Specialty (if any): Orthopedic Surgery

Keywords: diabetes, prosthetic joint infection, orthopedic surgery

Background: Diabetes mellitus (DM), encompassing both Type 1 (T1DM) and Type 2 (T2DM), is a significant risk factor for postoperative complications following spinal surgery. The prevalence of DM is increasing globally, and its impact on surgical outcomes is well-documented. Elevated preoperative HbA1c levels, indicative of poor glycemic control, have been associated with increased risks of surgical site infections (SSIs), prolonged hospital stays, and higher rates of reoperation and readmission. However, despite known pathophysiological mechanisms such as immune dysregulation, impaired wound healing, and altered inflammatory responses in diabetic patients, the specific mechanistic pathways linking diabetes to spinal implant infections remain unclear.

Objective: To elucidate the mechanistic basis by which T1DM and T2DM predispose to spinal implant infections using established diabetic murine models.

Methods: We developed two preclinical murine models to investigate infection susceptibility in diabetes. Stainless steel pins inoculated with bioluminescent Staphylococcus aureus Xen36 were surgically implanted into streptozotocin-induced T1DM mice and high-fat, sucrose diet-induced T2DM mice. Infection progression was longitudinally tracked using in vivo bioluminescent imaging (BLI). Bacterial burdens were quantified through tissue colony-forming unit (CFU) assays, and immune function was evaluated via ex vivo whole-blood bacterial killing assays. Data were analyzed statistically to identify differences between diabetic and nondiabetic control groups.

Results: Diabetic mice showed significantly prolonged peak infection durations compared to nondiabetic controls (p<0.05). Both diabetic groups demonstrated increased wound dehiscence and impaired bacterial clearance relative to controls (p<0.05 for both). Notably, wound dehiscence was more severe in T1DM mice, while bacterial clearance deficits were more pronounced in T2DM mice.

Conclusions: Our preclinical findings indicate that diabetes impairs wound healing and systemic bacterial clearance through distinct mechanisms specific to the diabetes subtype. These results highlight the necessity for rigorous perioperative management strategies in diabetic patients undergoing spinal surgery to mitigate infection risks. Future studies will investigate whether GLP-1 agonists, such as semaglutide, could serve a protective role against prosthetic joint infections (PJI) perioperatively.