Impaired wound healing in Diabetes is triggered by hyperglycemia, chronic inflammation, micro- and macro-circulatory dysfunction, hypoxia, autonomic and sensory neuropathy, and impaired neuropeptide signaling. 

The normal wound healing includes four programmed phases: hemostasis, inflammation, proliferation, and remodeling, though these phases are continuous and overlapped. However, diabetes results in delayed wound healing via multifarious biological mechanisms, which affect the transition of the organized phases. A series of mechanisms comprising disordered growth factor production, impaired angiogenesis, imbalanced lymphocyte proliferation, and macrophage dysfunction may contribute to the delayed diabetic wound healing.

Conventional therapeutic strategies of diabetic wound include glucose and infection control, debridement, wound off-loading, dressings, and revascularization. However, many of diabetic wounds are refractory to current treatments and fail to heal, persist for months or years, ultimately lead to amputation.

So, delayed wound healing in Diabetes is not only due to Hyperglycemia. Risk factors include  include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, immunosuppression, nutritional status, radiation therapy, and vascular insufficiencies.

The Most Important Factors Affecting Wound Healing

Advanced age

As you get older, hormonal changes and the cumulative effects of photoaging (sun damage) combine to leave your skin drier, thinner, more delicate, and less elastic. Besides leaving your skin more susceptible to injury, these age-related changes can substantially slow the healing process; older tissues simply don’t repair and regenerate as quickly as younger tissues.  

Excess body weight

People who are very overweight or obese are more likely to experience delayed wound healing as well as wound complications, including infection. Being overweight places more pressure on the wound itself, effectively decreasing the amount of nutrients and oxygen it receives to fuel the healing process. Wounds that occur within skin folds also tend to heal more slowly due to continuous friction and tissue breakdown.  

Chronic illness

Chronic conditions are a major factor in impaired wound healing for many people. Although the mechanisms at play tend to be numerous and varied, most persistent illnesses delay healing by interfering with one or more aspects of the immune system response. Diabetes can slow the healing process by making white blood cells less effective. Diabetes, cardiovascular disease, and other conditions that give rise to poor circulation may also make it harder for your body to deliver oxygen, nutrients, and reparative cells to an injured area.   

Stress

Stressors, such as anxiety and depression can impair wound healing by deregulation of the immune system. Psychological stress has been found to have profound effects on the hypothalamus, psychological responses (health-damaging behaviors), and autonomic nervous system. Cortisol, a stress-induced hormone can also impair wound healing by interfering with the production of pro-inflammatory cytokines. 

Obesity

The accumulation of fatty or adipose tissue in obese persons can impair the rate of wound healing. According to data from the CDC, obesity had a prevalence of 42.2% among adults in the United States between 2017 and 2018. It is known to increase the risk of many health conditions, including coronary heart disease, hypertension, and cancer, and also contributes to diabetes. Higher levels of glucose in the blood promote vasoconstriction, which results in low perfusion to the lower extremities. 

Medication

Use of certain medications, such as chemotherapy drugs and Non-steroidal Anti-inflammatory Drugs (NSAIDs) may interfere with wound healing processes, such as platelet formation or inflammatory responses. Chemotherapy drugs, used for the treatment of cancer, can cause venous irritation, delayed cellular migration, and lower collagen synthesis and fibroblast proliferation. Moreover, research suggests that NSAIDs like aspirin and Ibuprofen commonly used for pain relief can have a negative effect on wound healing.

Poor nutrition

Optimal wound healing requires optimal nutritional support. People who eat an unhealthy diet that doesn’t meet their basic nutritional needs are more likely to experience the kind of slow or delayed healing that can lead to chronic wounds or injuries that take longer than three months to heal completely. 

Lack of Hydration

A lack of moisture at the surface of a wound can halt cellular migration, decrease blood oxygenation, and seriously delay wound healing. Dehydration caused by either a depletion of sodium or water can delay all aspects of the healing process. 

Poor Blood Circulation

Since blood delivers the necessary components to tissue for the wound healing process to take place, people with low blood pressure or vascular disease can have problems with delayed healing. Blocked or narrowed blood vessels or diseases of the heart, kidneys and lungs can also cause issues in the body delivering vital wound healing components, including white blood cells and adequate oxygen, to wounded tissues.

Edema

While most traumatic injuries cause some tissue swelling, excessive edema can increase the pressure on blood vessels, resulting in poorer blood circulation in the wound area. Tissue swelling can be caused by heart conditions or blood vessel problems. Compression therapy is often effective at transporting fluids back into the circulatory system to reduce edema so proper healing can occur.

Repeated Trauma

Wounds that continue to be reinjured due to shear force or pressure against a surface can have their healing process delayed or even stopped. Repetitive trauma often occurs with bed-bound patients and can be treated by careful repositioning on a regular schedule or use of offloading or protective devices under the supervision of a health care professional.

Unhealthy habits

People who smoke cigarettes and drink alcohol are more likely to experience slower healing rates than those who don’t smoke or drink. Both habits inhibit wound healing by suppressing your body’s inflammatory response and restricting the flow of blood, oxygen, nutrients, and reparative cells to the injured area. Other patient behaviors that can affect wound healing are a lack of adequate sleep, failure to elevate the affected area, not properly cleaning the wound, using inadequate wound dressing procedures, not keeping the wound moist and not moving enough.