Patients with diabetes have greater short-term and long-term mortality after acute myocardial infarction (MI) than patients without diabetes, even in the era of thrombolytic therapy (1,2). Diabetes is also an independent predictor of mortality following other acute coronary syndromes (ACS), such as unstable angina or non-Q-wave MI (3). Even in patients without a previous diagnosis of diabetes, hyperglycemia on admission for an acute MI is associated with higher mortality (4-6). These cases may represent previously unrecognized diabetes or glucose intolerance (7).

Glycemic Control

Biochemical abnormalities associated with relative (or absolute) insulin deficiency may be harmful during the acute phase of MI (8). Studies that have examined glucose-insulin-potassium (GIK) infusion therapy in patients presenting with an acute MI, regardless of their admission blood glucose (BG) level, have yielded variable results, and its routine use remains controversial (9).

Insulin therapy in patients with diabetes presenting with an acute MI has been shown to be beneficial. The Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study compared the use of conventional therapy to an insulin-glucose infusion to maintain BG levels between 7.0 and 10.0 mmol/L, followed by multidose subcutaneous (SC) insulin (intensive insulin therapy). Intensive insulin therapy resulted in a nearly 30% reduction in long-term mortality out to 3.4 years. One life was saved for every 9 patients treated with intensive insulin therapy. Particular benefit was observed in patients who had fewer cardiovascular risk factors and those who were not using insulin prior to randomization. An unresolved issue under investigation is whether the reduction in long-term mortality observed in the intensive insulin therapy group was due to the acute effect of insulin treatment on the myocardium, the use of SC insulin after the MI or improved glycemic control after the MI (10,11). Given the magnitude of benefit seen in the DIGAMI study and the knowledge that diabetes is a predictor of mortality after ACS (3), use of an insulin-glucose infusion to improve glycemic control in the acute setting may be beneficial for all patients with diabetes presenting with an ACS. Patients who are treated with a multidose insulin regimen after an MI should be followed closely by a diabetes healthcare team with experience in managing intensified insulin therapy in order to safely maintain optimal glycemic control.

Recommendations

All patients with acute MI, regardless of whether or not they have a prior diagnosis of diabetes, should have a plasma glucose level measured on admission [Grade D, Consensus], and those with BG >12.0 mmol/L should receive insulin-glucose infusion therapy to maintain BG between 7.0 and 10.0 mmol/L for at least 24 hours, followed by multidose SC insulin for at least 3 months [Grade A, Level 1A (10,11)]. An appropriate protocol should be developed and staff trained to ensure the safe and effective implementation of this therapy and to minimize the likelihood of hypoglycemia [Grade D, Consensus].

References

1. Haffner SM, Lehto S, Rönnemaa T, et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229-234.
   
2. Mak K-H, Moliterno DJ, Granger CB, et al. Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. GUSTO-I Investigators. J Am Coll Cardiol. 1997;30:171-179.
   
3. Malmberg K, Yusuf S, Gerstein HC, et al. Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry. Circulation. 2000;102:1014-1019.
   
4. Capes SE, Hunt D, Malmberg K, et al. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet. 2000;355:773-778.
   
5. Bolk J, van der Ploeg T, Cornel JH, et al. Impaired glucose metabolism predicts mortality after a myocardial infarction. Int J Cardiol. 2001;79:207-214.
   
6. Wahab NN, Cowden EA, Pearce NJ, et al. Is blood glucose an independent predictor of mortality in acute myocardial infarction in the thrombolytic era? J Am Coll Cardiol. 2002;40:1748-1754.
   
7. Norhammar A, Tenerz Å, Nilsson G, et al. Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study. Lancet. 2002;359:2140-2144.
   
8. Malmberg K, McGuire DK. Diabetes and acute myocardial infarction: the role of insulin therapy. Am Heart J. 1999;138:S381-S386.
   
9. Fath-Ordoubadi F, Beatt KJ. Glucose-insulin-potassium therapy for treatment of acute myocardial infarction: an overview of randomized placebo-controlled trials. Circulation. 1997;96:1152-1156.
   
10. Malmberg K, Rydén L, Efendic S, et al. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol. 1995;26:57-65.
    
11. Malmberg K. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group. BMJ. 1997;314:1512-1515.