title: Plasma metabolomics reveal alterations of sphingo- and glycerophospholipid levels in non-diabetic carriers of the transcription factor 7-like 2 polymorphism rs7903146.
abstract: OBJECTIVE
  Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene have been shown to display a powerful association with type 2 diabetes. The aim of the present study was to evaluate metabolic alterations in carriers of a common TCF7L2 risk variant.
  
  
  METHODS
  Seventeen non-diabetic subjects carrying the T risk allele at the rs7903146 TCF7L2 locus and 24 subjects carrying no risk allele were submitted to intravenous glucose tolerance test and euglycemic-hyperinsulinemic clamp. Plasma samples were analysed for concentrations of 163 metabolites through targeted mass spectrometry.
  
  
  RESULTS
  TCF7L2 risk allele carriers had a reduced first-phase insulin response and normal insulin sensitivity. Under fasting conditions, carriers of TCF7L2 rs7903146 exhibited a non-significant increase of plasma sphingomyelins (SMs), phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs) species. A significant genotype effect was detected in response to challenge tests in 6 SMs (C16:0, C16:1, C18:0, C18:1, C24:0, C24:1), 5 hydroxy-SMs (C14:1, C16:1, C22:1, C22:2, C24:1), 4 lysoPCs (C14:0, C16:0, C16:1, C17:0), 3 diacyl-PCs (C28:1, C36:6, C40:4) and 4 long-chain acyl-alkyl-PCs (C40:2, C40:5, C44:5, C44:6).
  
  
  CONCLUSIONS
  Plasma metabolomic profiling identified alterations of phospholipid metabolism in response to challenge tests in subjects with TCF7L2 rs7903146 genotype. This may reflect a genotype-mediated link to early metabolic abnormalities prior to the development of disturbed glucose tolerance.
authors.affiliation: Medizinische Klinik und Poliklinik IV, Diabetes Zentrum - Campus Innenstadt, Klinikum der Universität München, Munich, Germany ; Clinical Cooperation Group Diabetes, Ludwig-Maximilians-Universität München and Helmholtz Zentrum München, Munich, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Then
authors.forename: Simone
authors.initials: S
authors.lastname: Wahl
authors.forename: Anna
authors.initials: A
authors.lastname: Kirchhofer
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.forename: Susanne
authors.initials: S
authors.lastname: Krug
authors.forename: Gabi
authors.initials: G
authors.lastname: Kastenmüller
authors.forename: Werner
authors.initials: W
authors.lastname: Römisch-Margl
authors.forename: Melina
authors.initials: M
authors.lastname: Claussnitzer
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Margit
authors.initials: M
authors.lastname: Heier
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.forename: Barbara
authors.initials: B
authors.lastname: Thorand
authors.forename: Cornelia
authors.initials: C
authors.lastname: Huth
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.forename: Ina
authors.initials: I
authors.lastname: Heukamp
authors.forename: Helmut
authors.initials: H
authors.lastname: Laumen
authors.forename: Andreas
authors.initials: A
authors.lastname: Lechner
authors.forename: Hans
authors.initials: H
authors.lastname: Hauner
authors.forename: Jochen
authors.initials: J
authors.lastname: Seissler
mesh_terms: D000483:Alleles; D001786:Blood Glucose / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics; D005838:Genotype; D005951:Glucose Tolerance Test / Q000379:methods; D020404:Glycerophospholipids / Q000097:blood; D006801:Humans; D007328:Insulin / Q000235:genetics; D008297:Male; D055442:Metabolome / Q000235:genetics*; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000097:blood; D011110:Polymorphism, Genetic / Q000235:genetics*; D013109:Sphingomyelins / Q000097:blood; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D020404:Glycerophospholipids; D007328:Insulin; D010713:Phosphatidylcholines; D013109:Sphingomyelins; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein