Monocyte-macrophage polarization balance in pre-diabetic individuals

Abstract

Pre-diabetes is characterized by increased cardiovascular risk and chronic inflammation. The activation of monocyte-macrophages plays major roles in vascular biology. Herein, we aimed to analyze monocyte-macrophage polarization status in subjects with IFG and/or IGT compared with normal glucose tolerant (NGT) individuals. We enrolled 87 middle-aged individuals with low prevalence of cardiovascular disease. Based on OGTT, they were divided into 49 NGT and 38 pre-diabetic (IFG and/or IGT). Using flow cytometry analysis of peripheral blood cells, we quantified traditional monocyte subsets based on CD14 and CD16 expression as well as novel monocyte-macrophage pro-inflammatory CD68(+)CCR2(+) M1 and anti-inflammatory CX3CR1(+)CD163(+)/CD206(+) M2 phenotypes. The M1/M2 ratio was taken to represent the polarization balance. There were no differences in traditional classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)) and nonclassical (CD14(+)CD16(+)) monocytes between groups. Rather, compared to NGT, pre-diabetic subjects showed a significant increase in pro-inflammatory M1 cells and percent expression of the oxLDL scavenger receptor CD68, without changes in anti-inflammatory M2 cells. M1 levels and CD68 expression were directly correlated with HbA1c. We show for the first time that otherwise healthy pre-diabetic subjects have excess M1 inflammatory cells in peripheral blood, which may contribute to cardiovascular risk.