title: Metabolic signature shift in type 2 diabetes mellitus revealed by mass spectrometry-based metabolomics.
abstract: OBJECTIVE
  Metabolic profiling of small molecules offers a snapshot of physiological processes. To identify metabolic signatures associated with type 2 diabetes and impaired fasting glucose (IFG) beyond differences in glucose, we used mass spectrometry-based metabolic profiling.
  
  
  METHODS
  Individuals attending an institutional health screen were enrolled. IFG (n = 24) was defined as fasting glucose (FG) of 6.1 to 6.9 mmol/L and 2-hour post glucose load <11.1 mmol/L or glycosylated hemoglobin <6.5%, type 2 diabetes (n = 27), FG ≥7.0 mmol/L, or 2-hour post glucose load ≥11.1 mmol/L, or glycosylated hemoglobin ≥6.5%, and healthy controls (n = 60), FG <6.1 mmol/L. Fasting serum metabolomes were profiled and compared using gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry.
  
  
  RESULTS
  Compared to healthy controls, those with IFG and type 2 diabetes had significantly raised fructose, α-hydroxybutyrate, alanine, proline, phenylalanine, glutamine, branched-chain amino acids (leucine, isoleucine, and valine), low carbon number lipids (myristic, palmitic, and stearic acid), and significantly reduced pyroglutamic acid, glycerophospohlipids, and sphingomyelins, even after adjusting for age, gender, and body mass index.
  
  
  CONCLUSIONS
  Using 2 highly sensitive metabolomic techniques, we report distinct serum profile change of a wide range of metabolites from healthy persons to type 2 diabetes mellitus. Apart from glucose, IFG and diabetes mellitus are characterized by abnormalities in amino acid, fatty acids, glycerophospholipids, and sphingomyelin metabolism. These early broad-spectrum metabolic changes emphasize the complex abnormalities present in a disease defined mainly by elevated blood glucose levels.
authors: School of Public Health, National University of Singapore, 16 Medical Drive MD3, Singapore 117597.
authors: Fengguo
authors: F
authors: Xu
authors: Subramaniam
authors: S
authors: Tavintharan
authors: Chee Fang
authors: CF
authors: Sum
authors: Kaing
authors: K
authors: Woon
authors: Su Chi
authors: SC
authors: Lim
authors: Choon Nam
authors: CN
authors: Ong
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D055432:Metabolomics; D008875:Middle Aged
chemical_list: D001786:Blood Glucose