2016
DOI: 10.1007/s00125-016-4041-1
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Non-targeted metabolomics combined with genetic analyses identifies bile acid synthesis and phospholipid metabolism as being associated with incident type 2 diabetes

Abstract: Aims/hypothesis Identification of novel biomarkers for type 2 diabetes and their genetic determinants could lead to improved understanding of causal pathways and improve risk prediction. Methods In this study, we used data from non-targeted metabolomics performed using liquid chromatography coupled with tandem mass spectrometry in three Swedish cohorts (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1138; Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS], n = 970; TwinGene, n = 1630… Show more

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Cited by 86 publications
(80 citation statements)
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References 43 publications
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“…To date, several amino acids, sugar metabolites, and lipids have been associated with T2D risk in observational studies and causality has been investigated using Mendelian Randomization (Mahendran et al 2013a, b;Tillin et al 2015;Wurtz et al 2012Wurtz et al , 2013Mook-Kanamori et al 2014;t Hart et al 2018;Guasch-Ferre et al 2016;Liu et al 2017;Wang et al 2017;Fall et al 2016;Rawat et al 2019;Newsholme et al 2005). The present study replicates these observational findings in participants without diabetes mellitus, indicating that alterations in plasma metabolites levels in relation to perturbed glucose metabolism are already present in the non-diabetic population.…”
Section: Discussionsupporting
confidence: 78%
See 1 more Smart Citation
“…To date, several amino acids, sugar metabolites, and lipids have been associated with T2D risk in observational studies and causality has been investigated using Mendelian Randomization (Mahendran et al 2013a, b;Tillin et al 2015;Wurtz et al 2012Wurtz et al , 2013Mook-Kanamori et al 2014;t Hart et al 2018;Guasch-Ferre et al 2016;Liu et al 2017;Wang et al 2017;Fall et al 2016;Rawat et al 2019;Newsholme et al 2005). The present study replicates these observational findings in participants without diabetes mellitus, indicating that alterations in plasma metabolites levels in relation to perturbed glucose metabolism are already present in the non-diabetic population.…”
Section: Discussionsupporting
confidence: 78%
“…Metabolomics offers the possibility to comprehensively measure a broad range of metabolites in tissues and biological fluids. Multiple observational and causal association studies revealed metabolites such as phospholipids, triacylglycerols, ketone bodies, sphingomyelins, acyl-carnitines and organic acids to be linked to future risk of T2D onset (Mahendran et al 2013a, b;Tillin et al 2015;Wurtz et al 2012Wurtz et al , 2013Mook-Kanamori et al 2014;t Hart et al 2018;Guasch-Ferre et al 2016;Liu et al 2017;Wang et al 2017;Fall et al 2016).…”
Section: Introductionmentioning
confidence: 99%
“…Others have also incorporated genetics to streamline the identification of unknown metabolites (37)(38)(39). A recent multistep approach (37) used a GWAS of known and unknown metabolites and correlation analysis of known metabolites with unknown ones, and then used published metabolic pathway information to guide the construction of networks that displayed these relationships as a function of metabolite class.…”
Section: Discussionmentioning
confidence: 99%
“…For instance, a study that pooled data from four European cohorts found that CYP7A1, which encodes the rate-limiting enzyme in bile acid synthesis, was associated with lower concentrations of deoxycholic acid and higher T2D risk. 78 In addition, this study also identified variants in or near the genes encoding sphingosine-1-phosphate phosphatase 1 (SGPP1), glucokinase regulator (GCKR), and fatty acid desaturase 1 and 2 (FADS1/2) that were associated with diabetesassociated phospholipids and T2D risk. Finally, using Mendelian randomization in combination with plasma metabolomics suggested a causal role for lower levels of palmitoleic acid and oleic acid on insulin resistance.…”
Section: Subclassification Of Type 2 Diabetesmentioning
confidence: 90%