Duc N. Nguyen (Denmark)
Comparative Pediatrics and Nutrition Department of Veterinary and Animal Sciences, University of Copenhagen, DenmarkAuthor Of 1 Presentation
LOW PARENTERAL GLUCOSE MODULATES IMMUNE-METABOLIC RESPONSES AND DECREASES SEPSIS SEVERITY IN INFECTED NEWBORN PRETERM PIGS
Abstract
Backgrounds:
Preterm infants have impaired immunity and high susceptibility to neonatal sepsis, and often rely on parenteral nutrition (PN) rich in glucose. Using preterm pigs as models, we have shown that high PN glucose caused hyperglycemia and severe sepsis following neonatal infection, whereas glucose restriction prevented sepsis but induced severe hypoglycemia. Now we aimed to examine possibilities of PN glucose levels to lower sepsis risks without inducing hypoglycemia.
Methods
In two experiments with similar setups, caesarian section-delivered preterm pigs (90% gestation) were infused with Staphylococcus epidermidis or saline and nourished with PN for 22 h. Systemic metabolic and immunological response to infection were evaluated over time. In experiment 1, animals were kept on either high (21%, 30 g/kg/d, n=25) or low (5%, 7.2 g/kg/d, n=25) glucose PN until sacrifice. In experiment 2 all animals (n=41) were started on high glucose PN and 1/3 of animals were switched to low glucose PN after 3 and 6 hours, respectively.
Results:
Experiment 1: Low parenteral glucose reduced mortality (25 vs 87%) and sepsis severity outcomes (higher blood pH, lower lactate and cytokines) while maintaining normoglycaemia. Proteomics and transcriptomics further revealed decreased inflammation and up-regulated anti-inflammatory apolipoproteins and complement proteins in blood, as well as decreased the hepatic Warburg effects (ratio of glycolysis/oxidative phosphorylation). Experiment 2: Switching from a high to a low glucose PN 3-6h post-infection did not change sepsis severity outcomes or mortality.
Conclusions/Learning Points:
Low parenteral glucose decreased systemic glycolytic activity and the severity of sepsis outcomes, but switching from high to low glucose levels 3-6h post-infection had minimal impact on the clinical or immunological responses. This suggests systemic glucose conditions at the time of infection are key in guiding the immune-metabolic responses leading to sepsis.