Soluble epoxide hydrolase‐derived linoleic acid diols, cerebral small vessel disease markers and white matter microstructural integrity in type 2 diabetes mellitus
Bibliographic record
Abstract
BACKGROUND: While polyunsaturated fatty acids can be metabolized into beneficial, anti-inflammatory epoxides, they are subsequently converted to inactive, cytotoxic diols by soluble epoxide hydrolase (sEH). Increased linoleic acid (LA)-derived diols have been associated with poorer cognitive performance in type 2 diabetes mellitus (T2DM). Furthermore, increased LA-derived diol to epoxide ratio has been associated with greater white matter hyperintensities (WMH) in patients with stroke. However, the relationship between diols and neuroimaging measures has yet to be explored in T2DM. Here, we examined LA-derived diols in relation to markers of cerebral small vessel disease and white matter microstructural integrity in T2DM. METHOD: 6.5%, or antidiabetic medication use. Two unesterified LA-derived diols (9,10-dihydroxyoctadecamonoenoic acid [DiHOME] and 12,13-DiHOME) were quantified via ultra-high-performance liquid chromatography-mass spectrometry/mass spectrometry from serum samples collected after fasting. Perivascular spaces (PVS), WMH, and lacunar infarct volumes were quantified through structural MRI. White matter microstructural integrity was measured as fractional anisotropy (FA) and mean diffusivity (MD) using diffusion tensor imaging. Multiple linear regressions controlling for demographic factors, intracranial volume, hypertension, APOE-ε4 status, HDL, HbA1c, neurodegenerative diagnoses, and antidiabetic medication use, were used. Results were Bonferroni adjusted for the two diol species tested, with p <0.025 considered as statistically significant. RESULT: Among 90 T2DM participants (20.0% female, age=69.4±7.2 years, MoCA=25±3.5), 9,10-DiHOME was associated with higher WMH (β=0.385, p <0.001) and lacunar infarct (β=0.283, p = 0.010) volumes, and higher MD (β=0.267, p = 0.018). The 12,13-DiHOME was associated with higher WMH volume (β=0.339, p = 0.001). In exploratory regional analyses, 9,10-DiHOME was associated with greater WMH (β=0.400, p <0.001) and lacunar infarct (β=0.281, p = 0.013) volumes, higher MD (β=0.364, p = 0.001), and lower FA (β=-0.245, p = 0.022) in the parietal lobe. The 12,13-DiHOME was associated with more WMH volume (β=0.352, p = 0.001) and higher MD (β=0.263, p = 0.018) in the parietal lobe. CONCLUSION: In diabetes, LA-derived sEH diols were associated with greater cerebral small vessel disease pathology and white matter microstructural damage. sEH may be a potential therapeutic target to mitigate neurovascular and white matter damage in diabetes.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| 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) | 0.001 | 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".