Glucose homeostasis, nutrition and infections during critical illness

Abstract

Critical illness is a complex life-threatening disease characterized by profound endocrine and metabolic alterations and by a dysregulated immune response, together contributing to the susceptibility for nosocomial infections and sepsis. Hitherto, two metabolic strategies have been shown to reduce nosocomial infections in the critically ill, namely tight blood glucose control and early macronutrient restriction. Hyperglycaemia, as part of the endocrine-metabolic responses to stress, is present in virtually all critically ill patients and is associated with poor outcome. Maintaining normoglycaemia with intensive insulin therapy has been shown to reduce morbidity and mortality, by prevention of vital organ dysfunction and prevention of new severe infections. The favourable effects of this intervention were attributed to the avoidance of glucose toxicity and mitochondrial damage in cells of vital organs and in immune cells. Hyperglycaemia was shown to impair macrophage phagocytosis and oxidative burst capacity, which could be restored by targeting normoglycaemia. An anti-inflammatory effect of insulin may have contributed to prevention of collateral damage to host tissues. Not using parenteral nutrition during the first week in intensive care units, and so accepting a large macronutrient deficit, also resulted in fewer secondary infections, less weakness and accelerated recovery. This was at least partially explained by a suppressive effect of early parenteral nutrition on autophagic processes, which may have jeopardized crucial antimicrobial defences and cell damage removal. The beneficial impact of these two metabolic strategies has opened a new field of research that will allow us to improve the understanding of the determinants of nosocomial infections, sepsis and organ failure in the critically ill.

Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion

“…Previous studies have correlated increased levels of circulating GLP-1 with the extent of concomitant critical illness in human subjects (Ingels et al, 2017;Kahles et al, 2014;Lebherz et al, 2017). Our current findings illuminate the importance of GLP-1 in this context by demonstrating that (1) LPS acutely induce GLP-1 secretion in humans and (2) the injured human gut responds rapidly to ischemic injury with increased GLP-1 secretion.…”

Metabolic profiling reveals nutrient preferences during carbon utilization in Bacillus species

“…Since previous studies have shown that pathogens thrive in carbohydrate-rich environments, we expected to observe a high degree of metabolic utilization for carbohydrates in general; our data reinforces this notion [43][44][45][46]. However, the type of carbohydrate each species preferred varied substantially.…”

When timing and dose of nutrition support were examined, the modified Nutrition Risk in Critically Ill (mNUTRIC) score did not differentiate high-risk patients who would derive the most benefit from nutrition support: a prospective cohort study

“…However, the mechanism of harm associated with early high energy intake is poorly studied. Some would attribute to mitochondrial toxicity caused by an oversupply of glucose and lipid [ 32 ], while others have linked it to the suppression of autophagy [ 33 , 34 ].…”