Biomarkers of Morbid Obesity and Prediabetes by Metabolomic Profiling of Human Discordant Phenotypes

Clin Chim Acta. 2016 Dec 1;463:53-61. doi: 10.1016/j.cca.2016.10.005. Epub 2016 Oct 5.

Abstract

Metabolomic studies aimed to dissect the connection between the development of type 2 diabetes and obesity are still scarce. In the present study, fasting serum from sixty-four adult individuals classified into four sex-matched groups by their BMI [non-obese versus morbid obese] and the increased risk of developing diabetes [prediabetic insulin resistant state versus non-prediabetic non-insulin resistant] was analyzed by LC- and FIA-ESI-MS/MS-driven metabolomic approaches. Altered levels of [lyso]glycerophospholipids was the most specific metabolic trait associated to morbid obesity, particularly lysophosphatidylcholines acylated with margaric, oleic and linoleic acids [lysoPC C17:0: R=-0.56, p=0.0003; lysoPC C18:1: R=-0.61, p=0.0001; lysoPC C18:2 R=-0.64, p<0.0001]. Several amino acids were biomarkers of risk of diabetes onset associated to obesity. For instance, glutamate significantly associated with fasting insulin [R=0.5, p=0.0019] and HOMA-IR [R=0.46, p=0.0072], while glycine showed negative associations [fasting insulin: R=-0.51, p=0.0017; HOMA-IR: R=-0.49, p=0.0033], and the branched chain amino acid valine associated to prediabetes and insulin resistance in a BMI-independent manner [fasting insulin: R=0.37, p=0.0479; HOMA-IR: R=0.37, p=0.0468]. Minority sphingolipids including specific [dihydro]ceramides and sphingomyelins also associated with the prediabetic insulin resistant state, hence deserving attention as potential targets for early diagnosis or therapeutic intervention.

Keywords: mass spectrometry; metabolic markers; obesity; observational study; prediabetes.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Humans
  • Male
  • Metabolomics*
  • Middle Aged
  • Obesity, Morbid / blood
  • Obesity, Morbid / diagnosis
  • Obesity, Morbid / metabolism*
  • Phenotype
  • Prediabetic State / blood
  • Prediabetic State / diagnosis
  • Prediabetic State / metabolism*

Substances

  • Biomarkers