In their article on hyperglycemia in subjects admitted with myocardial infarction, Dandona, Aljada, and Bandyopadhyay (1) summarize much of the current knowledge about the anti-inflammatory effects of insulin. They propose mechanisms to explain the decreased morbidity and mortality seen in subjects on insulin infusions with tight blood glucose control. This may explain the results seen in another trial (2) in the intensive care population.
However, the authors fail to mention another of the possible effects of insulin. One of the systemic responses to critical illness is acute protein breakdown. This is thought to permit release of amino acids from skeletal muscle for high-priority use in threatened tissues. This protein breakdown may be due to the catabolic actions of the counter regulatory hormones and/or through the actions of a variety of cytokines (3). The insulin resistance that occurs as a result of these excess hormones and cytokines may reduce the inhibitory effect that insulin has on the ATP-ubiquitin proteasome proteolytic pathway, thus leading to an increase in skeletal muscle protein loss (4). This breakdown occurs despite the provision of adequate enteral or parenteral nutrition (5).
The protein breakdown seen in critical illness is analogous to the situation seen during prolonged insulin deprivation in subjects with type 1 diabetes. Insulin has been shown to prevent this breakdown from occurring (6,7). Thus, one of the reasons for the improved outcomes in the intensive care population on insulin may be that they lose less protein. The anti-catabolic action of insulin in these patients results in fewer complications due to the maintenance of immunocompetence, reduced incidence of infection, normalized wound healing, less muscle weakness, and lower mortality seen in the hyperglycemic critically ill (8).
