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Circulating metabolites improve the prediction of renal impairment in patients with type 2 diabetes.
BMJ Open Diab. Res. Care 11:e003422 (2023)
Introduction Low glomerular filtration rate (GFR) is a leading cause of reduced lifespan in type 2 diabetes. Unravelling biomarkers capable to identify high-risk patients can help tackle this burden. We investigated the association between 188 serum metabolites and kidney function in type 2 diabetes and then whether the associated metabolites improve two established clinical models for predicting GFR decline in these patients. Research design and methods Two cohorts comprising 849 individuals with type 2 diabetes (discovery and validation samples) and a follow-up study of 575 patients with estimated GFR (eGFR) decline were analyzed. Results Ten metabolites were independently associated with low eGFR in the discovery sample, with nine of them being confirmed also in the validation sample (ORs range 1.3-2.4 per 1SD, p values range 1.9×10 -2 -2.5×10 -9). Of these, five metabolites were also associated with eGFR decline (ie, tiglylcarnitine, decadienylcarnitine, total dimethylarginine, decenoylcarnitine and kynurenine) (β range -0.11 to -0.19, p values range 4.8×10 -2 to 3.0×10 -3). Indeed, tiglylcarnitine and kynurenine, which captured all the information of the other three markers, improved discrimination and reclassification (all p<0.01) of two clinical prediction models of GFR decline in people with diabetes. Conclusions Further studies are needed to validate our findings in larger cohorts of different clinical, environmental and genetic background.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Biomarkers ; Diabetes Mellitus, Type 2 ; Inflammation ; Kidney Diseases; Chronic Kidney-disease; Plasma Metabolites; Function Decline; Risk; Mortality; Serum; Acid; Metabolomics; Kynurenine; Guidelines
ISSN (print) / ISBN
2052-4897
e-ISSN
2052-4897
Quellenangaben
Volume: 11,
Issue: 5,
Article Number: e003422
Publisher
BMJ Publishing Group
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Experimental Genetics (IEG)
Grants
EFSD/Sanofi Grant 2017
Ricerca corrente 2022- 2023
Ministero della Salute
PNRR M4C2I1.3 Heal Italia project
Ministero dell'Istruzione dell'Universita (PRIN) 2015
Ricerca corrente 2022- 2023
Ministero della Salute
PNRR M4C2I1.3 Heal Italia project
Ministero dell'Istruzione dell'Universita (PRIN) 2015