Print Email Facebook Twitter Evaluation of metabolite profiles as biomarkers for the pharmacological effects of thiazolidinediones in type 2 diabetes mellitus patients and healthy volunteers Title Evaluation of metabolite profiles as biomarkers for the pharmacological effects of thiazolidinediones in type 2 diabetes mellitus patients and healthy volunteers Author van Doorn, M. Vogels, J. Tas, A. van Hoogdalem, E.J. Burggraaf, J. Cohen, A. van der Greef, J. TNO Kwaliteit van Leven Publication year 2007 Abstract Aims: To explore the usefulness of metabolomics as a method to obtain a broad array of biomarkers for the pharmacological effects of rosiglitazone (RSG) in plasma and urine samples from patients with type 2 diabetes mellitus (T2DM) and healthy volunteers (HVs). Additionally, we explored the differences in metabolite concentrations between T2DM patients and HVs to identify a putative metabolic disease fingerprint for T2DM. Methods: 1H nuclear magnetic resonance (NMR) spectroscopy was used to profile blood plasma and urine samples of 16 T2DM patients and 16 HVs receiving RSG 4 mg or placebo twice daily for 6 weeks. Multivariate analyses were employed to identify treatment- and disease-related effects on global endogenous metabolite profiles. Results: RSG treatment led to a rapid relative reduction in urinary hippurate and aromatic amino acids as well as an increase in plasma branched chain amino acids and alanine, glutamine and glutamate in the T2DM group. No RSG treatment effects were noted in the HV group. Exploratory baseline analyses showed that urine and plasma metabolites discriminated between genders and disease state. T2DM patients showed a relative increase in urinary concentrations of several amino acids, citrate, phospho(enol)pyruvate and hippurate. Putative T2DM-related changes in plasma were largely attributable to increased plasma lipids. Conclusion: The results of this study indicate that NMR-based metabolomics of urine and blood plasma samples can yield a broad array of early responding biomarkers for the effects of RSG in T2DM patients, as well as nonglucose biomarkers that may reflect the T2DM state. © 2006 The Authors. Subject BiologyAnalytical researchBiomarkersDiabetesMetabolomicsMetabonomicsNMR2,4 thiazolidinedione derivativealaninearomatic amino acidbiological markerbranched chain amino acidcitric acidglutamic acidglutaminehippuric acidlipidphosphoenolpyruvateplaceborosiglitazoneadultagedamino acid blood levelamino acid urine levelarticleclinical articleclinical trialcontrolled clinical trialcontrolled studydiabetic patientdouble blind proceduredrug effectdrug mechanismevaluationfemalefinger dermatoglyphicsgenderhumanlipid blood levelmalemetabolic disordermetabolitemetabolomicsmultivariate analysisnon insulin dependent diabetes mellitusplasmapriority journalproton nuclear magnetic resonancerandomized controlled trialurinalysisvolunteerAdultAgedBiological MarkersBlood GlucoseDiabetes Mellitus, Type 2Double-Blind MethodFemaleHumansHypoglycemic AgentsMagnetic Resonance SpectroscopyMaleMiddle AgedPrincipal Component AnalysisThiazolidinediones To reference this document use: http://resolver.tudelft.nl/uuid:8aa4eb1d-8ab0-46a5-a6d2-6dc1c01d1bdb DOI https://doi.org/10.1111/j.1365-2125.2006.02816.x TNO identifier 239945 ISSN 0306-5251 Source British Journal of Clinical Pharmacology, 63 (5), 562-574 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.