Evaluation of metabolite profiles as biomarkers for the pharmacological effects of thiazolidinediones in type 2 diabetes mellitus patients and healthy volunteers
article
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.
Topics
Analytical 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
TNO Identifier
239945
ISSN
03065251
Source
British Journal of Clinical Pharmacology, 63(5), pp. 562-574.
Pages
562-574
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