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Identification of urine metabolites associated with 5-year changes in biomarkers of glucose homoeostasis

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@article{5118c606d8e746799e3ad9585bc4b5af,
title = "Identification of urine metabolites associated with 5-year changes in biomarkers of glucose homoeostasis",
abstract = "Aim: Metabolomics provides information on pathogenetic mechanisms and targets for interventions, and may improve risk stratification. During the last decade, metabolomics studies were used to gain deeper insight into the pathogenesis of diabetes mellitus. However, longitudinal metabolomics studies of possible subclinical states of disturbed glucose metabolism are limited. Therefore, the aim of this study was to analyze the associations between baseline urinary metabolites and 5-year changes in continuous markers of glucose homoeostasis, including fasting glucose, HbA1c and homoeostasis model assessment of insulin resistance (HOMA-IR) index values. Methods: Urine metabolites in 3986 participants at both baseline and 5-year follow-up of the population-based Inter99 study were analyzed by 1H-NMR spectroscopy. Linear regression and analyses of covariance models were used to detect associations between urine metabolites and 5-year changes in markers of glucose homoeostasis. Results: Higher baseline levels of urinary alanine, betaine, N,N-dimethylglycine (DMG), creatinine and trimethylamine were associated with an increase in HbA1c from baseline to follow-up. In contrast, formic acid and trigonelline levels were associated with a decrease in HbA1c over time. Analyses of 5-year changes in fasting glucose and HOMA-IR index showed similar findings, with high baseline levels of lactic acid, beta-d-glucose, creatinine, alanine and 1-methylnicotinamide associated with increases in both parameters. Conclusion: Several urine metabolites were found to be associated with detrimental longitudinal changes in biomarkers of glucose homoeostasis. The identified metabolites point to mechanisms involving betaine and coffee metabolism as well as the possible influence of the gut microbiome.",
keywords = "Betaine, Coffee consumption, Diabetes mellitus, Glucose homoeostasis, Metabolomics",
author = "N. Friedrich and T. Skaaby and Maik Pietzner and Klemens Budde and Thuesen, {B. H.} and M Nauck and A. Linneberg",
year = "2018",
doi = "10.1016/j.diabet.2017.05.007",
language = "English",
volume = "44",
pages = "261--268",
journal = "Diabetes and Metabolism",
issn = "1262-3636",
publisher = "Elsevier Masson Editeur",
number = "3",

}

RIS

TY - JOUR

T1 - Identification of urine metabolites associated with 5-year changes in biomarkers of glucose homoeostasis

AU - Friedrich, N.

AU - Skaaby, T.

AU - Pietzner, Maik

AU - Budde, Klemens

AU - Thuesen, B. H.

AU - Nauck, M

AU - Linneberg, A.

PY - 2018

Y1 - 2018

N2 - Aim: Metabolomics provides information on pathogenetic mechanisms and targets for interventions, and may improve risk stratification. During the last decade, metabolomics studies were used to gain deeper insight into the pathogenesis of diabetes mellitus. However, longitudinal metabolomics studies of possible subclinical states of disturbed glucose metabolism are limited. Therefore, the aim of this study was to analyze the associations between baseline urinary metabolites and 5-year changes in continuous markers of glucose homoeostasis, including fasting glucose, HbA1c and homoeostasis model assessment of insulin resistance (HOMA-IR) index values. Methods: Urine metabolites in 3986 participants at both baseline and 5-year follow-up of the population-based Inter99 study were analyzed by 1H-NMR spectroscopy. Linear regression and analyses of covariance models were used to detect associations between urine metabolites and 5-year changes in markers of glucose homoeostasis. Results: Higher baseline levels of urinary alanine, betaine, N,N-dimethylglycine (DMG), creatinine and trimethylamine were associated with an increase in HbA1c from baseline to follow-up. In contrast, formic acid and trigonelline levels were associated with a decrease in HbA1c over time. Analyses of 5-year changes in fasting glucose and HOMA-IR index showed similar findings, with high baseline levels of lactic acid, beta-d-glucose, creatinine, alanine and 1-methylnicotinamide associated with increases in both parameters. Conclusion: Several urine metabolites were found to be associated with detrimental longitudinal changes in biomarkers of glucose homoeostasis. The identified metabolites point to mechanisms involving betaine and coffee metabolism as well as the possible influence of the gut microbiome.

AB - Aim: Metabolomics provides information on pathogenetic mechanisms and targets for interventions, and may improve risk stratification. During the last decade, metabolomics studies were used to gain deeper insight into the pathogenesis of diabetes mellitus. However, longitudinal metabolomics studies of possible subclinical states of disturbed glucose metabolism are limited. Therefore, the aim of this study was to analyze the associations between baseline urinary metabolites and 5-year changes in continuous markers of glucose homoeostasis, including fasting glucose, HbA1c and homoeostasis model assessment of insulin resistance (HOMA-IR) index values. Methods: Urine metabolites in 3986 participants at both baseline and 5-year follow-up of the population-based Inter99 study were analyzed by 1H-NMR spectroscopy. Linear regression and analyses of covariance models were used to detect associations between urine metabolites and 5-year changes in markers of glucose homoeostasis. Results: Higher baseline levels of urinary alanine, betaine, N,N-dimethylglycine (DMG), creatinine and trimethylamine were associated with an increase in HbA1c from baseline to follow-up. In contrast, formic acid and trigonelline levels were associated with a decrease in HbA1c over time. Analyses of 5-year changes in fasting glucose and HOMA-IR index showed similar findings, with high baseline levels of lactic acid, beta-d-glucose, creatinine, alanine and 1-methylnicotinamide associated with increases in both parameters. Conclusion: Several urine metabolites were found to be associated with detrimental longitudinal changes in biomarkers of glucose homoeostasis. The identified metabolites point to mechanisms involving betaine and coffee metabolism as well as the possible influence of the gut microbiome.

KW - Betaine

KW - Coffee consumption

KW - Diabetes mellitus

KW - Glucose homoeostasis

KW - Metabolomics

UR - http://www.scopus.com/inward/record.url?scp=85021345271&partnerID=8YFLogxK

U2 - 10.1016/j.diabet.2017.05.007

DO - 10.1016/j.diabet.2017.05.007

M3 - Journal article

VL - 44

SP - 261

EP - 268

JO - Diabetes and Metabolism

JF - Diabetes and Metabolism

SN - 1262-3636

IS - 3

ER -

ID: 51504260