Header

UZH-Logo

Maintenance Infos

Fasting and meal-stimulated residual beta cell function is positively associated with serum concentrations of proinflammatory cytokines and negatively associated with anti-inflammatory and regulatory cytokines in patients with longer term type 1 diabetes


Pham, M N; Kolb, H; Battelino, T; Ludvigsson, J; Pozzilli, P; Zivehe, F; Roden, M; Mandrup-Poulsen, T; Schloot, N C (2013). Fasting and meal-stimulated residual beta cell function is positively associated with serum concentrations of proinflammatory cytokines and negatively associated with anti-inflammatory and regulatory cytokines in patients with longer term type 1 diabetes. Diabetologia, 56(6):1356-1363.

Abstract

AIMS/HYPOTHESIS: Cytokines may promote or inhibit disease progression in type 1 diabetes. We investigated whether systemic proinflammatory, anti-inflammatory and regulatory cytokines associated differently with fasting and meal-stimulated beta cell function in patients with longer term type 1 diabetes.
METHODS: The beta cell function of 118 patients with type 1 diabetes of duration of 0.75-4.97 years was tested using a standardised liquid mixed meal test (MMT). Serum samples obtained at -5 to 120 min were analysed by multiplex bead-based technology for proinflammatory (IL-6, TNF-α), anti-inflammatory (IL-1 receptor antagonist [IL-1RA]) and regulatory (IL-10, TGF-β1-3) cytokines, and by standard procedures for C-peptide. Differences in beta cell function between patient groups were assessed using stepwise multiple regression analysis adjusting for sex, age, duration of diabetes, BMI, HbA1c and fasting blood glucose.
RESULTS: High fasting systemic concentrations of the proinflammatory cytokines IL-6 and TNF-α were associated with increased fasting and stimulated C-peptide concentrations even after adjustment for confounders (p < 0.03). Interestingly, increased concentrations of anti-inflammatory/regulatory IL-1RA, IL-10, TGF-β1 and TGF-β2 were associated with lower fasting and stimulated C-peptide levels (p < 0.04), losing significance on adjustment for anthropometric variables. During the MMT, circulating concentrations of IL-6 and TNF-α increased (p < 0.001) while those of IL-10 and TGF-β1 decreased (p < 0.02) and IL-1RA and TGF-β2 remained unchanged.
CONCLUSIONS/INTERPRETATION: The association between better preserved beta cell function in longer term type 1 diabetes and increased systemic proinflammatory cytokines and decreased anti-inflammatory and regulatory cytokines is suggestive of ongoing inflammatory disease activity that might be perpetuated by the remaining beta cells. These findings should be considered when designing immune intervention studies aimed at patients with longer term type 1 diabetes and residual beta cell function.

Abstract

AIMS/HYPOTHESIS: Cytokines may promote or inhibit disease progression in type 1 diabetes. We investigated whether systemic proinflammatory, anti-inflammatory and regulatory cytokines associated differently with fasting and meal-stimulated beta cell function in patients with longer term type 1 diabetes.
METHODS: The beta cell function of 118 patients with type 1 diabetes of duration of 0.75-4.97 years was tested using a standardised liquid mixed meal test (MMT). Serum samples obtained at -5 to 120 min were analysed by multiplex bead-based technology for proinflammatory (IL-6, TNF-α), anti-inflammatory (IL-1 receptor antagonist [IL-1RA]) and regulatory (IL-10, TGF-β1-3) cytokines, and by standard procedures for C-peptide. Differences in beta cell function between patient groups were assessed using stepwise multiple regression analysis adjusting for sex, age, duration of diabetes, BMI, HbA1c and fasting blood glucose.
RESULTS: High fasting systemic concentrations of the proinflammatory cytokines IL-6 and TNF-α were associated with increased fasting and stimulated C-peptide concentrations even after adjustment for confounders (p < 0.03). Interestingly, increased concentrations of anti-inflammatory/regulatory IL-1RA, IL-10, TGF-β1 and TGF-β2 were associated with lower fasting and stimulated C-peptide levels (p < 0.04), losing significance on adjustment for anthropometric variables. During the MMT, circulating concentrations of IL-6 and TNF-α increased (p < 0.001) while those of IL-10 and TGF-β1 decreased (p < 0.02) and IL-1RA and TGF-β2 remained unchanged.
CONCLUSIONS/INTERPRETATION: The association between better preserved beta cell function in longer term type 1 diabetes and increased systemic proinflammatory cytokines and decreased anti-inflammatory and regulatory cytokines is suggestive of ongoing inflammatory disease activity that might be perpetuated by the remaining beta cells. These findings should be considered when designing immune intervention studies aimed at patients with longer term type 1 diabetes and residual beta cell function.

Statistics

Citations

5 citations in Web of Science®
5 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

1 download since deposited on 06 Feb 2014
0 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:06 Feb 2014 15:46
Last Modified:05 Apr 2016 17:32
Publisher:Springer
ISSN:0012-186X
Publisher DOI:https://doi.org/10.1007/s00125-013-2883-3
PubMed ID:23494449

Download

Preview Icon on Download
Content: Published Version
Filetype: PDF - Registered users only
Size: 275kB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations