Diabetic neuro-ischaemic foot syndrome and the key underlying interactions between chronic arterial disease and peripheral neuropathy

Chronic limb-threatening ischaemia and diabetic peripheral neuropathy are common complications of poorly controlled hyperglycaemia. Numerous clinical evidences suggest that peripheral arterial disease and diabetic peripheral neuropathy may be interconnected pathological entities with bidirectional interactions that respond to hyperglycaemia. The deleterious effects of hyperglycaemia manifest on a systemic scale as well as at the neuro-ischaemic limb level. Persistent hyperglycaemia-related injuries are induced by either direct cellular toxicity or indirect endothelial macrocirculatory damage, leading to cellular dysfunction, increased hypoxia, chronic inflammation, and cellular loss. This paper discusses some of the interactions between chronic limb-threatening ischaemia and diabetic peripheral neuropathy that constitute a complex bidirectional interplay. The scope of this editorial was to explore in depth these possible interactions, as encountered in daily clinical practice, from subclinical to clinical morphological and pathophysiological manifestations. It is also aimed to emphasize the important role played by these two entangled entities, as intricate risk factors for tissue and limb loss, linked to the harmful effects of persistent hyperglicaemia in diabetic, neuro-ischemic limbs.

Each significant clinical interaction (or groups of reciprocal interplay) is discussed in association with practical recommendations that are developed in distinct paragraphs, for better clinical applicability.