Hyper-Activation of Endogenous GLP-1 System to Gram-Negative Sepsis is Associated with Early Innate Immune Response and Modulated by Diabetes.

Bloch, Olga; Perl, Sivan H; Lazarovitch, Tsilia; Zelnik-Yovel, Dana; Love, Itamar; Mendel-Cohen, Lior; Goltsman, Galina; Flor, Hadar; Rapoport, Micha J

BACKGROUND Culture-positive Gram-negative sepsis induces greater magnitude of early innate immunity /inflammatory response compared with culture-negative sepsis. We previously demonstrated increased activation of anti-inflammatory Glucagon Like Peptide-1 (GLP-1) hormone in initial phase of sepsis more pronounced in diabetes patients. However, whether GLP-1 system is hyper-activated during the early innate immune response to Gram-negative sepsis and modulated by diabetes remains unknown. OBJECTIVES Total and active GLP-1, soluble Dipeptidyl peptidase 4 (sDPP-4) enzyme and innate immunity markers presepsin (sCD14) and procalcitonin (PCT) in plasma were determined by ELISA on admission and after 2 to 4 days in 37 adult patients with and without type 2 diabetes (T2D) and Gram-negative or culture-negative sepsis of different severity. RESULTS Severe but not non-severe sepsis was associated with markedly increased GLP-1 system response, which correlated with PCT and the organ dysfunction marker lactate. Culture-positive Gram-negative bacteria but not culture-negative sepsis induced hyper-activation of GLP-1 system, which correlated with increased innate immune markers sCD14, PCT and lactate. GLP-1 inhibitory enzyme sDPP-4 was down regulated by sepsis and correlated negatively with sCD14 in Gram-negative sepsis. Diabetic patients demonstrated increased GLP-1 response but significantly weaker innate immune response to severe and Gram-negative sepsis. CONCLUSIONS Early stage of Gram-negative sepsis is characterized by endogenous GLP-1 system hyperactivity associated with over activation of innate immune response and organ dysfunction, which are modulated by diabetes. Total GLP-1 may be novel marker for rapid diagnosis of Gram-negative sepsis and its severity.