Monocyte–macrophage polarization balance in pre-diabetic individuals

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 HbA_1c. 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.