Abstract 3072: Role of Vascular Reactivity and Inflammation in the Development and Healing of Diabetic Foot Ulceration
Objective. Diabetic foot ulceration (DFU) and impaired wound healing are major problems in diabetes. Our hypothesis was that vascular function and inflammation are important factors in the development and failure to heal DFU.
Methods. We followed 99 DM patients without peripheral arterial disease for a period of 22 ± 7 months (mean ± sd). We evaluated endothelium dependent and independent vasodilation in the macrocirculation [brachial artery, flow mediated dilation (FMD) and nitroglycerin-induced dilation (NID)], skin microcirculation [iontophoresis of acetylcholine (Ach)], skin oxygenated hemoglobin (oxyHb) by hyperspectral imaging, foot muscle energy reserves by MRI spectroscopy (MRI-S) and serum inflammatory cytokines and growth factors.
Results. DM patients, when compared to 19 healthy subjects, had reduced FMD (5.4% ± 1.8 vs 8.5 ± 3.0, p <0.0001) and NID (12.9 ± 4.5 vs 17.6 ± 3.6, p <0.0001). During the follow up period, 27 (27%) patients developed DFU (DFU group) and 62 (63%) did not (No-DFU). Risks for DFU development were: peripheral neuropathy [6.9 (2.3 – 21.0), OR (95 CI)], Ach in the lower quartile of [1.56 (1.02 – 2.37)] and oxyHb <27 [3.43 (1.23 – 9.58)]. Comparing to No-DFU group, DFU subjects had lower FMD (5.6 ± 1.8 vs 4.7 ± 1.4, p<0.05), NID (13.2 ± 2.7 vs 10.8 ± 2.6, p <0.001) and MRI-S (1.9 ± 1.3 vs 0.3 ± 0.7). Complete healing was achieved in 14 (52%) patients (DFU-Healers) while 13 (48 %) did not heal (DFU-Non Healers). There were no differences in the above parameters between the two groups but, as shown in the table⇓, Non Healers had higher TNFα, MCP-1 MMP-9 and FGF-2 when compared to Non Healers.
Conclusions: Systemic factors are present long before the development of DFU. Neuropathy and vascular function factors are related to the development of DFU and inflammation to the failure to heal it. Targeting these factors may prove helpful in the management of DFU.