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Association between age, IL‐10, IFNγ, stimulated C‐peptide and disease progression in children with newly diagnosed Type 1 diabetes
Author(s) -
Kaas A.,
Pfleger C.,
Kharagjitsingh A. V.,
Schloot N. C.,
Hansen L.,
Buschard K.,
Koeleman B. P. C.,
Roep B. O.,
Mortensen H. B.,
Alizadeh B. Z.
Publication year - 2012
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2011.03544.x
Subject(s) - medicine , diabetes mellitus , gastroenterology , interleukin , c peptide , genotype , immunology , cytokine , endocrinology , gene , biochemistry , chemistry
Diabet. Med. 29, 734–741 (2012) Abstract Aims 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. 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 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.