الفهرس 
PATHOGENESISOnly 14 pages are availabe for public view
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Abstract
Foot complications are already a major cause of admissions for diabetes, and comprise a disproportionately high number of hospital days because of increased surgical procedures and prolonged length of stay.
Diabetes is an important risk factor for LEAD (lower extremity arterial disease). Hypertension, smoking, and hyperlipidemia, which are frequently present in patients with diabetes, contribute additional risk for vascular disease.
The incidence and prevalence of LEAD increase with age in both diabetic and non diabetic subjects and, in those with diabetes, increase with duration of diabetes. Many elderly diabetic persons have LEAD at the time of diabetes diagnosis.
Diabetes accounts for about 50% of all non traumatic amputations in the United States. Mortality is increased in patients with LEAD, particularly: if foot ulcerations, infection, or gangrene occur.
The incidence and prevalence of LEAD increase with age in both diabetic and nondiabetic subjects and, in those with diabetes, increase with duration of diabetes.
LEAD in diabetes is compounded by the presence of peripheral neuropathy and by susceptibility to infection. These confounding factors in diabetic patients contribute to progression of LEAD to foot ulcerations, gangrene, and ultimately to amputation of part of the affected extremity.
In the patient with a confirmed diagnosis of PAD (peripheral arterial disease) in whom an assessment of the location and severity is desired, the next step would be a vascular laboratory evaluation for segmental pressures and pulse volume recordings (PVRs). Segmental pressures help with lesion localization, while PVRs provide segmental waveform analysis, a qualitative assessment of blood flow.
For patients with atypical symptoms or a normal ABI with typical symptoms of claudication, functional testing with a graded treadmill may help with diagnosis. Patients with claudication will typically exhibit a _20-mmHg DROP in ankle pressure after exercise.
For those patients in whom revascularization is considered and anatomical localization of stenoses or occlusions is important, an evaluation with a duplex ultrasound or a magnetic resonance angiogram (MRA) may be valuable. Duplex ultrasound can directly visualize vessels and is also useful in the surveillance of post procedure patients for graft or stent patency.
While MRA is a safe and promising new technology and noninvasive with minimal risk of renal insult, the gold standard for vascular imaging is X-ray angiography, and it is indicated primarily for the anatomical evaluation of the patient in whom a revascularization procedure is intended.
Prevention is an important component of LEAD management.
By the time LEAD becomes clinically manifest, it may be too late to salvage an extremity, or it may require more costly resources to improve the circulatory health of the extremity. The approach to the diabetic patient with signs and symptoms of vascular occlusive disease is separate from that utilized in the non diabetic population.
The management of a patient that presents with an ischemic diabetic foot should be approached in a premeditated and stepwise fashion. The initial priority is the prompt and thorough drainage and/or debridement of any infected or necrotic tissue.
Once the infection is controlled, the next step is determining the level of ischemia. This step should not be delayed, and can be pursued even in the presence of active infection. Once angiography is complete, planning for revascularization is undertaken. Once revascularization has been accomplished, attention can then again be turned to the repair of the initial foot lesion.
New treatment modalities have emerged recently in the era of management of peripheral vascular disorders in diabetics, these include: Hyperbaric oxygen therapy , Stem cell therapy and Gene therapy.
• Hyperbaric oxygen therapy:
Hyperbaric oxygen therapy has been demonstrated to have an antimicrobial effect and to increase oxygenation of the hypoxic wound tissues. This enhances the neutrophil killing ability, stimulates angiogenesis, and enhances fibroblasts activity and collagen synthesis.
• Stem cell therapy:
The concept of stem cell based revascularisation emerged in 1997, when Isner’s group described circulating cells in adults called endothelial progenitor cells (EPC) with the capacity to differentiate into endothelial cells (EC) and incorporate into new vessels in ischaemic tissue.
• Gene therapy:
The concept of therapeutic angiogenesis has been pursued and successful navigation through phase II and III clinical trials will require an iterative exchange between clinical and preclinical investigators. In addition, the definition of successful angiogenic gene therapy may also need to be reconsidered. Traditionally, therapies for treatment of vascular disorders must demonstrate improvements in morbidity or mortality, Avoiding hospitalization and other manifestations of progressive disease could also be appropriate goals for angiogenic gene therapy.