Plasma metabolomics reveal alterations of sphingo- and glycerophospholipid levels in non-diabetic carriers of the transcription factor 7-like 2 polymorphism rs7903146

PLoS One. 2013 Oct 24;8(10):e78430. doi: 10.1371/journal.pone.0078430. eCollection 2013.

Abstract

Aims/hypothesis: 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).

Discussion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Blood Glucose / genetics
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics
  • Genotype
  • Glucose Tolerance Test / methods
  • Glycerophospholipids / blood
  • Humans
  • Insulin / genetics
  • Male
  • Metabolome / genetics*
  • Metabolomics / methods
  • Middle Aged
  • Phosphatidylcholines / blood
  • Polymorphism, Genetic / genetics*
  • Sphingomyelins / blood
  • Transcription Factor 7-Like 2 Protein / genetics*

Substances

  • Blood Glucose
  • Glycerophospholipids
  • Insulin
  • Phosphatidylcholines
  • Sphingomyelins
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein

Grants and funding

The KORA research platform studies were initiated and financed by the Helmholtz Zentrum München—National Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Science, Research and Technology and by the State of Bavaria. The study was supported by a research grant from the Virtual Diabetes Institute (Helmholtz Zentrum München), the Clinical Cooperation Group LMU (Ludwig-Maximilians-Universität München - Helmholtz Zentrum Muenchen), the Clinical Cooperation Group TU (Else Kröner-Fresenius-Center for Nutritional Medicine, Technische Universität München - Helmholtz Zentrum München) and in part by the German Center for Diabetes Research (DZD e.V.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.