Spinal Implant-Associated Infection in Type 2 and Type 1 Diabetes: Phenotype-Specific Inflammatory Features and Therapeutic Response to Semaglutide
Abstract
Background: Diabetes mellitus (DM) is a major risk factor for postoperative infection and wound complications in spine surgery, yet distinctions between Type 2 (T2DM) and Type 1 (T1DM) pathophysiology are rarely addressed. This study compares infectious burden, wound healing, and immune response among a murine model of spinal implant-associated infection of T2DM, T1DM, and nondiabetic control mice before and after metabolic intervention with the GLP-1 receptor agonist (GLP-1RA), semaglutide.
Methods: Male C57BL/6J mice were rendered diabetic by streptozotocin induction (T1DM) or a high-fat, high-sucrose diet (T2DM). Spinal implants were placed and inoculated with bioluminescent Staphylococcus aureus. Infection progression was monitored longitudinally by in vivo bioluminescence imaging. Systemic inflammation was characterized through multiplex cytokine profiling, and paraspinal tissues were analyzed by histology and multiplex immunofluorescence.
Results: Both diabetic models demonstrated greater infection burden, delayed wound healing, and distinct systemic inflammatory profiles compared with controls. T2DM was characterized by chronically elevated baseline inflammation and a blunted acute response to infection, whereas T1DM exhibited low baseline activity but exaggerated and dysregulated cytokine induction. Semaglutide attenuated infection severity, improved wound integrity, and partially normalized inflammatory patterns. Histology and immunofluorescence corroborated these findings, showing reduced immune cell infiltration and improved tissue organization in semaglutide-treated cohorts.
Conclusions: T2DM and T1DM are associated with differing inflammatory and immune features in murine spinal implant-associated infection. Metabolic modulation with semaglutide restores immune balance, reduces infection severity, and promotes wound repair. These findings support exploration of GLP-1RA-based therapies to improve surgical outcomes in diabetic patients.
Authors: Thomas E Olson, Trevor S Lloyd, Christopher D Hamad, Rene F Chun, Joshua Wiener, Autreen Golzar, Joshua Mehany, Soroush Shahamatdar, Andrew Kittredge, Lauren Pearce, Kevin P Francis, Farres Obeidin, Langston T Holly, Michael R Yeaman, John S Adams, Nicholas M Bernthal, William L Sheppard
Journal: JOR spine
DOI: 10.1002/jsp2.70196