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

Am J Med. 2017 Jul;130(7):833-841.e3. doi: 10.1016/j.amjmed.2017.03.010. Epub 2017 Mar 31.

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.

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Critical Care
  • Critical Illness / mortality*
  • Critical Illness / therapy
  • Female
  • Glucagon-Like Peptide 1 / blood*
  • Glucagon-Like Peptide 1 / metabolism
  • Humans
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / mortality*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Renal Dialysis
  • Sepsis / blood
  • Sepsis / mortality
  • Sepsis / therapy
  • Young Adult

Substances

  • Biomarkers
  • Glucagon-Like Peptide 1