Vitamin E treatment in insulin-deficient diabetic rats reduces cardiac arrhythmias and mortality during severe hypoglycemia

In people with type 1 diabetes, hypoglycemia can induce cardiac arrythmias. In rodent experiments, severe hypoglycemia can induce fatal cardiac arrhythmias, especially so in diabetic models. Increased oxidative stress associated with insulin deficient diabetes was hypothesized to increase susceptibility to severe hypoglycemia induced fatal cardiac arrhythmias. To test this hypothesis, Sprague Dawley rats were made insulin deficient with streptozotocin and randomized into two groups: 1) control (n = 22) or 2) vitamin E treated (four doses of α-tocopherol, 400 mg/kg, n = 20). Following one week of treatment, rats were either tested for cardiac oxidative stress or underwent a hyperinsulinemic-severe hypoglycemic (10-15 mg/dl) clamp with electrocardiogram recording. As compared to controls, vitamin E treated rats had 3-fold less cardiac oxidative stress, 6-fold less mortality due to severe hypoglycemia, and 7-fold less incidence of heart block. In summary, vitamin E treatment and the associated reduction of cardiac oxidative stress in diabetic rats reduced severe hypoglycemia-induced fatal cardiac arrhythmias. These results indicate that in the setting of diabetes, pharmacological treatments that reduce oxidative stress may be an effective strategy to reduce the risk of severe hypoglycemia induced fatal cardiac arrhythmias.