Article: Pathophysiology Association between age, IL-10, IFNc, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes

Aims The relation of disease progression and age, serum interleukin 10 (IL-10) and interferon gamma (IFNc) 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 IFNc gene were genotyped and serum levels of IL-10 and IFNc 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, IFNc 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 IFNc genotypes was equal among patients from the progression groups. Conclusion 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 IFNc 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. Diabet. Med. 29, 734–741 (2012)