Relationships between 12,13 Metabolites of Linoleic Acid and Cognitive Performance in Patients with Type 2 Diabetes Mellitus

Background: Type 2 diabetes mellitus (T2DM) is linked with diabetes-related cognitive decline. Oxylipins are bioactive molecules derived from polyunsaturated free fatty acids. Hydrolysis of cytochrome p450-derived epoxides into diols by soluble epoxide hydrolase (sEH) are of relevant interest due to their involvement in diabetic microvascular disease. Methods: This thesis examines peripheral concentrations of 12,13-species of linoleic acid (LA)-derived oxylipins and associations with cognitive performance in patients with T2DM or prediabetes. Cognition was assessed through multiple cognitive tests evaluating domains including executive function and memory. Serum oxylipin concentrations were measured via ultra-high-performance liquid chromatography tandem mass-spectrometry. Results: Serum concentrations of 12(13)-EpOME and 12,13-DiHOME were negatively associated with executive function. Serum concentrations of 12(13)-EpOME were also negatively associated with verbal memory. Conclusions: In T2DM, concentrations of 12,13-species of LA-derived oxylipins were negatively associated with cognitive performance, suggesting a possible role in the pathogenesis of diabetes-related cognitive decline.M.Sc