Plasma Protein Growth Arrest–Specific 6 Levels Are Associated With Altered Glucose Tolerance, Inflammation, and Endothelial Dysfunction

Abstract

OBJECTIVE Plasma protein growth arrest–specific 6 (Gas6) is important to the inflammatory process and is involved in the development of diabetic renal and vascular complications. We set out to determine whether plasma Gas6 levels are associated with altered glucose tolerance, insulin sensitivity, inflammation, and endothelial dysfunction. RESEARCH DESIGN AND METHODS A total of 278 adults, including 96 with normal glucose tolerance (NGT), 82 with impaired glucose tolerance (IGT), and 100 with type 2 diabetes were recruited. Plasma Gas6 concentration and biochemical, proinflammatory, and endothelial variables were determined. Insulin sensitivity was examined by homeostasis model assessment. RESULTS Plasma Gas6 concentration was significantly lower among patients with type 2 diabetes compared with subjects with NGT (P < 0.001). The plasma Gas6 value was inversely correlated with fasting glucose, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and vascular cell adhesion molecule (VCAM)-1. In multivariate logistic regression analysis, after adjustment for established diabetes risk factors, higher plasma Gas6 concentrations were significantly associated with a decreased risk of type 2 diabetes. Moreover, the association became slightly stronger after further adjustment for TNF-α, IL-6, high-sensitive C-reactive protein, E-selectin, intercellular adhesion molecule-1, and VCAM-1. CONCLUSIONS Plasma Gas6 is associated with altered glucose tolerance, inflammation, and endothelial dysfunction. It also may represent a novel independent risk factor of type 2 diabetes and a potential surrogate marker of inflammation and endothelial dysfunction.