• Myocardial Infarction
• Diabetes & Endocrinology Clinical Trials

Acute myocardial infarction (AMI) in patients with diabetes increases the risk of poor outcome. In the Diabetes Mellitus-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study, insulin-glucose infusion, followed by multidose insulin treatment, improved long-term prognosis in diabetic patients with AMI at 1 year [Malmberg K et al. J Am Coll Cardoiol 1995].

In DIGAMI 2, patients with type 2 diabetes or blood glucose >11 mmol/L and suspected myocardial infarction (MI) were randomized to one of three treatment strategies: Group 1–acute insulin-glucose infusion followed by insulin-based long-term glucose control (n=474); Group 2-insulin-glucose infusion followed by standard glucose control (n=473); or Group 3–routine metabolic management according to local practice (n=306) [Malmberg K et al. Eur Heart J 2005]. Subjects were treated for a mean of 2.1 years and, in an extended part of the trial, followed up for a maximum of 8.3 years (median 4.1). At the end of the study, there were no significant differences in morbidity, expressed as nonfatal reinfarctions and strokes, among the three groups. The data did suggest that glucose level is a strong, independent predictor of long-term mortality in this patient category, indicating that glucose control seems to be an important part of their management.

Results of a later post hoc analysis from DIGAMI 2, assessing the impact of glucose-lowering treatment with insulin, sulfonylureas, or metformin on long-term mortality and morbidity prognosis, showed no significant difference in mortality between the three treatments. The risk of nonfatal MI and stroke increased significantly with insulin, while metformin was protective [Mellbin LG et al. Eur Heart J 2008].

Linda Mellbin, MD, Department of Cardiology, Karolinska Institutet, Stockholm, Sweden, discussed recent data from the extended follow-up (maximum 8.3 years; median 4.1 years) for 1145 subjects in the DIGAMI 2 study. Total mortality was 34% (24% cardiovascular [CV]; 9.5% malignancies). Cox regression analysis did not show any difference in total or CV mortality among the treatment groups. The total number of fatal malignancies was 37, with the highest risk in Group 1 (HR vs Group 2, 1.83; 95% CI, 0.90 to 3.71; p=0.10 and Group 3, 3.57; 95% CI, 1.22 to 10.39; p=0.02). Treatment with insulin was associated with a significant increase in the risk of nonfatal MI and stroke (OR, 1.90; 95% CI, 1.38 to 2.60; p<0.0001) but not mortality (OR, 1.30; 95% CI, 0.94 to 1.80; p=0.11), while metformin was associated with a lower mortality (HR, 0.65; 95% CI, 0.47 to 0.90) and a lower risk of death due to malignancies (HR, 0.25; 95% CI, 0.08 to 0.83).

Long-term mortality is high after MI in patients with type 2 diabetes. The drug that is used for glucose control appears to have a prognostic impact. Prof. Mellbin suggested that the beneficial effects of metformin may be due to 5' AMP-activated protein kinase-induced improved endothelial function, tumor suppression, and increased insulin sensitivity. The negative effects of insulin were attributed to it being proatherogenic, its effect on the insulin-like growth factor-1 axis, survival and proliferation of malignant cells, and hypoglycemia.

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