Metabolomics Profiling in Multi-ancestral Individuals with Type 2 Diabetes in Singapore Identified Metabolites Associated with Renal Function Decline

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2024 Dec 2

PMID 39621102

Authors

Yuqing Chen

Federico Torta

Hiromi W L Koh

Peter I Benke

Resham L Gurung

Jian-Jun Liu

Keven Ang

Yi-Ming Shao

Gek Cher Chan

Jason Chon-Jun Choo

Jianhong Ching

Jean-Paul Kovalik

Tosha Kalhan

Rajkumar Dorajoo

Chiea Chuen Khor

Yun Li

Wern Ee Tang

Darren E J Seah

Charumathi Sabanayagam

Radoslaw M Sobota

Kavita Venkataraman

Thomas Coffman

Markus R Wenk

Xueling Sim

Su-Chi Lim

E Shyong Tai

Affiliations

Soon will be listed here.

Abstract

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.

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