Sepsis-induced activation of endogenous GLP-1 system is enhanced in type 2 diabetes

Sivan H. Perl, Olga Bloch, Dana Zelnic-Yuval, Itamar Love, Lior Mendel-Cohen, Hadar Flor, Micha J. Rapoport*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: High levels of circulating GLP-1 are associated with severity of sepsis in critically ill nondiabetic patients. Whether patients with type 2 diabetes (T2D) display different activation of the endogenous GLP-1 system during sepsis and whether it is affected by diabetes-related metabolic parameters are not known. Methods: Serum levels of GLP-1 (total and active forms) and its inhibitor enzyme sDPP-4 were determined by ELISA on admission and after 2 to 4 days in 37 sepsis patients with (n = 13) and without T2D (n = 24) and compared to normal healthy controls (n = 25). Correlations between GLP-1 system activation and clinical, inflammatory, and diabetes-related metabolic parameters were performed. Results: A 5-fold (P <.001) and 2-fold (P <.05) increase in active and total GLP-1 levels, respectively, were found on admission as compared to controls. At 2 to 4 days from admission, the level of active GLP-1 forms in surviving patients were decreased significantly (P <.005), and positively correlated with inflammatory marker CRP (r = 0.33, P =.05). T2D survivors displayed a similar but more enhanced pattern of GLP-1 response than nondiabetic survivors. Nonsurvivors demonstrate an early extreme increase of both total and active GLP-1 forms, 9.5-fold and 5-fold, respectively (P <.05). The initial and late levels of circulating GLP-1 inhibitory enzyme sDPP-4 were twice lower in all studied groups (P <.001), compared with healthy controls. Conclusions: Taken together, these data indicate that endogenous GLP-1 system is activated during sepsis. Patients with T2D display an enhanced and prolonged activation as compared to nondiabetic patients. Extreme early increased GLP-1 levels during sepsis indicate poor prognosis.

Original languageEnglish
Article numbere2982
JournalDiabetes/Metabolism Research and Reviews
Volume34
Issue number4
DOIs
StatePublished - May 2018
Externally publishedYes

Keywords

  • active GLP-1
  • endogenous GLP-1system
  • sDPP-4
  • sepsis
  • total GLP-1
  • type 2 diabetes

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