Critical Care Medicine
Adult Critical Care
Death during Intensive Glycemic Therapy of Diabetes: Mechanisms and Implications
Cryer PE (Washington Univ in St Louis, MO) Am J Med 124:993-996, 2011§
Intensive glycemic therapy has documented microvascular and potential macrovascular benefits for patients with type 1 and type 2 diabetes, but the three most recent randomized clinical trials have not found any macrovascular or survival benefits. Intensive glycemic therapy can increase mortality in type 2 diabetes patients and critically ill persons. Giving insulin or an insulin secretagogue can cause fatal hypoglycemia in diabetic patients. As a result, it is reasonable to suspect that iatrogenic hypoglycemia may cause excess mortality during intensive glycemic therapy. It was proposed that when the target A1C of less than 6% was not attained, more aggressive glycemic therapy was instituted and excess mortality resulted.
Analysis of Evidence
Severe hypoglycemia may directly cause death or indicate vulnerability to another cause of death. Finding excess mortality or cardiovascular events in patients with type 2 diabetes whose A1C levels are lower or higher suggests that hypoglycemia exerts a direct effect. Prolonged, profound hypoglycemia can cause brain death, possibly through sustained increased glutamate release and receptor activation when plasma glucose concentrations fall below 18 mg/dL, the electroencephalogram is isoelectric, and brain glucose and glycogen levels are too low to measure. Because these conditions are rare in patients with diabetes, most fatal hypoglycemic episodes result from other mechanisms, usually cardiac arrhythmias. Impaired ventricular repolarization, reflected in a prolonged corrected QT (QTc) interval, is associated with lethal ventricular arrhythmias and seen in experimental and clinical hypoglycemia in type 1 diabetes.