Differential Clinical Outcomes Associated With Hypoglycemia and Hyperglycemia in Acute Myocardial Infarction

Background-In patients with acute myocardial infarction (AMI), hyperglycemia predicts death, but the prognostic significance of hypoglycemia is controversial. Methods and Results-We evaluated the prognostic significance of hypoglycemia and hyperglycemia in 30 536 AMI patients in a post hoc analysis of 2 large trials of glucose-insulin-potassium therapy in AMI. Glucose levels on admission and at 6 and 24 hours after admission, as well as 30-day mortality, were documented. In separate multivariable Cox models for admission and postadmission glucose, we compared the prognostic value of hypoglycemia (<= 70 mg/dL) and hyperglycemia (>= 140 mg/dL) with normoglycemia (>70 and <140 mg/dL). Analyses were repeated with hypoglycemia defined as glucose <= 60 mg/dL and in key subgroups based on diabetes or insulin (glucose-insulin-potassium) allocation status. Both high and low percentiles of admission glucose predicted increased 30-day mortality. However, for postadmission glucose, this U-shaped relationship was attenuated so that only high and not low glucose levels remained prognostic. Hyperglycemia (>= 140 mg/dL), both on admission (adjusted hazard ratio 1.43, 95% confidence interval 1.32 to 1.56, P < 0.0001) and after admission (adjusted hazard ratio 1.47, 95% confidence interval 1.31 to 1.66, P < 0.0001), predicted death compared with normoglycemia. In contrast, hypoglycemia (glucose <= 70 mg/dL) on admission was not prognostic (adjusted hazard ratio 1.16, 95% confidence interval 0.84 to 1.62, P = 0.37), nor was postadmission hypoglycemia (adjusted hazard ratio 0.96, 95% confidence interval 0.72 to 1.26, P = 0.75). Exploratory analyses that redefined hypoglycemia as glucose <= 60 mg/dL showed consistent results, as did analyses restricted to diabetic patients (18% of the study population). Postadmission hypoglycemia was more common in insulin (glucose-insulin-potassium)-treated patients (6.9%) than in untreated patients (3.4%) but did not predict mortality in either subgroup. Conclusions-Both admission and postadmission hyperglycemia predict 30-day death in AMI patients. In contrast, only hypoglycemia on admission predicted death, and this relationship dissipated after admission. These data suggest hypoglycemia may not be a direct mediator of adverse outcomes in AMI patients. (Circulation. 2009; 120: 2429-2437.)