Effective healing of diabetic skin wounds by using nonviral gene therapy based on minicircle vascular endothelial growth factor DNA and a cationic dendrimer.

BACKGROUND: The development of an efficient method to improve the wound healing process is urgently required for diabetic patients suffering a threat of limb amputations. Various growth factors have been proposed for treatment; however, more research still has to be carried out to maintain their curative effect. In the present study, we describe a simple nonviral gene therapy method for improving wound healing. METHODS: Minicircle plasmid DNA encoding vascular endothelial growth factor (VEGF) was combined with an arginine-grafted cationic dendrimer, PAM-RG4. The formed complexes were injected subcutaneously into the skin wounds of diabetic mice. RESULTS: Actively proliferating cells in wound tissue were efficiently transfected, resulting in a high level of VEGF expression. Within 6 days after injection, skin wounds in the diabetic mice were generally healed and displayed a well-ordered dermal structure, which was confirmed by histological staining. CONCLUSIONS: This simple and effective gene therapy method may represent a powerful tool for the treatment of diabetic foot ulcers and other diseases that are refractory to treatment.

Nateglinide and acarbose for postprandial glucose control after optimizing fasting glucose with insulin glargine in patients with type 2 diabetes.

AIMS: Basal insulin treatment is frequently used in type 2 diabetes, but the successful control of postprandial glucose is challenging. We compared the effect of preferential postprandial glucose targeting drugs for postprandial glucose control after optimizing fasting glucose with basal insulin. METHODS: This study was performed in 58, insulin naïve type 2 diabetes. After fasting glucose was optimized by insulin glargine, nateglinide or acarbose was initiated and then crossed over after second wash out period. 75 g oral glucose tolerance test and 7 point self monitoring blood glucose for 3 days at the end of each period was performed. RESULTS: Both drugs effectively reduced postprandial glucose levels compared with the insulin glargine monotherapy. No significant differences were found between nateglinide and acarbose in terms of mean glucose level, standard deviation of glucose levels, mean average glucose excursion and average daily risk range. Homeostasis model analysis (HOMA)% ß, corrected insulin response and insulin-to-glucose ratio were significantly higher in the responder group compared with the non-responder. There was no episode of severe hypoglycemia. CONCLUSIONS: Nateglinide and acarbose are equally effective in type 2 diabetes for postprandial glucose excursions during basal insulin treatment. The markers of beta cell function might be used for predicting response. (Clinical trial reg. no. NCT 00437918, clinicaltrial.gov.).