Abstract
AIMS: The trimethylamine N-oxide (TMAO) pathway is related to intestinal microbiota and has been associated to risk of cardiovascular disease (CVD). We investigated associations between four plasma metabolites in the TMAO pathway and risk of all-cause mortality, CVD and deterioration in renal function in individuals with type 2-diabetes (T2D) and albuminuria.
MATERIALS AND METHODS: Plasma concentrations of TMAO, choline, carnitine, and betaine were measured by liquid chromatography-tandem mass spectrometry at baseline in 311 individuals with T2D and albuminuria. Information on all-cause mortality and fatal/non-fatal CVD during follow-up was obtained from registries. The association of each metabolite, and a weighted sum score of all four metabolites, with the endpoints were examined. Serum creatinine was measured at follow-up visits and the renal endpoint was defined as eGFR-decline of ≥30%. Associations were analysed using proportional hazards models adjusted for traditional risk factors.
RESULTS: Baseline mean(SD) age was 57.2(8.2) years and 75% were males. Follow-up was up to 21.9 years (median (IQR) follow-up 6.8 (6.1-15.5) years for mortality and 6.5 (5.5-8.1) years for CVD events). The individual metabolites and the weighted sum score were not associated with all-cause mortality (n = 106) or CVD (n = 116) (adjusted p≥0.09). Higher choline, carnitine and the weighted sum score of the four metabolites were associated with higher risk of decline in eGFR (n = 106) (adjusted p = 0.001, p = 0.03 and p<0.001, respectively).
CONCLUSIONS: In individuals with T2D and albuminuria, higher choline, carnitine and a weighted sum of four metabolites from the TMAO pathway were risk markers for deterioration in renal function during long-term follow-up. Metabolites from the TMAO pathway were not independently related to risk of all-cause mortality or CVD.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | e0244402 |
| Tidsskrift | PLOS ONE |
| Vol/bind | 16 |
| Udgave nummer | 3 |
| Antal sider | 14 |
| ISSN | 1932-6203 |
| DOI | |
| Status | Udgivet - mar. 2021 |
Bibliografisk note
Funding Information:This work was funded by the Novo Nordisk Foundation, grant no. NNF 14OC0013659 as part of the PROTON (Personalizing Treatment of diabetic Nephropathy) study. The Novo Nordisk Foundation Center for Basic Metabolomics Research is an independent research center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.cbmr.ku.dk) (grant number NNF18CC0034900). SLH reports funding by NIH grant P01 HL147823 and the Leducq Foundation. SAW was funded by The Innovation Fund Denmark (grant number 5016-00150B) and Novo Nordisk A/ S provided support in the form of salary during the PhD fellowship for author SAW. JO and BJvS are after data collection employed by Novo Nordisk A/ S. The specific roles of these authors are articulated in the 'author contributions' section. The funding sources did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2021 Winther et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.