NICE, France ― New therapeutic approaches have emerged for preventing diabetic foot ulcers and promoting their healing. Endocrinologist and diabetes specialist Olivier Bourron, MD, of the Pitié-Salpêtrière Hospital in Paris, described these approaches at the 48th annual congress of the Francophone Diabetes Society.
A Common Complication
Unlike macroangiopathic complications (such as ischemic heart disease and stroke) and renal complications, foot ulcers are a diabetic complication for which there has been very little therapeutic progress over the past 20 years.
Nevertheless, they are common. “One to two diabetic patients in ten develop a foot ulcer during their lifetime,” said Bourron. Yet, he added that “this complication, which depends on uncontrolled hyperglycemia, is not unavoidable. It is linked to peripheral neuropathy, which induces sensory disturbances and deformities of the foot, causing the formation of ulcers.”
Foot ulcers are a particularly serious complication. If preventive measures are not adequately implemented, 5 to 10 diabetic patients in 100 will end up needing a lower limb amputation. “In France, there are around 8000 amputations a year, and this hasn’t been improving. So, to reduce the risk of them being needed, new therapeutic approaches have to be explored,” said Bourron.
These new approaches target two aspects of therapy: podiatric prevention and getting the ulcer to heal as quickly as possible to avoid infection.
Preventing Foot Ulcers
Podiatric prevention consists of trying to stop the occurrence of an ulcer for patients at risk, most often those with peripheral neuropathy. Bourron presented a pair of devices that work together to detect areas of the foot at risk even before the ulcer occurs.
“Smart mats,” which are in development, detect minute differences in temperature between both feet that predict the short-term occurrence (within 40 days) of a foot ulcer. Preventive measures such as pedicures, prescription footwear, and the prevention of traumatic factors in the foot at risk can then be implemented.
“There are also the insoles connected to these smart mats, equipped with sensors that measure the hyperpressures linked to morphostatic disorders,” said Bourron. “These disorders are linked to neuropathy and, in 90% of cases, cause the ulcer.” Bourron explained how the device is used. “A signal appears on a watch connected to the insole. The message is, ‘Caution: there is repeated hyperpressure on this area of the foot that may lead to a foot ulcer.’ ” Here, too, the doctor can suggest particularly suitable preventive measures. “Studies have shown that this limits the risk of foot ulcers in the short term,” he added.
As another measure to prevent podiatric risk, researchers and doctors are using new drugs in their effort to limit the development of occlusive arteritis of the lower limbs, which is a major risk factor for amputation. Among these new drugs, Bourron mentioned an anti-PCSK9 lipid-lowering agent that has been proven to reduce the risk for limb amputation. The investigators in this 2018 trial concluded that evolocumab may reduce the risk for a major event in the lower limbs (that is, the occurrence of acute ischemia, critical ischemia, and amputation) by 42%. “Anti-PCSK9 drugs, which are indicated for cases of familial dyslipidemia and to help prevent the recurrence of myocardial infarction, are a class of medications that need to be agreed on in advance. Their use is already in keeping with quite a few patients at podiatric risk,” said Bourron.
Rivaroxaban is another drug currently in the spotlight. In a recent trial with aspirin and this new oral anticoagulant that targets coagulation factor X, a very significant decrease was observed not only in major composite events (such as acute ischemia and critical ischemia) but also in the risk for amputation (−70%) for patients with arteritis. A large proportion of the participants had diabetes.
When ulcers occur despite preventive measures, healing can take several weeks to several months, during which time the patient is at risk for infection and amputation. Another objective of the new therapies is to promote the healing process.
Bourron noted a growing number of “well-done, randomized, double-blind” studies that present a high level of evidence for innovative local treatments, such as multilayer cell patches (that include white blood cells, platelets, and fibrin). Administered at the end of the patient’s bed, the LeucoPatch, obtained from centrifuged blood, is applied directly to the ulcer. “There are very significant results in terms of improving healing time or obtaining complete healing,” said Bourron. Local hyperbaric oxygen therapy is an even more recent topical treatment that also reduces healing time and promotes complete healing.
Dressings, which are very important in the treatment of foot ulcers, have also improved because of recent advances. For example, dressings with TLC-NOSF matrix technology make it possible to act on the factors that slow down healing. “They are already available in specialized diabetic foot care services. With these new technologies, we are optimistic about reducing this major complication of diabetes and the risk for amputation in diabetic patients” Bourron concluded.