title: Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes.
abstract: BACKGROUND
  The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism.
  
  
  METHODS
  To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation.
  
  
  CONCLUSIONS
  Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men.
authors.affiliation: Department Quality of Life, TNO, Zeist, the Netherlands. suzan.wopereis@tno.nl
authors.forename: Suzan
authors.initials: S
authors.lastname: Wopereis
authors.forename: Carina M
authors.initials: CM
authors.lastname: Rubingh
authors.forename: Marjan J
authors.initials: MJ
authors.lastname: van Erk
authors.forename: Elwin R
authors.initials: ER
authors.lastname: Verheij
authors.forename: Trinette
authors.initials: T
authors.lastname: van Vliet
authors.forename: Nicole H P
authors.initials: NH
authors.lastname: Cnubben
authors.forename: Age K
authors.initials: AK
authors.lastname: Smilde
authors.forename: Jan
authors.initials: J
authors.lastname: van der Greef
authors.forename: Ben
authors.initials: B
authors.lastname: van Ommen
authors.forename: Henk F J
authors.initials: HF
authors.lastname: Hendriks
mesh_terms: D001786:Blood Glucose / Q000502:physiology*; D002097:C-Reactive Protein; D005951:Glucose Tolerance Test; D005978:Glutathione; D006801:Humans; D007249:Inflammation; D007328:Insulin; D008297:Male; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D050177:Overweight
chemical_list: D001786:Blood Glucose; D007328:Insulin; D002097:C-Reactive Protein; D005978:Glutathione