Abstract
BackgroundType 1 diabetes (TID) is characterized by a loss of pancreatic islet beta cell function resulting in loss of insulin production. Genetic and environmental factors may trigger immune responses targeting beta cells thus generating islet antibodies (IA). Immune response pathways involve a cascade of events, initiated by cytokines and chemokines, producing inflammation which can result in tissue damage.MethodsA nested case-control study was performed to identify temporal changes in cytokine levels in 75 DAISY subjects: 25 diagnosed T1D, 25 persistent IA, and 25 controls. Serum samples were selected at four time points: (T1) earliest, (T2) just prior to IA, (T3) just after IA, and (T4) prior to T1D diagnosis or most recent. Cytokines (IFN-α2a, IL-6, IL-17, IL-1β, IP-10, MCP-1, IFN-γ, IL-1α, and IL-1ra) were measured using the Meso Scale Discovery system Human Custom Cytokine 9-Plex assay.ResultsMultivariate mixed models adjusting for HLA risk, first-degree relative status, age, and gender, showed MCP-1 and IFN-үto be significantly higher at T3 in T1D compared to IA subjects. At T4, IP-10 was significantly higher in IA subjects than controls.ConclusionsThis repeated measures nested case-control study identified increased inflammatory markers in IA children who developed T1D compared to IA children who had not progressed to clinical disease. It also showed increased inflammation in both T1D and IA children when compared to controls. Results suggest inflammation may be related to both the development of IA and progression to T1D.
Highlights
Type 1 diabetes (T1D) affects approximately 1.5 million people in the United States, with the incidence increasing over the past several decades worldwide
Multivariate mixed models adjusting for HLA risk, first-degree relative status, age, and gender, showed monocyte chemotactic protein (MCP)-1 and IFN-үto be significantly higher at T3 in T1D compared to islet autoimmunity (IA) subjects
At T4, induced protein (IP)-10 was significantly higher in IA subjects than controls. This repeated measures nested case-control study identified increased inflammatory markers in IA children who developed T1D compared to IA children who had not progressed to clinical disease
Summary
Type 1 diabetes (T1D) affects approximately 1.5 million people in the United States, with the incidence increasing over the past several decades worldwide. An area of investigation has focused on how the innate immune system may be involved in the pathogenesis of T1D Insults, such as microbial infections, initiate the innate immune system response and a cascade of events, including the expression of pro-inflammatory cytokines and chemokines occurs. These findings raise the question does systemic inflammation exist in the context of islet autoimmunity and T1D? Genetic and environmental factors may trigger immune responses targeting beta cells generating islet antibodies (IA). Immune response pathways involve a cascade of events, initiated by cytokines and chemokines, producing inflammation which can result in tissue damage
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