Prospective study on microangiopathy in type 2 diabetic foot ulcer

Abstract

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 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). 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.

Microvascular and Macrovascular Disease and Risk for Major Peripheral Arterial Disease in Patients With Type 2 Diabetes

“…Overall, these findings suggest that PAD is more likely to be linked to diabetic microangiopathy than kidney failure in patients with type 2 diabetes. Of note, a recent histopathological study showed microangiopathic abnormalities in patients with type 2 diabetes who underwent amputation for ischemic diabetic foot (15). Urine ACR is now accepted as an independent cardiovascular risk factor in patients with and without type 2 diabetes (16).…”

Microangiopathy: Is it relevant to wound healing in diabetic foot disease?

“…This delay was suggested to be due to a consequence of arteriolar occlusions which were commoner in the ischaemic patients and which correlated with a lower TcPO 2 that did improve after revascularization but remained still remained low when compared to neuropathic patients. However, this study did not include a control group of non‐diabetic patients with ischaemic ulceration where knowledge of their healing rates, frequency of arteriolar occlusion and TcPO 2 changes could be important before concluding that such differences are specific to the diabetic arteriolar occlusions …”

“…However, this study did not include a control group of non-diabetic patients with ischaemic ulceration where knowledge of their healing rates, frequency of arteriolar occlusion and TcPO 2 changes could be important before concluding that such differences are specific to the diabetic arteriolar occlusions. 33 Diabetic patients can have delayed healing of surgical wounds that appear to be related to poor glycaemic control and postoperative infection. There is some limited evidence that improving blood glucose levels in patients with type 1 diabetes is associated with an improvement of nailfold capillary (nutritive) blood flow, but if and to which extent these effects can be replicated in the diabetic foot remains to be determined.…”

Screening for the Presence of Cardiovascular Disease

“…In the UK Prospective Diabetes Study (UKPDS), age, A1C, systolic BP, high density lipoprotein cholesterol (HDL-C), previous CV disease and current smoking were found to be independent risk factors for PAD (53). In the BARI 2D trial, age, female sex, black African origin, smoking, pulse pressure, A1C and ACR were independent risk factors for PAD (54,55). The incidence rate of PAD was 3.5 times higher in BARI 2D than in ADVANCE, which may be explained by differences in each study's inclusion criteria and the definitions of PAD outcomes.…”