Novel Protein Glycan-Derived Markers of Systemic Inflammation and C-Reactive Protein in Relation to Glycemia, Insulin Resistance, and Insulin Secretion.

Abstract

N-acetylglucosamine/galactosamine (GlycA) and sialic acid (GlycB) moieties of glycosylated serum proteins are nonspecific measures of inflammation, but conclusive data on their relationship with insulin resistance or insulin secretion are missing. Therefore, we aimed to examine the relation of GlycA, GlycB, and C-reactive protein (CRP) to direct measures of insulin sensitivity (insulin sensitivity index [S_I]) and insulin secretion (acute insulin response [AIR]). This study used cross-sectional analyses and included 1,225 participants with and without type 2 diabetes in the Insulin Resistance Atherosclerosis Study (IRAS). S_I and AIR were measured using the frequently sampled intravenous glucose tolerance test, and GlycA and GlycB were measured using nuclear magnetic resonance spectroscopy. GlycA and GlycB had a strong correlation with CRP (<i>r</i> = 0.60 [<i>P</i> < 0.001] and <i>r</i> = 0.46 [<i>P</i> < 0.001], respectively). In a linear regression model with both GlycA and CRP as independent variables, GlycA (β × 1 SD, -0.04 ± 0.02; <i>P</i> < 0.01) and CRP (-0.06 ± 0.02; <i>P</i> < 0.001) were independently associated with S_I even after adjusting for demographics, smoking, physical activity, plasma glucose, and BMI. However, neither CRP nor GlycA had an independent relationship with AIR. GlycA may complement CRP in evaluating the relationship between inflammation, glucose tolerance, and insulin resistance.