CIRCULATING PEPTIDES OF THE TNF SUPERFAMILY AND TNF RECEPTOR SUPERFAMILY IN SUBJECTS WITH TYPE 1 DIABETES:...

Tumor Necrosis Factor Superfamily (TNFSF) and Tumor Necrosis Factor Receptor Superfamily (TNFRSF) molecules play an essential role in the regulation of immune and inflammatory reactions and may be involved in the pathogenesis of type 1 diabetes (T1D). In this study, we aimed to assess serum levels of TNFSF and TNFRSF peptides in T1D subjects depending on their clinical and metabolic parameters. Fifty-eight adults with T1D and 19 individuals with normal glucose tolerance (control) were included in the study. Concentrations of TNF-α, TNF-β, TWEAK, APRIL, BAFF, LIGHT, sTNFR1, sTNFR2, and sCD30 were assessed by multiplex bead array assay. Time in range (TIR) and glucose variability (GV) were assessed by continuous glucose monitoring. Patients with T1D had increased levels of TNF-α and decreased levels of LIGHT compared to control (р=0.03 and p=0.02 respectively). Patients with TIR <70% when compared with those with TIR >70% demonstrated higher levels of TNF-α (р=0.008), APRIL (р=0.01) and lower levels of BAFF (<0.0001). Serum APRIL and BAFF correlated differently with GV. Overweight or obese patients had higher levels of sTNFR1 and sTNFR2 than those with normal body weight (sTNFR1: p=0.01; sTNFR2: p=0.02). Patients with diabetic retinopathy compared to those without showed increased levels of APRIL (р=0.008) and patients with declined renal function had higher concentrations of APRIL (р=0.03), BAFF (р=0.03), and sCD30 (p=0.04). In multiple regression analysis, HbA1c was associated with TNF-α, eGFR was predictor for sCD30 and APRIL, BMI was associated with APRIL and sTNFR1, and TIR was associated with BAFF. The results show the relationships between TNFSF and TNFRSF peptides, hyperglycemia, GV, obesity, and diabetic complications in T1D. Among the studied molecules, TNF-α, APRIL, BAFF, sTNFR1, and sCD30 can be considered as promising biomarkers for assessing metabolic and vascular risk in subjects with T1D.