Increased inflammation is associated with islet autoimmunity and type 1 diabetes in the Diabetes Autoimmunity Study in the Young (DAISY)

• Published in: PloS one Vol. 12; no. 4; p. e0174840
• Main Authors: Waugh, Kathleen, Snell-Bergeon, Janet, Michels, Aaron, Dong, Fran, Steck, Andrea K., Frohnert, Brigitte I., Norris, Jill M., Rewers, Marian
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.04.2017; Public Library of Science (PLoS)
• Subjects: Age; Analysis; Antibodies; Autoimmunity; Autoimmunity - immunology; Beta cells; Biology and Life Sciences; Case studies; Case-Control Studies; Chemokines; Child; Child, Preschool; Children; Complications and side effects; Control methods; Cytokines; Cytokines - blood; Damage detection; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - immunology; Environmental factors; Families & family life; Family medical history; Female; Health aspects; Health care; Humans; IL-1β; Immune response; Immune system; Immunology; Infant; Inflammation; Inflammation - blood; Inflammation - immunology; Insulin; Islets of Langerhans - immunology; Male; Medical screening; Medicine and Health Sciences; Pathogenesis; Risk factors; Type 1 diabetes; Illinois; United States > US; Colorado
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0174840

Type 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. A 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. Multivariate 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. 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. 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.