Novel protein glycan side-chain biomarker and risk of incident type 2 diabetes mellitus

Arterioscler Thromb Vasc Biol. 2015 Jun;35(6):1544-50. doi: 10.1161/ATVBAHA.115.305635. Epub 2015 Apr 23.

Abstract

Objectives: 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.

Approach and 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.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.

Keywords: diabetes mellitus; epidemiology; glycoprotein; inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / metabolism*
  • Biomarkers / blood
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Inflammation / blood
  • Longitudinal Studies
  • Middle Aged
  • Polysaccharides / blood*
  • Risk Factors
  • Smoking / blood

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • Glycated Hemoglobin A
  • Polysaccharides

Associated data

  • ClinicalTrials.gov/NCT00000479