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

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.

• Authors: Akintunde O Akinkuolie, Aruna D Pradhan, Julie E Buring, Paul M Ridker, Samia Mora
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 35 Issue 6 Pg. 1544-50 (Jun 2015) ISSN: 1524-4636 [Electronic] United States
• PMID: 25908766 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Heart Association, Inc.

Chemical References

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

Topics

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