The Potential Therapeutic Role of Insulin in Acute Myocardial Infarction in Patients Admitted to Intensive Care and in Those With Unspecified Hyperglycemia

While acute myocardial infarction and patients admitted to intensive care units carry a serious risk of mortality and morbidity, the concomitant occurrence of hyperglycemia enhances this risk. This has been established through various studies over the past decade (1–3). More recently, it has been shown that the treatment of these conditions with intravenous infusions of insulin results in marked improvements in clinical outcomes (3–5). While the normalization of blood glucose concentration may be one factor in the improvement of these outcomes, insulin may exert benefits of its own, independently of the plasma glucose concentrations.

Both septicemia and acute myocardial infarction are inflammatory states with markedly enhanced catabolism. There may be hyperglycemia and an increase in plasma free fatty acid (FFA) concentrations in both of these conditions. Increased FFA concentrations are known to be associated with a deterioration of clinical outcomes and may have toxic effects of their own on vascular reactivity and on the myocardium (6–9). FFAs may have effects on endothelial nitric oxide (NO) production (6), prostacyclin production (10), and the stability of prostacyclin in plasma (11). FFAs may also induce a state of insulin resistance through the induction of protein kinase C and inflammation through the suppression of inhibitor κB (IκB) in the skeletal muscle (12). Proinflammatory changes are also induced in the mononuclear cells by FFAs as reflected in an increase in nuclear factor-κB (NF-κB), the major proinflammatory transcription factor, an increase in reactive oxygen species (ROS) generation, and an increase in p47 ^phox (13). Thus, the normalization of FFA concentrations by insulin may produce a benefit. Similarly, it can be argued that insulin administration may facilitate the uptake of glucose by insulin-responsive organs, including the myocardium, thus providing for their metabolic needs. These mechanisms are based on our understanding of …