Elevated plasma glucagon-like Peptide-1 levels are associated with enteral feeding intolerance in traumatic brain injury.

BACKGROUND AND AIMS: Enteral feeding intolerance is a frequent and clinically significant complication in patients with traumatic brain injury (TBI), yet its mechanisms remain poorly understood and predictive tools are lacking. We investigated a prospective study to determine whether elevated circulating glucagon-like peptide-1(GLP-1) is associated with feeding intolerance after TBI and to assess its predictive utility.

METHODS

A prospective cohort study in a tertiary neuro-ICU including 109 adults aged 18-80 years with TBI was conducted. A standardised enteral feeding strategy targeted 25 kcal/kg/d and was adjusted according to tolerance. Participants were classified by average caloric adequacy over 14 days: tolerance (≥70% of goal) vs intolerance (<70%). Blood was sampled during post-injury day (PID) windows 1-3, 4-7, 8-10, and 11-14. Longitudinal trajectories of circulating GLP-1, insulin, glucose, and glial fibrillary acidic protein. The Primary outcome was feeding intolerance within 14 days. Associations of biomarkers with feeding intolerance were evaluated, and discrimination was quantified using multivariable logistic regression and receiver operating characteristic analysis.

RESULTS

Insulin (P = 0.49) and glucose (P = 0.47) did not differ between intolerance (n = 50) and tolerance (n = 59) groups, whereas GLP-1 was higher in the intolerance group (P = 0.024). GLP-1 increased with injury severity (P = 0.034) and was greatest in patients with GCS 3-5 vs 6-12 (P < 0.001). GLP-1 correlated with glial fibrillary acidic protein over 14 days (r = 0.259; P < 0.001); intestinal permeability markers did not differ between groups. In multivariable models, GLP-1 at PID8-10 (OR, 1.029; P = 0.001), IL-6 at PID8-10 (OR, 1.033; P = 0.035), insulin at PID1-3 (OR, 1.025; P = 0.006), and admission SOFA score (OR, 1.646; P = 0.023) were independently associated with feeding intolerance. Combining insulin at PID1 and SOFA offered early risk stratification (AUC, 0.786; 95% CI, 0.693-0.879; P < 0.001; specificity 71.4%; sensitivity 75%).

CONCLUSIONS

Elevated plasma GLP-1 levels are associated with enteral feeding intolerance in patients with TBI. These findings are hypothesis-generating and suggest that altered GLP-1 signalling may contribute to feeding intolerance.

STATEMENT OF SIGNIFICANCE: We propose that disrupted central GLP-1 signalling diminishes afferent satiety input and efferent anorexigenic output, yielding central GLP-1 resistance with secondary GLP-1 accumulation in plasma; higher circulating GLP-1 may therefore indicate central GLP-1 resistance in TBI and associate with FI. Elevated circulating GLP-1 may serve as a pragmatic predictor of feeding intolerance after TBI and could inform feeding strategies.