Identification of biomarkers for glycaemic deterioration in type 2 diabetes.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 05 2023
03 05 2023
Historique:
received:
19
04
2021
accepted:
18
04
2023
medline:
5
5
2023
pubmed:
4
5
2023
entrez:
3
5
2023
Statut:
epublish
Résumé
We identify biomarkers for disease progression in three type 2 diabetes cohorts encompassing 2,973 individuals across three molecular classes, metabolites, lipids and proteins. Homocitrulline, isoleucine and 2-aminoadipic acid, eight triacylglycerol species, and lowered sphingomyelin 42:2;2 levels are predictive of faster progression towards insulin requirement. Of ~1,300 proteins examined in two cohorts, levels of GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, and ENPP7 are associated with faster progression, whilst SMAC/DIABLO, SPOCK1 and HEMK2 predict lower progression rates. In an external replication, proteins and lipids are associated with diabetes incidence and prevalence. NogoR/RTN4R injection improved glucose tolerance in high fat-fed male mice but impaired it in male db/db mice. High NogoR levels led to islet cell apoptosis, and IL-18R antagonised inflammatory IL-18 signalling towards nuclear factor kappa-B in vitro. This comprehensive, multi-disciplinary approach thus identifies biomarkers with potential prognostic utility, provides evidence for possible disease mechanisms, and identifies potential therapeutic avenues to slow diabetes progression.
Identifiants
pubmed: 37137910
doi: 10.1038/s41467-023-38148-7
pii: 10.1038/s41467-023-38148-7
pmc: PMC10156700
doi:
Substances chimiques
Blood Glucose
0
Insulin
0
Lipids
0
Biomarkers
0
CRELD1 protein, mouse
0
Cell Adhesion Molecules
0
Extracellular Matrix Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2533Subventions
Organisme : Wellcome Trust
ID : 102820/Z/13/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 212625/Z/18/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R022259/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J0003042/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L020149/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L02036X/1
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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