Transitioning To Advanced Therapies For DFUs: Are Four Weeks And 50 Percent The Magic Numbers?

Author(s): 
Chanel Houston, DPM, Samirah Mohammed, DPM, and Peter A. Blume, DPM, FACFAS

When do you make the transition to advanced modalities for diabetic foot ulcers? With this question in mind, these authors discuss key diagnostic pointers and offer salient insights from the literature on when physicians should consider advanced modalities to facilitate improved healing and outcomes.

The treatment of diabetic foot ulcers can be a long, multifaceted task. Not only does one need to address the actual ulcer, clinicians need to consider other contributing factors such as foot deformities, biomechanics, glycemic control, ischemia, and peripheral and autonomic neuropathy.1,2 For these reasons, the diabetic foot ulcer often proves recalcitrant to certain treatment modalities and can be a challenging feat for many patients and practitioners alike.

   Advanced therapies may be beneficial to patients with chronic diabetic foot ulcers. However, in order to consider the use of these modalities, one must examine the ulcer etiology, review the clinical findings, ensure a proper workup, determine if there is adequate vascularity and assess the length of time to adequate healing.

   In regard to the aforementioned etiological factors, the most significant predictor of diabetic foot ulcer formation is neuropathy. Peripheral neuropathy is basically altered sensation, which creates a basis for skin breakdown in the presence of pressure areas. Autonomic neuropathy impairs capillary vasodilatation in response to injury. While understanding that one of the main etiologies of ulcer formation is neuropathy, it is also very important to understand what leads to neuropathy in the patient with diabetes.

   Abnormalities in the polyol pathway and inadequate nerve regeneration are direct results of neuropathic changes in the patient with diabetes.2 The effects of diabetes impair wound healing by altering protein and lipid metabolism, and affect granulation tissue formation. Due to these alterations, there is a significant lack of normal enzymatic glycosylation. Excess glucose binds to lipids and proteins without any proper glycosylation, and become products that accumulate over surface cell membranes and proteins. These products become known as advanced glycation end products (AGEs), which are seen on extracelluar matrix proteins such as laminin, vitronectin and collagen. These matrix proteins become altered by advanced glycation end products through cross-linking, which produces tissue stiffness, granulation tissue and basement membrane thickening in arterioles and capillaries.

   Microangiopathy and atherosclerotic disease also impede adequate wound healing, and are highly prevalent in patients with diabetes. Diminished blood flow plays a crucial role in the development of ulceration and is a strong barrier to cellular proliferation and wound healing.3

   Chronic wounds, in particular, are extremely complex and slow to heal due to constant inflammation affecting the healing process. Chronic wounds are unable to enter the proliferative phase of healing and develop over time due to edema, inadequate perfusion, poor nutrition, infection, trauma and certain rheumatologic factors. Another huge contributor to chronic wounds is matrix metalloproteinase, which modifies the extracellular matrix by metabolizing collagen, elastins and proteoglycans. This in turn affects tissue reabsorption, remodeling, platelet aggregation, macrophage and neutrophil function, cell migration, and angiogenesis.2

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