title: Novel protein glycan side-chain biomarker and risk of incident type 2 diabetes mellitus.
abstract: OBJECTIVE
  Enzymatically glycosylated proteins partake in multiple biological processes, including glucose transport and inflammation. We hypothesized that a novel biomarker (GlycA) of N-acetyl methyl groups originating mainly from N-acetylglucosamine moieties of acute-phase glycoproteins is related to incident type 2 diabetes mellitus and compared it with high-sensitivity C-reactive protein.
  
  
  RESULTS
  In 26,508 initially healthy women free of diabetes mellitus, baseline GlycA and high-sensitivity C-reactive protein were quantified by nuclear magnetic resonance spectroscopy and immunoturbidimetry, respectively. During median follow-up of 17.2 years, 2087 type 2 diabetes mellitus cases occurred. In Cox models with adjustment for age, race, smoking, alcohol, activity, menopausal status, hormone use, family history, and body mass index, quartile 4 versus 1 hazard ratios and 95% confidence intervals were 2.67 (2.26-3.14) for GlycA and 3.93 (3.24-4.77) for high-sensitivity C-reactive protein; both P trend <0.0001. Associations for GlycA and high-sensitivity C-reactive protein were attenuated after additionally adjusting for lipids: 1.65 (1.39-1.95) and 2.83 (2.32-3.44), respectively, both P trend <0.0001, and after mutual adjustment: 1.11 (0.93-1.33; P trend=0.10) and 2.57 (2.09-3.16; P trend<0.0001), respectively.
  
  
  CONCLUSIONS
  Our finding of an association between a consensus glycan sequence common to a host of acute-phase reactants and incident type 2 diabetes mellitus provides further support for inflammation in the development of type 2 diabetes mellitus. Additional studies exploring the role of enzymatic glycosylation in the prevention of type 2 diabetes mellitus are warranted.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.
authors.affiliation: Divisions of Preventive Medicine (A.O.A., A.D.P., J.E.B., P.MR., S.M.) and Cardiovascular Medicine (P.MR., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Akintunde O
authors.initials: AO
authors.lastname: Akinkuolie
authors.affiliation: Divisions of Preventive Medicine (A.O.A., A.D.P., J.E.B., P.MR., S.M.) and Cardiovascular Medicine (P.MR., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Aruna D
authors.initials: AD
authors.lastname: Pradhan
authors.affiliation: Divisions of Preventive Medicine (A.O.A., A.D.P., J.E.B., P.MR., S.M.) and Cardiovascular Medicine (P.MR., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.affiliation: Divisions of Preventive Medicine (A.O.A., A.D.P., J.E.B., P.MR., S.M.) and Cardiovascular Medicine (P.MR., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.affiliation: Divisions of Preventive Medicine (A.O.A., A.D.P., J.E.B., P.MR., S.M.) and Cardiovascular Medicine (P.MR., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. smora@partners.org.
authors.forename: Samia
authors.initials: S
authors.lastname: Mora
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood; D008137:Longitudinal Studies; D008875:Middle Aged; D011134:Polysaccharides / Q000097:blood*; D012307:Risk Factors; D012907:Smoking / Q000097:blood
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D006442:Glycated Hemoglobin; D011134:Polysaccharides
keywords: diabetes mellitus; epidemiology; glycoprotein; inflammation