Inflammatory profile associated with hyperglycemia in children with type 1 diabetes

Complications of type 1 diabetes (T1D) are associated with exposure to hyperglycemia. Inflammation is involved in microvascular and macrovascular complications, but associations between hyperglycemia and inflammatory mediators across multiple classes have not been comprehensively described. We aimed to characterize the inflammatory profile associated with hyperglycemia in children with T1D.

We comprehensively evaluated blood inflammatory mediators (cytokines, chemokines, growth factors, matrix metalloproteinases (MMPs)) using multiplex immunoassays in 117 children with T1D. We used multiple linear regression analyses to assess the relations between inflammatory mediators (transformed to robust z-scores) and hemoglobin A1c (HbA1c), adjusting for age, diabetes duration and body mass index. We computed an inflammatory composite as the within-person mean of significantly associated robust z-scores.

Levels of multiple inflammatory mediators were associated with HbA1c (p < 0.05 and False Discovery Rate-adjusted q < 0.10). These included cytokines [interleukin (IL)-1β, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-8, IL-13, IL-17A, IL-17F, IL-18, IL-20, IL-21, IL-23, IL-33, interferon-γ, tumor necrosis factor (TNF)-α, TNF-related apoptosis inducing ligand (TRAIL), thrombopoietin, stem cell factor, leukemia inhibitory factor, chemokines (CCL1, CCL2, CCL4, CCL7, CCL8, CCL13, CCL26, CCL27, CXCL1, CXCL5, CXCL13), growth factors (vascular endothelial growth factor-A, transforming growth factor-α, platelet derived growth factor-AA), and MMPs (MMP-1, MMP-2, tissue inhibitor of MMP-1). Each percentage point increase in HbA1c was associated with a 0.16 increase in inflammatory composite score.

A broad range of inflammatory mediators are correlated with HbA1c in children with T1D. These inflammatory changes precede development of T1D complications, suggesting that possible pathophysiologic involvement should be investigated.