WOUND CARE AND DIABETIC ULCER TREATMENT

THE PATHOPHYSIOLOGY OF DIABETES, AND IMPACT ON TISSUE DAMAGE & VASCULAR HEALTH

The effects of diabetes mellitus on the body are complex, but the primary mechanism of tissue damage is protein glycation. This process occurs when excess glucose enters cells, drawing in water and causing osmotic swelling. The result is arteriole constriction, reduced oxygen delivery, and eventual cell dysfunction or death.

How Diabetes Affects the Body

🔹 Blood Vessels (Diabetic Angiopathy):

The smooth muscle cells in arteriole walls absorb glucose without insulin, leading to arteriole constriction and reduced capillary oxygen delivery.

🔹 Nerves (Diabetic Neuropathy):

High glucose levels convert into aldose reductase, which damages Schwann cells in nerves, leading to nerve dysfunction and loss of sensation.

🔹 Kidneys (Diabetic Nephropathy):

Glycation in the kidneys causes albumin leakage from glomeruli, leading to proteinuria and elevated creatinine, which can progress to kidney failure.

🔹 Eyes & Capillary Damage (Diabetic Retinopathy):

Similar osmotic glycation damage occurs in the retina, which can lead to blindness if left uncontrolled. Excess glucose is converted into sorbitol, which damages capillaries and causes oxygen loss and albumin leakage—a major factor in chronic wounds.

Why Diabetics Are at High Risk for Foot Ulcers

The plantar skin of the feet requires significant oxygen supply, making it highly vulnerable to diabetic foot ulcers due to diabetic angiopathy (vascular damage).

The feet, eyes, kidneys, and nerves are among the body’s most oxygen-dependent tissues.

Because diabetic vascular disease reduces oxygen delivery, diabetic foot ulcerations, neuropathy, nephropathy, and retinopathy are common complications.

Managing blood sugar levels, improving circulation, and utilizing advanced wound care treatments are critical for prevention and treatment of diabetes-related complications.

Understanding these mechanisms, and early intervention can help preserve vascular health, nerve function, and organ integrity.

THE PATHOPHYSIOLOGY OF DIABETIC FOOT WOUNDS - ULCERS

Diabetic foot ulcers result from diabetes-induced microvascular damage (diabetic angiopathy), where glycation restricts oxygen flow to the skin, leading to tissue breakdown. This lack of oxygen causes tissue breakdown, making the feet vulnerable to ulceration and slow healing.

Why Wound Healing Is Impaired in Diabetes

• Hyperglycemia (high blood sugar) causes protein glycation, restricting oxygen supply.
• Neutrophils (first responders) cannot escape the blood vessels to fight infection.
• Macrophages fail to release proper growth factors, preventing fibroblast activation.
• New capillary and tissue formation is significantly delayed, leading to chronic wounds.

This impaired healing process explains why diabetic foot ulcers are slow to recover and require specialized treatment approaches to restore proper function.

➡️ Dr. Reed’s advanced wound care protocols address these underlying diabetic complications, promoting faster and more effective healing.

HOW DIABETES EFFECTS FIGHTING INFECTIONS AND WOUND HEALING

Hyperglycemia, or high blood sugar, has two major effects on the wound healing process that contribute to poor healing and increased risk of complications, such as infection and amputations.

1. Restricted Microvascular Flow

• Glycation caused by excess glucose constricts the arterioles, reducing blood flow to the injured tissue.
• Under normal conditions, arterioles dilate to ensure proper blood supply when a wound occurs. However, in diabetic patients, this restricted blood flow prevents the release of essential growth factors (such as platelet-derived growth factor), which are critical to initiate wound healing.
• As a result, the wound becomes stagnant, prone to infection, and unable to progress through the necessary healing stages.
• Oral antibiotics and basic wound care (like bandage changes) often fail to address the root cause, leading to deep bone infections (osteomyelitis) and amputations.

2. Leukocyte Dysmotility

• Leukocytes (white blood cells), which are crucial for fighting infection and clearing dead tissue, become enlarged due to excessive glucose.
• This dysmotility prevents these cells from properly migrating out of the arteriole walls to the site of injury.
• The inability of white blood cells to reach the wound site leads to poor infection control and delayed tissue repair.
• Without proper immune response, the wound is more susceptible to infection, and the infection can spread, threatening deeper tissues, including the bones.



• Supporting Studies:
• Spampinato SF, et al. 714-528-3668: Discusses the treatment of impaired wound healing in diabetes, emphasizing the role of old drugs. (Pharmaceuticals (Basel). 2020 Apr 1; 13(4):60)
• Pezhman L, Tahrani A, Chimen M. 714-528-3668: Explores dysregulation of leukocyte trafficking in Type 2 diabetes and potential therapeutic avenues. (Front Cell Dev Biol. 2021 Feb 22; 9:714-528-3668

These two key issues—restricted blood flow and impaired immune response—lead to wound stagnation, increased risk of infection, and potential for osteomyelitis (bone infection), which is why wounds in diabetic patients often fail to heal and may ultimately require amputation.

By addressing these underlying issues, advanced wound care treatments like microvascular vasodilation and wound stimulation technologies can help reverse these complications and promote healing.

DIABETIC NEUROPATHY (DNP) CHALLENGES AND NITROGLYCERIN

Diabetic neuropathy remains one of the most significant and challenging complications of diabetes. It typically manifests as neuropathic pain or numbness in the extremities, which often significantly impacts the quality of life.

Neuropathy pain and numbness remain major complications of diabetes, often resistant to traditional treatments like Lyrica or Gabapentin, which only mask pain and can cause sleep disturbances.

For over 33 years, Dr. Mark Reed has used nitroglycerin patches to increase microcirculation in the lower extremities, reversing oxygen ischemia—similar to its effect in treating angina. Applied for 12 hours daily, these patches have been highly effective in reducing or eliminating radiating burning pain in the feet.

Additionally, for wound healing, Dr. Reed places an extra patch near the ulcer to increase oxygenation, improve white blood cell migration, and accelerate tissue repair. Research supports the significant pain reduction achieved with transdermal nitroglycerin. (Taheri A, Farbood et al., J Diabetes Metab Disord, 2015).

Traditional Treatments

• Common medications for diabetic neuropathic pain include Lyrica and Gabapentin. While these drugs can provide pain relief, they mask the symptoms rather than addressing the root cause.
• These medications are non-narcotic pain relievers but are often associated with side effects such as sleep disturbances and other complications.

Nitroglycerin for Neuropathy and Wound Healing

• A breakthrough treatment that addresses the root cause of diabetic neuropathy involves Nitroglycerin, which has been used for over 75 years to treat oxygen ischemia in conditions like angina pectoris through microcirculatory vasodilation.
• Dr. Mark Reed has successfully employed transdermal Nitroglycerin patches for over 33 years to improve microcirculation in the lower extremities.
• The patches are worn for 12 hours a day and help reverse the ischemic effects in the feet, significantly reducing or even eliminating the burning pain often associated with diabetic neuropathy.
• Studies, such as those by Taheri et al., have demonstrated the pain-reducing effects of transdermal Nitroglycerin for diabetic peripheral neuropathy.

Nitroglycerin's Role in Wound Healing

• In addition to pain relief, Nitroglycerin is used to enhance oxygenation in the area surrounding diabetic foot ulcers.
• The increased oxygen supply helps improve white blood cell migration to the wound, boosting infection control and stimulating healing.
• By applying an additional patch proximal to the ulcer, the treatment helps the body naturally promote healing by enhancing the oxygen delivery to tissues involved in the wound healing process.

This approach offers a more comprehensive solution for managing both neuropathic pain and chronic wound healing in diabetic patients, addressing the underlying circulatory issues rather than just masking symptoms. For more information click here!

DIABETES AND LARGE VESSEL PERIPHERAL VASCULAR DISEASE

In 50% of diabetic patients, large vessel disease (atherosclerosis) occurs alongside microvascular damage caused by hyperglycemia. This condition results from atherosclerotic plaque—a buildup of fibrous material, lipids, and cholesterol—often affecting arteries in the thigh and below the knee, increasing the risk of limb loss.

Atherosclerosis worsens oxygen deprivation in the feet by restricting blood flow to the microcirculation (arterioles and capillaries), compounding the effects of diabetes-induced ischemia. Every diabetic patient with weak pulses or neuropathy should be screened for peripheral vascular disease (PVD). If arterial Doppler studies and ankle-brachial index (ABI) tests indicate reduced circulation, revascularization may be required.

A simple analogy: Large arteries are like the main water pipe supplying a house, while arterioles are the smaller pipes leading to faucets. Diabetes constricts these smaller vessels, preventing oxygen delivery. Nitroglycerin patches help by dilating arterioles, restoring oxygen flow to tissues, reducing complications, and improving healing.

Atherosclerotic Disease in Diabetes

In addition to the well-known effects of hyperglycemia on the microcirculation, diabetic patients often experience large vessel disease (LVD) due to atherosclerosis.

Atherosclerosis in diabetics accelerates due to factors such as chronic high blood glucose, which contributes to the formation of plaques in the arteries. These plaques consist of a fibrous cap that overlying a core of necrotic cellular debris, foam cells, lipid, and cholesterol crystals. Atherosclerosis typically begins at the trifurcation below the knee, impacting arteries like the popliteal artery, which can restrict blood flow to the lower extremities.

The Impact on Diabetic Patients

• Atherosclerosis causes thickening or hardening of the arteries, resulting in arterial occlusion or narrowing that severely restricts blood flow to tissues.
• This is compounded in diabetic patients, who already have microvascular damage due to hyperglycemia-induced glycation, leading to oxygen ischemia in tissues like the feet.
• The combination of large vessel disease and microvascular damage places diabetic patients at high risk of limb loss due to inadequate blood supply, impaired tissue healing, and increased risk of infection.

Pathophysiology Analogy

An analogy to understand this vascular compromise is comparing the human circulation system to plumbing:

• Large Arteries = Main six-inch pipe supplying water to the house. These large vessels are impacted by atherosclerosis but not by hyperglycemia.
• Arterioles and Capillaries = Smaller three-quarter inch pipes supplying water to faucets. These smaller vessels are impacted by hyperglycemia-induced microvascular damage, leading to vasoconstriction and impaired oxygen delivery.

In diabetes, the smaller pipes (arterioles) become constricted due to glycation, restricting blood flow to the tissues. Nitroglycerin works as a vasodilator, helping to relax the constricted arterioles and improve oxygenation to the tissues.

Screening for Peripheral Arterial Disease (PAD)

Given the significant risk of large vessel disease in diabetic patients, it’s essential to screen for peripheral vascular disease (PVD), which is commonly associated with poorly palpable pulses or diabetic neuropathy. The following diagnostic tools help identify PAD:

1. Arterial Doppler Study: This test helps assess blood flow in the arteries of the legs.
2. Ankle-Brachial Index (ABI): The comparison of blood pressure in the arm to the ankle or toe can help identify abnormalities in blood flow and confirm the presence of PVD.
3. Referral for Revascularization: If ABI or doppler results are abnormal, a vascular specialist should evaluate the patient for potential revascularization to restore blood flow to the affected tissues and prevent limb loss.

This comprehensive approach to understanding and managing diabetic vascular disease underscores the importance of identifying both microvascular and large vessel issues in order to provide effective treatment and prevent severe complications like limb amputation.

UNDERSTANDING GLYCATED HEMOGLOBIN (HBA1C) MONITORING

Glycated hemoglobin (HbA1c) is a key marker for assessing osmotic microcirculation ischemic cell damage from high blood sugar (glycation). Since red blood cells have a 120-day lifespan, HbA1c provides a reliable measure of medium-term blood sugar control in diabetes.

The goal for diabetic patients is to maintain HbA1c below 6, achieving diabetic remission—a state where microcirculation damage is minimized. This helps prevent serious complications, including:

✅ Diabetic foot ulcers

✅ Neuropathy (nerve damage)

✅ Retinopathy (vision loss)

✅ Nephropathy (kidney disease)

✅ Cardiopathy (heart disease)

Monitoring and controlling HbA1c levels is essential for long-term health and complication prevention in diabetes.

One of the most important assessments of diabetic osmotic microcirculation ischemic cell damage from hyperglycemia (glycation) is the damage occurring in the red blood cells by measuring glycated hemoglobin. The Red blood cells have a consistent lifespan of 120 days and are accessible for measurement of amount of damage occurring to cells as glycated hemoglobin. Measurement of HbA1c that is the predominant form of glycated hemoglobin, enables medium-term blood sugar control to be monitored in diabetes. The goal of every diabetic patient is to have their glycated hemoglobin results to below 6 that would place a diabetic patient in what is defined as “diabetic remission” where the effects of damaging tissues from microcirculation ischemia would be controlled to prevent the long-term complications of diabetic foot ulcerations, retinopathy, neuropathy, nephropathy and cardiopathy.

Understanding Glycated Hemoglobin (HbA1c)

Glycated hemoglobin (HbA1c) is a critical marker in monitoring long-term blood glucose control in diabetic patients. Hemoglobin is a protein found in red blood cells that carries oxygen throughout the body. When blood glucose levels are high, glucose molecules bind to hemoglobin, forming glycated hemoglobin (HbA1c). This process is known as glycation, which can lead to cellular damage in various tissues.

• HbA1c Test: The HbA1c test measures the percentage of hemoglobin that has glucose attached to it, reflecting the average blood sugar levels over the past 2-3 months. Since red blood cells have a lifespan of about 120 days, the HbA1c provides a reliable measure of medium-term blood sugar control.
• Normal HbA1c Levels: For most individuals, the normal range for HbA1c is typically between 4% and 5.6%. Diabetic patients should aim for a target HbA1c level of below 6%, which is considered diabetic remission.

Diabetic Remission and Its Importance

• Achieving an HbA1c level below 6% indicates good blood sugar control and suggests that microvascular damage caused by hyperglycemia (such as glycation-induced ischemia) is being minimized.
• Maintaining an HbA1c level below 6% is associated with a reduced risk of developing long-term complications of diabetes, including:
• Diabetic foot ulcerations
• Retinopathy (damage to the eyes)
• Neuropathy (nerve damage)
• Nephropathy (kidney damage)
• Cardiopathy (heart disease)



The Goal of Diabetic Remission

• The ultimate goal of diabetes management is to achieve diabetic remission, where blood sugar levels are well-controlled, and the damaging effects of microvascular ischemia (caused by hyperglycemia and glycation) are minimized. This helps to prevent or delay the onset of complications like foot ulcers, nerve damage, and other vascular complications.
• Aiming for HbA1c below 6% requires a combination of consistent blood sugar monitoring, medication, lifestyle changes (including diet and exercise), and sometimes specialized treatments to reduce glycation effects on tissues.

By achieving diabetic remission through careful control of HbA1c levels, diabetic patients can significantly reduce their risk of long-term complications, improving overall quality of life and health outcomes.

OC Center for Wound Healing & Foot Care addresses a wide range of wound types, each requiring specific care and treatment protocols to ensure optimal healing. The following are the types of ulcers and wounds commonly treated:

1. Diabetic Wounds

• Diabetic foot ulcers are common among individuals with diabetes due to the microvascular damage caused by hyperglycemia. These wounds often occur in areas of pressure or trauma, and effective management includes controlling blood glucose levels, promoting circulation, and managing infection.

2. Pressure Ulcers (Bedsores)

• Caused by prolonged pressure on the skin, usually in immobile patients, these ulcers can range from mild skin damage to deep, necrotic tissue. Treatment involves relieving pressure, improving circulation, and preventing infection.

3. Venous Stasis Ulcers

• Typically seen in individuals with chronic venous insufficiency, these ulcers often occur on the lower legs. They result from poor circulation and are often treated with compression therapy, as well as managing any underlying venous disease.

4. Skin Lacerations

• Lacerations caused by trauma, accidents, or surgical procedures can be treated by cleaning, debridement, and suturing or using other wound closure methods. Infection prevention is crucial.

5. Traumatic Injuries

• Any injury from accidents, falls, or other physical trauma that results in broken skin or deeper tissue damage is treated with appropriate wound cleaning, debridement, and sometimes surgical repair to ensure proper healing.

6. Ischemic Ulcers with or without Gangrene

• Ischemic ulcers are caused by poor blood flow due to narrowed or blocked arteries (often due to atherosclerosis). If left untreated, these ulcers can progress to gangrene (tissue death). Treatments often involve revascularization procedures or amputation if gangrene has set in.

7. Post-Surgical Incision Wounds

• After surgery, patients may develop wounds or incisions that require specialized care to prevent infection and promote healing. This includes careful dressing changes and monitoring for signs of infection or complications.

8. Infected Wounds

• Infected wounds can result from surgical procedures, trauma, or chronic conditions like diabetes. They require appropriate antibiotics, wound cleaning, and debridement to remove dead tissue and promote healthy tissue regeneration.

9. Post-Cancer Radiation Wounds

• Radiation therapy for cancer can cause skin damage, leading to radiation burns or wounds that require special care to soothe, heal, and prevent further damage. Treatment often includes topical ointments, wound dressings, and managing the underlying radiation effects.

10. Lymphedema Ulcerations

• Lymphedema, which causes swelling in the limbs due to fluid accumulation, can lead to ulcerations. Treatment often involves compression therapy, elevation, and careful management of skin integrity to prevent infection and further injury.

11. Burn Wounds

• Burns, depending on severity, require immediate cooling, cleaning, and dressing. Severe burns may need more complex treatments such as skin grafts or surgical repair to promote healing.

Treatment Protocols for Various Ulcers

Each of these wound types has specific care requirements to promote healing and prevent complications like infection or tissue death. OC Center for Wound Healing & Foot Care utilizes advanced technologies such as negative pressure wound therapy, hyperbaric oxygen therapy, and skin grafts in combination with traditional wound care methods to optimize healing outcomes for each patient.

Wound Care Interventions for Chronic Wounds

Effective wound care involves a variety of therapeutic interventions designed to promote healing and address underlying factors contributing to wound stagnation. These treatments are used when a wound has not shown significant healing after 30 days or when chronic conditions complicate the healing process, such as diabetic ulcers, pressure sores, or venous stasis ulcers. Below are the advanced treatments commonly utilized:

1. Topical Wound Medications

• Purpose: Prevents bacterial growth and infection in the wound.
• Examples: Antiseptic creams, antibiotics, or silver sulfadiazine can be applied to minimize bacterial contamination and promote a sterile environment.

2. Hydrogel Dressings

• Purpose: Maintains moisture balance in the wound and allows observation of exudate drainage.
• Benefit: These dressings are ideal for wounds with dry or necrotic tissue and help promote healing by preventing desiccation of the wound bed.

3. Debridement

• Purpose: Removal of non-viable, infected, or necrotic tissue from the wound site.
• Benefit: Promotes the release of platelet-derived growth factors (PDGF) and enables the wound to enter the next phase of healing by preparing the tissue bed for new tissue growth.

4. Skin Substitutes (e.g., Amniotic Membrane Grafts)

• Purpose: These biologic dressings provide a scaffold for tissue regeneration.
• Benefit: They offer temporary protection and support while encouraging tissue growth and reducing the chance of infection.

5. Off-Loading (e.g., Total Contact Cast, Walking Cast, or Pneumatic Walking Boot)

• Purpose: Reduces pressure on the ulcerated area, improving circulation and oxygenation.
• Benefit: These devices help re-establish proper blood flow to the affected tissues, promoting healing, particularly in diabetic foot ulcers.

6. Hyperbaric Oxygen Therapy

• Purpose: Increases oxygen concentration in tissues by having the patient breathe 100% oxygen in a pressurized chamber.
• Indication: Only used for chronic, diabetic osteomyelitis (bone infection).
• Benefit: Enhances the body’s ability to fight infection and promotes the healing of difficult-to-treat wounds.

7. Nitroglycerin / Sildenafil Citrate (Arteriole Dilators)

• Purpose: These medications dilate the arterioles, increasing oxygenated blood flow to the wound site.
• Benefit: This is particularly effective for improving microcirculation in diabetic ulcers, enhancing the oxygenation needed for tissue repair and reducing pain.

8. Wound Vacuum Assisted Closure (VAC)

• Purpose: Uses negative pressure to promote the formation of granulation tissue and reduce wound size.
• Benefit: Encourages tissue growth, reduces edema, and aids in the closure of chronic wounds over fascia, muscle, tendon, and bone.

9. Platelet-Derived Growth Factors (PDGF)

• Purpose: Derived either from the patient's own blood or through recombinant technology (yeast-based), these growth factors stimulate tissue regeneration and wound healing.
• Benefit: PDGF accelerates the inflammatory phase of wound healing, stimulates cell proliferation, and enhances the formation of new blood vessels.

10. Autologous Skin Graft Transfers

• Purpose: Uses the patient’s own healthy skin to cover the wound, providing a natural barrier to infection.
• Benefit: Promotes quicker healing and minimizes the risk of rejection or allergic reactions, as the graft is from the patient’s own body.

11. Sliding Metatarsal Head Osteotomy

• Purpose: A surgical procedure to rebalance pressure across the metatarsals, typically done in diabetic patients with foot deformities.
• Benefit: Helps distribute the forces during walking, reducing the formation of pressure ulcers and improving foot function.

12. Percutaneous Achilles Tendon Lengthening

• Purpose: A procedure to lengthen the Achilles tendon to off-load pressure from the forefoot.
• Benefit: Helps prevent or treat ulcers caused by excessive pressure and deformities in the foot.

13. Compressive Dressings

• Purpose: Reduces edema (swelling) and helps the wound heal by applying a uniform, controlled pressure.
• Benefit: Particularly useful for venous ulcers and other types of wounds where edema is a contributing factor to delayed healing.

14. Gradient Compression Stockings

• Purpose: Reduces lymph edema and enhances blood flow in patients with chronic venous insufficiency or lymphatic issues.
• Benefit: These stockings help reduce swelling, improve circulation, and support the healing of ulcers.

Each wound type and patient condition requires an individualized treatment plan, which may involve one or several of the above advanced wound care interventions. The goal is to optimize tissue healing by addressing the underlying causes of the wound, improving circulation, and preventing infection, all while minimizing the risks of complications like osteomyelitis or amputation.

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