title: 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.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Internal Medicine I, University Hospital Aachen, Pauwelsstraße 30, 52074, Aachen, Germany. clebherz@ukaachen.de.
authors: Corinna
authors: C
authors: Lebherz
authors: Department of Internal Medicine I, University Hospital Aachen, Pauwelsstraße 30, 52074, Aachen, Germany. fkahles@ukaachen.de.
authors: Florian
authors: F
authors: Kahles
authors: Helmholtz Institute Munich, German Research Center for Environmental Health, Neuherberg, Munich, Germany. katja.piotrowski@gmx.de.
authors: Katja
authors: K
authors: Piotrowski
authors: Institute of Laboratory Medicine, University Hospital Munich (LMU), Campus Grosshadern, Munich, Germany. Michael.Vogeser@med.uni-muenchen.de.
authors: Michael
authors: M
authors: Vogeser
authors: Department of Medical Statistics, University Hospital Aachen, Aachen, Germany. afoldenauer@ukaachen.de.
authors: Ann Christina
authors: AC
authors: Foldenauer
authors: Department of Anesthesiology, Campus Grosshadern, Munich, Germany. Kirsten.Nassau@med.uni-muenchen.de.
authors: Kirsten
authors: K
authors: Nassau
authors: Department of Anesthesiology, Campus Grosshadern, Munich, Germany. Erich.Kilger@med.uni-muenchen.de.
authors: Erich
authors: E
authors: Kilger
authors: Department of Internal Medicine I, University Hospital Aachen, Pauwelsstraße 30, 52074, Aachen, Germany. nmarx@ukaachen.de.
authors: Nikolaus
authors: N
authors: Marx
authors: Department of Internal Medicine II, University Hospital Munich (LMU), Campus Grosshadern, Munich, Germany. Klaus.Parhofer@med.uni-muenchen.de.
authors: Klaus G
authors: KG
authors: Parhofer
authors: Department of Internal Medicine I, University Hospital Aachen, Pauwelsstraße 30, 52074, Aachen, Germany. mlehrke@ukaachen.de.
authors: Michael
authors: M
authors: Lehrke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D007700:Kinetics; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; C508600:IL6 protein, human; D007328:Insulin; D015850:Interleukin-6; D052216:Glucagon-Like Peptide 1; D006854:Hydrocortisone