531-P: Metabolomics Identifies Novel Plasma Metabolomic Signatures Associated with Diabetic Neuropathy in a Cohort with Screen-Tested Type 2 Diabetes: ADDITION-Denmark
Bibliographic record
Abstract
Peripheral neuropathy (PN) is a common complication of diabetes that develops in up to 50% of people with diabetes. Obesity and the metabolic syndrome are risk factors for PN in patients with type 2 diabetes (T2D). However, the lipid metabolites associated with PN development are unknown. We compared the metabolomic profile of plasma from T2D patients with and without PN compared to lean control patients to identify metabolic changes that underlie PN associated with T2D. PN was evaluated in a cohort of T2D patients from the Danish portion of the Anglo-Danish-Dutch study of Intensive Treatment of Diabetes in Primary Care (ADDITION). The Toronto criteria was used to assess PN based on symptoms of neuropathy and abnormal nerve conduction studies. To identify metabolomic signatures that associate with PN, plasma samples from 9 lean control, 49 T2D, and 48 T2D patients with PN were submitted to Metabolon® for a global metabolomics analysis. We used least absolute shrinkage and selection operator (LASSO) and Welch’s two-sample t-test to identify metabolites that differed between PN and non-PN subjects. Metabolomics identified plasma lipid metabolites that were dysregulated in T2D including cholesterol, sphingolipids, and acylcarnitines. Cholesterol and three classes of sphingolipid metabolites (dihydrosphingomyelin, glucosylceramide, and sphingomyelin) were significantly lower in plasma from T2D patients irrespective of PN compared to lean controls. Interestingly, long-chain and very long-chain acylcarnitines were also reduced in T2D patients while short-chain acylcarnitines were unchanged. Only a small number of metabolites were uniquely regulated by PN; of these, two very long-chain acylcarnitine species (C26:1 and C24) were significantly diminished in T2D patients with PN compared to those without. These results suggest an association with lipid markers of impaired mitochondrial β-oxidation and PN in T2D. Disclosure A.E. Rumora: None. F. Alakwaa: None. S.T. Andersen: None. M.E. Jørgensen: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S. M. Charles: Other Relationship; Self; Novo Nordisk A/S. B.C. Callaghan: None. T.S. Jensen: None. E.L. Feldman: Consultant; Self; Novartis Pharmaceuticals Corporation. Funding American Diabetes Association (7-12-BS-045 to E.L.F.); Novo Nordisk Foundation (NNF14OC0011633); National Institutes of Health (1R24082841, 1DP3DK094292); National Institute of Diabetes and Digestive and Kidney Diseases (T32DK101357, F32DK112642, K99DK119366); NeuroNetwork for Emerging Therapies; A. Alfred Taubman Medical Research Institute
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 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".