Abstract 18807: Novel Protein Glycan Derived Biomarker is Associated With Incident Diabetes
Background: Enzymatically glycosylated proteins partake in multiple cellular processes, including glucose transport and inflammation. In addition, most inflammatory proteins are enzymatically glycosylated. GlycA is a novel nuclear magnetic resonance (NMR) biomarker whose signal originates from the N-acetyl groups of N-acetylglucosmine and N-acetylgalatosamine moieties of protein glycans. We hypothesized that GlycA is directly related to the risk of incident diabetes, possibly mediated by inflammation as assessed by high-sensitivity C-reactive protein (hsCRP), a well-established inflammatory biomarker.
Method: Baseline GlycA was quantified by NMR spectroscopy (LipoScience, NC) in 26,539 Women’s Health Study participants free of diabetes at enrollment (median follow-up 16 years; 1,990 incident diabetes cases). Multivariable Cox regression models were adjusted for age, race, treatment assignment, smoking, menopausal status, hormone use, family history of diabetes, and BMI.
Result: GlycA correlated with hemoglobin A1c (Spearman r=0.21), HDL cholesterol (r= -0.21), triglycerides (r=0.46), BMI (r=0.40), and hsCRP (r=0.61), all p< 0.0001. Multivariable-adjusted HRs (95% CIs) for incident diabetes across increasing quartiles of GlycA were 1.00, 1.44 (1.20-1.73), 1.93(1.63-2.29) and 2.74 (2.32-3.24), p-trend<0.0001. This was attenuated but remained significant after additionally adjusting for lipids (p-trend <0.0001). Additional adjustment for hsCRP further attenuated the association (p-trend=0.02; Table).
Conclusion: In this population of 26,539 women followed for 16 years, baseline GlycA levels were directly associated with the risk of incident diabetes independent of traditional risk factors. The association of GlycA with diabetes was attenuated after further adjusting for hsCRP, suggesting a novel role for protein glycans in the development of diabetes possibly mediated through subclinical inflammation.
- © 2013 by American Heart Association, Inc.