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. 2016 Feb 3:15:21.
doi: 10.1186/s12933-016-0330-8.

Interleukin-6 predicts inflammation-induced increase of Glucagon-like peptide-1 in humans in response to cardiac surgery with association to parameters of glucose metabolism

Corinna Lebherz  1 , Florian Kahles  2 , Katja Piotrowski  3 , Michael Vogeser  4 , Ann Christina Foldenauer  5 , Kirsten Nassau  6 , Erich Kilger  7 , Nikolaus Marx  8 , Klaus G Parhofer  9 , Michael Lehrke  10
Affiliations

Interleukin-6 predicts inflammation-induced increase of Glucagon-like peptide-1 in humans in response to cardiac surgery with association to parameters of glucose metabolism

Corinna Lebherz et al. Cardiovasc Diabetol. .

Abstract

Objective: Glucagon-like peptide-1 (GLP-1) is an incretin hormone, which gets secreted in response to nutritional stimuli from the gut mediating glucose-dependent insulin secretion. Interestingly, GLP-1 was recently found to be also increased in response to inflammatory stimuli in an interleukin 6 (IL-6) dependent manner in mice. The relevance of this finding to humans is unknown but has been suggested by the presence of high circulating GLP-1 levels in critically ill patients that correlated with markers of inflammation. This study was performed to elucidate, whether a direct link exists between inflammation and GLP-1 secretion in humans.

Research design and methods: We enrolled 22 non-diabetic patients scheduled for cardiac surgery as a reproducible inflammatory stimulus with repeated blood sampling before and after surgery.

Results: Mean total circulating GLP-1 levels significantly increased in response to surgery from 25.5 ± 15.6 pM to 51.9 ± 42.7 pM which was not found in a control population. This was preceded by an early rise of IL6, which was significantly associated with GLP-1 under inflammatory but not basal conditions. Using repeated measure ANCOVA, IL6 best predicted the observed kinetics of GLP-1, followed by blood glucose concentrations and cortisol plasma levels. Furthermore, GLP-1 plasma concentrations significantly predicted endogenous insulin production as assessed by C-peptide concentrations over time, while an inverse association was found for insulin infusion rate.

Conclusion: We found GLP-1 secretion to be increased in response to inflammatory stimuli in humans, which was associated to parameters of glucose metabolism and best predicted by IL6.

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Figures

Fig. 1
Fig. 1
Kinetics of GLP-1 (a), IL6 (b), Glucose (c), C-Peptide (d) and Insulin-Infusion-Rate (e) over time with time point 1 illustrating blood drawn directly before surgery (baseline), time point 2: at arrival to the intensive care unit (4–6 h post initiation of surgery), time point 3: 6 h post arrival to the ICU (10–12 h post initiation of surgery) and the morning of the first (time point 4) and second (time point 5) postoperative days. P-values indicate the comparison to baseline (time point 1) with * <0.05; ** <0.01; *** <0.001 using a paired t-tests and Wilcoxon signed rank sum tests for the differences
Fig. 2
Fig. 2
Fit-blot demonstrating the correlation of IL6 and log GLP-1 at arrival to the intensive care unit (time point 2)
See this image and copyright information in PMC

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