1351-P: Diabetes Predisposes to More Extensive Brain Damage Resulting from Insulin-Induced Hypoglycemia

Introduction and Objective: We sought to determine if diabetes per se increases susceptibility to insulin-induced severe hypoglycemia (SH) and mechanisms involved. Methods: 10-week-old Sprague-Dawley rats were assigned to 1 of 4 treatment groups: 1) saline treated euglycemic controls, 2) treatment with insulin-induced SH, 3) saline treated streptozotocin (STZ)-diabetic rats, and 4) STZ-diabetic rats treated with insulin-induced SH. SH (10-15mg/dL) was maintained for 90 minutes followed by glycemic restoration. One week later, animals were euthanized, perfused and brains extracted. Sections from the hippocampus (40µm) were stained using Fluoro-Jade C (FJC-neuronal degeneration marker), 4-Hydroxynonenal (4HNE-reactive oxygen species marker), and Cleaved Caspase 3 (CC3- apoptosis marker). Stains were analyzed using ImageJ and one-way ANOVA. Results: As compared to euglycemic controls, SH increased CC3, 4HNE, and FJC-stained cells (Fig. 1). In the diabetic cohort, SH induced an 11-fold increase in FJC+ cells, a 1.5-fold increase in CC3+ cells, and a 3-fold increase in 4HNE+ areas (Fig. 1). In summary, SH induced more extensive brain damage in STZ-diabetic rats as noted by FJC, CC3, and 4HNE immunohistochemistry staining. Conclusion: In this rodent model, as compared to euglycemic controls, diabetes markedly increased susceptibility to hypoglycemia-induced brain damage, specifically biomarkers associated with apoptosis, neuronal degeneration, and oxidative stress. Disclosure A. Thompson: None. H. Riley: None. H.G. Miller: None. V.S. Patel: None. S. Stone: None. R. Zohary: None. L. Schoeder: None. Z. Beckner: None. M. Devore: None. S. Fisher: None. Funding NIDDK (R01DK118082)