title: Association between age, IL-10, IFNγ, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes.
abstract: OBJECTIVE
  The relation of disease progression and age, serum interleukin 10 (IL-10) and interferon gamma (IFNγ) and their genetic correlates were studied in paediatric patients with newly diagnosed Type 1 diabetes.
  
  
  METHODS
  Two hundred and twenty-seven patients from the Hvidoere Study Group were classified in four different progression groups as assessed by change in stimulated C-peptide from 1 to 6 months. CA repeat variants of the IL-10 and IFNγ gene were genotyped and serum levels of IL-10 and IFNγ were measured at 1, 6 and 12 months.
  
  
  RESULTS
  IL-10 decreased (P < 0.001) by 7.7% (1 month), 10.4% (6 months) and 8.6% (12 months) per year increase in age of child, while a twofold higher C-peptide concentration at 1 month (p = 0.06), 6 months (P = 0.0003) and 12 months (P = 0.02) was associated with 9.7%, 18.6% and 9.7% lower IL-10 levels, independent of each other. IL-10 concentrations did not associate with the disease progression groups. By contrast, IFNγ concentrations differed between the four progression groups at 6 and 12 months (P = 0.02 and P = 0.01, respectively); patients with rapid progressing disease had the highest levels at both time points. Distribution of IL-10 and IFNγ genotypes was equal among patients from the progression groups.
  
  
  CONCLUSIONS
  IL-10 serum levels associate inversely with age and C-peptide. As age and C-peptide also associate, a triangular association is proposed. Genetic influence on IL-10 production seems to be masked by distinct disease mechanisms. Increased serum IFNγ concentrations associate with rapid disease progression. Functional genetic variants do not associate with a single progression pattern group, implying that disease processes override genetically predisposed cytokine production.
authors.affiliation: Department of Paediatrics, Glostrup Hospital and University of Copenhagen, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Kaas
authors.forename: C
authors.initials: C
authors.lastname: Pfleger
authors.forename: A V
authors.initials: AV
authors.lastname: Kharagjitsingh
authors.forename: N C
authors.initials: NC
authors.lastname: Schloot
authors.forename: L
authors.initials: L
authors.lastname: Hansen
authors.forename: K
authors.initials: K
authors.lastname: Buschard
authors.forename: B P C
authors.initials: BP
authors.lastname: Koeleman
authors.forename: B O
authors.initials: BO
authors.lastname: Roep
authors.forename: H B
authors.initials: HB
authors.lastname: Mortensen
authors.forename: B Z
authors.initials: BZ
authors.lastname: Alizadeh
mesh_terms: D000293:Adolescent; D000375:Aging / Q000097:blood* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D002096:C-Peptide / Q000097:blood* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D018450:Disease Progression; D005215:Fasting; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000097:blood* / Q000235:genetics; D016753:Interleukin-10 / Q000097:blood* / Q000235:genetics; D008297:Male
chemical_list: D015415:Biomarkers; D002096:C-Peptide; D016753:Interleukin-10; D007371:Interferon-gamma