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

Abstract

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-1β, IL-1Ra, IL-2Rα, IL-3, IL-6, IL-7, IL-12 p40, IL-16, IL-17A, LIF, M-CSF, IFN-α2, IFN-γ, MCP-1, MCP-3, and TNF-α. Patients with TIR ≤ 70% had higher levels of IL-1α, IL-1β, IL-6, IL-12 p70, IL-16, LIF, M-CSF, MCP-1, MCP-3, RANTES, TNF-α, TNF-β, and b-NGF, and lower levels of IL-1α, IL-4, IL-10, GM-CSF, and MIF than those with TIR > 70%. Serum IL-1β, IL-10, IL-12 p70, MCP-1, MCP-3, RANTES, SCF, and TNF-α correlated with TIR and time above range. IL-1β, IL-8, IL-10, IL-12 p70, MCP-1, RANTES, MIF, and SDF-1α were related to at least one amplitude-dependent GV metric. In logistic regression models, IL-1β, IL-4, IL-10, IL-12 p70, GM-CSF, HGF, MCP-3, and TNF-α 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.

Evaluation of Tumor Necrosis Factor Alpha, Insulin, glucose, HbA1c% and HOMA-IR as Predictors for Cardiovascular Diseases in Patients with Type 2 Diabetes

“…40,41 Furthermore, it has been hypothesised that insulin resistance has a significant and autonomous role in the susceptibility to type 2 diabetes mellitus and cardiovascular ailments; 42,43 Several different approaches have been developed as surrogate measures of insulin resistance in order to distinguish people with different degrees of insulin sensitivity, given the intrusive nature of directly assessing insulin resistance. 44,45 Nevertheless, it is worth noting that these indices fail to provide insight into the glycemic condition over a period of 2-3 months, a timeframe that is significantly linked to insulin resistance. Hence, it is important to establish the precise function of HbA1c as a surrogate marker for insulin resistance and determine the most effective threshold value.…”

The Impact of Metabolic Memory on Immune Profile in Young Patients with Uncomplicated Type 1 Diabetes

“…Diabetes complications, such as delayed wound healing, retinopathy, atherosclerosis [ 36 ], and neuropathy [ 37 ], are mediated by the IL-12 family of cytokines. Abnormal levels may worsen glucose variability and increase the risk of diabetic complications [ 48 ]. IL-35 levels have also been found to have a significant negative correlation with high HbA1c levels.…”