Hormonal and Metabolic Responses to Glucose Infusion in Sepsis Studied by the Hyperglycemic Glucose Clamp Technique

Abstract

Although nutritional support is vital to treatment of severe sepsis, the septic patient does not respond normally to glucose infusion. We have used the hyperglycemic glucose clamp technique to investigate the initial hormonal and metabolic responses of the septic patient to glucose under controlled conditions. The plasma glucose concentration was raised to and maintained at 12 mmol/liter for 2 hr in 12 septic patients and 11 normal controls. Glucose utilization, assessed from the amount infused, was significantly depressed in the patients, despite similar plasma insulin concentrations in the two groups. Forearm glucose uptake was similarly impaired. Despite very similar plasma free fatty acid concentrations in the two groups, which were suppressed equally by the glucose infusion, whole-body fat oxidation was elevated in the patients compared with the controls, and suppressed to a lesser extent in response to glucose. Glycerol and ketone body concentrations were elevated in the patients in keeping with a picture of accelerated release, clearance, and oxidation of fatty acids. Plasma cortisol, epinephrine, and norepinephrine concentrations were elevated in the septic patients in a severity-related manner, but not to high levels compared with experimental work. Norepinephrine showed no response to the glucose infusion in either group. Plasma glucagon concentrations were not significantly elevated in the septic patients. We conclude that the hyperglycemic glucose clamp provides a useful model for studying glucose intolerance in sepsis. Impaired glucose utilization in septic patients is associated with increased fat oxidation, although the hormonal basis for these changes is still unclear.

Surviving sepsis campaign: research priorities for sepsis and septic shock

“…Decreased activity in electron transport chain complexes I, III, IV and ATP synthase has also been demonstrated [183,184]. Sepsis is also known to alter substrate preference, with a decrease in the utilization of glucose (glucose intolerance) relative to fat and protein [204,205]. As a result, septic patients tend to be hyperglycemic.…”

Hyperglycaemia and pulmonary infection

“…Despite increased insulin resistance in acute stress (White et al 1987), insulin therapy is effective in the normalisation of blood glucose and reduction of adverse outcomes in acute illness. In a prospective study of 1548 patients admitted to a cardiothoracic surgical ICU (Van den Berghe et al 2001) intensive blood glucose control with insulin (blood glucose 4 .…”

Insulin regulates Il-1α, Ifn-y and Il-4 release from murine splenocytes stimulated with staphylococcal protein A, toxic shock syndrome toxin-1 and streptococcal lysin S

“…It is possible to hypothesize that the cytokine interaction induces a mechanism of regulation which limits the tissue damage. Multiple disturbances by insulin characterize glucose metabolism during experimental infections in animals [20] and natural infections in humans [21][22][23]. During non-lethal hypermetabolic sepsis, insulin-stimulated glucose utilization is impaired [24].…”