Advances in the Treatment of Peripheral Vascular Disease in Diabetes and Reduction of Major Amputations

Abstract

In recent years, life expectancy has increased in many societies consequent to better health conditions. Although the trends of decreasing mortality rates from ischemic heart disease and stroke have continued into the 21st century, both causes continue to be the biggest killers in the Western societies. No change is predicted in the foreseeable future and consequently both these conditions contribute significantly to the burden of disease. 1 Diabetes is considered a cardiovascular disease equivalent and with diabetes patients share the benefits of the improved approach to the treatment of cardiovascular disease. However, because of the longer life span and disease duration, other chronic complications such as peripheral arterial disease (PAD) may well become more evident. In a recent survey, PAD was present in 21% of newly diagnosed type 2 diabetic patients 2 and in about 50% of the patients admitted to a diabetic foot clinic on account of a new foot ulcer. It is interesting to emphasize that half of those patients had concomitant peripheral neuropathy. 3 Neuropathy can mask the classic PAD symptoms as claudication, thereby delaying a diagnosis. On the other hand, the presence of PAD may limit the use of total contact cast that is considered the “gold standard” treatment for neuropathic ulcerations. PAD alone is responsible for the increased risk of lower limb amputation observed in patients with diabetes. 4,5 In type 1 diabetes, the overall 25-year cumulative incidence of lower extremity amputation (LEA) is 10.1%. History of heavy smoking, high HbA1c, presence of hypertension are all factors related to PAD and major determinants associated with LEA. 6 In addition, major complex gender differences exist in diabetes-related LEA: Men are more likely to undergo LEA. 7 The presence of a foot infection increases the risk of LEA. A multidisciplinary approach to diabetic foot problems is mandatory to reduce the frequency of LEA, particularly when PAD is complicated by the presence of infected foot ulcers. 8 Today significantly better outcomes are expected for patients with diabetes affected by critical limb ischemia (CLI) based on improved technical options in peripheral revascularization, new options in antibiotic therapy, and aggressive wound debridement and wound care. Until recently, open peripheral arterial bypass has been the firstline surgical treatment option for PAD. Although open bypass is associated with successful results, the invasive nature of the surgery can limit optimal overall outcome. Endovascular procedure is less invasive; however, it reaches similar limb salvage rates in patients with CLI, 9 with the added benefits of fewer wound complications and a shorter hospital stay. As expected, endovascular therapy is increasingly being considered as a first-line treatment option in carefully selected PAD diabetic patients. With the widespread adoption of endovascular therapy, there has been a profound shift in practice patterns for lower extremity PAD. In the past decade, there has been a consistent increase in the number of patients treated by peripheral transluminal angioplasty because of CLI. 10 Hong et al 10 reported that in the general population the average annual number of endovascular interventions is increased by 78% while there is a concomitant decrease in open bypass by 20%. The same authors found that the trends in amputation were consistent with the increase in endovascular therapy. The number of major amputations (ankle to above-the-knee level) decreased by 21% and the number of minor amputations, defined as involving the toe and forefoot, showed a moderate decrease of 5%. Although better outcomes for CLI have been observed in the general population, the LEA observed in patients with diabetes are reportedly reduced, unchanged, or even increased. A recent survey conducted in England reported that the number and incidence of amputations decreased in the aging nondiabetic population whereas the overall population