Diabetic Foot Ulcer: A Historical Overview

Abstract

This chapter reviews the historical discoveries and the evolution of medical practices in the management of diabetic foot ulcers (DFUs). The knowledge acquired by ancient civilizations such as Babylon, China, Egypt, and India was further developed by the Greeks and Romans, who made significant improvements in foot amputations. The Arabs preserved and expanded these records, making them accessible to scientists during the European Renaissance. It was not until the early twentieth century that a better understanding of the complex etiological factors of DFUs began to emerge. A turning moment in the history of DFUs occurred in 1921 with the discovery of insulin, which effectively divided the timeline into two distinct periods: pre-insulin and post-insulin. While the role of revascularization in treating ischemic DFUs was established in the 1950s and 1960s, the importance of offloading was recognized in the 1970s and 1980s. Recently, the focus of DFU management has shifted to prevention, and multidisciplinary care involving podiatrists, nurses, endocrinologists, surgeons, and infectious disease specialists. Through the utilization of advanced technology and innovative therapies, we are now closer than ever to a future where DFUs will no longer pose a threat to patients’ health.

1. Introduction

Studying the history of medicine enables us to understand the historical development of diabetic foot ulcers, to learn from the successes and failures of past medical interventions, to identify the gaps and challenges in current medical research and practice, and to anticipate the future trends and needs in medical innovation and care. Medical history, like other arts and sciences, is an ongoing and continuous journey. The knowledge and techniques we possess today did not emerge suddenly, but rather evolved over centuries through the accumulation of observations and experiments. The flourishing of medical practice throughout various historical civilizations serves as a testament to the stability they achieved.

The understanding of diabetic foot ulcers has been greatly shaped by countless discoveries throughout centuries, ranging from the prehistoric era all the way to the present day. Nevertheless, historical records pertaining to diabetic foot ulcers are scarce, primarily due to their frequent classification as a type of gangrene or foot infection. The discovery of insulin in 1921 represents a great milestone in the history of diabetic foot as individuals with diabetes have been able to enjoy longer lives, resulting in a significant increase in the prevalence of diabetic foot ulcers. This milestone marks a clear division in the history of diabetic foot ulcers, separating it into two distinct eras: the pre-insulin and post-insulin periods.

• The pre-insulin era, which spans from the ancient times to the early twentieth century, when diabetes was a fatal disease and foot ulcers were often overlooked and treated with ineffective remedies or improper dressings. Medical science has evolved and progressed over time through different historical periods, including the prehistoric era before written records, as well as ancient civilizations such as Babylon, China, Egypt, and India. The first descriptions of diabetic foot ulcers date back to ancient Egypt, India, and Greece. The term “diabetes” was coined by the Greek physician Aretaeus of Cappadocia in the second century AD. The Greeks and Romans played a crucial role in establishing the foundations for the fields of dressing, debridement, and amputations. The Arabs played a pivotal role in the preservation, translation, and expansion of medical knowledge from ancient civilizations. Moreover, they made significant original contributions to various fields of medicine. Arab surgeons were responsible for inventing or enhancing numerous surgical instruments including scalpels, forceps, scissors, needles, syringes, and catheters. They recognized the importance of debridement, the removal of foreign bodies, and the utilization of sterile dressings to maintain a moist environment to enhance healing, described the use of topical medications made from natural substances, such as honey, and used sutures made of animal gut. The European Renaissance stimulated curiosity, creativity, and innovation among physicians. They sought to better understand the human body and its functions, leading to new discoveries and innovations that laid the foundations for modern medicine. During the wars of that era, surgeons gained significant expertise in the treatment of firearm-inflicted wounds.

• The post-insulin era, which spans from the discovery of insulin in 1921 to the present time, when diabetes became a chronic condition and foot ulcers became a major complication. The introduction of insulin therapy improved the treatment of diabetes and its complications, but also exposed the patients to long-term metabolic and vascular disorders that increased the risk of foot ulcers. The role of ischemia and peripheral neuropathic disease in diabetic foot ulcers was elucidated. The first classification systems for diabetic foot ulcers were proposed by Meggitt-Wagner in 1976 and University of Texas in 1996. From the late twentieth century to the present day, diabetes became a global epidemic and foot ulcers became a major public health problem. The role of glycemic control, offloading, debridement, wound dressings, antibiotics, revascularization, and education in diabetic foot ulcer prevention and treatment was established by various randomized controlled trials and meta-analyses. The multidisciplinary approach to diabetic foot care was pioneered by the brilliant work of Elliott Joslin in the first half of the twentieth century. This innovative approach changed the way we manage diabetes, as it focused on numerous aspects of diabetes management.

2. The prehistoric era

Amazingly, the care for wounds in prehistoric times was universal in some sense. The techniques employed in various regions of the world are remarkably similar, including the utilization of herbal medicines, the application of astringent or disinfectant-acting powders and infusions, protective bandaging, heat, and massage, as well as the use of naturally occurring styptic chemicals to control bleeding [1]. Wound care encompassed wound cleansing and dressing, provision of pain relief, and the potential application of natural substances like honey or plant-derived poultices, cloths, cobwebs, and even dung [2]. Physicians were unaware of the presence of bacteria and other germs, and the importance of keeping them away from wounds, until the emergence of germ theory in the late 1800s. However, the natural hardiness of the ancient and the absence of the extremely resistant germs encountered in the recent century could be the main causes of favorable outcomes, in addition to the clever techniques that were frequently employed.

In Paleolithic deposits found in both France and England, bone needles with eyelets were discovered. These needles were synthesized from bone splinters and were used to close wounds. Similarly, American Indian tribes utilized sinew and bone needles to create sutures. The needles were left in place while the thread was wound around them. This technique can be likened to the skewer technique, where the needle is inserted, and the thread is wrapped around it. Remarkably, this technique persisted until the late Renaissance period [3]. The Dakota Indians potentially utilized a drainage technique by inserting wicks crafted from soft tree bark to treat their wounds. Moreover, they employed a unique syringe made from a feather quill and a bladder to cleanse the wounds thoroughly [4].

Colonists discovered that natives in Australia could sew up wounds and encapsulate shattered bones in mud to heal them. Medical historians think that these abilities existed throughout prehistory. In Victoria, Australia, the locals preferred bleeding to cleanse wounds. They had developed a practice that involved promoting blood flow through suction, adjusting posture, and massaging the affected tissues. After effectively cleansing the wound using these methods, they would apply a lump of resin as a dressing. Interestingly, this tribe also acknowledged the potential danger of retained wound secretions and would reopen the wound if it closed prematurely. The Indigenous people of Australia utilized clay to treat wounds, while in Europe, tar has been a cherished and customary folk dressing. Alternatively, fresh leaves are occasionally employed as dressings, while at other times, a poultice made from herbs, or the tender bark of trees is applied to the wound.

In various parts of the world, including India, East Africa, and Brazil, termites or ants were utilized to close wounds, specifically abdominal wounds. This technique, which was one of the most astonishing practices of that era, involves pressing the edges of the wounds together, allowing the termites to bite through them. The strong jaws of these insects effectively keep the margins of the wound in close alignment, acting as metal clips. Once their task is complete, the insects’ bodies are then separated from the wound [5].

The Maasai people also utilized thorns for suturing wounds. They would wrap a strip of durable vegetable fiber around the thorn in a figure-eight pattern, applying it in succession to approximate the wound. Firstly, they would cleanse the wound with a specific herbal juice, followed by the insertion of a hot metal to burn the tissues and control bleeding. While applying a poultice made of cow dung and dust to a lesion may seem less unpleasant, it still represents a rudimentary form of wound care. This method, although less painful, was horrible. Although amputations were rarely performed by these primitive societies, the Maasai of Africa did practice it when necessary. They would tightly tie a ligature above the level of amputation and swiftly cut off the limb with a skillful swordsmanship motion [6].

Shawiya, from Algeria, employed an incredibly unique combination of ashes, rags, and dirty wool soaked in olive oil. Additionally, she incorporated green leaves, dried goat dung, and earth to create a poultice specifically designed for wound dressing [7].

While the need for amputation has likely existed since ancient times, most prehistoric communities were deeply disturbed by these invasive treatments, especially when it involved their own bodies. In Tibet, amputations were carried out for medical reasons, but tragically, the consequences were frequently deadly [4].

3. The ancient history

Thomas Sydenham, the esteemed author of the textbook “Medical Observations,” remarked that just as the origins of clothing and shelter to combat harsh weather remain unknown, the beginning of Medicine is equally mysterious, comparable to the mystery surrounding the source of the Nile. The world’s oldest medical manuscript was discovered on a Sumerian clay tablet dating back to approximately 2100 BC, marking a significant milestone in written historical records [8]. This ancient artifact sheds light on the “three healing gestures” that formed the foundation of wound treatment during that era: washing the wound, applying dressings or plasters, and carefully bandaging the affected area. Remarkably, these principles continue to underpin modern wound care practices. Interestingly, the Sumerians also employed beer as a prominent component in their treatments. This beverage, with its antiseptic properties, likely played a beneficial role in the healing of wounds and skin lesions. Unveiling this ancient medical manuscript not only provides us with a glimpse into the medical practices of our ancestors but also emphasizes the enduring relevance of their knowledge. The simplicity and effectiveness of the “three healing gestures” serve as a testament to the timeless wisdom of the Sumerians in the realm of wound treatment.

The ancient Egyptians, Indians, and Greeks described wounds that attracted ants and flies, which could potentially be attributed to diabetic foot ulcers. In ancient Egypt, compound fracture wounds were treated in a rather interesting manner. The Egyptians would prepare an ostrich egg, mix it with grease, and insert it into the wound. This served as a cover for the wound, allowing it to dry properly. Another fascinating method employed by the Egyptians involved the use of honey as a bandage. In the Egyptian Papyrus, honey was frequently utilized either on its own or mixed with meat and smeared over absorbent lint. This ancient practice has been revived in recent times, with numerous scientific journals publishing studies highlighting the benefits of honey as a wound dressing throughout the twentieth century [9, 10].

In ancient Babylon and Assyria, Hammurabi, an influential ruler of Babylon, established a comprehensive set of regulations. Notably, this code stipulated that “a doctor’s hands should be amputated if they cause a lethal injury while operating or if they employ a knife to incise an abscess and extract an eye” [11].

The Greeks and Romans inherited and expanded upon the medical knowledge of these ancient civilizations. They emphasized the role of rationality and observation in medicine, establishing the foundations of anatomy, physiology, pathology, pharmacology, and surgery. During this period, influential figures such as Hippocrates, Aristotle, and Galen emerged, leaving a lasting impact on the field. The earliest description of ancient Greek medical practice derives from the two epic poems attributed to Homer. His prominent works, “The Iliad” and “The Odyssey,” offer precise depictions of various types of injuries [12].

During the fifth century B.C., Hippocrates, known as the Father of Medicine, had a strong belief in the healing power of nature and preferred using simple dressings in his treatments. Whether it was vinegar, wine, oil, or honey, he would combine them with lukewarm or cold water for the dressing. He understood the importance of avoiding oily dressings and favored keeping wounds dry rather than moist. Additionally, he emphasized the significance of keeping clean wound edges as close together as possible, aligning with the concept of healing through first intention. He demonstrated his unwavering faith in the body’s ability to heal itself [13].

The term “diabetes “was coined by the Greek physician Aretaeus of Cappadocia in 150 A.D. to describe the sweet taste of urine. He gave a detailed description of the disease, which he considered to be a disorder of the kidneys and the bladder and described it as a condition characterized by the melting down of flesh and limbs into urine. Aretaeus wrote about the understanding and description of various diseases, including diabetes mellitus, in his work titled “On the Causes and Signs of Chronic Diseases” [14], however, he failed to mention diabetic foot as a distinct condition.

The surgeons of the Roman Empire possessed a remarkable understanding of surgical techniques, including both flap amputation and the circular method. Heliodorus, for instance, cautioned against amputating above the elbow or knee due to the significant risk posed by the size of the vessels involved. Roman medicine was an extension of Greek medicine. Most Rome’s medical practitioners were Greeks and slaves, with only a few Roman physicians like Celsus. Celsus, a notable Roman physician, dealt with and described various post-wound consequences such as erysipelas and gangrene [15]. Celsus, a pioneering figure, recommended a method of tying an injured vessel in two places and then dividing it between them. Notably, Celsus was the first to describe the four cardinal signs of inflammation—heat, pain, redness, and swelling—which remain fundamental knowledge for every medical student. Galen, building upon these signs, introduced a fifth one—loss of function.

Galen advocated for a more conservative approach, favoring resection over amputation, and provided meticulous guidelines for wound treatment, emphasizing the crucial role of monitoring the patient’s overall well-being [4]. Galen was the second most famous figure in ancient medicine, following Hippocrates. He acquired extensive expertise in treating wounds as a physician to gladiators before relocating to Rome, where he served as the personal physician to the Roman emperors and established the largest medical practice in the city. Galen recognized the crucial role of overall health in relation to wound healing and advocated for conservative resection rather than amputation. Galen’s prominence in the field of medicine during ancient times was only surpassed by the legendary Hippocrates. Prior to his illustrious career in Rome, Galen honed his skills by tending to the wounds of gladiators, amassing invaluable experience. His reputation as a healer led him to become the trusted physician of the Roman emperors, solidifying his position as the most sought-after medical practitioner in the bustling city of Rome. One of Galen’s notable contributions to the medical field was his emphasis on the significance of general health in the process of wound healing. He recognized that a person’s overall well-being played a pivotal role in their ability to recover from injuries. Furthermore, Galen advocated for conservative resection as a preferred method over amputation. He believed in preserving as much of the affected area as possible, rather than resorting to drastic measures such as limb removal. This approach showcased Galen’s commitment to finding the most effective and least invasive treatments for his patients [13, 16].

The Greeks and Romans did not make many changes to traditional wound-dressing recipes. Nevertheless, they played a crucial role in establishing the foundations for the fields of dressing, debridement, and amputations, which saw remarkable advancements in skill. This period also witnessed the emergence of surgical literature, enabling individuals to compare their own experiences to those of others [4].

Amputations were often performed by barber-surgeons or other non-specialized practitioners. Techniques were crude, using saws, knives, or cautery tools. The procedure was often associated with a high risk of infection and mortality. The Greeks held a strong opposition to amputating limbs. However, Hippocrates believed in removing only the dead tissue from gangrenous limbs, rather than resorting to full amputations. Despite this, Celsus regarded amputation as a last resort, emphasizing its sorrowful nature. Interestingly, some of Hippocrates’ contemporaries and immediate successors did perform amputations using techniques that were remarkably like those used in modern times. One such example is Archigenes, who carried out amputation procedures in a manner comparable to present-day practices [17].

To perform a successful amputation, Archigenes recommended a specific procedure. First, the entire area that requires amputation should be thoroughly soaked with cold water. Next, it should be carefully bandaged, ensuring cleanliness and protection. Finally, a cord should be tightly tied above the intended site of amputation to securely constrict the limb. In cases where this method is not feasible, Archigenes suggested severing and knotting the main arteries leading to the affected area. By following these guidelines, He aimed to minimize the risks associated with amputation and increase the chances of a successful outcome.

Both the flap-based and circular amputation techniques have been familiar to Roman doctors. Heliodorus suggested using a saw to cut the bone, carefully separating the muscle from the blood vessels, and tightly tying a ligature above the amputation site to minimize bleeding. He criticized surgeons who attempted to perform the operation in a single stroke [18].

4. The middle ages

The Middle Ages, often referred to as the Dark Ages, saw the downfall of the Greek and Roman scientific legacy. During this period, the number of physicians in Western Europe was extremely limited, and there were no medical colleges established. Those who pursued the study of medicine with dedication were primarily members of the Church. Their approach to healthcare centered around spiritual practices such as prayer, intercession, and the veneration of saints known for their healing abilities. While a small number of esteemed doctors catered to the needs of kings and the nobility, the responsibility of tending to wound and injuries was primarily entrusted to barbers and other individuals lacking formal education [19]. That mistreatment was about to change with the rise of the great universities of Western Europe [20].

Salerno, a city in southern Italy, became famous for its medical school, the Schola Medica Salernitana, which was founded in the ninth century and flourished in the tenth and eleventh centuries. The school was influenced by the Arabic medical writing, which had preserved and developed the ancient Greek and Roman medical knowledge. One of the most influential figures in the transmission of Arabic medical texts to Salerno was Constantine the African, a scholar who translated many Arabic works into Latin, including those by Hippocrates, Galen, and Haly Abbas. His translations introduced the West to the Islamic world’s extensive knowledge of medicine and had a lasting impact on European medical practice [21].

The notion that suppuration was a necessary step in wound healing for a long-time hindered advancement in wound care. Wounds were treated with a variety of unpleasant and dirty ointments and concoctions [22]. One of those who taught that suppuration was a hindrance to wound healing was Henri de Mondeville (1260–1320). He was a surgeon for France kings, Louis X of France, and Philip the Fair, and he also taught at Montpellier. In place of cautery, he employed ligation to control bleeding [23]. Hugh of Lucca and his son Theodoric worked for the University of Bologna. Theodoric produced a “Chyrurgia” that was distinctly original. He was the first to reject the idea that suppuration is a necessary component of normal wound healing and to strongly advocate against messy applications that impede healing. He also advised only using simple dressings to treat wounds [24]. Unlike Henri de Mondeville, Guy de Chauliac (1300–67), the author of Chirurgia Magna and the most renowned surgeon of the late Middle Ages, preferred to apply salves instead of simple dressings and to use cautery instead of ligation [25].

At the end of the medieval era, two German surgeons had special experience of war wound. One of them was Heinrich von Pfolspeundt, a Bavarian army surgeon who converted his 40 years of experience of campaigns into a book on bandaging and the treatment of wounds [26]. The other surgeon, Hans von Gersdorff wrote a book about his war experience. He explained how he used a special instrument to remove foreign bodies and dressed them with warm rather than boiling oil, as the last one was well known to be used for war wounds. He recommended to cover the stump of amputation by an animal bladder [27].

During the Dark Ages in Europe, there was a remarkable advancement in the field of medical sciences in Islamic countries. The classical Islamic medical texts contain valuable principles and practices for overall healthcare, and preventive measures, such as proper nutrition, physical activity, hygiene, and self-care. One notable figure in the field, Al-Razi (854–925 CE), also known as Rhazes [28], provided significant insights into wound management and care. In his book, Kitab al-Hawi, he emphasized the need for thorough examination and observation of wounds, considering factors like location, size, depth, and signs of infection. Al-Razi recognized the significance of debridement, the removal of necrotic tissue or foreign bodies, to facilitate healing. He also discussed various types of dressings and bandages, including materials like cotton, linen, and silk. Clean and sterile dressings were highlighted as essential for protecting wounds from further contamination and maintaining a moist environment conducive to healing. Rhazes held the esteemed position of chief physician at the prestigious hospital in Baghdad. An intriguing anecdote surrounds the selection of the hospital’s location, as it is said that Rhazes hung pieces of meat at different points throughout the city, carefully observing the rate of putrefaction. Ultimately, he chose the site where decay was most significantly delayed, showcasing his meticulous approach to medical care. Additionally, Al-Razi described the use of topical medications made from natural substances, such as honey, to prevent infection, reduce inflammation, and support the healing process. One of his notable contributions was the introduction of animal guts as a material for sutures, a discovery that greatly enhanced the success of surgical procedures [29]. Albucasis (936–1013) was born near Cordova Andalusia [30], he introduced 200 surgical instruments and his writings of 30 volumes of medical encyclopedia “Kitab al-Tasrif” were invaluable. He gave a description for the treatment of abdominal wounds. He advises using big ants to stitch the borders of the wound together for treating bowel damage. Al-Zahrawi provided detailed descriptions of various types of dressings that could be utilized to protect and promote healing in wounds. He also emphasized the importance of patient positioning and offloading pressure from affected areas to facilitate healing. Furthermore, Avicenna (960–1037), an Arab physician, accurately described the clinical features and potential complications of diabetes, such as peripheral neuropathy, gangrene, and erectile dysfunction. His influential book, Kanon, had a significant impact on the field of medicine [31].

5. The European renaissance

The European Renaissance was a remarkable era of cultural, artistic, and scientific resurgence that followed the Middle Ages. Spanning from the fourteenth to the seventeenth century, this period witnessed a profound revival of classical knowledge and wisdom. Moreover, the Renaissance was not limited to the arts and sciences alone. It permeated all aspects of society, influencing politics, religion, and education. One of the most remarkable outcomes of the Renaissance was the heightened fascination with the structure and function of the human body, which brought about a revolutionary transformation in surgical practices. During the wars of that era, surgeons acquired extensive expertise in treating wounds inflicted by firearms after the introduction of the arquebus. These wounds were particularly severe and highly prone to infection. The prevailing method involved cauterizing the wounds by injecting scalding oil. Additionally, bleeding was managed by employing hot irons or boiling oil. During the Renaissance, surgery started to gain a more prominent status compared to previous eras, where it had primarily been performed by barbers. It began to be practiced by individuals with significantly higher levels of education and training. This shift marked a significant advancement in the field of surgery during this period.

One of the most prominent Italian surgeons during that era was John of Vigo (1450–1525), who held the esteemed position of surgeon to Pope Julius II. His seminal surgical textbook, initially published in 1514, underwent over forty editions and was translated into various languages including French, Italian, Spanish, German, and English. Notably, he held the belief that gunshot wounds were contaminated, thus advocating for their treatment through cautery and the application of a plaster composed of pulverized frogs, worms, vipers, and the rust of old kettles. Tragically, even individuals with seemingly minor injuries often succumbed to their wounds.

Thomas Gale (1507–1587), a Tudor surgeon with extensive experience in wartime, vividly recounts the appalling conditions he encountered at Montreuil in 1544 during the reign of Henry VIII. In his detailed account, Gale exposes the alarming reality of unqualified individuals, such as sow-gelders, tinkers, and cobblers, assuming the role and responsibilities of surgeons. These impostors treated wounds with a repugnant concoction typically used to grease horses’ feet, as well as an ointment composed of shoemakers’ wax and the rust of old kettles. Shockingly, even those with seemingly minor injuries succumbed to their wounds due to the lack of proper medical care. His exceptional writings, distinguished by their practical and insightful teachings, include the notable work titled “An Excellent Treatise on Wounds made with Gunneshot” (1563) [4].

Ambroise Paré (1510–1590) changed medical practices by rejecting the conventional method of applying boiled oil to wounds and reintroducing the ligation of vessels. Instead of cauterizing the great vessels with hot irons during amputations, Paré began tying them off. This innovative approach eventually led to the widespread adoption of ligatures in amputation procedures, becoming the new standard practice in medicine [32, 33, 34].

Fabricius Hildanus (1560–1634) is credited with introducing the tourniquet and pioneering the technique of amputating through healthy tissue in cases of gangrene. He is recognized for his innovative technique of amputation using a red-hot knife. While this method had previously been employed by Arabic surgeons, Fabricius made significant improvements by increasing the instrument’s thickness. This modification enabled the knife to maintain its heat consistently throughout the operation. As a result, this method offers reduced pain, minimal bleeding, and superior muscle retraction, allowing for higher bone division. Notably, Fabricius skillfully employed this hot knife technique to amputate the leg above the knee of a severely ill patient afflicted with gangrene [35, 36].

John Woodall (1569–1643) strongly opposed indiscriminate amputation and believed that it was better to cut off a foot than a leg and even better to sacrifice a toe rather than a foot [37].

During the late seventeenth century, James Yonge, a naval surgeon from Plymouth, revolutionized the traditional circular amputation technique. In 1679, he introduced the flap operation using double flap rather than a single flap, which quickly gained popularity despite undergoing numerous modifications. Initially limited to the leg, the method expanded to include other limbs as well. However, in military practice, particularly in cases of gunshot and shattering wounds, the circular method continued to be favored [38, 39].

Thomas Willis (1621–1675) described the occurrence of gangrene and ulcers in individuals with diabetes. He was a British physician who lived in the seventeenth century, pioneered the studies of the anatomy and physiology of the brain and the nervous system, and described the circle of Willis, a ring of arteries at the base of the brain that supplies blood to the brain and surrounding structures [40].

Richard Wiseman (1622–1676) challenged the prevailing belief that gunshot wounds were venomous, instead recognizing the risk of retained foreign bodies, especially fragments of clothing. He advised extracting these foreign objects, understanding their removal as crucial for the wound’s healing process. He applied fine lawn fabric soaked in oil of bitter almonds, oil of elders, egg yolks, and stramonium, among other substances. This meticulous method aimed to promote the recovery of the afflicted area [41].

In the eighteenth century, Jean Louis Petit (1674–1750), a French surgeon invented the famous screw tourniquet, a device specifically designed for amputation procedures. This ingenious invention involved the attachment of a circular bandage to a screw, which, when tightened, applied targeted pressure to a precise location. Additionally, a leather pad was incorporated into the design to enhance the effectiveness of the tourniquet [42].

Dominique Anel (1679–1730) was a French surgeon who was a pupil of J. L. Petit. He observed a common practice of sucking wounds to eliminate clots and foreign objects that hindered the healing process. However, this method was both unhygienic and perilous. In response, Anel ingeniously devised a suction syringe as a safer and more effective alternative. He is best known for his operation for aneurysms, which involved tying off the artery above and below the bulge and making an incision to drain the blood [43].

The name of François Chopart (1743–1795) is perpetuated in the amputation through the forefoot at the midtarsal joint using a long flap of the sole of the foot to cover the stump [44].

Baron Larrey (1766–1842) was a distinguished figure who played a crucial role in the Napoleonic wars. His notable contribution to medical innovation was the invention of the revolutionary “flying ambulances.” Larrey’s meticulous wound treatment involved excising all ragged and torn parts, as well as removing any foreign bodies or fragments of bone. Unlike many of his contemporaries, Larrey advocated against close suturing, except for facial wounds. Instead, he preferred to employ adhesive plasters and bandages to approximate the edges of wounds. This approach not only minimized scarring but also allowed for better healing [4].

The name of James Syme (1799–1870), a Professor of Surgery at the University of Edinburgh, is spread by the term “Syme’s amputation,” a disarticulation of the ankle joint, wherein a carefully crafted long heel flap meticulously mobilized to cover the wound [6].

Surgical anesthesia using ether and chloroform was not introduced until 1846 and 1847, respectively. Antisepsis, on the other hand, did not become common practice until after the turn of the century. The advent of anesthesia and antisepsis revolutionized the field of surgery, empowering surgeons to perform procedures that were previously deemed impossible, such as extensive amputations [45].

William Thomas Green Morton (1819–1868), an American dentist is regarded as the discoverer of surgical anesthesia, using the Ether to help the surgeon to do amputations [46].

Significant progress was made in understanding the pathophysiology and management of diabetes and its foot complications during the late nineteenth and early twentieth centuries.

Louis Pasteur (1822–1895) made important discoveries about bacteria and other microorganisms by his studies of the fermentation and putrefaction processes.

The antiseptic system was initially introduced by Lister in 1865 when he successfully treated a complex leg fracture with open wounds. Two years later, Lister published his new findings, documenting eleven cases, with nine patients fully recovering both life and limb, one requiring amputation, and one yielding astonishing result. This pivotal moment marked the widespread adoption of antisepsis, propelling it into the medical mainstream [47].

In 1928, Alexander Fleming discovered a blue mold thriving in a Petri dish. He observed that the mold had the extraordinary ability to annihilate all the bacteria surrounding it. The first article documenting the successful treatment of streptococcal meningitis with penicillin was published in 1943, marking a turning point in medical history. The advent of antibiotic medicines became paramount in the management of acute wounds and chronic lesions, as well as in the prevention of potential complications such as cellulitis, osteomyelitis, and sepsis. Antibiotics, such as penicillin, have become indispensable tools in the fight against bacterial infections [48].

Thomas Hodgkin (1798–1866) was a British physician and pathologist who is best known for describing Hodgkin’s lymphoma. He recognized a connection between diabetes and foot gangrene. He suggested that diabetes could cause damage to the nerves and blood vessels of the foot, leading to ulcers and gangrene [49].

All of Lister’s publications were studied by Richard von Volkmann (1830–1889), who later served as the philosopher’s most ardent defender in Germany. A British surgeon who visited Volkmann’s clinic in 1879 provided a detailed account of how the antiseptic ritual was carried out there. I-in-20 carbolic lotion was liberally applied to all wounds while the “donkey engine” or spray pumped antiseptic vapor into the air. When Volkmann yelled “watering can,” long-spouting gardeners’ watering cans filled with carbolic lotion and were emptied out by the surgeon and his assistants, who were both wearing long rubber boots. “If dirt be unavoidable, it must be antiseptic dirt,” read the clinic’s catchphrase. The outbreak of the Franco-Prussian War provided a remarkable opportunity to put Lister’s methods to the test. Professor von Nussbaum of Munich had a particularly striking experience. In 1872, at his hospital, eighty percent of all wounds were plagued by pyemia and gangrene, a truly terrifying rate. However, with the introduction of the antiseptic method, within a week, von Nussbaum was able to report a remarkable transformation: “Not another case of hospital gangrene appeared… Our results continue to improve, healing times shorten, and pyemia and erysipelas have completely disappeared.”

Frederick Treves (1853–1923), famous for performing the first appendectomy in 1888, had established three crucial principles in the treatment of ulceration of the foot: sharp debridement, offloading pressure, and education regarding foot care and appropriate footwear. Following debridement, an antiseptic cream is applied, and plaster is subsequently utilized to alleviate pressure on the healed ulcer [49].

Jean-Martin Charcot (1825–1893) in 1883 described “Charcot foot” named after him in patients with tabes dorsalis. Charcot foot is mostly seen in diabetic neuropathy, which has replaced syphilis as a frequent cause of peripheral nerve dysfunction. Neuropathic osteoarthropathy is characterized by relatively painless swelling together with extensive damage in bones and joints, predominantly in the feet and ankles. The uncontrolled natural course of the condition leads to gross foot deformity, skin pressure ulceration, spreading infections, and sometimes amputation [50].

6. The discovery of insulin

In 1673, Johann Brunner noticed that a dog experienced excessive thirst and polyuria after the removal of its pancreas [51]. In 1884, Friedrich von Frerichs from Berlin reported that 20 percent of his diabetic patients exhibited significant changes in their pancreas. During the same year, French researchers Xavier Arnozan and Louis Vaillard found that ligation of the pancreatic ducts led to the degeneration of the acinar tissue while leaving the islets intact [52].

In 1890, Joseph von Mering and Oskar Minkowski from Strasbourg found that total removal of the pancreas in a dog resulted in diabetes. These pioneering experiments established the pancreas’s involvement in diabetes and provided compelling evidence linking the pancreas to the regulation of sugar levels. Ultimately, their work laid the foundation for the study of diabetes, leading to the discovery of insulin as an effective treatment [53].

The stage was set for the collaboration between Frederick Banting and Charles Best, who made groundbreaking contributions in the field of medicine. At the time, Banting was a 29-year-old orthopedic surgeon practicing in London, Ontario. However, he was uncertain about the success of his practice. In 1921, Banting approached John Macleod, a distinguished Professor of Physiology in Toronto, seeking his approval to work in his laboratory. Macleod, recognizing Banting’s potential, granted him permission to conduct his research. It was during this time that Banting enlisted the help of Charles Best, a promising medical student, to assist him in his endeavors. Their journey was not without its challenges. They faced numerous setbacks, heartbreaking trials, and disagreements along the way. With the invaluable assistance of James Collip, a talented biochemist, they successfully prepared an extract that proved effective in treating diabetic dogs and patients. Their remarkable achievement was documented in the seminal paper titled “The Internal Secretion of the Pancreas,” which was published in 1922. This remarkable work caught the attention of the scientific community, ultimately leading to Banting and Macleod being jointly awarded the prestigious Nobel Prize in Medicine and Physiology in 1923 [54].

The introduction of insulin into medical therapy reformed the treatment of diabetes, leading to better glycemic control and reduced risk of foot complications [55]. Subsequent research has greatly enhanced our comprehension of the etiology behind diabetic foot ulcers, consequently paving the way for numerous technological innovations and valuable tools. This exciting progress has altered our understanding of this condition, propelling us toward more effective treatments and improved patient outcomes.

7. Toward a better understanding

The etiology of diabetic foot ulcer is complex. It involves the interaction of various factors, such as neuropathy, ischemia, infection, inflammation, and wound healing. Many scientists have contributed to the explanation of diabetic neuropathy. One of the pioneers of research in leprosy was Paul Brand (1914–2003), an orthopedic surgeon, who taught us the principles of management of the insensitive foot, repeatedly emphasizing the need for offloading plantar neuropathic ulcers, which frequently went on to heal even in the days prior to antibiotics. He was the first surgeon in the world to use reconstructive surgery to correct the deformities of leprosy in the hands and feet. The findings from his research on leprosy were applicable to neuropathic diabetic foot care [56].

The discovery of capillary microaneurysms by Ballantyne and Loewenstein in the field of diabetic retinopathy in the 1940s brought about significant advancements [57]. However, it was the meticulous and continuous clinical observations made by Lundbaek that truly altered our understanding of diabetic microangiopathy, also known as diabetic small vessel disease. This term has now become the most comprehensive way to describe the consequences of arterioles, capillaries, and venules being affected by diabetes [58]. In the 1950s, the electron microscope emerged as a crucial tool in diabetes research, particularly in the study of the kidney. Through anatomical and biochemical investigations, it was determined that the capillary basement membrane in individuals with diabetes undergoes both thickening and chemical composition alterations. These valuable insights have significantly enhanced our comprehension of the long-term complications that manifest clinically in individuals with diabetes [59].

8. A higher standard of care

The work of Elliott Joslin (1869–1962, USA), during the first half of the twentieth century, focused on various aspects of diabetes management, including foot care. Joslin noted that mortality from diabetic coma had fallen from 60 to 5% after the introduction of insulin. As people began to live longer, they experienced complications that had not previously been seen. Deaths from diabetic gangrene of the lower extremity have risen significantly. He believed that diabetic gangrene was preventable. He introduced the team approach that included foot care, diet, exercise, prompt treatment of foot infections, and specialized surgical care. He founded the Joslin Diabetes Center in 1898. Through the efforts of Joslin and members of the Massachusetts Chiropody Association, the first hospital foot clinic was established at the New England Deaconess Hospital (NEDH) in 1928 [60]. In 1957, the term “chiropodist” was changed to podiatrist and the National Association of Chiropodists (NAC) became the American Podiatry Association (APA). In 1984, the APA became the American Podiatric Medical Association (APMA). Leland McKittrick, MD (1893–1978) was recruited by Joslin. He suggested that amputation might be safely performed at a more distal level with a reasonable chance of success after controlling invasive infection with antibiotics. Frank C. Wheelock (1919–2006) was the first American surgeon to use an end-to-side femoral popliteal bypass graft. In 1984, the Division of Vascular Surgery at the NEDH developed the distal revascularization techniques, in particular, the dorsalis pedis bypass graft to restore pulsatile flow to the forefoot. Consequently, there was a growing recognition of the importance of foot preservation, leading to the development of distal revascularization methods aimed at restoring proper foot perfusion [60]. In 1992, Frank LoGerfo and colleagues noted that distal arterial reconstruction has greatly reduced the need for toe or transmetatarsal amputation.

Angioplasty was first described by interventional radiologist Charles Dotter in 1964 [61, 62]. In January of that year, he successfully dilated a superficial femoral artery in an 82-year-old patient. As the twentieth century progressed, the angioplasty technique underwent further development, enabling the revascularization of distal arteries all the way down to foot arteries. This breakthrough has proven to be a safe and effective method for limb salvage in patients with diabetes. Since then, revascularization has become a crucial component of the diabetic foot service.

R.D. Lawrence (1900–1987, UK) was a British physician who also faced the challenges of living with type 1 diabetes himself. His remarkable autobiography, “Young Dr. Jude” (1957), explained his personal journey and struggles with diabetes. In addition to his medical achievements, Lawrence co-founded the British Diabetic Association, now known as Diabetes UK. Through this organization, he actively worked to raise awareness about diabetes and tirelessly advocated for enhanced care and support for those affected by the condition [63].

The establishment of worldwide multidisciplinary diabetic foot teams marked a significant milestone in the field of healthcare. Recognizing the need for comprehensive care alongside targeted treatment for lower limbs disease, it became evident that patients with diabetic foot disease needed specialized attention from a diverse team of experts working not only in a dedicated diabetic foot clinic but also caring for the patient when admitted to the hospital. By assembling a diverse group of professionals, including podiatrists, endocrinologists, wound care specialists, and vascular surgeons, these teams ensure that patients receive comprehensive and specialized care [64].

The significance of diabetic foot disease on a global scale led the International Diabetes Federation (IDF) to devote the entire year of 2005 to Diabetic Foot Care. This comprehensive effort aimed to emphasize the potential for amputation prevention. Concurrently, the Lancet, a highly respected general medical journal, released an issue solely focused on diabetic foot disease, further amplifying the significance of this condition on World Diabetes Day.

9. Recent developments and future directions

The recent improvements bring forth a wave of hope and opportunities for patients suffering from DFUs. These remarkable advancements have the potential to change the way we approach and treat these patients. With each new development, we inch closer to a future where DFUs no longer pose a significant threat to patients’ well-being. The cutting-edge techniques and innovative treatments that have emerged in recent times hold immense promise in healing these stubborn wounds and restoring patients’ quality of life. Thanks to these exciting developments, we are now witnessing a paradigm shift in the way we address DFUs.

Recent advances in debridement techniques include hydro surgery and ultrasound. These aim to remove nonviable (necrotic) tissue, which can hinder the healing process by obstructing the migration of cells across the wound, thereby inhibiting the natural development of the wound bed, and preventing the formation of granulation tissue.

Hydrosurgery (also known as jet lavage) uses sterile water delivered at high pressure to wash away dead tissue. Low-frequency ultrasound breaks down dead tissue. Water jet techniques have been used in industrial cutting for more than 30 years. The first medical applications were reported in the early 1980s, when the water jet was used to cut organs. These methods are painless and reduce bacterial burden. However, special training is required, and the patient will require several treatment sessions [65, 66].

In 1662, Henshaw, a British physician first utilized hyperbaric therapy, placing patients in a steel container that was pressurized with air. In 1937, Behnke and Shaw first used hyperbaric oxygen successfully for the treatment of decompression sickness. Hyperbaric oxygen therapy (HBOT) was initially used in 1885 for medical purposes, specifically to treat pneumonia. It was found to improve cellular, tissue, and organ oxygenation, exert anti-inflammatory and anti-bacterial effects, and enhance tissue repair mechanisms. It can alleviate or even heal diabetic foot ulcers (DFU) that are caused by the lack of adequate microcirculation and innervation in the extremities of diabetic patients [67].

Negative pressure wound therapy (NPWT) has been used in medicine for over 2,000 years. During the Roman era, medical personnel were attached to various armies. These individuals were believed to possess hereditary powers of healing and were assigned the task of providing direct suction to wounds by mouth. The renowned historian Suetonius documented an incident where one of these healers was instructed to apply suction to Cleopatra’s wound in an attempt to revive her from the bite of an asp. In the pursuit of medical advancements, the technique of utilizing “cupping glasses” emerged. These dome-shaped glasses were employed to draw fluid out of open wounds. Placed over the wound site, they were left in position for at least an hour after being activated by applying heat to the inside of the cup. As the cup cooled, the suction effect intensified, aiding in the extraction of fluid. Advance rapidly to the eighteenth century, Dominique Anel, a French Surgeon, invented the first suction syringe. This device was primarily used to cleanse wounds from clots and foreign bodies, marking a significant milestone in medical history. In the twentieth century, Soviet Surgeon Dr. Nail Bagaoutdinov introduced a negative pressure unit with foam dressings in 1985 to treat infected wounds. This innovative approach paved the way for the development of modern Negative Pressure Wound Therapy (NPWT) systems. Drs. Louis Argenta and Michael Morykwas of Wake Forest University School of Medicine played a pivotal role in this advancement by pioneering the use of polyurethane foam and a mechanical vacuum in the 1990s [68]. It promotes wound healing in diabetic foot ulcers (DFUs) [69]. The National Institute for Health and Care Excellence (NICE, 2019) recommends the consideration of NPWT following surgical debridement for DFUs, particularly when advised by the multidisciplinary foot care service.

The complex interaction between depression and diabetes has been established in diabetics with DFUs. Earlier management of patients’ depression may have implications for improved healing for those with DFUs as well [70].

Since the initial definition of the term “tissue engineering” in the late 1990s, biomaterial-based scaffolds have played a vital role in offering structural stability and creating a conducive environment for cellular regeneration, thereby mimicking the functionality of native tissue [71]. Biological scaffolds have been used to promote diabetic wound healing [72]. The use of Human Skin Equivalent (HSE) has proven to be more effective than the standard treatment of saline-moistened gauze in reducing amputation and infection rates, as well as improving the rate of ulcer healing [73]. In the realm of medical advancements, topical growth factors, with a particular focus on platelet-derived growth factors, have emerged as a highly effective intervention for promoting the healing of ulcers. In comparison to a placebo, these growth factors have consistently shown their ability to significantly enhance the rate at which ulcers heal. This is primarily due to their crucial role as immediate mediators of wound healing. When administered in the context of DFU, these growth factors work to expedite the healing process, providing a much-needed boost to patients suffering from this condition [74].

Lew Alexandrovitch Yutkin, a Russian engineer, patented the use of shock waves to break up kidney stones in 1950. He did this by employing an endoscopic electro-hydraulic generator. After seeing how a lightning strike may break a log underwater, he came up with this concept and applied the same logic to the plates. The first kidney stone to disintegrate in-vitro utilizing shockwaves without making direct contact with the stone was documented by Haeusler and Kiefer in 1971. By the end of 1985, ESWL had already become a widely used operational approach [75].

Extracorporeal shockwave therapy (ESWL) has been found to expedite the healing process of soft tissue wounds in the treatment of diabetic foot ulcers (DFU). Encouraging results from clinical trials have demonstrated the superior effectiveness of ESWL over traditional methods for DFU treatment [76].

Multiple reports have demonstrated that stem cells have the ability to enhance angiogenesis in ischemic regions. Stem cell transplantation, as an innovative technology, remains a subject of controversy within the field of diabetic angiopathies when it comes to treating diabetic foot ulcers [77].

The potential advantages of using amnion/chorion membranes have been a subject of theoretical speculation for quite some time. However, recent studies have started to shed light on the practical benefits that these membranes can offer to patients. Several clinical trials have been conducted to investigate the safety and effectiveness of dehydrated amnion chorion membrane (dHACM) in the treatment of diabetic and venous lower extremity ulcers. These studies have revealed a notable improvement in the rate of wound healing among patients treated with dHACM compared to standard of care (SOC) and bilayered skin substitutes [78].

Digital applications in the daily management of DFUs have evolved rapidly in recent years to a level of remote diagnosis and monitoring of wounds in community settings. The COVID-19 pandemic has accelerated research and development of such innovative technological applications. Photographic monitoring of foot ulcers has been practiced in many centers across the world in the past few decades. The invention of digital photographic technology in 1975 further boosted DFU care because of the ease of electronic archiving of ulcer images during clinical follow-up. Photography using mobile phone cameras has become a huge leap forward in this direction in recent years empowering patients and clinicians to further improve DFU care.

AI-based digital algorithms are currently being developed rapidly through collaborative global effort between AI experts and clinical teams. Mobile camera-based digital technologic applications are under development to enhance remote diagnosis, monitoring, and follow-up care of DFUs. Prediction models of wound healing are also under development now making use of linking the ulcer characteristics of DFU images to the clinical and laboratory parameters of diabetic patients. These collaborative efforts between clinicians and computer scientists across the world should revolutionize such discoveries to empower diabetic foot patients to self-monitor and manage their DFUs to a greater extent [79].

10. Conclusion

Studying the captivating history of diabetic foot ulcers enables us to explore the fascinating evolution of diagnosis and treatment across diverse regions and populations. By doing so, we can identify the prevailing gaps and challenges, paving the way for the establishment of standardized guidelines. It is crucial to acknowledge the profound impact that diabetic foot ulcers have on the quality of life, morbidity, and mortality of patients with diabetes and their families. This knowledge ignites our enthusiasm as we embark on a journey to learn from both the triumphs and setbacks of past and present interventions. With an enthusiastic tone, we eagerly embrace the opportunity to unravel the mysteries of diabetic foot ulcers, unraveling the secrets of their historical development and unlocking the potential for innovative advancements.