Molecular Signature of Prediabetes With High‐Risk of Diabetes Revealed by Deep Plasma Proteome
Authors' conclusion
Proteome-based molecular subtyping stratifies IFG individuals with similar fasting glucose levels but distinct biology and future diabetes risk
Study context
- Population
- Participants with impaired fasting glucose (IFG) from the NHAPC discovery cohort (China); validated in the independent Shanghai Brain Aging Study (SBAS) cohortdiscovery cohort
- Participants
- 538 participants
- Exposure
- High-risk vs low-risk proteomic IFG subtype
- Outcome
- Proteome-based IFG subtypes and diabetes risk
Methodological detailsplasma proteomics, consensus clustering, independent validation cohort, 2584 plasma proteins quantified by liquid chromatography-mass spectrometry
- Plasma proteomics
- Consensus clustering
- Independent validation cohort
- 2584 plasma proteins quantified by liquid chromatography-mass spectrometry
Main finding
As reported in the abstract
- Two reproducible IFG molecular subtypes based on plasma proteomics were identified
- High-risk subtype: higher incident diabetes and greater 6-year decline in insulin sensitivity vs low-risk subtype
- High-risk subtype: enrichment of glycolysis/gluconeogenesis, insulin signalling and neutrophil degranulation, with a dyslipidemic lipidomic profile
- Low-risk subtype: higher complement cascade and HDL particle remodelling signature
Observational data: associations, not effects.
Further findings
Proteins and lipids associated with longitudinal decline in insulin sensitivity in the high-risk subtype
- Stronger associations in the high-risk subtype, including PPBP, PGK1, ALDOA, PE-P 18:0/20:3 and PE-P 18:1/20:3
Original publication
Molecular Signature of Prediabetes With High‐Risk of Diabetes Revealed by Deep Plasma Proteome. Diabetes Obes Metab. Published 4 June 2026. doi:10.
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