Reduced circulating sphingolipids and <i>CERS2</i> activity are linked to T2D risk and impaired insulin secretion
Bibliographic record
Abstract
Gestational diabetes mellitus (GDM), a transient form of diabetes that resolves postpartum, is a major risk factor for type 2 diabetes (T2D) in women. While the progression from GDM to T2D is not fully understood, it involves both genetic and environmental components. By integrating clinical, metabolomic, and genome-wide association study (GWAS) data, we identified associations between decreased sphingolipid biosynthesis and future T2D, in part through the rs267738 allele of the CERS2 gene in Hispanic women shortly after a GDM pregnancy. To understand the impact of the CERS2 gene and risk allele on glucose regulation, we examined whole-body Cers2 knockout and rs267738 knock-in mice. Both models exhibited glucose intolerance and impaired insulin secretion in vivo. Islets isolated from these models also demonstrated reduced β cell function, as shown by decreased insulin secretion ex vivo. Overall, reduced circulating sphingolipids may indicate a high risk of GDM-to-T2D progression and reflect deficits in CERS2 activity that negatively affect glucose homeostasis and β cell function.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| 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) | 0.002 | 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".