title: Metabolomic biomarkers for personalised glucose lowering drugs treatment in type 2 diabetes.
abstract: We aimed to identify metabolites to predict patients' response to glucose lowering treatment during the first 5 years after detection of type 2 diabetes. Metabolites were measured by GC-MS in baseline samples from 346 screen-detected type 2 diabetes patients in the ADDITION-NL study. The response to treatment with metformin and/or sulphonylurea (SU) was analysed to identify metabolites predictive of 5 year HbA1c change by multiple regression analysis. Baseline glucose and 1,5 anhydro-glucitol were associated with HbA1cdecrease in all medication groups. In patients on SU no other metabolite was associated with HbA1c decrease. A larger set of metabolites was associated with HbA1c change in the metformin and the combination therapy (metformin + SU) groups. These metabolites included metabolites related to liver metabolism, such as 2-hydroxybutanoic acid, 3-hydroxybutanoic acid, 2-hydroxypiperidine and 4-oxoproline). Metabolites involved in oxidative stress and insulin resistance were higher when the HbA1c decrease was larger in the metformin/sulphonylurea group. The associations between baseline metabolites and responsiveness to medication are in line with its mode of action. If these results could be replicated in other populations, the most promising predictive candidates might be tested to assess whether they could enhance personalised treatment.
authors.affiliation: Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Str. 6.131, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: den Ouden
authors.affiliation: TNO, Microbiology and Systems Biology Group, Utrechtseweg 48, 3704 HE Zeist, The Netherlands.
authors.forename: Linette
authors.initials: L
authors.lastname: Pellis
authors.affiliation: Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Str. 6.131, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Guy E H M
authors.initials: GEHM
authors.lastname: Rutten
authors.affiliation: TNO, Microbiology and Systems Biology Group, Utrechtseweg 48, 3704 HE Zeist, The Netherlands.
authors.forename: Ilse K
authors.initials: IK
authors.lastname: Geerars-van Vonderen
authors.affiliation: TNO, Microbiology and Systems Biology Group, Utrechtseweg 48, 3704 HE Zeist, The Netherlands.
authors.forename: Carina M
authors.initials: CM
authors.lastname: Rubingh
authors.affiliation: TNO, Microbiology and Systems Biology Group, Utrechtseweg 48, 3704 HE Zeist, The Netherlands.
authors.forename: Ben
authors.initials: B
authors.lastname: van Ommen
authors.affiliation: TNO, Microbiology and Systems Biology Group, Utrechtseweg 48, 3704 HE Zeist, The Netherlands.
authors.forename: Marjan J
authors.initials: MJ
authors.lastname: van Erk
authors.affiliation: Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Str. 6.131, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Joline W J
authors.initials: JWJ
authors.lastname: Beulens
keywords: Metabolomics; Metformin; Personalised medicine; Sulphonylurea