Cargando…
Plasma metabolites associated with type 2 diabetes in a Swedish population: a case–control study nested in a prospective cohort
AIMS/HYPOTHESIS: The aims of the present work were to identify plasma metabolites that predict future type 2 diabetes, to investigate the changes in identified metabolites among individuals who later did or did not develop type 2 diabetes over time, and to assess the extent to which inclusion of pre...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448991/ https://www.ncbi.nlm.nih.gov/pubmed/29349498 http://dx.doi.org/10.1007/s00125-017-4521-y |
_version_ | 1783408772295688192 |
---|---|
author | Shi, Lin Brunius, Carl Lehtonen, Marko Auriola, Seppo Bergdahl, Ingvar A. Rolandsson, Olov Hanhineva, Kati Landberg, Rikard |
author_facet | Shi, Lin Brunius, Carl Lehtonen, Marko Auriola, Seppo Bergdahl, Ingvar A. Rolandsson, Olov Hanhineva, Kati Landberg, Rikard |
author_sort | Shi, Lin |
collection | PubMed |
description | AIMS/HYPOTHESIS: The aims of the present work were to identify plasma metabolites that predict future type 2 diabetes, to investigate the changes in identified metabolites among individuals who later did or did not develop type 2 diabetes over time, and to assess the extent to which inclusion of predictive metabolites could improve risk prediction. METHODS: We established a nested case–control study within the Swedish prospective population-based Västerbotten Intervention Programme cohort. Using untargeted liquid chromatography-MS metabolomics, we analysed plasma samples from 503 case–control pairs at baseline (a median time of 7 years prior to diagnosis) and samples from a subset of 187 case–control pairs at 10 years of follow-up. Discriminative metabolites between cases and controls at baseline were optimally selected using a multivariate data analysis pipeline adapted for large-scale metabolomics. Conditional logistic regression was used to assess associations between discriminative metabolites and future type 2 diabetes, adjusting for several known risk factors. Reproducibility of identified metabolites was estimated by intra-class correlation over the 10 year period among the subset of healthy participants; their systematic changes over time in relation to diagnosis among those who developed type 2 diabetes were investigated using mixed models. Risk prediction performance of models made from different predictors was evaluated using area under the receiver operating characteristic curve, discrimination improvement index and net reclassification index. RESULTS: We identified 46 predictive plasma metabolites of type 2 diabetes. Among novel findings, phosphatidylcholines (PCs) containing odd-chain fatty acids (C19:1 and C17:0) and 2-hydroxyethanesulfonate were associated with the likelihood of developing type 2 diabetes; we also confirmed previously identified predictive biomarkers. Identified metabolites strongly correlated with insulin resistance and/or beta cell dysfunction. Of 46 identified metabolites, 26 showed intermediate to high reproducibility among healthy individuals. Moreover, PCs with odd-chain fatty acids, branched-chain amino acids, 3-methyl-2-oxovaleric acid and glutamate changed over time along with disease progression among diabetes cases. Importantly, we found that a combination of five of the most robustly predictive metabolites significantly improved risk prediction if added to models with an a priori defined set of traditional risk factors, but only a marginal improvement was achieved when using models based on optimally selected traditional risk factors. CONCLUSIONS/INTERPRETATION: Predictive metabolites may improve understanding of the pathophysiology of type 2 diabetes and reflect disease progression, but they provide limited incremental value in risk prediction beyond optimal use of traditional risk factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-017-4521-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users. |
format | Online Article Text |
id | pubmed-6448991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-64489912019-04-17 Plasma metabolites associated with type 2 diabetes in a Swedish population: a case–control study nested in a prospective cohort Shi, Lin Brunius, Carl Lehtonen, Marko Auriola, Seppo Bergdahl, Ingvar A. Rolandsson, Olov Hanhineva, Kati Landberg, Rikard Diabetologia Article AIMS/HYPOTHESIS: The aims of the present work were to identify plasma metabolites that predict future type 2 diabetes, to investigate the changes in identified metabolites among individuals who later did or did not develop type 2 diabetes over time, and to assess the extent to which inclusion of predictive metabolites could improve risk prediction. METHODS: We established a nested case–control study within the Swedish prospective population-based Västerbotten Intervention Programme cohort. Using untargeted liquid chromatography-MS metabolomics, we analysed plasma samples from 503 case–control pairs at baseline (a median time of 7 years prior to diagnosis) and samples from a subset of 187 case–control pairs at 10 years of follow-up. Discriminative metabolites between cases and controls at baseline were optimally selected using a multivariate data analysis pipeline adapted for large-scale metabolomics. Conditional logistic regression was used to assess associations between discriminative metabolites and future type 2 diabetes, adjusting for several known risk factors. Reproducibility of identified metabolites was estimated by intra-class correlation over the 10 year period among the subset of healthy participants; their systematic changes over time in relation to diagnosis among those who developed type 2 diabetes were investigated using mixed models. Risk prediction performance of models made from different predictors was evaluated using area under the receiver operating characteristic curve, discrimination improvement index and net reclassification index. RESULTS: We identified 46 predictive plasma metabolites of type 2 diabetes. Among novel findings, phosphatidylcholines (PCs) containing odd-chain fatty acids (C19:1 and C17:0) and 2-hydroxyethanesulfonate were associated with the likelihood of developing type 2 diabetes; we also confirmed previously identified predictive biomarkers. Identified metabolites strongly correlated with insulin resistance and/or beta cell dysfunction. Of 46 identified metabolites, 26 showed intermediate to high reproducibility among healthy individuals. Moreover, PCs with odd-chain fatty acids, branched-chain amino acids, 3-methyl-2-oxovaleric acid and glutamate changed over time along with disease progression among diabetes cases. Importantly, we found that a combination of five of the most robustly predictive metabolites significantly improved risk prediction if added to models with an a priori defined set of traditional risk factors, but only a marginal improvement was achieved when using models based on optimally selected traditional risk factors. CONCLUSIONS/INTERPRETATION: Predictive metabolites may improve understanding of the pathophysiology of type 2 diabetes and reflect disease progression, but they provide limited incremental value in risk prediction beyond optimal use of traditional risk factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-017-4521-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users. Springer Berlin Heidelberg 2018-01-18 2018 /pmc/articles/PMC6448991/ /pubmed/29349498 http://dx.doi.org/10.1007/s00125-017-4521-y Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Article Shi, Lin Brunius, Carl Lehtonen, Marko Auriola, Seppo Bergdahl, Ingvar A. Rolandsson, Olov Hanhineva, Kati Landberg, Rikard Plasma metabolites associated with type 2 diabetes in a Swedish population: a case–control study nested in a prospective cohort |
title | Plasma metabolites associated with type 2 diabetes in a Swedish population: a case–control study nested in a prospective cohort |
title_full | Plasma metabolites associated with type 2 diabetes in a Swedish population: a case–control study nested in a prospective cohort |
title_fullStr | Plasma metabolites associated with type 2 diabetes in a Swedish population: a case–control study nested in a prospective cohort |
title_full_unstemmed | Plasma metabolites associated with type 2 diabetes in a Swedish population: a case–control study nested in a prospective cohort |
title_short | Plasma metabolites associated with type 2 diabetes in a Swedish population: a case–control study nested in a prospective cohort |
title_sort | plasma metabolites associated with type 2 diabetes in a swedish population: a case–control study nested in a prospective cohort |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448991/ https://www.ncbi.nlm.nih.gov/pubmed/29349498 http://dx.doi.org/10.1007/s00125-017-4521-y |
work_keys_str_mv | AT shilin plasmametabolitesassociatedwithtype2diabetesinaswedishpopulationacasecontrolstudynestedinaprospectivecohort AT bruniuscarl plasmametabolitesassociatedwithtype2diabetesinaswedishpopulationacasecontrolstudynestedinaprospectivecohort AT lehtonenmarko plasmametabolitesassociatedwithtype2diabetesinaswedishpopulationacasecontrolstudynestedinaprospectivecohort AT auriolaseppo plasmametabolitesassociatedwithtype2diabetesinaswedishpopulationacasecontrolstudynestedinaprospectivecohort AT bergdahlingvara plasmametabolitesassociatedwithtype2diabetesinaswedishpopulationacasecontrolstudynestedinaprospectivecohort AT rolandssonolov plasmametabolitesassociatedwithtype2diabetesinaswedishpopulationacasecontrolstudynestedinaprospectivecohort AT hanhinevakati plasmametabolitesassociatedwithtype2diabetesinaswedishpopulationacasecontrolstudynestedinaprospectivecohort AT landbergrikard plasmametabolitesassociatedwithtype2diabetesinaswedishpopulationacasecontrolstudynestedinaprospectivecohort |