Does Time Heal All Wounds?

Why do wounds not heal in patients with Type II Diabetes? That, as Dr. Johnston puts it, is the “Million-Dollar Question.” Unfortunately, there is no easy answer to this question. Rather than being only one error in the healing response that results in the formation of a chronic wound, it is likely a number of issues.

When thinking of tragic health conditions, myriad cancers or a wide array of infectious diseases initially come to mind. Despite increased healthcare service and global advancements in medicine, many patients still find themselves either responding poorly to treatment or failing to receive the care they need. This is tragic, to be sure. Type II Diabetes is a condition that seemingly evades the label of being a tragic condition. But, why? Rarely does an individual succumb directly to Type II Diabetes in the same way that one does from leukemia or malaria. Deaths from the latter conditions are more directly attributed to the disease itself. While it does not account for the marked cause of death, Type II Diabetes is in some sense more insidious than other illnesses because, despite it being perceived as a relatively low-threat condition, it dramatically increases the risk of death in various ways. The risk of heart attack or stroke, for instance, increases considerably in individuals with Type II Diabetes. It is also thought to be a risk factor in the development of other chronic health conditions, such as kidney disease, neuropathy, glaucoma, sleep apnea, and even Alzheimer’s Disease. Type II Diabetes is a condition that’s root pathology is insulin resistance. Insulin resistance refers to cells in the body being less responsive to the effects of insulin. Healthy cells respond to insulin by up-taking glucose from the bloodstream. In those with Type II Diabetes, however, insulin resistance results in cells taking in glucose from the bloodstream only with much greater difficulty. This has major significance in the context of energy production, since glucose is a major source of energy for cells throughout the body. With such a basic feature of cellular function being hindered, it is quite understandable how there is such a wide-ranging list of adverse symptoms associated with this illness. At the University of Prince Edward Island, Dr. Adam Johnston and his team in the Applied Human Sciences Department are particularly interested in why the wounds of Type II Diabetes patients do not heal as they should. 

Chronic wounds result from the body’s inability to heal in an orderly set of stages and in a predictable amount of time. Typically, when the body is wounded, a cascade of events occurs which ultimately results in wound healing. Initially, the body enters a homeostasis phase of healing which begins at the onset of the injury and has a primary objective of stopping the loss of blood. In this phase, the blood clotting system releases platelets which bind to collagen and clot the wound. With the wound coagulated, the immune system fires up and the inflammatory phase ensues, during which blood vessels dilate and white blood cells fight off any bacteria or debris that has entered the wound. A clean wound allows for the proliferative phase to begin, which typically lasts between four days to four weeks, depending on the severity of the wound. During this phase, the wound is filled and covered by new epithelial skin cells. This process is known as epithelialization. Finally, the skin is remodelled in the maturation phase, with collagen fibres reorganized in such a way that the tensile force begins to steadily increase at the site of the wound. In due time, the site of the wound becomes nearly indistinguishable from neighbouring sites and normal function is restored. To healthy, disease-free individuals, tissue reparation follows the aforementioned, predictable procedure. To individuals diagnosed with Type II Diabetes, however, the process is inefficient and not well understood. 

Wound repair difficulties are manifest in many ways. An error in the immune response results in an exaggerated degree of inflammation and cells located near the wound do not divide as quickly as they should. In summation, the cascade of responses becomes very dysfunctional. Another well-documented characteristic of Type II Diabetes is that it is a vascular disease, which is a major contributor to the development of chronic wounds. The defining feature of vascular disease is the impediment of adequate blood flow to a given area in the body. Due to this lack of blood flow, there is likely to be insufficient oxygen and nutrients being delivered to the area. It is easy to see how this would be problematic at the site of a wound since the body relies on a consistent source of oxygen and nutrients in its effort to heal. What is more difficult to understand is the way in which the nervous system is implicated in the wound healing process. 

In March of 2019, Dr. Adam Johnston received funding from the Canadian Institutes of Health Research to study peripheral neuropathy in patients with chronic wounds. This type of ailment to the nervous system is prevalent in individuals with Type II Diabetes and therefore, could be implicated in the development of chronic wounds commonly observed in these patients. When considering how these wounds develop, Dr. Johnston said that the role of the nervous system is often overlooked. 

“What they don’t really appreciate is ‘Does [peripheral neuropathy] influence how the skin heals itself?’ and that’s really what we’re studying because we have some data that has demonstrated that if you don’t have enough nerves in and around that wound area, then the wound doesn’t heal well.”

Peripheral neuropathy is characterized by damaged sensory nerves in the peripheral nervous system. The result is the loss of sensation in peripheral areas, most commonly in appendages such as the fingers or toes, a symptom often reported by Type II Diabetes patients. Since diabetics suffer from chronic wound development and peripheral neuropathy, the interplay between these factors can be studied in individuals with this condition. Dr. Johnston and his team hope to gain a better understanding of how cells communicate with each other in the effort to heal a wound and how this process fails in diabetics.

For both patients and clinicians, the treatment of a chronic wound is a difficult and costly procedure. In fact, the treatment of these wounds is thought to be a multi-million dollar burden on the Canadian health care system. From both a health-related and economic standpoint, it is very important that improved treatment methods be developed in an effort to lessen the suffering of diabetics and to mitigate the financial consequences that result from the current cost-inefficient therapeutic regimes.


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