title: The systemic immune network in recent onset type 1 diabetes: central role of interleukin-1 receptor antagonist (DIATOR Trial).
abstract: BACKGROUND
  The hypothesis was tested that the systemic immune milieu in recent-onset type 1 diabetes is associated with residual beta cell function and other metabolic patient characteristics.
  
  
  RESULTS
  All patients (n = 89, 40% female) of the Diabetes and Atorvastatin (DIATOR) Trial were analyzed at recruitment, i.e. prior to receiving the study medication. Inclusion criteria were insulin dependent diabetes for 2 weeks to 3 months, age range 18-39 years, and islet cell autoantibodies. Blood samples were analyzed for 14 immune mediators by standard methods. Concentrations of all mediators correlated with at least one other mediator (p<0.05, Spearman correlation) giving rise to a network. Interleukin 1 receptor antagonist (IL1-RA) held a central position and was associated with both pro- and anti-inflammatory mediators. Further central elements were the pro-inflammatory mediators CRP and IL-6, the soluble adhesion molecules sICAM-1 and E-selectin, and MCP-4 which held a central position in the chemokine network. The two Th1-associated mediators IFNγ and IP-10 remained outside the network but correlated with each other. All correlations were positive (r = 0.25-0.72), i.e., high levels of pro-inflammatory mediators were accompanied by increased levels of anti-inflammatory mediators. IL-1RA was the only mediator associated with fasting and liquid mixed meal stimulated C-peptide concentrations (r = 0.31 and 0.24, p = 0.003 and 0.025, after adjustment for age, sex, BMI). There were associations between the immune mediator network and BMI (IL-1RA, CRP, IL-6, MCP-4, MIP-1ß) but few or no associations with HbA1c, insulin dose, lipid parameters, age or sex.
  
  
  CONCLUSIONS
  In patients with recent onset type 1 diabetes, systemic acute phase proteins, cytokines, chemokines and soluble adhesion molecules form a network. Among the few central elements IL-1RA has a dominant role. IL-1RA is associated with all other groups of mediators and is the only mediator which correlates (positively) with residual beta cell function.
  
  
  BACKGROUND
  ClinicalTrials.gov registration number: NCT00974740.
authors.affiliation: West-German Centre of Diabetes and Health, Verbund Katholischer Kliniken Düsseldorf, Düsseldorf, Germany. hubert.kolb@uni-duesseldorf.de
authors.forename: Hubert
authors.initials: H
authors.lastname: Kolb
authors.forename: Kathrin
authors.initials: K
authors.lastname: Lückemeyer
authors.forename: Tim
authors.initials: T
authors.lastname: Heise
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.forename: Nanette C
authors.initials: NC
authors.lastname: Schloot
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.forename: Lutz
authors.initials: L
authors.lastname: Heinemann
authors.forename: Stephan
authors.initials: S
authors.lastname: Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000502:physiology*; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D055815:Young Adult
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein