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GLP-1 Levels Predict Mortality in Patients with Critical Illness as Well as End-Stage Renal Disease - 27/09/17

Doi : 10.1016/j.amjmed.2017.03.010 
Corinna Lebherz, MD a, Georg Schlieper, MD b, Julia Möllmann, MD a, Florian Kahles, MD a, Marvin Schwarz, MD a, Jan Brünsing, MD c, Nada Dimkovic, MD d, Alexander Koch, MD c, Christian Trautwein, MD c, Jürgen Flöge, MD b, Nikolaus Marx, MD a, Frank Tacke, MD c, Michael Lehrke, MD a,
a Department of Internal Medicine I, University Hospital Aachen, Germany 
b Department of Internal Medicine II, University Hospital Aachen, Germany 
c Department of Internal Medicine III, University Hospital Aachen, Germany 
d Center for Renal Diseases, Zvezdara University, Medical Center, Belgrade, Serbia 

Requests for reprints should be addressed to Michael Lehrke, MD, Department of Internal Medicine I, University Hospital Aachen, Pauwelsstraße 30 D-52074, Aachen, Germany.Department of Internal Medicine IUniversity Hospital AachenPauwelsstraße 30 D-52074AachenGermany

Abstract

Background

Glucagon-like peptide 1 (GLP-1) is an incretin hormone, which stimulates glucose-dependent insulin secretion from the pancreas and holds immune-regulatory properties. A marked increase of GLP-1 has been found in critically ill patients. This study was performed to elucidate the underlying mechanism and evaluate its prognostic value.

Methods

GLP-1 plasma levels were determined in 3 different patient cohorts: 1) critically ill patients admitted to our intensive care unit (n = 215); 2) patients with chronic kidney disease on hemodialysis (n = 173); and 3) a control group (no kidney disease, no acute inflammation, n = 105). In vitro experiments were performed to evaluate GLP-1 secretion in response to human serum samples from the above-described cohorts.

Results

Critically ill patients presented with 6.35-fold higher GLP-1 plasma level in comparison with the control group. There was a significant correlation of GLP-1 levels with markers for the severity of inflammation, but also kidney function. Patients with end-stage renal disease displayed 4.46-fold higher GLP-1 concentrations in comparison with the control group. In vitro experiments revealed a strong GLP-1-inducing potential of serum from critically ill patients, while serum from hemodialysis patients only modestly increased GLP-1 secretion. GLP-1 levels independently predicted mortality in critically ill patients and patients with end-stage renal disease.

Conclusions

Chronic and acute inflammatory processes like sepsis or chronic kidney disease increase circulating GLP-1 levels. This most likely reflects a sum effect of increased GLP-1 secretion and decreased GLP-1 clearance. GLP-1 plasma levels independently predict the outcome of critically ill and end-stage renal disease patients.

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Keywords : Chronic kidney disease, CKD, Critically ill, GLP-1, Hemodialysis, Inflammation, Kidney function, Mortality, Prognosis, Sepsis


Esquema


 Funding: This study was supported by grants from the Hans Lamers Foundation and the Marga und Walter Boll Foundation.
 Conflict of Interest: NM is a speaker and/or advisory board member of the following companies: Astra-Zeneca, MSD, NovoNordisk, BMS. The other authors declare no conflicts of interest.
 Authorship: CL: experimental design, wrote the first draft of the manuscript; GS: experimental design, edited the first draft of the manuscript, performed statistical analysis, provided the end-stage renal disease cohort; JM and FK performed GLUTag experiments and reviewed/edited the manuscript; MS collected cardiovascular biobank samples and reviewed/edited the manuscript; JM collected sepsis samples and reviewed/edited the manuscript; ND end-stage renal disease samples and reviewed/edited the manuscript; AK collected sepsis samples and reviewed/edited the manuscript; CT, JF, and NM carried out critical discussion of results and reviewed/edited the manuscript; FT carried out experimental design, performed statistical analysis, provided the critically ill cohort, and carried out critical discussion of the results and editing of the manuscript; ML carried out experimental design, wrote the manuscript, and is the guarantor of this work, and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
 CL and GS contributed equally.


© 2017  Elsevier Inc. Reservados todos los derechos.
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Vol 130 - N° 7

P. 833 - juillet 2017 Regresar al número
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