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Plasma trimethylamine N-oxide and its metabolic precursors and risk of mortality, cardiovascular and renal disease in individuals with type 2-diabetes and albuminuria

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Winther, SA, Øllgaard, JC, Hansen, TW, von Scholten, BJ, Reinhard, H, Ahluwalia, TS, Wang, Z, Gæde, P, Parving, H-H, Hazen, S, Pedersen, O & Rossing, P 2021, 'Plasma trimethylamine N-oxide and its metabolic precursors and risk of mortality, cardiovascular and renal disease in individuals with type 2-diabetes and albuminuria', PLoS One, vol. 16, no. 3, pp. e0244402. https://doi.org/10.1371/journal.pone.0244402

APA

Winther, S. A., Øllgaard, J. C., Hansen, T. W., von Scholten, B. J., Reinhard, H., Ahluwalia, T. S., Wang, Z., Gæde, P., Parving, H-H., Hazen, S., Pedersen, O., & Rossing, P. (2021). Plasma trimethylamine N-oxide and its metabolic precursors and risk of mortality, cardiovascular and renal disease in individuals with type 2-diabetes and albuminuria. PLoS One, 16(3), e0244402. https://doi.org/10.1371/journal.pone.0244402

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Author

Winther, Signe Abitz ; Øllgaard, Jens Christian ; Hansen, Tine Willum ; von Scholten, Bernt Johan ; Reinhard, Henrik ; Ahluwalia, Tarunveer Singh ; Wang, Zeneng ; Gæde, Peter ; Parving, Hans-Henrik ; Hazen, Stanley ; Pedersen, Oluf ; Rossing, Peter. / Plasma trimethylamine N-oxide and its metabolic precursors and risk of mortality, cardiovascular and renal disease in individuals with type 2-diabetes and albuminuria. In: PLoS One. 2021 ; Vol. 16, No. 3. pp. e0244402.

Bibtex

@article{af8707923571448186476fdcfec5f62e,
title = "Plasma trimethylamine N-oxide and its metabolic precursors and risk of mortality, cardiovascular and renal disease in individuals with type 2-diabetes and albuminuria",
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.",
author = "Winther, {Signe Abitz} and {\O}llgaard, {Jens Christian} and Hansen, {Tine Willum} and {von Scholten}, {Bernt Johan} and Henrik Reinhard and Ahluwalia, {Tarunveer Singh} and Zeneng Wang and Peter G{\ae}de and Hans-Henrik Parving and Stanley Hazen and Oluf Pedersen and Peter Rossing",
year = "2021",
doi = "10.1371/journal.pone.0244402",
language = "English",
volume = "16",
pages = "e0244402",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

RIS

TY - JOUR

T1 - Plasma trimethylamine N-oxide and its metabolic precursors and risk of mortality, cardiovascular and renal disease in individuals with type 2-diabetes and albuminuria

AU - Winther, Signe Abitz

AU - Øllgaard, Jens Christian

AU - Hansen, Tine Willum

AU - von Scholten, Bernt Johan

AU - Reinhard, Henrik

AU - Ahluwalia, Tarunveer Singh

AU - Wang, Zeneng

AU - Gæde, Peter

AU - Parving, Hans-Henrik

AU - Hazen, Stanley

AU - Pedersen, Oluf

AU - Rossing, Peter

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0244402

DO - 10.1371/journal.pone.0244402

M3 - Journal article

C2 - 33657115

VL - 16

SP - e0244402

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 3

ER -

ID: 64863347