Molecular mechanisms by which metabolic control may improve outcomes

Objective: To summarize available evidence providing potential explanations for metabolic and nonmetabolic abnormalities during conditions of acute stress and possible mechanisms whereby insulin therapy may affect these changes. Results: Recent studies have demonstrated a remarkable effect of intensive insulin therapy and reductions in morbidity and mortality in patients in intensive-care units and other hospital settings. The mechanisms involved in these effects are under thorough investigation. Insulin therapy improves glucose and lipid homeostasis, both of which are deleterious to the tissues, especially during severe stress. In addition, insulin has direct effects on the levels of inflammatory cytokines and other proteins that may influence the overall outcome of patients undergoing various stressful conditions. Conclusion: Analysis of published studies suggests that the beneficial effects of insulin therapy may be derived from both direct and indirect mechanisms.