637-P: Sex-Specific Associations between Fatty Acid–Derived Oxylipins and Executive Function in T2DM
Bibliographic record
Abstract
T2DM increases the risk of cognitive decline, especially in women. Sex-specific associations between lipids and cognition have been reported, though underlying mechanisms remain unclear. Disruptions in the cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) pathway have been linked to both T2DM and cognitive dysfunction. CYP450s convert long-chain polyunsaturated fatty acids into epoxides which are anti-inflammatory and help resolve inflammation, however sEH metabolizes these into inactive or cytotoxic diols, limiting their benefits. We hypothesized that oxylipin epoxides and diols of arachidonic acid (AA) and docosahexaenoic acid (DHA) would be associated with cognition in people with T2DM, particularly in women. Women and men with T2DM were recruited as part of the study. Twenty-two fasting serum free oxylipins were quantified by ultra-high performance liquid chromatography tandem mass spectrometry. Executive function was assessed using a composite z-score from the following tests: Stroop Colour-Word Interference Victoria Version, FAS Verbal Fluency, Digit Symbol Substitution, and Trails Making Test Part B. All analyses controlled for age, sex, BMI, HbA1c and years of education. Among 72 individuals with T2DM (mean age 61.8±9.2, mean HbA1c 7.4±0.1%, 53% women), demographic characteristics, oxylipin concentrations and cognitive performance did not differ between women and men. Some CYP450-derived epoxides of DHA and AA were associated with lower executive function scores in women, but with higher scores in men. Epoxide × sex interactions were found for 3 of 4 DHA epoxides (16(17) [F=20.2, p<0.001]; 13(14) [F=8.5, p=0.005]; and 10(11) [F=7.4, p=0.009]), and for the 14(15) AA epoxide [F=3.9, p<0.05]). Circulating concentrations of the corresponding diols were not associated with executive function. These associations between epoxides and executive function suggest a sex difference in the relevance of the CYP450 pathway to cognitive performance in T2DM. Disclosure S.Ryoo: None. B.R.Shah: None. J.Gilbert: Speaker's Bureau; Abbott, AstraZeneca, Amgen Canada, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Sanofi, Dexcom, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Novo Nordisk Canada Inc. A.Assal: None. I.Halperin: Advisory Panel; Sanofi, Speaker's Bureau; 3Boehringer Ingelheim Canada Ltd./Ltée, Abbott Diabetes, Dexcom, Inc., Novo Nordisk. A.Taha: None. W.Swardfager: None. N.Z.Anita: None. C.Major-orfao: None. W.Lin: None. S.Noor: None. F.Kwan: None. K.L.Lanctôt: Consultant; Exciva, GW Pharmaceuticals, ICG Farma, Merck Sharp & Dohme Corp., Novo Nordisk, Sumitomo Pharma Co. Ltd., Other Relationship; BioXcel, Cerevel Therapeutics, H Lundbeck A/S. N.Herrmann: None. P.Oh: Advisory Panel; Novartis Canada. Funding Canadian Institutes of Health Research; Banting & Best Diabetes Centre; National Institute of Diabetes and Digestive and Kidney Diseases
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.006 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".