3.3.1. Nerve pathophysiology: key features that need to be represented in animal models
Diabetic neuropathy, characterised by damage to peripheral nerve function, is a highly prevalent complication of diabetes occurring in at least 6%-50% of diabetic patients depending on age and duration of diabetes[131, 132]. Diabetic patients often experience a high degree of morbidity, including poor balance and co-ordination leading to frequent falls, numbness, pain and ulceration of the lower limbs that can lead to limb amputation. Amongst the different forms of neuropathy, distal symmetric polyneuropathy commonly affecting the hands and lower limbs, is the most prevalent form of diabetic neuropathy. Hyperglycaemia induces accumulation of acylcarnitines that can trigger axonal degeneration. In addition, increased glucose levels lead to increased ROS, inflammation and AGE production, contributing to nervous system dysfunction[131]. Despite its high prevalence, the exact aetiology remains unknown, with available treatment options mostly ineffective, leaving the focus for patients mainly on improving glycaemic control or advocating for lifestyle modifications.