The effects of diabetes mellitus on fracture healing in BB Wistar rats.

摘要

Type I diabetes mellitus has been associated with impaired fracture healing in both a clinical and experimental setting. Past experimental studies have routinely utilized a chemically induced diabetic animal model. These models do not serve as the most clinically relevant to the Type I diabetic condition. The purpose of this study was to establish and validate a reproducible femoral fracture model in diabetic BB Wistar rats and to evaluate endogenous levels of growth factors critical for the healing process. The onset of diabetes in the BB Wistar rat is spontaneous and caused by a selective, autoimmune destruction of the pancreatic beta cells. The BB Wistar rat offers advantages over chemical induction of the disease and currently represents the closest homology to Type I diabetes in man.; The fracture healing process is severely impaired in the poorly controlled diabetic BB Wistar rat. The process is restored to normal with appropriate amounts of exogenous insulin to ensure physiologic blood glucose control in the diabetic animals.; Reductions in PDGF, TGF-β1, IGF-I and VEGF were observed in poorly controlled diabetic fracture callus 4 days post fracture. These reductions were noted in both protein and mRNA expression. The reduction in diabetic callus PDGF-B, TGF-β1 and IGF-I mRNA was restored to values not significantly different from non-diabetic fracture callus by 7 days post fracture. VEGF, however, was significantly reduced in diabetic fracture callus at 7 days.; The data obtained regarding the reduction in growth factors suggests that the gene expression cascade necessary for sufficient fracture healing is perturbed in the diabetic condition leading to severely impaired fracture callus properties. The application of one or a combination of these growth factors directly to the fracture site may be a possible future treatment in poorly controlled diabetic patients. Further analysis to determine whether insulin has a direct role at the fracture site is currently being performed. In addition to the local restoration of growth factors to the fracture site, local insulin delivery may also prove to be a beneficial treatment for Type I diabetics who have complications in fracture repair.