Noninvasive management of the diabetic foot with critical limb ischemia: current options and future perspectives

Abstract

Foot ulcers are a major complication in patients with diabetes mellitus and involve dramatic restrictions to quality of life and also lead to enormous socio-economical loss due to the high amputation rate. The poor and slow wound healing is often aggravated by the frequent comorbidity of foot ulcers with peripheral arterial disease, making the treatment of this condition even more complicated. While the local treatment of foot ulcers is mainly based on mechanical relief and prevention or treatment of infection, improving perfusion of the impaired tissue remains the major challenge in peripheral arterial disease. While focal arterial stenosis is the domain of interventional angioplasty or vascular surgery, patients with critical limb ischemia and lacking options for revascularization have a much worse prognosis, because current treatment options avoiding amputation are scarce. However, based on recent research efforts, there is rising hope for promising and more-effective therapeutic approaches for these patients. Here, we discuss the current improvements of established therapies aimed at an improvement of limb perfusion, as well as the development of novel cutting-edge therapies based on stem-cell technology. The experiences of a 'high-volume center' for treatment of diabetic foot syndrome with a current major amputation rate of 4% are discussed.

Effect of Systemic Urokinase Infusion After Lower Limb Percutaneous Transluminal Angioplasty on Limb Salvage Rate in Patients with Late-stage Critical Limb Ischemia

“…8 Besides diabetic foot, there is increasing interest in extending the application of UK to the perioperative treatment of borderline amputations. 9 In the present study, after administering UK for 5 days, there was an increase in the number of patients who underwent minor amputation and a decrease in the number of patients who underwent major amputation. Although there were significantly (p ¼ .0251) more patients with diabetes in the PTA AE stent group, when patients with diabetes were equally distributed in both groups (47 patients each) there was a significant (p ¼ .0051) reduction in major amputations.…”

“…7 In some studies, low-dose systemic urokinase (UK) was used alone, without any intervention in patients with diabetes in order to improve microcirculation and thereby the limb salvage rates, suggesting that there may be an increased clot load at the microcirculation level in these patients. 8,9 It was postulated that patients with critical limb ischemia (CLI) may have increased clot load at tissue level due to decreased flow with diseased pedal arteries, and embolization due to the intervention. Therefore, use of systemic UK as an adjunctive method to improve blood flow at the tissue level following endovascular interventions was planned to theoretically decrease the clot load at tissue level.…”

Structured health care for subjects with diabetic foot ulcers results in a reduction of major amputation rates

“…If vascular reconstruction or interventional radiologic procedures were not possible, prostaglandins, low-dose urokinase or autologous bone marrow derived mononuclear cells (“stem cells”, intramuscular application) were applied in order to improve perfusion [8]. …”

Therapeutic application of adipose-derived stromal vascular fraction in diabetic foot

“…Recently, the incidence of diabetes is increasing in the world, and the age of onset has decreased year by year. Diabetes has become a health problem that cannot be ignored and the prolonged presence of hyperglycemia could induce various complications including diabetic foot [1].…”