Systemic TNFα correlates with residual ß-cell function in children and adolescents newly diagnosed with type 1 diabetes.

BACKGROUND: Type 1 diabetes (T1D) is caused by immune-mediated destruction of the ß-cells. After initiation of insulin therapy many patients experience a period of improved residual ß-cell function leading to partial disease remission. Cytokines are important immune-modulatory molecules and contribute to ß-cell damage in T1D. The patterns of systemic circulating cytokines during T1D remission are not clear but may constitute biomarkers of disease status and progression. In this study, we investigated if the plasma levels of various pro- and anti-inflammatory cytokines around time of diagnosis were predictors of remission and residual ß-cell function in children with T1D followed for one year after disease onset. METHODS: In a cohort of 63 newly diagnosed children (33% females) with T1D with a mean age of 11.3 years (3.3-17.7), ten cytokines were measured of which eight were detectable in plasma samples by Mesoscale Discovery multiplex technology at study start and after 6 and 12 months. Linear regression models were used to evaluate association of cytokines with stimulated C-peptide. RESULTS: Systemic levels of tumor necrosis factor (TNF)-α, interleukin (IL)-2 and IL-6 inversely correlated with stimulated C-peptide levels over the entire study (P < 0.05). The concentrations of TNFα and IL-10 at study start predicted stimulated C-peptide level at 6 months (P = 0.011 and P = 0.043, respectively, adjusted for sex, age, HbA1c and stage of puberty). CONCLUSIONS: In recent-onset T1D, systemic cytokine levels, and in particular that of TNFα, correlate with residual ß-cell function and may serve as prognostic biomarkers of disease remission and progression to optimize treatment strategies. TRIAL REGISTRATION: The study was performed according to the criteria of the Helsinki II Declaration and was approved by the Danish Capital Region Ethics Committee on Biomedical Research Ethics (journal number H-3-2014-052). The parents of all participants gave written consent.