Prospective study on microangiopathy in type 2 diabetic foot ulcer.
We investigated the significance of microangiopathy in the development of foot ulcer, which is still disputed.



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.



In the diabetic patients, capillaries in the dermal papillary layer were fewer (-22.2%, 159 ± 43 vs 205 ± 52 mm(2) 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 μm(2), 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).



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.



ClinicalTrials.gov NCT02610036.
Unit of Bio-Imaging, Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Via La Masa 19, 20156, Milan, Italy. fabio.fiordaliso@marionegri.it.
Fabio
F
Fiordaliso
Diabetic Foot Center, IRCCS MultiMedica, Sesto San Giovanni, Milan, Italy.
Giacomo
G
Clerici
Unit of Bio-Imaging, Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Via La Masa 19, 20156, Milan, Italy.
Serena
S
Maggioni
Diabetic Foot Center, IRCCS MultiMedica, Sesto San Giovanni, Milan, Italy.
Maurizio
M
Caminiti
Unit of Bio-Imaging, Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Via La Masa 19, 20156, Milan, Italy.
Cinzia
C
Bisighini
Unit of Bio-Imaging, Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Via La Masa 19, 20156, Milan, Italy.
Deborah
D
Novelli
Diabetic Foot Center, IRCCS MultiMedica, Sesto San Giovanni, Milan, Italy.
Daniela
D
Minnella
Unit of Bio-Imaging, Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Via La Masa 19, 20156, Milan, Italy.
Alessandro
A
Corbelli
Department of Orthopedics, IRCCS MultiMedica, Sesto San Giovanni, Milan, Italy.
Riccardo
R
Morisi
Department of Ophthalmology, IRCCS MultiMedica, Sesto San Giovanni, Milan, Italy.
Alberto
A
De Iaco
Diabetic Foot Center, IRCCS MultiMedica, Sesto San Giovanni, Milan, Italy.
Ezio
E
Faglia
D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D003925:Diabetic Angiopathies / Q000473:pathology*; D005260:Female; D016523:Foot Ulcer / Q000473:pathology*; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D011446:Prospective Studies
Amputation; Arteriolar occlusions; Basement membrane thickness; Capillary density; Diabetic foot; Neuroischaemic foot; Neuropathic foot; Skin biopsy; Small vessel disease; Wound healing time