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.

Background: Whether insulin resistance is underlying the deep venous thrombosis (DVT) development in patients with traumatic brain injury (TBI) is elusive. To associate kinetics of plasma insulin level in patients with TBI with developing DVT in ICU.Methods:A prospective observational study of 73 patients with TBI who had measurements of insulin, glucose, glucagon-like peptide 1 (GLP-1), inflammatory factors, and hematological profile within 4 preset time periods during the 14 days after TBI. Ultrasonic surveillance of DVT was tracked weekly for time-to-event analyses. Two-way ANOVA analysis was applied to determine whether the above factors could discriminate between patients with and without DVT, or with and without insulin therapy. Partial correlations of insulin level with all the variables were carried out separately in patients with or without DVT. Factors associated with DVT were analyzed by multivariable logistic regression. Neurological outcome 6 months after TBI was assessed for Glasgow Outcome Scale (GOS).Results:Among patients with an average (SD) age of 53±16 years, DVT developed in 20 (27%) on mean (median) TBI day 10±8. The 14-day insulin levels were higher in patients with DVT (P=0.01). Platelet profile discriminated significantly between patients with and without DVT. Surprisingly, none of other factors differed between the two groups. Patients with insulin therapy had significant higher insulin (P=0.006), glucose (P<0.001) and GLP-1 (P=0.01) levels, and were more likely to develop DVT (60% vs. 15%, P<0.001) with concomitant platelet depletion. Insulin levels correlated with glucose, GLP-1 levels, and platelet count exclusively in patients without DVT. Conversely, in patients with DVT, insulin correlated negatively with GLP-1 level (r=-0.297, P=0.016). Age (P=0.01) and elevated insulin level at day 4-7 (P=0.04) were independently associated with DVT. Patients with insulin therapy also showed worse GOS (P=0.001).Conclusions:Elevated insulin level in the first 14 days after TBI may present insulin resistance in TBI, which was associated with consistent platelet activation, thus increasing risk of DVT. Our data suggest that insulin resistance index may be a predictive biomarker for DVT. Trial registration: 2021-RE-017.