PI-105 - EFFECT OF INDUCED HYPOGLYCEMIA ON OXIDATIVE STRESS IN HEALTHY VOLUNTEERS AND THE POTENTIAL APPLICATIONS OF N-ACETYLCYSTEINE

E. Letscher¹, E. Seaquist², A. Kumar², A. Moheet², L. Eberly², L. Coles³; ¹University of Minnesota, Minneapolis, MN, United States of America, ²University of Minnesota, Minneapolis, MN, United States, ³University of Minnesota, Minneapolis, MN.

Background: Hypoglycemia is a severe risk for patients with diabetes that can cause seizures, cardiovascular events, and death. The reactive oxygen species (ROS) produced during hypoglycemic episodes are thought to play a role in impaired awareness of hypoglycemia, leading to more severe and dangerous episodes. N-acetylcysteine (NAC) is an FDA approved antioxidant used as a rescue for acetaminophen overdose. In rat models, NAC reduced hypoglycemia-induced ROS. The objective of this study was to characterize the effect of hypoglycemia on markers of oxidative stress in humans as well as evaluate the ability of NAC to alleviate these effects.

Methods: Blood samples were collected from 18 healthy volunteers in a double blinded, placebo controlled, crossover study. An IV infusion of NAC or saline was administered to participants over 60 minutes. Hypoglycemia was then induced via insulin clamp. Markers of oxidative stress, malondialdehyde (MDA) and catalase activity, were measured using thiobarbituric acid reactive substances assays and catalase assay kits, respectively (Cayman Chemical, Ann Arbor, MI). Placebo samples collected before and after the induction of hypoglycemia were compared to assess the relationship between hypoglycemia and oxidative stress. To assess the antioxidant effect of NAC under hypoglycemic conditions, samples collected post-NAC infusion were compared to those collected post-saline infusion.

Results: The mean difference in MDA in placebo samples before and during hypoglycemia was 2.14 µM (95% CI, 0.06 - 4.21 µM; p = 0.02). MDA levels before and during hypoglycemia were not significantly different in NAC-treated samples. The mean difference in MDA levels after NAC vs. saline treatment was 6.53 µM (95% CI, 1.59 - 11.47 µM; p = 0.008). The changes in catalase activity were not statistically significant for NAC or placebo treated samples, however NAC treatment did result in a larger average decrease in catalase activity than placebo (-0.08 U vs. -0.002 U).

Conclusion: Measures of oxidative stress increased with the induction of hypoglycemia. Pre-treatment with NAC prevented this increase in oxidative stress from occurring post-induction. This provides evidence that NAC has the potential to ameliorate the oxidative stress caused by hypoglycemia.