Impact of the duration of preoperative glycemic control on perioperative neutrophil functions in diabetic mice with chronic hyperglycemia: a laboratory research report

Abstract

BACKGROUND: The risk of surgical site infection has been reported to be higher in patients with poorly controlled diabetes. Since chronic hyperglycemia impairs neutrophil functions, preoperative glycemic control may restore neutrophil function. However, long-term insulin therapy may lead to a delay in surgery, which may be a problem especially in cancer surgery. It is therefore unfortunate that there was no study to investigate the optimal duration of perioperative glycemic control for diabetes with chronic hyperglycemia. Therefore, we investigated the effects of preoperative long-term insulin therapy and short-term insulin therapy on perioperative neutrophil functions in diabetic mice with chronic hyperglycemia. METHODS: Five-week-old mice were administered streptozotocin to induce diabetes. We divided the diabetic mice into three groups: a group of mice with untreated diabetes (untreated group), a group of mice that received insulin therapy for 6 hours before surgery (short-term group) and a group of mice that received insulin therapy for 5 days before surgery (long-term group). A group of non-diabetic mice were used as a control group. At 14 weeks of age, abdominal surgery with intestinal manipulation was performed in all four groups. We carried out a phagocytosis assay by fluorescent microspheres and a reactive oxygen species (ROS) production assay by DCFH-DA (2’,7’-dichlorodihydrofluorescin diacetate) before and after surgery using FACSVerse™ with BD FACSuite™ software. Phagocytosis rate (%) was calculated by dividing the number of phagocytic beads by neutrophil count. Fluorescence from DCF (dichlorofluorescein) in the neutrophils was measured and expressed as mean fluorescence intensity (MFI). RESULTS: Blood glucose was lowered by insulin therapy in the short-term and long-term groups before the operation. Neutrophilic phagocytosis activities before and after the operation were significantly restored in the long-term group compared with those in the untreated group (before: p = 0.0008, after: p = 0.0005). However, they were not significantly restored in the short-term group. Neutrophilic ROS production activities before and after the operation were not restored in either the short-term group or long-term group. CONCLUSIONS: Preoperative and postoperative phagocytosis activities are restored by insulin therapy for 5 days before the operation but not by insulin therapy for 6 hours before the operation.