Soluble epoxide hydrolase derived oxylipins as a link between insulin resistance and cognitive progression in patients with type 2 diabetes
Description: Type 2 diabetes mellitus (T2DM) is a serious and prevalent health condition characterized by increased insulin resistance. Insulin resistance is commonly measured using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Individuals with T2DM are more likely than the general population to develop cognitive impairment, and this may be attributable to their increased insulin resistance. The cytochrome P450 oxylipin pathway is a metabolic process in the body which converts dietary fatty acids into epoxides, which are compounds that help resolve inflammation; however soluble epoxide hydrolase (sEH) can further break down these epoxides into less active and potentially harmful species known as diols. This pathway is disrupted in people with T2DM, as they have been found to have more sEH activity resulting in higher serum diol levels, which has also been linked to poorer cognitive performance in this population. This study aims to assess a link between serum oxylipin, (epoxide and diol), levels and the degree of insulin resistance in T2DM, and to understand the relationship between these processes and cognitive decline over time. I hypothesize that serum diol levels will be 1) associated with HOMA-IR at baseline, 2) predict lower cognitive scores over 3-month, 6-month, and 18-month periods, and 3) mediate an effect of HOMA-IR on the decline in cognitive performance over time. This will be a prospective observational study including human participants who have prediabetes or a T2DM diagnosis. This study will offer new insight into the mechanisms that link insulin resistance and cognitive decline over time in T2DM and provide evidence to support pharmacological targets for treatment.
Amount: CA$27,000
Funding type: fellowship
Funder scheme: Master's Award: Canada Graduate Scholarships
Start date: 2024-09-01
End date: 2025-08-31
Investigator: Sofia Perfetto (lead)
Institution: University of Toronto
Subfield: Biochemistry
Domain: Life Sciences
Funded outputs count: 0
Funder award ID: 194884_1
OpenAlex ID: G4655963512