Related Experiment Video
Updated: Jun 6, 2025
Author Spotlight: Multi-Layered Approach to Understand Postnatal Functions of Pancreatic Islets in Non-Human Primates
Published on: November 8, 2024
Metabolomics profiling in multi-ancestral individuals with type 2 diabetes in Singapore identified metabolites
Yuqing Chen1, Federico Torta2,3, Hiromi W L Koh4
1Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Republic of Singapore.
Aims/Hypothesis:
This study aims to explore the association between plasma metabolites and chronic kidney disease progression in individuals with type 2 diabetes.
Methods:
We performed a comprehensive metabolomic analysis in a prospective cohort study of 5144 multi-ancestral individuals with type 2 diabetes in Singapore, using eGFR slope as the primary outcome of kidney function decline. In addition, we performed genome-wide association studies on metabolites to assess how these metabolites could be genetically influenced by metabolite quantitative trait loci and performed colocalisation analysis to identify genes affecting both metabolites and kidney function.
Results:
Elevated levels of 61 lipids with long unsaturated fatty acid chains such as phosphatidylethanolamines, triacylglycerols, diacylglycerols, ceramides and deoxysphingolipids were prospectively associated with more rapid kidney function decline. In addition, elevated levels of seven amino acids and three lipids in the plasma were associated with a slower decline in eGFR. We also identified 15 metabolite quantitative trait loci associated with these metabolites, within which variants near TM6SF2, APOE and CPS1 could affect both metabolite levels and kidney functions.
Conclusions/Interpretation:
Our study identified plasma metabolites associated with prospective renal function decline, offering insights into the underlying mechanism by which the metabolite abnormalities due to fatty acid oversupply might reflect impaired β-oxidation and associate with future chronic kidney disease progression in individuals with diabetes.
