Activation of Peripheral Blood CD14⁺ Monocytes Occurs in Diabetes

Abstract

Blood levels of inflammatory markers associated with endothelial dysfunction and atherosclerosis are increased in diabetic patients; the highest levels occur in poorly controlled diabetes. We investigated the activation state of peripheral blood monocytes in diabetes with respect to scavenger receptor (CD36) expression and monocyte chemoattractant protein-1, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and peroxisome proliferator–activated receptors mRNA expression. CD14⁺ monocytes were isolated from peripheral blood of type 1 and type 2 diabetic patients with good (HbA_1c <7.0%) or poor (>9.4%) glycemic control and a group of nondiabetic subjects. Monocytes from diabetic subjects displayed increased CD36 cell surface expression (P < 0.0005) and increased uptake of oxidized LDL (P < 0.05). Monocyte chemoattractant protein-1 gene expression was increased in monocytes from both groups of diabetic subjects (P < 0.05). Both CD68 and peroxisome proliferator–activated receptor-γ gene expression were increased in the poorly controlled diabetic group (P < 0.05 for each), whose monocytes also displayed increased attachment to endothelial monolayers (P < 0.0005 vs. nondiabetic control subjects). In poorly controlled diabetes, CD14⁺ monocytes are functionally activated and show some of the differentiation markers associated with macrophages. These monocytes also demonstrate an increased ability for attachment to normal endothelial cells, one of the early stages in atherogenesis.