What is the primary source of fuel in sepsis, a life-threatening condition (Systemic Inflammatory Response Syndrome)?

From the Guidelines

The main source of fuel in sepsis is glucose (option A). During sepsis, the body undergoes significant metabolic changes characterized by hypermetabolism and increased energy expenditure. Despite adequate or even elevated glucose levels in the bloodstream, there is a phenomenon called "accelerated glucose metabolism" where glucose becomes the predominant fuel source. This occurs because sepsis triggers a stress response that increases glucose production by the liver through glycogenolysis and gluconeogenesis, while simultaneously causing insulin resistance in peripheral tissues. This metabolic shift prioritizes glucose utilization, particularly by immune cells and vital organs, to meet the high energy demands during the inflammatory response. While fatty acids and amino acids are also metabolized during sepsis as alternative energy sources, glucose remains the primary and preferred fuel substrate, especially in the early phases of sepsis when the body is mounting an intense immune response 1.

Some key points to consider:

• Hyperglycaemia is a common metabolic alteration seen in human infection, resulting from a dysregulation in glycogen metabolism and significant insulin resistance 1.
• The induction of catabolic processes during infection is triggered by inflammatory cytokines, including interleukin (IL)-1β and tumor necrosis factor (TNF), which also trigger sickness-associated anorexia (SAA) and reduce energy intake 1.
• Lipolysis of lipid stores is upregulated during infection, but inflammation can down-regulate the utilization of free fatty acids (FFAs) by reducing production of enzymes involved in fatty acid oxidation (FAO) and ketone production 1.
• Glucose is redirected to immune cells, promoting aerobic glycolysis and immune function, but excessive immune activation can actually do more harm than good 1.

Overall, the evidence suggests that glucose is the primary source of fuel in sepsis, particularly in the early phases of the disease. This is supported by the most recent and highest quality study available 1.

From the Research

Main Source of Fuel in Sepsis

• The main source of fuel in sepsis is glucose, as evidenced by the increased glucose uptake in tissues during the hyperglycemic phase of sepsis 2.
• Studies have shown that sepsis predisposes to disordered metabolism and dysglycemia, which is a broad term that includes hyperglycemia, hypoglycemia, and glycemic variability 3.
• The increased tissue glucose uptake observed during the early phase of sepsis is a consequence of concomitant changes in plasma glucose and insulin 2.
• In contrast, during the euglycemic and hypoglycemic stages of sepsis, glucose uptake in macrophage-rich tissues remains elevated and is independent of changes in glucose and insulin 2.
• Hyperglycemia is a risk marker of morbidity and mortality in acute critical illness, and insulin therapy seems to be beneficial in this patient group 4.

Alternative Sources of Fuel

• Fatty acids are also released and used during sepsis, but glucose is the primary source of fuel 4.
• Amino acids are also affected by the metabolic derangements in sepsis, but they are not the primary source of fuel 4.
• Ketones are not mentioned as a primary source of fuel in sepsis in the provided studies.

Summary of Findings

• Glucose is the main source of fuel in sepsis, especially during the hyperglycemic phase 2.
• Insulin therapy may be beneficial in septic patients by counteracting the metabolic changes and modulating inflammatory pathways 4.
• The metabolic derangements in sepsis are complex and involve changes in glucose, fatty acids, and amino acids 4.