TNF-α therapy, IL-1 blockade, IL-6 antagonist, Janus kinase inhibitor and phospho-diesterase type 4 blocker can reduce IR and improve diabetic hyper-glycemia in autoimmune-mediated arthritis.

Keywords: Insulin resistance; Diabetes mellitus; Tumor necrosis factor-α-targeted therapy; Non-tumor necrosis factor-α-targeted therapy; Rheumatoid arthritis; Psoriatic arthritis

Core Tip: The crucial mechanism leading to development of diabetes mellitus is the resistance of target cells to insulin, i.e. insulin resistance (IR), indicating the ineffective strength of signaling transduction from the receptor, downstream to the final substrates of insulin action. Autoimmune-mediated arthritis including rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, with the involvement of proinflammatory cytokines like tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β as their central pathogenesis, has been demonstrated to be associated with IR. Anti-TNF-α therapy, IL-1 blockade, IL-6 antagonist, Janus kinase inhibitor and phosphodiesterase type 4 blocker can reduce IR and improve diabetic hyperglycemia in autoimmune-mediated arthritis.