Plasma metabolite association profiles for type 2 diabetes genetic clusters in Finnish men - PubMed
5 hours ago
- #Metabolomics
- #Type 2 diabetes
- #Genetic clusters
- Study focused on plasma metabolite association profiles for eight genetic clusters of type 2 diabetes in Finnish men.
- Analyzed 10,015 Finnish men with 979 plasma metabolites using Metabolon HD4 mass spectrometry.
- Identified 337 metabolites significantly associated with type 2 diabetes genetic risk, with 242 exclusive to cluster-partitioned polygenic risk scores (PRSs).
- Found 26 metabolites with significantly heterogeneous associations across clusters.
- Enrichment observed in 33 metabolic pathways among cluster-associated metabolites.
- Distinct pathways enriched for pancreatic beta cell-related clusters: beta cell + proinsulin (PI) cluster in fructose, mannose, and galactose metabolism; beta cell - PI cluster in branched-chain amino acid metabolism.
- Mediation analysis suggested over 50% of metabolites may mediate associations between PRSs and incident type 2 diabetes.
- Highlights metabolic heterogeneity across genetic clusters, potentially guiding personalized interventions.
- Data available in dbGaP (accession IDs: phs000743.v4.p1 and phs004033.v1.p1).
- Supported by NIH, American Diabetes Association, Academy of Finland, and other grants.