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Association between age, IL-10, IFN gamma, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes
Department of Paediatrics, Glostrup Hospital and University of Copenhagen, Denmark.
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at the Heinrich-Heine University Düsseldorf, Germany.
Department of Medical Genetics, University Medical Center Utrecht, the Netherlands.
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at the Heinrich-Heine University Düsseldorf, Germany; University of Düsseldorf, Medical Faculty, Department of Metabolic Diseases, Düsseldorf, Germany .
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2012 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 29, no 6, 734-741 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2012. Vol. 29, no 6, 734-741 p.
Keyword [en]
disease progression; interferon gamma; interleukin 10; Type 1 diabetes
National Category
Endocrinology and Diabetes Medical Genetics
Identifiers
URN: urn:nbn:se:oru:diva-58708DOI: 10.1111/j.1464-5491.2011.03544.xISI: 000304087700008PubMedID: 22150609OAI: oai:DiVA.org:oru-58708DiVA: diva2:1127733
Note

Funding Agencies:

Novo Nordisk  

German Diabetes Centre  

Leibniz Centre for Diabetes Research at Heinrich Heine University Dusseldorf  

German Federal Ministry of Health and Social Security  

Ministry of Science and Research of the State North Rhine-Westphalia  

German Diabetes foundation 'Das zuckerkranke Kind'  

Dutch Diabetes Research Foundation  

Netherlands Organization for Health Research and Development (ZonMW)  

Juvenile Diabetes Research Foundation International (JDRF)  2001.10.004 

Available from: 2017-07-18 Created: 2017-07-18 Last updated: 2017-09-14Bibliographically approved

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