IL-1 inhibition improves insulin resistance and adipokines in rheumatoid arthritis patients with comorbid type 2 diabetes

Abstract

Recently, it has been shown that some well-known pathogenic mediators in rheumatoid arthritis (RA), such as interleukin-1β (IL-1β) and tumor necrosis factor (TNF), could play a pathogenic role in insulin resistance and (IR) and type 2 diabetes (T2D). In this 6-month longitudinal study, we aimed at investigating if the inhibition of IL-1 or TNF is associated with an improvement of IR in RA patients with comorbid T2D and the possible effects on selected serum adipokines. RA patients with comorbid T2D were recruited among those undergoing treatment with anakinra (ANA) or with TNF inhibitor (TNFi). The 1998-updated version of the Homeostasis Model Assessment (HOMA2) was used to calculate surrogate indexes of IR (HOMA2-IR) and steady-state beta cell function (%B) from fasting values of glucose and C-peptide. Glucagon, adiponectin, adipsin, leptin, and resistin were also measured. All these parameters were collected at baseline, after 3 and 6 months of treatment. ANA-treated patients showed a significant improvement in HOMA2-%β, HOMA2-IR, and glucagon. In TNFi-treated patients, no significant difference was observed analyzing these metabolic parameters. Adipsin and resistin decreased after 6 months in ANA-treated patients whereas, no difference was recognized analyzing adiponectin and leptin. In TNFi-treated patients, leptin and resistin significantly increased, whereas no difference was found analyzing adiponectin and adipsin, during the follow-up. Our data may suggest a beneficial effect of IL-1 inhibition on measures of metabolic derangement in RA-associated T2D. If further confirmed by larger studies, IL-1 targeting therapies may represent a tailored approach in these patients.

Platelet concentrate and type II IL-1 receptor are risk factors for allergic transfusion reactions in children

“…These results showed that the dynamic equilibrium between IL-1-dependent intracellular signaling and IL1R2 was associated with the progression of human diseases. IL-1-dependent intracellular signaling attributes to the pathogenesis of many diseases including arteriosclerosis [8], rheumatoid arthritis [25], type 2 diabetes [25,26], and pustular psoriasis [27]. The inhibition of IL-1, Fig.…”

Fasting triglycerides and glucose index: a useful screening test for assessing insulin resistance in patients diagnosed with rheumatoid arthritis and systemic lupus erythematosus

“…TLR2/4 activation causes a proinflammatory response in autoimmune diseases and contributes to an obesity-induced inflammatory response by increasing TNF-a and IL-6 levels in RA and TNF-a, IL-6, IL-23, and IL-10 levels in SLE [7]. Some inflammatory mediators of the TLR2/4 pathway, including JNK, IL-1, and IL-6, induce IR by impairing insulin receptor substrates and PI3K–AKT pathway activation [34, 36]. Additionally, an increase in free fatty acids, which is observed in IR, decreases the secretion of adiponectin, an anti-inflammatory adipokine that increases the secretion of and sensitivity to insulin.…”

Dietary Quality Associated with Self-Reported Diabetes, Osteoarthritis, and Rheumatoid Arthritis among Younger and Older US Adults: A Cross-Sectional Study Using NHANES 2011–2016

“…The prevalence rates of DM and AR in those with any disability are more than doubled compared to those without disability [ 4 ]. Furthermore, previous studies reported a high prevalence of AR among individuals with DM and vice versa [ 5 , 6 , 7 , 8 , 9 , 10 ], which has motivated researchers to examine the links between the two diseases [ 11 , 12 , 13 , 14 , 15 ].…”