Impaired efferocytosis by monocytes and monocyte-derived macrophages in patients with poorly controlled type 2 diabetes.

Background: Deficient efferocytosis (i.e., phagocytic clearance of apoptotic cells) by macrophages has been frequently reported in experimental models of type 2 diabetes (T2D).

Aim: To translate these findings to humans by testing whether the efferocytosis capacity of blood monocytes and monocyte-derived macrophages is impaired in T2D patients.

Methods: Overall, 30 patients with poorly controlled T2D [glycosylated hemoglobin (HbA1c) ≥ 8.0%] and 30 age- and sex-matched control subjects were enrolled in the study. The efferocytosis capacities of peripheral blood monocytes and monocyte-derived macrophages were assessed by flow cytometry and immunostaining. Macrophage membrane CD14 expression was examined by flow cytometry. Metabolic factors such as 25(OH)D and immune factors such as interleukin-1β were also measured.

Results: The mean monocyte efferocytosis index in the diabetes group was significantly lower than that in the control group. Notably, efferocytosis remained impaired after monocytes differentiated into macrophages. Additionally, the percentages of classical monocytes (CD14⁺⁺CD16^- monocytes) and CD14⁺ macrophages were significantly lower in the diabetes group. Multivariate linear regression analysis in diabetes patients demonstrated that the monocyte efferocytosis index was independently associated with the HbA1c level, and that the macrophage efferocytosis index was significantly associated with the percentage of CD14⁺ macrophages.

Conclusion: Impaired efferocytosis was observed in T2D patients, with poor glycemic control affecting both blood monocytes and monocyte-derived macrophages. The efferocytosis index was negatively associated with metrics of glycemic control, and glucotoxicity may impact efferocytosis through reducing CD14 expression on both monocytes and macrophages.