Current Challenges and Opportunities in the Prevention and Management of Diabetic Foot Ulcers

Abstract

Diabetic foot ulcers remain a major health care problem. They are common, result in considerable suffering, frequently recur, and are associated with high mortality, as well as considerable health care costs. While national and international guidance exists, the evidence base for much of routine clinical care is thin. It follows that many aspects of the structure and delivery of care are susceptible to the beliefs and opinion of individuals. It is probable that this contributes to the geographic variation in outcome that has been documented in a number of countries. This article considers these issues in depth and emphasizes the urgent need to improve the design and conduct of clinical trials in this field, as well as to undertake systematic comparison of the results of routine care in different health economies. There is strong suggestive evidence to indicate that appropriate changes in the relevant care pathways can result in a prompt improvement in clinical outcomes.Despite considerable advances made over the last 25 years, diabetic foot ulcers (DFUs) continue to present a very considerable health care burdendone that is widely unappreciated. DFUs are common, the median time to healing without surgery is of the order of 12 weeks, and they are associated with a high risk of limb loss through amputation (1-4). The 5-year survival following presentation with a new DFU is of the order of only 50-60% and hence worse than that of many common cancers (4,5). While there is evidence that mortality is improving with more widespread use of cardiovascular risk reduction (6), the most recent datadderived from a Veterans Health Adminstration populationdreported that 1-, 2-, and 5-year survival was only 81, 69, and 29%, respectively, and the association between mortality and DFU was stronger than that of any macrovascular disease (7). Iversen et al. (8) have also shown that the occurrence of a DFU was an independent predictor of mortality even at 10 years.The cost to health care services is also enormous. The estimated global cost of diabetes in 2015 was $1.3 trillion (9), and it has been reported that up to one-third of diabetes expenditure is on lower-limb-related problems in the U.S. (10). The latest data from the U.K. estimate that the total annual cost of management of DFUs exceeds £1 billion ($1.32 billion) and represents almost 1% of the total National Health Service budget (11). The equivalent figure from the U.S. has been estimated to be $9-13 billion (12). GEOGRAPHIC DIFFERENCES IN CLINICAL OUTCOMEThere is also wide variation in clinical outcome within the same country (13-15), suggesting that some people are being managed considerably less well than others.

Validity of diagnostic codes and estimation of prevalence of diabetic foot ulcers using a large electronic medical record database

“…Leg ulcers and foot ulcers, although often leading to the similar untoward outcome of amputation, are distinct clinical entities with different epidemiology, pathophysiology, and treatment, as was demonstrated in our database and shown by others . DFU is a pathology stemming from neuropathy, often combined with PAD, and is treated by multidisciplinary care including local wound care, offloading, metabolic control, antibiotics, and revascularization if needed . Leg ulcers are more likely to be secondary to venous insufficiency and the mainstay of their treatment other than local wound care is compression stockings .…”

Regional variations in amputation rates: are regional diabetic foot services the reason?

“…After adjustment, Jeffcoate still found a six‐ to sevenfold variation in UK amputation rates, which was only slightly lower than the sevenfold to 10‐fold variation they earlier found using crude rates . They hypothesized that the remaining variation could only be explained by factors not adjusted for, namely, comorbidities and available diabetic foot services …”

Roxadustat promotes angiogenesis through HIF‐1α/VEGF/VEGFR2 signaling and accelerates cutaneous wound healing in diabetic rats

“…Approximately, 9.1–26.1 million people are estimated to develop this condition annually . The median healing time of diabetic foot ulcers is up to 12 weeks, which is associated with a high risk of amputation . Decreased local neovascularization and diminished peripheral blood flow are critical factors that contribute to the delayed wound healing in diabetic patients .…”