Association between age, IL-10, IFNγ, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes
Diabetic Medicine, 06/01/2012
Kaas A et al. – 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.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.
- 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.