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.