Insulin resistance and glucose-induced thermogenesis in critical illness

Critical illness is associated with a marked increase in metabolic rate and progressive wasting, despite aggressive nutritional support. The metabolic events which are responsible for these phenomena are unclear, but are char acterised by marked impairment of the anabolic effects of insulin on glucos e metabolism and excessive activation of the sympathetic nervous system. It has been suggested that critical illness may be associated with impaired c arbohydrate oxidation and a marked increase in the loss of heat energy asso ciated with glucose administration (glucose-induced thermogenesis). This si tuation may result in impaired efficiency of nutrient assimilation. Studies employing combinations of nutrient infusions both at clinically-relevant r ates and in association with euglycaemic hyperinsulinaemia have, however, d emonstrated that nutrient-induced thermogenesis is unaffected in critical i llness in human subjects, and that defective glucose utilization occurs as a consequence of impaired insulin-mediated glucose storage rather than oxid ation. Although the cellular and molecular mechanisms underlying these chan ges are controversial, the recent validation of a human model of insulin re sistance in critical illness should provide a means of studying this respon se in future, and allow the identification of therapeutic targets. This inf ormation should increase the efficacy of nutritional support in some of our most seriously-ill patients.