TY - JOUR

T1 - Systemic TNF alpha correlates with residual beta-cell function in children and adolescents newly diagnosed with type 1 diabetes

AU - Overgaard, Anne Julie

AU - Madsen, Jens Otto Broby

AU - Pociot, Flemming

AU - Johannesen, Jesper

AU - Storling, Joachim

PY - 2020

Y1 - 2020

N2 - Background: Type 1 diabetes (T1D) is caused by immune-mediated destruction of the beta-cells. After initiation of insulin therapy many patients experience a period of improved residual beta-cell function leading to partial disease remission. Cytokines are important immune-modulatory molecules and contribute to beta-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 antiinflammatory cytokines around time of diagnosis were predictors of remission and residual beta-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)-alpha, interleukin (IL)-2 and IL-6 inversely correlated with stimulated C-peptide levels over the entire study (P <0.05). The concentrations of TNF alpha 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 TNF alpha, correlate with residual beta-cell function and may serve as prognostic biomarkers of disease remission and progression to optimize treatment strategies.

AB - Background: Type 1 diabetes (T1D) is caused by immune-mediated destruction of the beta-cells. After initiation of insulin therapy many patients experience a period of improved residual beta-cell function leading to partial disease remission. Cytokines are important immune-modulatory molecules and contribute to beta-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 antiinflammatory cytokines around time of diagnosis were predictors of remission and residual beta-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)-alpha, interleukin (IL)-2 and IL-6 inversely correlated with stimulated C-peptide levels over the entire study (P <0.05). The concentrations of TNF alpha 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 TNF alpha, correlate with residual beta-cell function and may serve as prognostic biomarkers of disease remission and progression to optimize treatment strategies.

KW - beta-cell function

KW - Cytokines

KW - TNF

KW - Inflammation

KW - Type 1 diabetes

KW - Remission

KW - IL-10

KW - ASSOCIATION

U2 - 10.1186/s12887-020-02339-8

DO - 10.1186/s12887-020-02339-8

M3 - Journal article

C2 - 32967650

VL - 20

JO - BMC Pediatrics

JF - BMC Pediatrics

SN - 1471-2431

IS - 1

M1 - 446

ER -