Potential use of insulin as an anti-inflammatory drug

Acute hyperglycemia worsens morbidity and mortality in critically ill patients. The control of hyperglycemia with insulin improves clinical outcomes in patients with a stay of more than 3-5 days in the intensive care unit (ICU) and in coronary artery bypass graft (CABG) patients. However, clinical benefits of insulin infusion have not been seen consistently in patients with acute coronary syndromes. Since all previous studies in the ICU have centered on the normalization of glycemia, we still do not know whether insulin exerts beneficial effects over and above those observed with reduction of blood glucose concentrations. The regimens used in acute coronary syndromes infuse fixed doses of insulin with high rates of glucose and are usually associated with hyperglycemia; this may neutralize the beneficial effects of insulin. In this article, we discuss data demonstrating an anti-inflammatory effect of insulin and a pro-inflammatory effect of glucose. We provide a mechanistic justification for the benefits of maintaining euglycemia with insulin infusions in the hospitalized patients. To investigate the clinical benefits of the anti-inflammatory effects of insulin, we also suggest further investigations directed toward optimization of insulin infusion regimens to determine whether restoration of glucose levels toward normal with higher infusion rates and concentrations of insulin will lead to further improvement in outcomes in the critical care and acute coronary syndromes.