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Fifteen Percent Of Diabetics Will Develop Foot Ulcers

How prevalent are foot ulcers among patients with diabetes? About 2.4 million diabetes patients, representing 15 percent of the estimated 16 million Americans afflicted with the disease, will develop serious foot ulcers during their lifetimes. In fact, ulcers and other foot complications cause 20 percent of the nearly 3 million hospitalizations related to diabetes every year. John Giurini, DPM, an Associate Professor of Surgery at Harvard University Medical School, reported on these alarming statistics at the recent ACFAS Diabetic Foot Symposium. “Unfortunately, many of these patients eventually must undergo lower extremity amputations as a result of infection brought on by untreated foot ulcers,” emphasizes Dr. Giurini. Why do ulcers go untreated? There are a variety of reasons. Often, foot ulcers in diabetic patients are the result of sensory neuropathy, a common complication of the disease. Kenneth Rehm, DPM, also points out that access to professional care may be a problem. Dr. Rehm notes that he practices in a Hispanic rural area in El Centro, Calif., where people do not have easy access to doctors. Therefore, they do not go to doctors unless they perceive they have major problems. Emphasizing Proactive Measures While Dr. Rehm says 85 percent of his diabetic patients have ulcerations, he says only about 2 to 5 percent of them end up with lower extremity amputations. “Because I hospitalize a lot of the ulcers that would eventually wind up as amputations, we are able to head off most of them by taking care of their circulation and infection,” explains Dr. Rehm. Taking a proactive approach to care is the key. Dr. Giurini says early detection of the risk factors associated with ulcer formation is essential for overall treatment, as it can significantly reduce the incidence of ulcers and eventual amputation. Richard Brietstein, DPM, a wound specialist who practices in Florida, also sees a large majority of diabetic patients who have foot ulcers. He uses techniques such as aggressive debridement and offloading and says the healing rate at his practice is “exceedingly high” and only 5 percent of his patients need amputations. Alexander Reyzelman, DPM, the Clinical Director at the Pacific Coast Wound Care Institute, says between 2 and 5 percent of his diabetic patients have ulcerations. His treatment includes using felt to foam dressings to offload the ulcers along with the use of removable walking boots (Aircast, DH-Walker, etc.). Employing enzymatic debridement agents and bioengineered skin equivalents, Dr. Reyzelman says his success rate at healing these ulcerations is 95 percent. About 2 to 4 percent of Dr. Reyzelman’s diabetic patients need amputations. Be Aware Of The Risk Factors In addition to major risk factors like vascular disease, structural deformities and previous ulcers, environmental or external risks include living alone, frostbite, burns and patients removing calluses and corns themselves. Dr. Brietstein adds obesity to the list of factors which could lead to ulcers. Dr. Rehm notes some other risk factors are venous insufficiency; pedal edema; depression; kidney disease and dialysis; poor nutrition reflected in the total protein, albumin and prealbumin blood tests; diabetic dermopathy and skin diseases; and being confined to a wheelchair or bed. Dr. Reyzelman says the limitation in joint range of motion “is certainly a risk factor for ulcer formation.” Gene Therapy Update: Study Hints At Healing Promise Of HIF-1a Often, you may find it challenging to treat the wounds of patients with diabetic peripheral vascular disease. Now a new study may shed some light on promoting blood vessel growth in such oxygen-starved tissues. As reported in a recent issue of Genes and Development, researchers from the University of California, San Francisco (UCSF) have found some intriguing results that indicate the molecule HIF-1a may be an effective target for fostering healthy blood vessels. After overexpressing the molecule in the skin cells of mice, researchers saw an approximately 70 percent increase in the amount of capillaries. Unlike previous studies in which researchers overexpressed the growth factor for VEGF, the blood vessels did not leak or cause swelling or inflammation. As they told, the study’s authors were very pleased with the results and noted that it could set the stage for further research. “The vessels looked like normal capillaries,” noted the study’s senior author Jeffrey M. Arbeit, M.D., an Associate Professor of Surgery at UCSF. “This finding, along with the fact that the vessels didn’t leak, is extremely exciting.” “We know that VEGF plays a crucial role in blood vessel growth,” adds lead author David Elsen, a UCSF Staff Research Associate. “We need to determine how over-expression of HIF-1a harnesses VEGF in a way that could be beneficial therapeutically.” Assessing The Potential Of Future Research In addition to being researched as an impetus for blood vessel growth in ischemic tissue, the gene is being investigated as a possible therapy for treating recalcitrant wounds and as a possible aid for promoting artifical skin grafts for burn and diabetic patients. David G. Armstrong, DPM, says researchers are only now earnestly exploring issues related to modulation of the microenvironment of the wound in general and to angiogenesis specifically. “The potential benefit of targeted gene therapy cannot be overstated,” says Dr. Armstrong, the Director of Research and Education in the Department of Surgery, Podiatry Section at the Southern Arizona Veterans Affairs Medical Center. “I agree with Dr. Arbeit and his co-investigators that translation of results from the benchtop or animal models into daily clinical use is a major, time- and resource-consuming hurdle.” Indeed, HIF-1a is known to regulate 30 genes, but it may regulate up to 100, according to Dr. Arbeit. The more scientists learn about the role of genes in such molecular pathways, the more opportunity they have to learn to manipulate genes to treat disease. Dr. Armstrong says gene therapy is another step in the evolution of medicine in general and medicine is slowly moving away from “shotgun” to “rifle” based therapies. “The phenomenally rapid expansion of pharmacogenomics is changing drug development even more rapidly,” he says. “I see a time within the next generation when drugs will be developed not just to treat a specific disease, but rather to treat a specific person with a specific disease. This will complicate FDA drug testing and trials tremendously, but I think the upside is just limitless.”

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