Hypoglycaemic neuropathy: microvascular changes due to recurrent hypoglycaemic episodes in rat sciatic nerve

Intensive diabetes treatment causes a considerable increase in the number of severe hypoglycaemic episodes which could aggravate the progression of diabetic neuropathy. However, the effect of repeated hypoglycaemic episodes on nerve morphology has never been previously investigated. The aims of the present study were: (i) to establish a rat model of recurrent episodes of severe hypoglycaemia, and (ii) to assess morphological changes after repeated hypoglycaemic episodes in rat sciatic nerves. We induced hypoglycaemic episodes, blood glucose level <3.0 mmol/l for 3 h, by injecting regular insulin intravenously on 4 consecutive days. We found endothelial swelling of endoneurial microvessels at the thigh level of sciatic and tibial nerves 24 h after four daily episodes of hypoglycaemia. Endothelial swelling was confirmed by vascular morphometry which showed significantly increased endothelial and pericyte areas. No obvious abnormalities were seen on nerve fibres. In conclusion, recurrent hypoglycaemic episodes cause early vascular anomalies in endoneurial microvessels in rat sciatic nerves without any observable changes in nerve fibres.