Association between age, IL-10, IFN¿, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes

A Kaas; Claudia Christina Pfleger; A V Kharagjitsingh; N C Schloot; L Hansen; K Buschard; B P C Koeleman; B O Roep; H B Mortensen; B Z Alizadeh; Hvidoere Study Group On Childhood Diabetes; Thomas Mandrup-Poulsen

doi:10.1111/j.1464-5491.2011.03544.x

Association between age, IL-10, IFN¿, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes

A Kaas, Claudia Christina Pfleger, A V Kharagjitsingh, N C Schloot, L Hansen, K Buschard, B P C Koeleman, B O Roep, H B Mortensen, B Z Alizadeh, Hvidoere Study Group On Childhood Diabetes, Thomas Mandrup-Poulsen

21 Citations (Scopus)

Abstract

Aims The relation of disease progression and age, serum interleukin10 (IL-10) and interferon gamma (IFNγ) and their genetic correlates were studied in paediatric patients with newly diagnosed Type1 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 6months. 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 12months. Results IL-10 decreased (P<0.001) by 7.7% (1month), 10.4% (6months) and 8.6% (12months) per year increase in age of child, while a twofold higher C-peptide concentration at 1month (p=0.06), 6months (P=0.0003) and 12months (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 12months (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.

Original language	English
Journal	Diabetic Medicine Online
Volume	29
Issue number	6
Pages (from-to)	734-741
Number of pages	8
ISSN	1464-5491
DOIs	https://doi.org/10.1111/j.1464-5491.2011.03544.x
Publication status	Published - Jun 2012

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10.1111/j.1464-5491.2011.03544.x

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Kaas, A., Pfleger, C. C., Kharagjitsingh, A. V., Schloot, N. C., Hansen, L., Buschard, K., Koeleman, B. P. C., Roep, B. O., Mortensen, H. B., Alizadeh, B. Z., Hvidoere Study Group On Childhood Diabetes, & Mandrup-Poulsen, T. (2012). Association between age, IL-10, IFN¿, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes. Diabetic Medicine Online, 29(6), 734-741. https://doi.org/10.1111/j.1464-5491.2011.03544.x

Kaas, A, Pfleger, CC, Kharagjitsingh, AV, Schloot, NC, Hansen, L, Buschard, K, Koeleman, BPC, Roep, BO, Mortensen, HB, Alizadeh, BZ, Hvidoere Study Group On Childhood Diabetes & Mandrup-Poulsen, T 2012, 'Association between age, IL-10, IFN¿, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes', Diabetic Medicine Online, vol. 29, no. 6, pp. 734-741. https://doi.org/10.1111/j.1464-5491.2011.03544.x

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title = "Association between age, IL-10, IFN¿, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes",

abstract = "Aims The relation of disease progression and age, serum interleukin10 (IL-10) and interferon gamma (IFNγ) and their genetic correlates were studied in paediatric patients with newly diagnosed Type1 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 6months. 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 12months. Results IL-10 decreased (P<0.001) by 7.7% (1month), 10.4% (6months) and 8.6% (12months) per year increase in age of child, while a twofold higher C-peptide concentration at 1month (p=0.06), 6months (P=0.0003) and 12months (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 12months (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.",

author = "A Kaas and Pfleger, {Claudia Christina} and Kharagjitsingh, {A V} and Schloot, {N C} and L Hansen and K Buschard and Koeleman, {B P C} and Roep, {B O} and Mortensen, {H B} and Alizadeh, {B Z} and {Hvidoere Study Group On Childhood Diabetes} and Thomas Mandrup-Poulsen",

note = "{\textcopyright} 2011 The Authors. Diabetic Medicine {\textcopyright} 2011 Diabetes UK.",

year = "2012",

month = jun,

doi = "10.1111/j.1464-5491.2011.03544.x",

language = "English",

volume = "29",

pages = "734--741",

journal = "Diabetic Medicine Online",

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TY - JOUR

T1 - Association between age, IL-10, IFN¿, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes

AU - Kaas, A

AU - Pfleger, Claudia Christina

AU - Kharagjitsingh, A V

AU - Schloot, N C

AU - Hansen, L

AU - Buschard, K

AU - Koeleman, B P C

AU - Roep, B O

AU - Mortensen, H B

AU - Alizadeh, B Z

AU - Hvidoere Study Group On Childhood Diabetes

AU - Mandrup-Poulsen, Thomas

PY - 2012/6

Y1 - 2012/6

N2 - Aims The relation of disease progression and age, serum interleukin10 (IL-10) and interferon gamma (IFNγ) and their genetic correlates were studied in paediatric patients with newly diagnosed Type1 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 6months. 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 12months. Results IL-10 decreased (P<0.001) by 7.7% (1month), 10.4% (6months) and 8.6% (12months) per year increase in age of child, while a twofold higher C-peptide concentration at 1month (p=0.06), 6months (P=0.0003) and 12months (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 12months (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.

AB - Aims The relation of disease progression and age, serum interleukin10 (IL-10) and interferon gamma (IFNγ) and their genetic correlates were studied in paediatric patients with newly diagnosed Type1 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 6months. 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 12months. Results IL-10 decreased (P<0.001) by 7.7% (1month), 10.4% (6months) and 8.6% (12months) per year increase in age of child, while a twofold higher C-peptide concentration at 1month (p=0.06), 6months (P=0.0003) and 12months (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 12months (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.

U2 - 10.1111/j.1464-5491.2011.03544.x

DO - 10.1111/j.1464-5491.2011.03544.x

M3 - Journal article

C2 - 22150609

SN - 1464-5491

VL - 29

SP - 734

EP - 741

JO - Diabetic Medicine Online

JF - Diabetic Medicine Online

IS - 6

ER -

Association between age, IL-10, IFN¿, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes

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