Diabetic Neuropathic Foot Ulcers

Lower-extremity ulcers are a serious complication of diabetes. More than 16 million people in the U.S. have diabetes, and 15% of them can expect to develop a foot ulcer at some point in their lives (1–3). Diabetic patients admitted to the hospital with lower-extremity ulcers were hospitalized longer on average than those who were hospitalized and did not have ulcers (1,3). Whereas only 4% of the population has diabetes, 46% of those admitted to a hospital with a foot ulcer had diabetes, and half of all lower-extremity amputations in hospitalized patients occurred in diabetic patients (1,3). Those with a lower-extremity amputation have a diminished quality of life and increased health costs, often have many concomitant medical ailments, are more likely to have the contralateral limb amputated, and are more likely to die within the next 5 years than those with no amputation (4,5). There are many pathways for the development of a diabetic foot ulcer. In general, they include a combination of lowerlimb arterial insufficiency, lower-limb diabetic neuropathy, and local trauma (6). About 20% of diabetic patients with foot ulcers will primarily have inadequate arterial blood flow, 50% will primarily have diabetic neuropathy, and 30% will be afflicted with both conditions (1,6). Inadequate arterial blood flow is usually treated by a variety of surgical techniques that improve blood flow (7). For this study, foot ulcers on individuals with diabetes who lack protective sensation and have adequate arterial blood flow to their foot are termed diabetic neuropathic foot ulcers (DNFUs) (8–10). The treatment of a DNFU usually consists of debridement of necrotic tissue, use of a moist wound dressing, and the use of a device that protects the wound from pressure or trauma related to ambulation and other acts of daily living. Several devices are commonly used, including contact casts, crutches, wheelchairs, and special footwear (9,11–15). This type of care is often the standard care arm in randomized clinical trials and was recently discussed in a consensus statement from the American Diabetes Association (8–12,15). Recently the U.S. Food and Drug Administration approved several new treatments, making this an exciting time for those who treat patients with DNFUs (8– 10,12,16). These agents represent two new treatment classes, growth factors and cell therapies, and are used in combination with the standard therapy described above. Even with the advent of these new products, success in treating DNFUs is dismal. About 10–33% of the patients in the standard-care arms of clinical trials will heal by 12–20 weeks of care, whereas 30–50% of the individuals that receive one of the new products will heal by 12–20 weeks of care (8–10,12,16). We hypothesize that several risk factors can be identified that are associated with a DNFU healing by the 20th week of standard care. This information is important to clinicians—it should help them decide who might respond to standard therapy, who might be better off receiving an adjuvant early in the treatment plan, and who should receive specialized care. The goal of this study was to evaluate ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●