Alterations in cerebral perfusion and substrate metabolism in type 2 diabetes: interactions with APOE-ε4
Bibliographic record
Abstract
Epidemiological studies indicate that type 2 diabetes increases the risk for Alzheimer’s disease. Alterations in cerebral metabolism have been proposed as a potential mechanism underlying this association. A better understanding of these metabolic changes may elucidate potential pathways linking type 2 diabetes to Alzheimer’s disease. The aim of the current exploratory study was to investigate whether cerebral metabolism, including glucose and fatty acid uptake as well as cerebral blood flow, is altered in individuals with type 2 diabetes compared with both overweight individuals and lean control individuals. This exploratory study included 38 participants (ten with type 2 diabetes, 13 overweight individuals and 15 lean control individuals). Brain metabolism was assessed using multiple imaging techniques: [18F]fluorodeoxyglucose and [18F]fluoro-6-thiaheptadecanoic acid positron emission tomography for glucose and fatty acid uptake; arterial spin-labelling MRI for cerebral perfusion; and 1H-magnetic resonance spectroscopy for specific metabolites. Neurodegeneration markers were evaluated from lumbar puncture samples. Group comparisons were assessed using one-way ANOVA and unpaired t tests, and correlations were assessed with linear regression. Individuals with type 2 diabetes exhibited lower cerebral glucose uptake compared with both lean and overweight groups (p<0.01). Cerebral perfusion was reduced in both participants with type 2 diabetes and overweight participants relative to lean control participants (p<0.01). Both glucose uptake and perfusion correlated negatively with HOMA-IR, insulin and HbA1c levels (p<0.001–p<0.05). White matter fatty acid uptake was elevated in the diabetes group compared with the lean group (p<0.05). Post hoc analyses revealed that lean APOE-ε4 carriers had increased fatty acid uptake in the entire brain relative to lean non-carriers. Among non-carriers of APOE-ε4, those with type 2 diabetes showed higher fatty acid uptake than lean control individuals (p<0.01–p<0.05), and this uptake correlated positively with HOMA-IR, insulin and HbA1c levels (p<0.05). Type 2 diabetes was associated with decreased cerebral perfusion and glucose uptake but increased fatty acid uptake in white matter. The elevated fatty acid uptake observed both in individuals with type 2 diabetes and in APOE-ε4 carriers suggests a common metabolic dysfunction for these Alzheimer’s disease risk factors and suggests that targeting cerebral metabolic dysfunction, particularly fatty acid metabolism, could be a potential strategy for reducing the risk for neurodegeneration in individuals with type 2 diabetes.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".