Soluble urokinase-plasminogen activator receptor (suPAR) and natural phosphorylcholine IgM antibodies in patients at clinical onset of diabetes mellitus

Abstract

We have studied the presence of novel inflammatory markers as soluble urokinase plasminogen activator receptor (suPAR) and natural IgM antibodies directed against phosphorylcholine (αPC-IgM) in Swedish diabetic patients (n = 164) and in healthy control subjects (n = 41). SuPAR is expressed by several types of immune cells and has been shown to be a marker of disease severity and predict mortality during infections. It has also been associated with low-grade inflammation. High levels of αPC-IgM have been shown to negatively associate with the risk of cardiovascular disease and vascular inflammation. This has been suggested to be more common among diabetic patients than in the background population. The patients were 15-34 years of age and were included in the diabetes incidence study in Sweden (DISS). They were all clinically diagnosed to have either T1D (n = 82) or T2D (n = 82). All subjects were matched in gender and age. Commercially available ELISA was used to detect suPAR and αPC-IgM. We found that suPAR levels were higher in diabetic patients (n = 164, Q2 = 4.5 mg/L) compared to in healthy control subjects (n = 41, Q2 = 2.7 mg/L; p 2 = 4.9) compared to in patients classified with T1D (n = 82; p=0.0002). The difference between T2D and T1D was even more obvious when LADA (n = 17) was extracted from the T2D group. SuPAR levels did also correlate with BMI (rs = 0.50; p s = 0.23; p s = 0.58; p < 0.0001). Titers of αPC-IgM did not significantly differ between patients and controls. This is the first study to show the difference in suPAR levels between T1D and T2D patients. The high levels of suPAR in T2D patients indicate a strong activation of the immune system and its relation to disease progression needs to be further investigated. However, our data do not support a role for αPC-IgM in the development of diabetes.