Hyperglycemia, Insulin, and Insulin Resistance in Sepsis

Critically ill patients frequently have hyperglycemia. This event may reflect severe stress with an imbalance between anabolic hormones and catabolic hormones. Alternatively, it may reflect alterations in either insulin levels or insulin function. Insulin is a pleiotropic hormone with multiple important metabolic effects. In patients with sepsis, insulin levels are increased but insulin sensitivity is decreased. However, there is variability in insulin sensitivity, and this creates variability in glucose levels and insulin requirements and increases the frequency of hypo- and hyperglycemia. The factors that influence insulin sensitivity are complex and include inhibition of tyrosine kinase activity of the beta subunit, increased proteolytic activity resulting in loss of receptors from the plasma membrane, and possibly the transfer of insulin receptors into the nucleus where they bind to gene promoters. Better understanding of the role of insulin in critically ill patients requires prospective studies measuring insulin levels in various patient groups and the development of a simple measure of insulin sensitivity.