Metabolic Mechanisms of Stress Hyperglycemia

Stress hyperglycemia has gained the attention of virtually every physician who encounters critically ill patients, with the emergence of clinical data supporting tight glycemic control and intensive insulinization for optimal outcome. In order to effectively manage stress hyperglycemia, newer theories of critical illness and the interactions of the brain, neuroendocrine axis, and immune system need to be explored. Nonlinear physiologic processes, glucose allostasis, immune-neuroendocrine axis activation, and molecular mechanisms of insulin receptor signal transduction contribute to a novel model of stress hyperglycemia. In chronic critical illness, allostatic overload leads to a plurality of organ-system derangements and eventually death. Intervention not only involves insulinization according to neurofuzzy logic but also targeting more proximate events with cognitive/behavioral therapy and hypothalamic releasing factors.