Mechanisms of Adverse Effects of Hyperglycemia in Acute Illness: A Review of the Basic Science

Key Points

  • Hyperglycemia and insulin regulation play both a direct and indirect role in the cellular mechanisms underlying inflammation and oxidative stress.

  • Free fatty acids generated by hyperglycemia and insulin deficiency also result in endothelial dysfunction and the generation of reactive oxygen species.

  • Hyperglycemia consistently promotes inflammation.

  • The role of insulin in mediating inflammation is more complicated.

    • In some studies, cytokines appear to be generated in the inflammatory process in the presence of insulin; in other studies, cytokines appear to be suppressed by insulin.

    • The resolution of this apparent conflict is that insulin and glucose co-modulate inflammation.

      • With euglycemia, insulin suppresses inflammatory processes.

      • However, in the presence of hyperglycemia, insulin promotes inflammation.

  • This may explain apparent discrepancies in the results of some clinical trials, especially when hyperglycemia has not been controlled meticulously.

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