Rheumatoid Arthritis Treatment Options and Type 2 Diabetes: Unravelling the Association

Abstract

Multiple lines of evidence have increasingly suggested a pathogenic connection between rheumatoid arthritis (RA) and the mechanisms of type 2 diabetes (T2D) in a vicious circle perpetuated by glucose derangement and inflammatory mediators. These findings have been further reinforced by clinical studies showing that the inhibition of interleukin (IL)-1 and IL-6 may allow the treatment of RA and concomitant T2D at the same time. Interestingly, IL-1 inhibition induced a more evident reduction of glycated haemoglobin (HbA1c) in patients with concomitant RA and T2D than in previous studies on IL-1 inhibition in patients with this metabolic disease alone. Thus, the inflammatory pathogenic mechanisms of T2D could be exaggerated in the context of a rheumatic disease, possibly explaining these findings. In fact, IL-1 inhibition could not only palliate glycaemia, but also decrease the progressive decline in insulin secretion associated with T2D, interfering with apoptosis of β-cells, improving their function, and ameliorating the peripheral insulin resistance. Moreover, the maintenance of clinical remission of rheumatic disease could further improve the glucose derangement and reduce the occurrence of T2D in RA. On these bases, the presence of T2D may allow the physicians to perform a better profile of patients with RA according to the principles of precision medicine, tailoring the medical treatment to the individual characteristics. In this context, the benefits of targeting the inflammatory process, mainly by IL-1 inhibition, may be suggested in patients with RA and concomitant T2D.

Differential Causal Effects of Type 1 and Type 2 Diabetes on Osteomyelitis Risk: Insights from Mendelian Randomization Analysis

“…For the significant causal associations in the univariable MR analysis, the MVMR analysis was performed using the MVMR-IVW method, aiming to adjust for potential confounding factors BMI 21 . Mediation MR analysis Clinical studies indicate that RA is associated with an increased risk of OM 9 . To explore whether DM mediates this association, we conducted two-step mediation MR analysis, assessing three key estimates: (i) the total effect of RA on OM (β_all); (ii) the direct effect of RA on DM (β1); and (iii) the direct effect of DM on OM (β2).…”

“…Additionally, they underscore the importance of comprehensive risk assessment in diabetic patients, beyond glycemic control alone. Previous research has established RA as a common risk factor for both T2DM and OM 7,9,10 . Our study further investigated their associations with T2DM and OM risk, revealing the extent to which T2DM mediates RA's causal effect on OM.…”

“…Clinical studies indicate that RA is associated with an increased risk of OM 9 . To explore whether DM mediates this association, we conducted two-step mediation MR analysis, assessing three key estimates: (i) the total effect of RA on OM (β_all); (ii) the direct effect of RA on DM (β1); and (iii) the direct effect of DM on OM (β2).…”

“…RA is also associated with diabetes due to a vicious circle perpetuated by glucose derangement and inflammatory mediators. 9,10 . Given the shared risk profile of RA with both diabetes and OM, we employed mediation MR analysis to investigate the mediating role of DM between RA and OM.…”

Interleukin-19 promotes bone resorption by suppressing osteoprotegerin expression in BMSCs in a lipopolysaccharide-induced bone loss mouse model

“…Immune system malfunction has an important role in the development of primary osteoporosis, while inflammation is a direct contributor to osteoporosis. Various inflammatory markers, such as IL-1, IL-6, IL-17, and TNF-α, may upregulate RANKL expression in joints of patients with rheumatoid arthritis, [25][26][27] which in turn induces osteoclastogenesis. Combined deficiency of IL-1/IL-6 has been reported to markedly ameliorate TNF-mediated arthritis and bilateral sacroiliitis.…”