Psoriatic arthritis (PsA) and diabetes mellitus type 2 (DM 2) - an autoimmune spondyloarthropathy and one of the most common diseases today. How are the two diseases related? A recent study shows that PsA patients have a significantly higher risk of developing diabetes than the general population. The question is, what is the cause of this association and, more importantly, what are the implications of this association for the choice of therapy?
PsA is a rheumatoid factor-negative arthritis that usually manifests in the peripheral joints, but also in the knee, ankle or spine. As a rule, it occurs in patients with pre-existing psoriasis, in a few cases at the same time or without accompanying skin symptoms. The background of the present study is the observation that the inflammatory joint disease is also frequently associated with other concomitant symptoms such as obesity, metabolic syndrome or DM type 2. The evaluation showed that the risk for DM type 2 in the general population is on average between 2.4 and 14.8%, but in PsA patients it is on average between 6.1 and 20.2%. The greatest risk was observed in women with particularly severe PsA.
The exact mechanism of this association is not yet clear, but there are various explanations. In the pathogenesis of PsA, the increased release of inflammatory mediators such as TNF-α, interferon-γ, IL-2 and IL-17 plays a central role. The increased concentrations in the synovial fluid of the affected joints induce the inflammation and thus the symptoms typical of the disease. Apart from this, TNF-α has other effects. It inhibits the autophosphorylation of insulin receptors and the expression of the glucose transporter GLUT4, which inhibits glucose uptake into skeletal muscle, cardiac muscle and fat cells, thus promoting insulin resistance. In addition, TNF-α increases blood cortisol levels by activating steroid 11β-hydroxylase, which also increases insulin resistance. On the one hand, the gluconeogenesis activated by cortisol in the liver increases the blood sugar level. On the other hand, it also prevents the incorporation of GLUT4 transporters and thus glucose uptake in peripheral tissues.
Similar effects are also suspected for IL-17. It leads to an increased expression of further proinflammatory cytokines (IL-1β, IL-6, TNF- α), which also influence the insulin-mediated signalling pathways and subsequently lead to an increase in insulin resistance. The inflammatory mediators mentioned also inhibit the secretion of anti-inflammatory adipokines. These physiologically increase insulin sensitivity and have vasoprotective and anti-atherosclerotic effects. The loss of the protective effect could have an additional influence on the development of diabetes. Studies have shown that adipokine levels are decreased in people with psoriasis and metabolic syndrome.
However, the observed effects do not only serve as an explanation for the association of the two diseases, but above all influence the choice of therapy. The range of treatment options available for PsA is wide. The European League Against Rheumatism (EULAR) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) recommend treatment regimens with different mechanisms of action, consisting of intra-articular administration of glucocorticoids, methotrexate, anti-TNF-α and anti-IL-17 antibodies and apremilast. However, there are major differences with regard to the influence on glucose metabolism. While glucocorticoids and cyclosporine have additional negative effects on insulin sensitivity and serum glucose levels, drugs such as anti-TNF-α or apremilast have no such effects on glucose metabolism and can be used accordingly in PsA patients with additional DM type 2.
Reference:
1. Dal Bello G, Gisondi P, Idolazzi L, Girolomoni G. Psoriatic arthritis and diabetes mellitus: a narrative review. Rheumatol Ther. June 2020;7(2):271-85.