Central GLP-1 Resistance Induced by Severe Traumatic Brain Injury Was Associated with Persistent Hyperglycemia in Humans

Abstract

Introduction: Whether central glucagon-like peptide 1 (GLP-1)/GLP-1 receptor system mediated peripheral glucose homeostasis in patients with traumatic brain injury (TBI) is not clear. We aim to determine if plasma GLP-1 level could distinguish the non-survivors from the survivors during the first 14 days after TBI that could prognose 6 months mortality. Methods: Metabolic, inflammatory, and hematological profiles were examined in 73 patients with TBI in neuro-ICU. Factors that discriminate non-survivors from survivors were determined by Two-way ANOVA. Biomarkers associated with mortality were determined by Binary logistic regression and Cox proportional hazard regression. Results: The non-survivors had higher infectious SOFA scores (P<0.001), lower first 3 days’ body temperature (P=0.017), greater chance of cerebral hernia (P=0.048) and decompressive craniectomy (P=0.001) than the survivors. Higher 14-days plasma GLP-1 (P<0.0001), glucose (P=0.002) and IL-6 (P=0.005) levels, in contrast with lower insulin level at days 4-7 (P=0.020) were found in non-survivors than in survivors. Except the survivors had an increased 14-days platelet number (P<0.001), the two groups did not differ in hematological profile and intestinal barrier function. Although GLP-1 correlated closely with IL-6 in both the two groups, it correlated with neither insulin nor glucose in each group. GLP-1 on days 8-10 and IL-6 on days 1-3 were positively, while insulin on days 4-7 was negatively associated with mortality. Conclusion：Persistent higher GLP-1 level in non-survivors over the survivors may present more severe central resistance to endogenous GLP-1 in non-survivors, which may be associated with progressive hyperglycemia with increased mortality in TBI.