Long-term preoperative glycemic control restored the perioperative neutrophilic phagocytosis in diabetic mice.

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 have been few studies in which the optimal duration of perioperative glycemic control for diabetes with chronic hyperglycemia was investigated. 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 male C57BL/6J mice were divided into four groups (Untreated (Diabetes Mellitus: DM), Short-term (DM), Long-term (DM), and Non-diabetic groups). Diabetes was established by administrating repeated low-dose streptozotocin. The Short-term (DM)group received insulin therapy for 6 hours before the operation and the Long-term (DM)group received insulin therapy for 5 days before the operation. The Untreated (DM) group and the Non-diabetic group did not receive insulin therapy. At 14 weeks of age, abdominal surgery with intestinal manipulation was performed in all four groups. We carried out a phagocytosis assay with fluorescent microspheres and a reactive oxygen species (ROS) production assay with DCFH-DA (2’,7’-dichlorodihydrofluorescein diacetate) before and 24 hours after the operation using FACSVerse™ with BD FACSuite™ software. RESULTS: Blood glucose was lowered by insulin therapy in the Short-term (DM) and Long-term (DM) groups before the operation. Neutrophilic phagocytosis activities before and after the operation were significantly restored in the Long-term (DM) group compared with those in the Untreated (DM) group (before: p = 0.0008, after: p = 0.0005). However, they were not significantly restored in the Short-term (DM) group. Neutrophilic ROS production activities before and after the operation were not restored in either the Short-term (DM) group or Long-term (DM) 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.