Effect of insulin therapy on nonglycemic variables during acute illness.
OBJECTIVE
To review the possible mechanisms for the reported clinical finding of better outcomes for hospitalized and critically ill patients as the result of improved metabolic control.


RESULTS
Insulin inhibits free fatty acids, proinflammatory cytokines, and inflammatory growth factors, all of which may be detrimental in critically ill patients. Furthermore, insulin enhances nitric oxide synthesis, which promotes vasodilation. The mechanisms of insulin regulation of these factors are complex, although insulin seems to have a direct effect on the transcriptional factor, nuclear factor-kappabeta (NF-kappabeta). In turn, NF-kappabeta modulates the proinflammatory cytokines, adhesion molecules, and chemokines. In a euglycemic or slightly hyperglycemic environment, NF-kappabeta is suppressed by insulin; however, with more profound hyperglycemia, NF-kappabeta is induced and the proinflammatory cytokines are thus increased.


CONCLUSIONS
Although considerable research must be completed to identify the apparent relationship between stringent metabolic control and improved outcomes in acutely ill patients, current evidence suggests that both the treatment (glucose-insulin-potassium infusion) and the resultant plasma glucose concentrations may be independent important components of the underlying mechanisms.
Hirsch
Irl B
IB
University of Washington School of Medicine, Seattle, Washington, USA.
D000208:Acute Disease / Q000628:therapy*; D016207:Cytokines / Q000037:antagonists & inhibitors; D004338:Drug Combinations; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000627:therapeutic use; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D007328:Insulin / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D011188:Potassium / Q000627:therapeutic use
D016207:Cytokines; D004338:Drug Combinations; D005230:Fatty Acids, Nonesterified; D006133:Growth Substances; D018836:Inflammation Mediators; D007328:Insulin; D009569:Nitric Oxide; D005947:Glucose; D011188:Potassium