Prospective study on microangiopathy in type 2 diabetic foot ulcer

Aims/hypothesis: We investigated the significance of microangiopathy in the development of foot ulcer, which is still disputed. Methods: We assessed microangiopathy by histological analysis of the capillary ultrastructure using transmission electron microscopy and capillary density and arteriolar morphology in paraffin-embedded sections from the skin of type 2 diabetic patients: 30 neuroischaemic patients (Isc) revascularised with peripheral angioplasty and 30 neuropathic patients (Neu) with foot ulcer, compared with ten non-diabetic volunteers. Results: In the diabetic patients, capillaries in the dermal papillary layer were fewer (−22.2%, 159 ± 43 vs 205 ± 52 mm² in non-diabetic volunteers, p <0.01). They also showed detrimental remodelling, with a 2.2-fold increase in capillary basement membrane thickness (3.44 ± 1.19 vs 1.53 ± 0.34 μm in non-diabetic volunteers, p <0.001) and a 57.7% decrease in lumen area (14.6 ± 11.1 vs 34.7 ± 27.5 μm², p <0.001). No differences were observed between the diabetic Isc or Neu patients. Isc were more prone to develop arteriolar occlusion than Neu (16.8 ± 6.9% vs 6.7 ± 3.7%, respectively, p <0.001). No patient had been amputated at 30 days and healing time was significantly longer in Isc (180 ± 120 vs 64 ± 50 days in Neu, p <0.001). Conclusions/interpretation: Capillary microangiopathy is present in equal measure in neuroischaemic and neuropathic diabetic foot skin. The predominance of arteriolar occlusions with neuroischaemia indicated the existence of an additional ‘small vessel disease’ that did not affect an effective revascularisation and did not worsen the prognosis of major amputations but slowed the healing process of the neuroischaemic foot ulcer. Trial registration:: ClinicalTrials.gov NCT02610036.