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

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

Author information

1
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.
2
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.

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

PMID:
25908766
PMCID:
PMC4441588
DOI:
10.1161/ATVBAHA.115.305635
[Indexed for MEDLINE]
Free PMC Article

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