Assessing Type 2 Diabetes and GLP-1 agonist response trajectories with a proteogenomic atlas of disease progression
- Design
- Mendelian randomization · Intermediate outcome
- Match to healthy normal-weight adults aged 55–75
- Population unclear[Auto] Population characteristics not extractable from abstract (age/BMI not reported in abstract). Needs manual review.
- Could weight loss explain it?
- Unknown[Auto] Not addressed in abstract.
- Study tier
- Preliminary[Auto] Not peer reviewed (preprint, abstract or registration). Early-warning only.
- Assessment
- Version 1 · automatic, not yet reviewed by a person · Sep 13, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75. This item has not been peer reviewed.
[Auto, unreviewed; last sentences of abstract] These persistent proteins are associated with incident coronary artery disease and overlap with targets of approved therapies, nominating candidates for combination strategies beyond GLP-1RA monotherapy. HighlightsO_LIMAP-D maps 2,923 proteins across three hallmarks and glycemic stages C_LIO_LIAdiposity reshapes the proteome; glycemia is driven by upstream proteins C_LIO_LIPersistent proteins remain dysregulated despite GLP-1RA treatment C_LIO_LIPersistent proteins predict incident CAD and are druggable targets C_LI
What the study reported
- Drugs
- Semaglutide
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- Not extracted
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Diabetes status
- diabetes mentioned
- Cvd status
- cardiovascular disease present in population (see abstract)
Study quality details
- Study design
- Mendelian randomization
- Sample size
- not extracted
- Randomization
- no
- Blinding
- not stated
- Comparator
- not stated
- Follow up duration
- not stated
- Outcome type
- intermediate
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- UNKNOWN
- Statistical precision
- not extracted
- Risk of bias
- not assessed (auto)
- Funding conflicts
- unclear
- Peer review status
- no
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- None identified
- Sponsor role
- not reported in abstract
- Author conflicts
- not available in metadata
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
The source, as retrieved
Abstract
Type 2 diabetes (T2D) progresses through heterogeneous pathways that glycemic staging alone does not resolve. We constructed the Metabolic Atlas of the Proteome in Diabetes (MAP-D), leveraging Olink measurements of 2,923 circulating proteins in [~]42,000 UK Biobank participants to map associations with three cardiometabolic hallmarks - adiposity (BMI), a proxy for insulin resistance (triglyceride-to-HDL cholesterol ratio), and glycemia (HbA1c) - across normoglycemia, prediabetes, and incident T2D. We triangulated cross-sectional associations with bidirectional Mendelian randomization and semaglutide trial proteomics to infer causal directionality. This revealed three distinct causal architectures: adiposity predominantly reshapes the proteome, glycemia is driven by upstream proteins, and insulin resistance shows bidirectional feedback. Integration with trial data identified proteins reversed by therapy and a subset of persistent proteins that remain dysregulated despite GLP-1RA treatment. These persistent proteins are associated with incident coronary artery disease and overlap with targets of approved therapies, nominating candidates for combination strategies beyond GLP-1RA monotherapy. HighlightsO_LIMAP-D maps 2,923 proteins across three hallmarks and glycemic stages C_LIO_LIAdiposity reshapes the proteome; glycemia is driven by upstream proteins C_LIO_LIPersistent proteins remain dysregulated despite GLP-1RA treatment C_LIO_LIPersistent proteins predict incident CAD and are druggable targets C_LI
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| medrxiv:medrxiv | Sep 13, 2026 | 10.1101/2025.09.26.25336579 first ingestion |