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

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 pos...

Full description

Saved in:
Bibliographic Details
Published in:Diabetes & metabolism 2018-06, Vol.44 (3), p.261-268
Main Authors: Friedrich, N., Skaaby, T., Pietzner, M., Budde, K., Thuesen, B.H., Nauck, M., Linneberg, A.
Format: Article
Language:English
Subjects:
Betaine
Coffee consumption
Diabetes mellitus
Glucose homoeostasis
Metabolomics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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. 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. 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.
ISSN:1262-3636
1878-1780
DOI:10.1016/j.diabet.2017.05.007