chairman of the Department of Medicine, George Washington University, Washington, DC.

If only we could do for diabetes what we have done in the past decade for hyperlipidemia. Statins have made this problem at least treatable in most patients. One pill drops low-density lipoprotein cholesterol levels and reduces the risk of cardiovascular events. Where are the pills to reduce the risk of cardiovascular events (CVEs) in patients with diabetes or enhance weight loss in patients prone to developing diabetes?

and colleagues analyzed the Gruppo Italiano por lo Studio della Sopravvivenza nell’Infarto Mio&shy;cardico (GISSI-Prevenzione) trial database, as&shy;sessed the prevalence and the prognostic role of the metabolic syndrome (METS), and studied diabetes in patients with previous myocardial infarction (MI).

 Amazingly, 50% of patients enrolled in the study had either type 2 diabetes or METS. Both groups had a higher risk of death and CVEs compared with a control population over 3.5 years of follow-up. Diabetic patients, however, were more likely to be hospitalized for congestive heart failure and to die during the last 2.5 years of follow-up, which suggests diabetes prevention would be life-saving in post-MI patients. 

 Weight becomes critical in patients with METS. Those who gained weight had a significant risk of developing diabetes; those who lost weight had a significantly lower risk. Independently, weight change did not show any significant effect on the risk of CVEs. Weight loss may be too little, too late or the follow-up time may not have been long enough to accurately evaluate its benefit on CVEs, but the reduction in the incidence of diabetes should be enough stimulus for patients and clinicians to aggressively address. 

 Weight loss is not easy. It often involves major lifestyle changes in diet and exercise, and it is even more difficult to maintain achieved weight loss. The success of the current lipid-lowering campaign is entirely due to the ability to treat patients pharmaceutically with once-a-day medications that have little-to-no side effects. Would weight loss be so easy? The closest thing to successful pharmacologic therapy for weight loss, fen-phen, was removed from the market in 1997 when serious side effects came to light.

 So until the next great pharmaceutical breakthrough, we must engage patients in dietary changes that require significant willpower and motivation. 

 Primary and even secondary reduction in CVEs would seem to be a powerful incentive, but it didn’t work for lipids in the era before statins. Reduction in the development of diabetes may prove to be an easier sell. Enough studies have shown the association between METS and multiple bad outcomes that if Root Boy Slim were still alive, he might revise his little ditty

: Dare to be fat, Fat’s where it’s at,      Having a ball with cholesterol, C’mon y’all, Fat don’t      matter at all!  

 Sorry, it does matter. In fact, it is a matter of life and death.  

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If only we could do for diabetes what we have done in the past decade for hyperlipidemia.

A weighty problem

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

 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.

 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.

 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. 

 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. 

chairman of the Department of Medicine, George Washington University, Washington, DC.

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