Does Preoperative Glycemic Control Restore Immune Defense Against Implant-related Infection in Mice With Diabetes?

The presence of Type II diabetes is a well-established risk factor for bone and joint infection, especially in patients with poor glycemic control. However, few studies have investigated the effect of the duration of preoperative glycemic intervention. For patients with poor glycemic control, the effect of the duration of preoperative glycemic intervention remains unknown. Many glycemic biomarkers including hemoglobin A1c (HbA1c), fructosamine, and 1,5-anhydroglucitol have different response rates to glycemic change. It is unclear which biomarker is more closely related to the decrease in infection proportion after preoperative glycemic intervention. (1) Is there an effect of the duration of preoperative insulin therapy in mice with diabetes receiving an experimental intra-articular implant? (2) Of the three commonly used biomolecules for monitoring blood glucose levels (HbA1c, fructosamine, and 1,5-anhydroglucitol), is one more closely related to decrease in infection proportion after presurgical insulin therapy? With a well-established protocol, Type II diabetes was modeled in female 10-week-old C57BL/6 mice by maintaining them on a high-fat diet (60% fat) for 8 months; control mice without diabetes received a normal low-fat diet (10% fat). Mice with Type II diabetes were randomized into groups to receive preoperative glycemic intervention with insulin for 0, 1, 3, 5, 7, 14, or 28 days, and investigators were blinded to the randomization. Mice with and without diabetes then received a surgically inserted wire into the femoral canal in a retrograde fashion and received a local or systemic challenge with Staphylococcus aureus or Escherichia coli (n = 20 for each bacteria challenge [systemic or local]/timepoint). The proportion of culture-positive joint samples was calculated. An additional 10 mice with Type II diabetes were treated with insulin for 28 days and the HbA1c, fructosamine, and 1,5-anhydroglucitol levels were consecutively monitored. Fisher exact tests and nonparametric Wilcoxon rank sum tests were used to analyze the different between different groups, with p < 0.05 taken as significant. When insulin therapy was administered, the proportion of bone and joint infections decreased in mice with Type II diabetes, reaching asymptotic levels after 3 days of treatment for the systemic (S. aureus: 7 of 20 mice with diabetes on 3-day therapy, p < 0.001; 8 of 20 on 5-day, p = 0.002; 10 of 20 on 7-day, p = 0.01; 9 of 20 on 14-day, p = 0.006; and 8 of 20 o