INTRODUCTION:

Diabetes mellitus is a metabolic, endocrine disorder results for a relative or absolute deficiency of insulin. Prevalence of diabetes is increasing globally¹ and rate of increase is higher in developing countries¹. “Health is Wealth”, according to this saying if wealth is lost nothing is lost but if health is lost everything is lost. Therefore, when an individual is in diseased condition, he should try to get out of it without endangering his/ her health². According to WHO (1994) Diabetes Mellitus is characterised by hyperglycaemia and disturbance of the carbohydrate, fat and protein metabolism that is associated with the absolute or relative deficiencies of insulin action or secretion³. Extensive epidemiological surveys have indicated that between 40% and 70% of all lower extremity amputations are related to diabetes. This means that every 30 seconds a lower limb is lost to diabetes⁴.

Diabetes is a chronic disease that is strongly associated with both micro vascular and macro vascular complications resulting in organ and tissue damage in approximately one third of people with diabetes resulting in significant morbidity and mortality. Persistent high blood glucose levels due to poor management of disease have been attributed to the development of complications. Diabetes is a major factor that influence the symptomatology of patients with ACS, especially in elderly due to their comorbidities^5,6. In 2014 the global prevalence of diabetes was estimated to be 9% among adults aged 18+ years¹. In 2012, an estimated 1.5 million deaths were directly caused by diabetes⁷. Total deaths from diabetes are projected to rise by more than 50% in the next 10 years. WHO projects that diabetes will be the 7th leading cause of death in 2030 (WHO)⁸. The management of diabetes poses a challenge to the medical and nursing staff as well as to the patients themselves. Since diabetes is a chronic disease, most diabetic patients need to continue their treatment for the rest of their lives. The emphasis is usually therefore, on the control of the condition through a tight schedule of blood glucose and urine sugar monitoring, medication and adjustment to dietary modification⁹.

The wounds inflected on the foot remains untreated can lead to the severe infection likely to be person with diabetic condition, the diabetic condition favors the development of ulcer as high sugar level is also reason for the cause of neuropathy.¹⁰ A diabetic foot ulcer is such an open lesion or sore located on the feet of patients diagnosed with diabetes that extends to penetrate through the epidermal layers, involving at least a portion of the dermis. It occurs as a result of repeated trauma or chronic pressure on areas of the foot, which have lost their sensation due to peripheral neuropathy or ischemia from poor circulation. DFUs are associated with high risks of infection, slow healing, and potential complications of amputation if managed inadequately.¹¹

These lesions are those that take place in the feet of a diabetic patient diagnosed with either type 1 or type 2 diabetes. About one-third of the people diagnosed with diabetes will develop at least one foot ulcer within their lifetime.¹² Diabetic foot ulcers affect about 18.6 million patients worldwide and 1.6 million in the US annually. Half of diabetic foot ulcers become infected, and approximately 20% of the infections lead to part or whole amputation of the foot.¹³

Amongst complications from poor diabetes management, there are foot and lower limb ulcers. Failure to heal can lead to the loss of toes, parts of the foot, or parts of the lower leg. Diabetes damages blood vessels throughout the body. Tiny blood vessels in the legs feed into the nerves, and a small leak in them can cause burning pain or numbness in the feet (peripheral neuropathy) and a decreased ability to feel pain. Calluses, blisters, cuts, burns, and ingrown toenails all can cause diabetic foot ulcers. Due to peripheral neuropathy, a patient may not feel these minor injuries, and ulcers may form and enlarge before their presence is realized.⁵Diabetes can also affect larger blood vessels in the legs, leading to poor circulation, known as peripheral artery disease. Healing ulcers may be slow in people with peripheral artery disease. High blood glucose levels also impede healing. Daily foot examination is an important part of diabetes management and can prevent foot ulcers.¹⁴

Types:

There are mainly 3 types of DFU.

A. Neuropathic Ulcer:

These ulcers are caused by peripheral neuropathy, where high blood sugar levels damage nerves for a long period. The nerve damage usually results in a loss of sensation in the feet, thus, cuts, blisters, or other minor injuries may not be detected and become worse with time. Neuropathic ulcers normally occur on the weight-bearing areas of the foot, such as the heel, ball, or tips of the toes^15,16

B. Ischemic Ulcer:

These ulcers are caused by ischemia, which is when part of the body has not had enough blood flowing to it. Diabetes causes damage to the blood vessels in the legs, and this will make there be reduced blood flow. With low circulation, minor wounds or sores on the feet can't heal easily. Ischemic ulcers commonly occur on the edges of the foot or toes.^17,18

C. Neuro-ischemic Ulcer:

These ulcers arise due to a combination of neuropathic and ischemic factors. They are caused due to the presence of neuropathy along with poor circulation of blood. Neuro-ischemic ulcers are tougher to treat because they involve two types of factors: a lack of sensation and poor healing capacity.^17,18

Sign and Symptoms:

The signs and symptoms are explained and examined by the Gardner, Hillis, and Frantz (2009) that gives detailed description of DFU^19,20

A. Classic Signs of Infection:

Increased Pain: This is the increased amount of pain around the ulcer. Pain can be a key sign of infection, even in diabetic neuropathic patients who have lost sensation.

Erythema: This is the redness that occurs around the ulcer. It signifies inflammation and infection. The redness can extend beyond the edges of the ulcer.

Edema: Swelling in the area surrounding the ulcer. This swelling is due to the accumulation of fluid and is a common sign of infection.

Heat: Increased warmth around the ulcer site. This happens due to the body's inflammatory response to infection.

Purulent Exudate: Pus, which consists of dead white blood cells, bacteria, and tissue debris, forms a thick yellowish or greenish fluid. It is a visible indication of infection.

B. Specific Signs for Secondary Wounds:

Serous Exudate: Clear or watery discharge from an ulcer. Although it often is not indicative of the infection, it can be a sign if other characteristics are present.

Sanguinous Exudate: Oozing blood from an ulcer. It may refer to damage to blood vessels and in many cases occurs with secondary infection.

Delayed Healing: When the ulcer heals slower than anticipated. Infections can delay the healing process, thus prolonging the time taken for wound closure.

Colored Granulation Tissue: Tissue within the ulcer that appears abnormal in color, such as dark red, brown, or black. Such discoloration may be indicative of necrosis or infection.

Friable Granulation Tissue: Tissue that bleeds easily when touched. Such tissue is usually indicative of infection and poor wound health.

Bad Odor: Wound emits a bad odor. This odor develops because of the bacteria accumulation and tissue breakdown.

Wound Base Pocketing: A pocket or cavity forms at the base of the wound. The bacteria hide here, and it is therefore a harder infection to fight.

Wound Breakdown: The breakdown of the wound, where the ulcer degrades instead of healing up. This is a complete sign of infection and will need immediate attention.

Evaluation of Diabetic foot ulcer²¹

4. Evaluation of Diabetic foot ulcer:

A. Basic Examination:

i. Occurrence of any infection any conditions like swelling with redness, accumulation of white and yellowish pus.

ii. Duration of wound the wound takes more time than the normal cuts and wounds the healing is rather slow and wound is unaffected after days of infliction.

iii. Depth the ulcer may go into further into sub-cutaneous skin to bones while the superficial ulcer may only damage the skin (upper surface).

B. Examination of Peripheral Artery Disease (PAD):

Person with diabetes is at risk of PAD, which decreases blood flow and slows down wound healing. Non-invasive vascular lab tests include.

i. Ankle Branchial Index ABI is the blood pressure ratio of ankle and Arm that shows the difference in the blood pressure, higher value indicates peripheral artery diseases while lower value may sign of stiffened blood vessels

ii. Toe Branchial index - The ratio of Systolic blood pressure between the big toe to the arm,

iii. Doppler Ultrasound-It is used to assess blood flow through the peripheral arteries. Arterial Plague can be identified using this technique which common in the diabetic patient.

C. Laboratory Diagnostic:

i. Erythrocytes sedimentation - used to detect the inflammation in the cell

ii. C-reactive Protein (CRP): Can also be tested for at an additional cost to determine the level of systemic inflammation.

iii. Blood tests for white blood cell count and procalcitonin can aid in the diagnosis of systemic infection.

D. Imaging Studies:

i. Plain Radiograph (X-Ray) it Frequently used as the first imaging modality to identify gas in soft tissues (indicating gas gangrene) or bony changes consistent with osteomyelitis such as periosteal reaction or bone destruction.

ii. Magnetic Resonance Imaging (MRI): MRI is a gold standard for detection of early bone infection and for evaluating the extent of involvement in case of possible osteomyelitis. MRI is also able to discriminate soft tissue infection from osteomyelitis.

E. Ulcer Classification²²:

Intended to assist accurate risk stratification so therapy may be tailored.

1. Wagner Classification Grade 0 (intact skin) to Grade 5 (gangrene of the whole foot)

2. University of Texas Classification: It takes into account of depth, infection presence, and ischemia.

3. PEDIS System It takes five aspects for the evaluation Perfusion, Extend, Depth, Infection and Sensation which further looked to proceed for the treatment, it is recommended by the International Working Group on Diabetic Foot.

F. Probability of Amputation:

i. The worst ISCHEMIA, extensive infection and if deep tissue the injury level more serious it will also increase the risk of amputation.¹⁶

ii. Multidisciplinary teams (podiatrists, vascular surgeons, endocrinologists, and infectious disease specialists) are often needed to maximize outcomes and salvage the limb.²³

Epidemiology:

Over 550million people worldwide and 37million people in the United States have diabetes. Worldwide, about 18.6million patients suffering from diabetes develop a foot ulcer every year. Up to about 34% of people living with type 1 or type 2 diabetes develop an ulcer on the foot throughout their lifetime. Diabetes in America as estimated, 37million Americans suffer from diabetes. This has also increased with time and it has emerged as one public health concern.²⁴

Diabetic foot ulcer is common and serious complications of diabetes person that is seen mostly in elderly age group. In total, it is estimated that around the world annually, 18.6 million people who have diabetes develop a new foot ulcer. The lifetime risk of developing a foot ulcer in those with either type 1 or type 2 diabetes ranges from 19% to 34%, some complications with serious outcomes, such as infections, hospitalization, amputations of lower limbs, and even death, may arise from the foot ulcers. So, the morbidity and mortality of diabetic foot ulcers emphasize the need for early detection, proper management, and preventive measures.²⁵

Diabetic foot ulcers can be dangerous to the lives of diabetes patients and cause serious complications such as infections and amputations. For example, it is estimated that as many as 20% of those who have developed a DFU, minor (involving only part of the foot) or major (above the foot), will require a lower extremity amputation. Infections and progression ofgangrene are the most common reasons for these amputations, as about 50% of diabetic foot ulcers become infected. Hospitalization is required in about 20% of patients with diabetic foot ulcers, and of those patients, In the untreatable condition of wounds 15-20% will require amputation of a lower extremity.²⁶ More than 150,000 non-traumatic lower extremity amputations are performed yearly on people diagnosed with diabetes in the United States.²⁷

This translates to approximately 1.6 million amputations each year around the world, of which about 33% are major amputations. These figures indicate a huge demand for proper management and prevention strategies in order to decrease risks from diabetic foot ulcers. Proper foot care, early detection, and multidisciplinary treatment can greatly reduce the incidence and severity of such complications.

Inequities in diabetes-related foot complications in the United States. Among Medicare beneficiaries (total sample, 92 929)²⁷with a newly diagnosed diabetic foot ulcer or diabetic foot infection, long-term rates of major lower extremity amputation are higher among those who identify as non-Hispanic Black (3.8%), Hispanic of any race (2.1%), and Native American (5.1%) compared with those identifying as non-Hispanic White (1.5%). 15 Those who identify as non-Hispanic Black and Hispanic of any race have more severe initial diabetic foot ulcers and peripheral artery disease and experience more frequent lower.

Diabetes-related foot complications are a common inequity in the United States. Among 92,929 Medicare beneficiaries with newly diagnosed diabetic foot ulcers or infections, long-term major lower extremity amputation rates were substantially higher for non-Hispanic Black patients (3.8%), Hispanic of any race (2.1%), and Native American patients (5.1%) compared to non-Hispanic White patients (1.5%). These observed disparities are associated with a higher incidence of severe diabetic foot ulcers and peripheral artery disease at the time of first presentation in non-Hispanic Black and Hispanic populations, which increases the likelihood of needing a lower extremity amputation. This points to the critical need for targeted interventions and equitable healthcare practices to address these disparities and improve outcomes across all racial and ethnic groups.^28,29

Mechanism of Wound Healing:

In the early stages of wound healing the Platelets does a significant role by initiating the clot process during hemostasis, these platelets release the growth factors like PDGF and TGF-β that initiate the healing process which leads to the inflammation phase where blood vessels expands and immune cells like macrophage and neutrophils enters to kill pathogens and remove dead cell and tissues, send signals to new healing cells to regenerate the area. Fibroblast makes new tissue via producing collagen, extracellular matrix and other proteins, at the same time new blood vessels form to bring oxygen and nutrient this form new tissue called granulation tissue and in the final phase the collagen (type III which was form initially) replaced by the type I collagen which is more durable and tissue becomes more organized.^30,31

Effect of Diabetes in Wound Healing Process

Diabetes directly affects molecular mechanisms of wound healing by development of chronic and non-healing wounds, production of Hyperglycemia and impaired cytokine disrupt the key cellular functions like macrophage activity, angiogenesis, collagen deposition and even migration of keratinocytes and fibroblasts. Such disruption leads to the reductions of tissue formation and impairs skin repair systems. Accumulation of advanced glycation end-product (AGEs) that modify protein structure like collagen which result in anormal glycosylated collagen ultimately leads to the disrupting tissue repair system, furthermore they increase oxidative stress by production of reactive oxygen species (ROS) can damage the cellular components, reduced level of antioxidants enzymes such as extracellular superoxide dismutase (SOD3) even slow down the healing process.³²

Novel Approach to wound Healing:

Wound Dressing:

The ideal wound dressing should have properties to maintainmoisture, eliminate excess exudates, protect from the infections have antibiotic feature and mechanically durable, hydrogels provide all these functions as benefits it is highly absorbent and maintain the moist environment around the wound its soft material soothe and cool the wound and infected area. Aquaform Hydrogel, DermaGel Hydrogel Wound Dressing. Medline Skintengrity Hydrogel Wound Dressing and Coloplast Baitain Silicone Hydrogel Dressing these are the marketed hydrogels-based wound. dressing products.^33,34

Tissue Engineering:

The idea behind the tissue engineering is to culture a tissue to replace the damaged or diseased cells and tissue of an organ, culturing a tissue is complex process involves selection and isolation of a cell, provide a platform for cell formation (scaffold fabrication), signaling molecules for growth and cellular functions (protein, lipids and nanoamides), device for the cell expansion and growth (bioreactors). Hydrogels are used as the scaffolds in the tissue culture as it can replicate functions as those of natural tissue, it can provide a solid strength and support tissue construct in their 3D frame network. Ibrahim M. El-Sherbiny et al explains hydrogels scaffolds for the tissue culture and design criteria for the hydrogel scaffolds in tissue engineering.^29,30

Silica Aerogels:

They are synthesized by extracting the water molecules from the gels made of silicon compounds process called supercritical drying, after that low density. extremely porous with high surface area material left aka "frozen smoke" due to its light and translucent appearance. It is used in the many industries due to its unique properties like light weight, high thermal insulating properties which is used in the aerospace, construction and electronics and Medical Sciences.^35,36

CONCLUSION:

The Diabetic Foot Ulcer (DFUs) is one most challenging, serious and dangerous complication that is a result of diabetes which most of the people often ignore due to its initially small size and misunderstanding it to a normal wound leads to prolonged hospital stays, infections, amputation and sometimes even mortality. The hyperglycemia which impairs angiogenesis leads to the reductions in immune cell efficiency, alter collagen synthesis and delay the healing process sometimes completely restrict the healing process, turning the wound into a chronic and dead tissue cluster. While there are conventional methods and approach to the DFUs they take lots of time often unable to treat such complication, in the recent years novel approach such as Hydrogel-based dressings, nanomaterial loaded systems, tissue engineering and growth factors therapies are advancing into new areas and they are continuing to develop and research, they show tremendous growth in wound repair and skin restore integrity. Even with technical approach the DFUs spread further and affects more people every year, which leads to the awareness of this complication to the common people and better approach to comprehend this complication.

ACKNOWLEDGEMENT:

We Mr. Shubham Portey and Mr. Vinayak Kaushik confirms sole responsibility for the following: study conception and design, data collection, analysis and interpretation of results, and manuscript preparation. I would also like to thank my guide Ms. Geetanjali Sahu for her continuous guidance and my colleague Ms. Suruchi Prasad for her consistent support throughout completion of this article

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Received on 11.06.2025 Revised on 17.07.2025

Accepted on 16.08.2025 Published on 08.10.2025

Available online from October 17, 2025

Asian J. Pharm. Tech. 2025; 15(4):357-362.

DOI: 10.52711/2231-5713.2025.00052

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.