Significance of hyperglycemia and platelet function in diabetic patients

Glucose-insulin-potassium (GIK) was initially advocated as a treatment of acute myocardial infarction (MI) to promote electrical stability.

Glucose-insulin-potassium (GIK) was initially advocated as a treatment of acute myocardial infarction (MI) to promote electrical stability.1 Since the 1960s, it was also touted as an agent to provide metabolic support. Significant benefits were attributed to GIK in many small, poorly designed clinical trials that persisted into the 21st century.2,3 GIK, therefore, continued to have its advocates, but usage dwindled in the face of new therapies for acute MI, such as thrombolytic therapy and percutaneous coronary intervention.

In 2005, results of the Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction/Estudios Cardiologicas Latin American (CREATE-ECLA) were reported.4 In this trial, which was conducted in 470 centers, 20,201 patients with ST-segment elevation MI presenting within 12 hours of symptoms onset were randomly assigned to receive either a 24-hour infusion of GIK or usual care. No difference in any major endpoint was observed, probably putting to rest once and for all any question about the efficacy of this treatment. Predetermined subgroup analysis also showed a lack of benefit in those with and without diabetes.

Horowitz and Chirkov took the K out of GIK and emphasized the importance of reducing glucose levels with intravenous insulin as soon as possible in patients with acute ischemic syndromes. They found a significant inverse relationship between admission glucose levels and platelet dysfunction. This abnormality in platelet function potentially contributes to a prothrombotic state. Improvement in platelet function was observed with intravenous insulin infusion after 12 hours of therapy.

Combine this abnormality in platelet function with abnormal reactivity of endothelium to hyperglycemia and it is hard to argue with the authors' recommendation to aggressively and urgently treat hyperglycemia in all cases of acute coronary syndrome. The rationale is not that normal myocardial metabolism will be restored and infarct size may be limited, but instead, it is more of a therapeutic means to improve platelet physiology. However, to believe that it is likely that "this relatively simple maneuver may reduce the risk of ongoing ischemia, increase the safety of percutaneous coronary intervention procedures, and diminish the need for extensive therapy with antiaggregatory agents, such as glycoprotein IIb/IIIa inhibitors" sounds a bit overreaching without additional collaborative data. The fact that it sounds so logical cries out for a clinical trial. Although the use of GIK may have been finally put to rest in the treatment of acute coronary syndrome, at least for now, it appears that the "I" has been salvaged from the GIK.

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