Serum Cytokines and Growth Factors in Subjects with Type 1 Diabetes: Associations with Time in Ranges and Glucose Variability

The detrimental effect of hyperglycemia and glucose variability (GV) on target organs in diabetes can be implemented through a wide network of regulatory peptides. In this study, we assessed a broad panel of serum cytokines and growth factors in subjects with type 1 diabetes (T1D) and estimated associations between concentrations of these molecules with time in ranges (TIRs) and GV. One hundred and thirty subjects with T1D and twenty-seven individuals with normal glucose tolerance (control) were included. Serum levels of 44 cytokines and growth factors were measured using a multiplex bead array assay. TIRs and GV parameters were derived from continuous glucose monitoring. Subjects with T1D compared to control demonstrated an increase in concentrations of IL-1 beta, IL-1Ra, IL-2R alpha, IL-3, IL-6, IL-7, IL-12 p40, IL-16, IL-17A, LIF, M-CSF, IFN-alpha 2, IFN-gamma, MCP-1, MCP-3, and TNF-alpha. Patients with TIR <= 70% had higher levels of IL-1 alpha, IL-1 beta, IL-6, IL-12 p70, IL-16, LIF, M-CSF, MCP-1, MCP-3, RANTES, TNF-alpha, TNF-beta, and b-NGF, and lower levels of IL-1 alpha, IL-4, IL-10, GM-CSF, and MIF than those with TIR > 70%. Serum IL-1 beta, IL-10, IL-12 p70, MCP-1, MCP-3, RANTES, SCF, and TNF-alpha correlated with TIR and time above range. IL-1 beta, IL-8, IL-10, IL-12 p70, MCP-1, RANTES, MIF, and SDF-1 alpha were related to at least one amplitude-dependent GV metric. In logistic regression models, IL-1 beta, IL-4, IL-10, IL-12 p70, GM-CSF, HGF, MCP-3, and TNF-alpha were associated with TIR <= 70%, and MIF and PDGF-BB demonstrated associations with coefficient of variation values >= 36%. These results provide further insight into the pathophysiological effects of hyperglycemia and GV in people with diabetes.