36-LB: Linoleic Acid Derived Oxylipins, Memory, and Microvascular Retinal Complications in Patients with Type 2 Diabetes Mellitus

Introduction: Memory decline is accelerated in type 2 diabetes mellitus (T2DM), and it is thought that microvascular disease may be a contributor. Oxylipins, bioactive lipid species derived from polyunsaturated free fatty acids such as linoleic acid, can act on small vessels. Cytochrome p450 derived epoxides may be immunologically active, whereas their hydrolysis into diols by soluble epoxide hydrolase (sEH) may render them inactive or cytotoxic. We examine linoleic acid epoxide and diol concentrations in peripheral blood and their associations with memory performance and retinal microvascular disease in patients with T2DM or prediabetes. Methods: Patients with T2DM or prediabetes were recruited from 3 sites. Memory was assessed via California Verbal Learning Test 2nd Edition (CVLT-II). Patient history of retinopathy was recorded. Serum oxylipin concentrations were measured via ultra-high-performance liquid chromatography tandem mass-spectrometry. Results: In people with T2DM or prediabetes (n=76, 55% women, 63±9 years old, HbA1C=7.4±1.2% mmol/mol, duration of diabetes 8±10 years), 9.2% had retinopathy, and the mean CVLT-II was -0.07±1.01 Z-score units (indicating generally average performance). The linoleic acid derived epoxide 12(13)-epoxyoctadecenoic acid concentration was negatively correlated with CVLT-II performance (β=-0.298, p=0.003), whereas the diol derived from that species (12,13-dihydroxyoctadecenoic acid) was elevated in people with retinopathy (9.1±4.1 nM vs. 6.5±11.5 nM, U=72.0, p=0.008). Discussion: Oxylipins generated by cytochrome p450 and sEH should be explored as potential biomarkers for cognitive complications and microvascular disease in T2DM. The observed relationships might suggest the presence of a cytochrome p450-mediated response that may generate differential response and lack benefit in T2DM, possibly due to sEH-mediated conversion of epoxides into diols, warranting further study.