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Session: Nutritional Neuroscience: Nutrition and the Brain (Oral 4)

(OR04-02-23) Central GLP-1 Resistance Induced by Severe Traumatic Brain Injury Was Associated With Persistent Hyperglycemia in Humans

Saturday, July 22, 2023
2:42 PM – 2:54 PM ET
Location:  Commonwealth

    Presenting Author(s)

  • Haiyan Liu, MD

    associate professor
    The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China
    Hefei, Anhui, China (People's Republic)

    Disclosure(s): Chinese National Natural Science Foundation: Grant/Research Support (Terminated, December 31, 2022)

    • Co-Author(s)

  • MZ

    Min Zhou, Doctor

    The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China
    Hefei, Anhui, China (People's Republic)

  • RT

    Rui Tang

    The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China

  • QZ

    Qing-Hong Zhang

    Trauma Repair and Tissue Regeneration Center, Department of Medical Innovation Study, Chinese People's Liberation Army General Hospital

Disclosure(s):
Haiyan Liu, MD: Chinese National Natural Science Foundation: Grant/Research Support (Terminated, December 31, 2022)
Objectives: Whether central glucagon-like peptide 1 (GLP-1) resistance is involved in the hyperglycemia and mortality in patients with traumatic brain injury (TBI) has never been studied. We aim to define the associations between 14-days plasma GLP-1 level and 6 months survival in patients with severe TBI.

Methods: A prospective observational study including 73 patients measured plasma GLP-1, insulin, glucose, inflammatory factors, and hematological profile at 4 time-points at the first 14 days after TBI. Two-way ANOVA analysis was used to determine the GLP-1 and other factors that discriminated between the survivors and the non-survivors. Cerebrospinal fluid (CSF) from patients at days 4-7 was subjected to hormone analysis. Factors associated with 6 months mortality and survival time were analyzed by Binary multivariable logistic regression and Cox proportional hazard regression respectively.

Results: Although the demographic characteristics were similar between the non-survivors and survivors, the non-survivors exhibited higher infection SOFA scores (P < 0.001), and were more likely to have cerebral hernia (P=0.048) or decompressive craniectomy (DC) (P=0.001) than the survivors. Except for the non-survivors had lower insulin level at days 4-7 than the survivors (P=0.020), they showed consistently higher plasma levels of GLP-1 (P < 0.0001), glucose (P=0.002) and IL-6 (P=0.005) than the survivors during the 14 days. Although plasma GLP-1 level correlated with IL-6 closely in both groups, it correlated with neither insulin nor glucose levels in any group. CSF IL-6 level was 10 times as that in plasma; however, CSF GLP-1 and insulin levels were minimal.

Binary logistic regression analysis revealed that GLP-1 at days 8-10, insulin at days 4-7, and DC were the higher risk factors for 6 months mortality. Cox regression analysis verified that GLP-1 at day 8-10 and IL-6 at days 1-3 were positively, whereas insulin at days 4-7, hypertension, and DC were negatively associated with mortality.

Conclusions: During the first 14 days after TBI, the persistent elevated GLP-1 level in the non-survivors relative to the survivors may present central GLP-1 resistance to the insulitropic effect of endogenous GLP-1, which was associated with progressive hyperglycemia that increased the risk for mortality.

Funding Sources: Chinese National Natural Science Foundation