Serum and urinary levels of MIF, CD74, DDT and CXCR4 among patients with type 1 diabetes mellitus, type 2 diabetes and healthy individuals: Implications for further research

Abstract

Background

Macrophage migration inhibitory factor (MIF) is a highly conserved cytokine with pleiotropic properties, mainly pro-inflammatory. MIF seems to exert its pro-inflammatory features by binding to its transmembrane cellular receptor CD74. MIF also has CXCR4, which acts as a co-receptor in this inflammatory process. Apart from MIF, D-dopachrome tautomerase (DDT) or MIF2, which belongs to the MIF superfamily, also binds to receptor CD74. Therefore, these molecules, MIF, CD74, DDT and CXCR4 are suggested to work together orchestrating an inflammatory process. Diabetes mellitus is characterised by chronic low-grade inflammation. Therefore, the aim of the present study was to evaluate serum and urinary levels of the aforementioned molecules among patients with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and among healthy controls.

Methods

We enrolled 13 patients with T1DM, 74 patients with T2DM and 25 healthy individuals as controls. Levels of CD74, CXCR4, DDT, and MIF were measured using ELISA Kits according to the manufacturer's instructions.

Results

We documented increased serum MIF levels together with higher urinary CD74 levels among patients with T1DM, when compared to patients with T2DM and healthy adults. In particular, patients with T1DM showed significantly increased levels of MIF compared to T2DM (p = 0.011) and healthy controls (p = 0.0093). CD74 in urine were significantly higher in patients with T1DM compared to those affected with T2DM (p = 0.0302) and healthy group (p = 0.0099). On the contrary, serum CD74 were similar among the three groups. No statistical differences were identified in CXCR4 levels both in serum and in urine of all groups. Patients with T2DM and overweight/obesity had increased urinary levels of CD74, when compared to lean patients with T2DM.

Conclusion

The increased serum MIF levels and urinary CD74 levels among patients with T1DM may be attributed to the autoimmune milieu, which characterises patients with T1DM, when compared to patients with T2DM. These two findings merit further attention as they could pave the way for further research regarding the potential beneficial effects of inhibitors of MIF among patients with T1DM, especially in the early stages of T1DM. Finally, the role of inhibitors of MIF could be further explored in the context of obesity among patients with T2DM.