title: Increased inflammation is associated with islet autoimmunity and type 1 diabetes in the Diabetes Autoimmunity Study in the Young (DAISY).
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Waugh
authors.affiliation: Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Janet
authors.initials: J
authors.lastname: Snell-Bergeon
authors.affiliation: Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Aaron
authors.initials: A
authors.lastname: Michels
authors.affiliation: Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Fran
authors.initials: F
authors.lastname: Dong
authors.affiliation: Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Steck
authors.affiliation: Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Brigitte I
authors.initials: BI
authors.lastname: Frohnert
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, University of Colorado, Aurora, Colorado, United States of America.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
authors.affiliation: Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
mesh_terms: D015551:Autoimmunity / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male
chemical_list: D016207:Cytokines