title: Novel metabolic markers for the risk of diabetes development in American Indians.
abstract: OBJECTIVE
  To identify novel metabolic markers for diabetes development in American Indians.
  
  
  METHODS
  Using an untargeted high-resolution liquid chromatography-mass spectrometry, we conducted metabolomics analysis of study participants who developed incident diabetes (n = 133) and those who did not (n = 298) from 2,117 normoglycemic American Indians followed for an average of 5.5 years in the Strong Heart Family Study. Relative abundances of metabolites were quantified in baseline fasting plasma of all 431 participants. Prospective association of each metabolite with risk of developing type 2 diabetes (T2D) was examined using logistic regression adjusting for established diabetes risk factors.
  
  
  RESULTS
  Seven metabolites (five known and two unknown) significantly predict the risk of T2D. Notably, one metabolite matching 2-hydroxybiphenyl was significantly associated with an increased risk of diabetes, whereas four metabolites matching PC (22:6/20:4), (3S)-7-hydroxy-2',3',4',5',8-pentamethoxyisoflavan, or tetrapeptides were significantly associated with decreased risk of diabetes. A multimarker score comprising all seven metabolites significantly improved risk prediction beyond established diabetes risk factors including BMI, fasting glucose, and insulin resistance.
  
  
  CONCLUSIONS
  The findings suggest that these newly detected metabolites may represent novel prognostic markers of T2D in American Indians, a group suffering from a disproportionately high rate of T2D.
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health, New Orleans, LA jzhao5@tulane.edu.
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health, New Orleans, LA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Biostatistics, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Noorie
authors.initials: N
authors.lastname: Hyun
authors.affiliation: Department of Biostatistics, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Donglin
authors.initials: D
authors.lastname: Zeng
authors.affiliation: Division of Pulmonary Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: Karan
authors.initials: K
authors.lastname: Uppal
authors.affiliation: Division of Pulmonary Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: ViLinh T
authors.initials: VT
authors.lastname: Tran
authors.affiliation: Department of Biostatistics and Bioinformatics, Emory University School of Public Health, Atlanta, GA.
authors.forename: Tianwei
authors.initials: T
authors.lastname: Yu
authors.affiliation: Division of Pulmonary Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: Dean
authors.initials: D
authors.lastname: Jones
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health, New Orleans, LA.
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.affiliation: Center for American Indian Health Research, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Elisa T
authors.initials: ET
authors.lastname: Lee
authors.affiliation: Medstar Health Research Institute and Georgetown and Howard Universities Centers for Translational Sciences, Washington, DC.
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D001713:Biphenyl Compounds / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000208:ethnology*; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D007198:Indians, North American / Q000208:ethnology*; D007333:Insulin Resistance / Q000208:ethnology; D007529:Isoflavones / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D055432:Metabolomics; D009842:Oligopeptides / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: C113215:7-hydroxy-2',3',4',5',8-pentamethoxyisoflavan; D015415:Biomarkers; D001713:Biphenyl Compounds; D007529:Isoflavones; D009842:Oligopeptides; D010713:Phosphatidylcholines; C004369:2-phenylphenol