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
Biology
Analytical research
Biomarkers
Diabetes
Metabolomics
Metabonomics
NMR
2,4 thiazolidinedione derivative
alanine
aromatic amino acid
biological marker
branched chain amino acid
citric acid
glutamic acid
glutamine
hippuric acid
lipid
phosphoenolpyruvate
placebo
rosiglitazone
adult
aged
amino acid blood level
amino acid urine level
article
clinical article
clinical trial
controlled clinical trial
controlled study
diabetic patient
double blind procedure
drug effect
drug mechanism
evaluation
female
finger dermatoglyphics
gender
human
lipid blood level
male
metabolic disorder
metabolite
metabolomics
multivariate analysis
non insulin dependent diabetes mellitus
plasma
priority journal
proton nuclear magnetic resonance
randomized controlled trial
urinalysis
volunteer
Adult
Aged
Biological Markers
Blood Glucose
Diabetes Mellitus, Type 2
Double-Blind Method
Female
Humans
Hypoglycemic Agents
Magnetic Resonance Spectroscopy
Male
Middle Aged
Principal Component Analysis
Thiazolidinediones
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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