Identification of biomarkers for glycaemic deterioration in type 2 diabetes
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
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.
Details
Original language | English |
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Article number | 2533 |
Journal | Nature communications |
Volume | 14 |
Issue number | 1 |
Publication status | Published - Dec 2023 |
Peer-reviewed | Yes |
External IDs
PubMed | 37137910 |
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Keywords
Sustainable Development Goals
ASJC Scopus subject areas
Keywords
- Mice, Animals, Male, Diabetes Mellitus, Type 2/metabolism, Blood Glucose/metabolism, Islets of Langerhans/metabolism, Insulin/metabolism, Lipids, Biomarkers/metabolism, Cell Adhesion Molecules/metabolism, Extracellular Matrix Proteins/metabolism