Persons with diabetes have a higher incidence of fractures compared with persons without diabetes. However, there is little published information concerning the deleterious effect of late-stage diabetes on fracture healing. There are no studies using animal models that evaluate the effect of advanced diabetes on fracture healing. The purpose of our study was to evaluate cytokine expression, specifically macrophage inflammatory protein 1 (MIP-1) and vascular endothelial growth factor, in fracture healing in a type 2 diabetes rat model.
We evaluated biomarker expression after femur fracture using a rat model. The two groups consisted of 24 Zucker diabetic rats (study group) and 12 Zucker lean rats (control group). An independent reviewer was used to assess delayed union. We evaluated serum samples 2, 4, 7, and 14 days after surgery for MIP-1, vascular endothelial growth factor, leptin, and other cytokine levels.
At 3 weeks, Kaplan-Meier estimates showed that 45.8% of femur fractures in Zucker diabetic rats had healed, whereas 81.8% of those in Zucker lean rats had healed (P = .02). A logistic regression model to predict fast healing that included the three cytokines and diabetes status showed that the only factor achieving significance was MIP-1α. Vascular endothelial growth factor was the only biomarker to show significance compared with delayed healing.
These results confirm significant differences in biomarker expression between diabetic and nondiabetic rats during bone healing. The key factors for bone healing may appear early in the healing process, whereas differences in diabetes versus nondiabetes are seen later in the healing process. Increased levels of MIP-1α were associated with the likelihood of delayed healing.
Dialysis therapy is associated with an increased incidence of lower-extremity wounds and amputations. We compared the incidence of foot ulcers and amputations before and after the start of dialysis.
We evaluated 150 consecutive diabetic patients receiving dialysis and compared the incidence of foot complications 30 months before and after initiation of hemodialysis. We used claims data for diabetes, ulceration, and dialysis and abstracted medical records to verify diagnoses and dates of ulcers and amputations. We compared initial and cumulative ulcer/amputation incidence to account for multiple events in the same person over time. We used the same formula to determine the incidence rate difference and 95% confidence intervals (CIs) to compare new ulcers and amputations during the study.
There was no significant difference in the incidence of first foot ulcers before (91.7 per 1,000 patient-years; 95% CI, 73.7–112.3 per 1,000 patient-years) and after (82.7; 95% CI, 65.7–102.3) the start of hemodialysis. The incidence of cumulative ulcers was significantly higher before (304.0 per 1,000 patient-years; 95% CI, 270.8–340.2) compared with after (210.7 per 1,000 patient-years; 95% CI, 183.0–240.9) dialysis. There was no difference in the incidence of first amputation before (29.3 per 1,000 patient-years; 95% CI, 1 9.4–41.7 per 1,000 patient-years) and after (37.3 per 1,000 patient-years; 95% CI, 19.4–41.7 per 1,000 patient-years) dialysis or in the cumulative incidence of amputations before (61.3 per 1,000 patient-years; 95% CI, 46.7–8.4 per 1,000 patient-years) and after (58.7 per 1,000 patient-years; 95% CI, 44.5–75.5 per 1,000 patient-years) dialysis.
There was no increase in the incidence of ulcers or amputations after beginning hemodialysis.
Background: To evaluate complications and risk factors for nonunion in patients with diabetes after ankle fracture.
Methods: We conducted a retrospective study of 139 patients with diabetes and ankle fractures followed for 1 year. We evaluated the incidence of wounds, infections, nonunions, Charcot’s arthropathy, and amputations. We determined Fracture severity (unimalleolar, bimalleolar, trimalleolar), nonunion, and Charcot’s arthropathy from radiographs. Nonunion was defined as a fracture that did not heal within 6 months of fracture. Analysis of variance was used to compare continuous variables, and χ2 tests to compare dichotomous variables, with α = 0.05. Logistic regression was performed with a binary variable representing nonunions as the dependent variable.
Results: Complications were common: nonunion (24.5%), Charcot’s arthropathy (7.9%), wounds (5.2%), wound site infection (17.3%), and leg amputation (2.2%). Patients with nonunions were more likely to be male (55.9% versus 29.5%; P = .005), have sensory neuropathy (76.5% versus 32.4%; P < .001), have end-stage renal disease (17.6% versus 2.9%; P < .001), and use insulin (73.5% versus 40.1%; P < .001), β-blockers (58.8% versus 39.0%; P = .049), and corticosteroids (26.5% versus 9.5%; P = .02). Among patients with nonunion, there was an increased risk of wounds (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.46–7.73), infection (OR, 2.04; 95% CI, 0.72–5.61), amputation (OR, 7.74; 95% CI, 1.01–100.23), and long-term bracing (OR, 9.51; 95% CI, 3.8–23.8). In the logistic regression analysis, four factors were associated with fracture nonunion: dialysis (OR, 7.7; 95% CI, 1.7–35.2), insulin use (OR, 3.3; 95% CI, 1.5–7.4), corticosteroid use (OR, 4.9; 95% CI, 1.4–18.0), and ankle fracture severity (bimalleolar or trimalleolar fracture) (OR, 2.5; 95% CI, 1.1–5.4).
Conclusions: These results demonstrate risk factors for nonunions: dialysis, insulin use, and fracture severity after ankle fracture in patients with diabetes.