title: Metabolomic determination of pathogenesis of late-onset preeclampsia.
abstract: OBJECTIVE
  Our primary objective was to apply metabolomic pathway analysis of first trimester maternal serum to provide an insight into the pathogenesis of late-onset preeclampsia (late-PE) and thereby identify plausible therapeutic targets for PE.
  
  
  METHODS
  NMR-based metabolomics analysis was performed on 29 cases of late-PE and 55 unaffected controls. In order to achieve sufficient statistical power to perform the pathway analysis, these cases were combined with a group of previously analyzed specimens, 30 late-PE cases and 60 unaffected controls. Specimens from both groups of cases and controls were collected in the same clinical centers during the same time period. In addition, NMR analyses were performed in the same lab and using the same techniques.
  
  
  RESULTS
  We identified abnormalities in branch chain amino acids (valine, leucine and isoleucine) and propanoate, glycolysis, gluconeogenesis and ketone body metabolic pathways. The results suggest insulin resistance and metabolic syndrome, mitochondrial dysfunction and disturbance of energy metabolism, oxidative stress and lipid dysfunction in the pathogenesis of late PE and suggest a potential role for agents that reduce insulin resistance in PE.
  
  
  CONCLUSIONS
  Branched chain amino acids are known markers of insulin resistance and strongly predict future diabetes development. The analysis provides independent evidence linking insulin resistance and late-PE and suggests a potentially important therapeutic role for pharmacologic agents that reduce insulin resistance for late-PE.
authors: a Department of Obstetrics and Gynecology , Beaumont Health , Royal Oak , MI , USA.
authors: Ray O
authors: RO
authors: Bahado-Singh
authors: b Harris Birthright Research Centre for Fetal Medicine , Division of Women's Health, King's College Hospital , London , UK.
authors: Argyro
authors: A
authors: Syngelaki
authors: c Department of Biological Sciences , University of Alberta , Edmonton, Alberta , Canada , and.
authors: Rupsari
authors: R
authors: Mandal
authors: a Department of Obstetrics and Gynecology , Beaumont Health , Royal Oak , MI , USA.
authors: Stewart F
authors: SF
authors: Graham
authors: b Harris Birthright Research Centre for Fetal Medicine , Division of Women's Health, King's College Hospital , London , UK.
authors: Ranjit
authors: R
authors: Akolekar
authors: c Department of Biological Sciences , University of Alberta , Edmonton, Alberta , Canada , and.
authors: Beomsoo
authors: B
authors: Han
authors: c Department of Biological Sciences , University of Alberta , Edmonton, Alberta , Canada , and.
authors: Trent C
authors: TC
authors: Bjondahl
authors: c Department of Biological Sciences , University of Alberta , Edmonton, Alberta , Canada , and.
authors: Edison
authors: E
authors: Dong
authors: a Department of Obstetrics and Gynecology , Beaumont Health , Royal Oak , MI , USA.
authors: Samuel
authors: S
authors: Bauer
authors: a Department of Obstetrics and Gynecology , Beaumont Health , Royal Oak , MI , USA.
authors: Zeynep
authors: Z
authors: Alpay-Savasan
authors: a Department of Obstetrics and Gynecology , Beaumont Health , Royal Oak , MI , USA.
authors: Onur
authors: O
authors: Turkoglu
authors: a Department of Obstetrics and Gynecology , Beaumont Health , Royal Oak , MI , USA.
authors: Dotun
authors: D
authors: Ogunyemi
authors: b Harris Birthright Research Centre for Fetal Medicine , Division of Women's Health, King's College Hospital , London , UK.
authors: Liona C
authors: LC
authors: Poon
authors: c Department of Biological Sciences , University of Alberta , Edmonton, Alberta , Canada , and.|d Department of Computing Sciences , University of Alberta , Edmonton, Alberta , Canada.
authors: David S
authors: DS
authors: Wishart
authors: b Harris Birthright Research Centre for Fetal Medicine , Division of Women's Health, King's College Hospital , London , UK.
authors: Kypros H
authors: KH
authors: Nicolaides
mesh_terms: D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007532:Isoleucine / Q000097:blood*; D007930:Leucine / Q000097:blood* / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D011225:Pre-Eclampsia / Q000097:blood / Q000209:etiology* / Q000628:therapy; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011446:Prospective Studies; D015203:Reproducibility of Results; D014633:Valine / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007532:Isoleucine; D007930:Leucine; D014633:Valine
keywords: Insulin resistance; metabolomics; preeclampsia