Diabetes and the Diabetic Foot Ulcer

November is Diabetes Awareness Month, an opportunity for healthcare communities across the country to come together and raise awareness of diabetes and the impact it has on the American people. With its growing prevalence, many of us probably know someone affected by diabetes; however, not everyone understands the implications and potential risks associated with a diabetes diagnosis. In addition to the disease itself, diabetes also invites a host of complications including diabetic foot ulcers which can have a severe impact on a patient’s quality of life. So, how does diabetes start, who does it impact, what is a diabetic foot ulcer, and what can we do to improve the outcomes of patients with diabetes and diabetic foot ulcers? Let’s find out.

Impact of Diabetes in the United States and Globally

When you search for ‘diabetes’ or ‘diabetes mellitus’(DM) on the internet, a host of statistics present themselves. We’ve provided a few to illustrate the impact DM has not only on the United States, but the entire globe. As of 2018, the Centers for Disease Control and Prevention estimates that more than 10% of the overall U.S. population suffers from DM, surpassing a total of more than 34 million people.¹ Of those individuals, approximately 210,000 are children and adolescents younger than 20 years of age.¹ Prevalence of DM in the United States has been on the rise for the last several years. Between 2004 and 2012, the average prevalence of adults diagnosed with DM in the U.S. more than doubled, and by 2016, the prevalence of diagnosed DM was recorded at a troubling range of 12.2-33.0%.¹

According to the World Health Organization the number of adults world-wide living with DM has almost quadrupled since 1980 to more than 420 million and is expected to increase to more than 690 million by the year 2045.² In 2019, the International Diabetes Federation cited DM as the underlying cause of at least $720 billion USD in health care expenditure and 4.2 million deaths globally.^3,4 When considered altogether, these numbers are staggering, and the idea that they are predicted to continually rise is cause for concern.²

What Exactly is Diabetes Mellitus?

Diabetes mellitus is taken from the Greek word diabetes which means to siphon or pass through, and the Latin word mellitus meaning sweet.⁵ DM is a group of disorders that culminate in the inadequate control of the sugar molecule glucose in the body. Hyperglycemia, or elevated levels of blood glucose, is the main hallmark of DM resulting from defects in the body’s ability to secrete insulin, loss of insulin sensitivity, or a combination of both.^2-5 Insulin is a crucial factor in the maintenance of blood glucose levels within the body by stimulating target tissues to absorb glucose, the body’s main source of energy, from the blood. The metabolic abnormalities associated with DM can cause a decrease in insulin production and/or insulin sensitivity resulting in habitually high volumes of glucose in the bloodstream.^2-6

The American Diabetes Association (ADA) has classified four main types of DM – type 1 diabetes mellitus, type 2 diabetes mellitus, gestational diabetes mellitus, and specific types of diabetes due to other causes.² In this month’s blog post, we will be focusing on types 1 and 2, but keep your eyes out for spotlights on other types of diabetes in future posts. Type 1 diabetes mellitus (T1DM) is caused by the autoimmune destruction of pancreatic ß-cells which are the primary producers of and storage facility for insulin. This results in a progressive decline in insulin production.^3,4,6,7 This type of diabetes is often diagnosed in children and adolescents because they begin to demonstrate symptoms of hyperglycemia that requires lifelong insulin replacement therapy.^4,7

Type 2 diabetes mellitus (T2DM) is caused by the progressive loss of insulin sensitivity in tissues that normally utilize insulin to absorb glucose from the blood. This loss in insulin sensitivity eventually results in the loss of insulin production by pancreatic ß-cells.^2,3,4,6 Between 90% and 95% of diabetic patients have T2DM and are mostly adults; however, in recent years the incidence of T2DM in patients 20 years old or younger has been on the rise and the increase in childhood obesity rates is thought to be the main culprit.^3,6

Pathophysiology of the Diabetic Foot Ulcer

One major complication associated with the progression of DM is the diabetic foot ulcer (DFU). The development of a DFU can lead to serious disability, reduction in patient quality of life and high financial burden on society. In 2015, as many as 15% of diabetic patients had DFUs which were estimated to lead to more than 80,000 amputations in the United States. In fact, DFUs preceded nearly 84% of lower limb amputations secondary to DM in 2015.⁸ The pathophysiology of DFUs involves neuropathic, vascular and immune system components, which are all affected by the hyperglycemic state associated with DM. Hyperglycemia may induce damage to motor neurons in the foot, leading to anatomic deformities and changes in pressure points on the foot. Autonomic nerves also sustain damage due to hyperglycemia which causes the impairment of sweat glands, leading to skin break down and cracks in the epidermal layer of the skin. Lastly, patients may not notice foot wounds for some time due to damage in their peripheral nerves that allow them to sense pain.^8,9

Neuropathy has been diagnosed in approximately 75% of diabetic patients undergoing foot and ankle surgery, and the chances of developing a DFU is 7 times higher in diabetic patients with moderate or severe sensory loss compared to patients who still have sensation in their lower extremities.⁹ Vascular changes also occur due to hyperglycemia which results in vessel constriction and decreased blood flow to the feet.^8,9 Patients with DFUs are more likely to be affected by vascular diseases that require revascularization and about 50% of patients with diabetic foot disease have some degree of peripheral artery disease (PAD).⁹ Hyperglycemia also causes the destruction of immune cells, which impairs the healing response and responses to infection when an ulcer forms.⁸ Infections can occur in as many as 58% of patients who have new foot ulcers.⁹

Factors that increase the chances of DFUs in diabetic patients include previous lower extremity amputations, history of a foot ulcer, infection of new foot ulcers, anatomic foot deformity, peripheral vascular disease, diabetic nephropathy in those receiving dialysis, poor glycemic control, and smoking.^8,9

Treatment of DFUs

Treatment of DFUs begins with classification of the ulcer. Appropriate classification of DFUs may improve communication amongst providers and accurately identify the severity of the ulcer. The Wagner and University of Texas Wound Classification Systems are the most commonly used systems and are often used together to identify ulcer depth, presence of abscesses, osteomyelitis, joint sepsis, gangrene and the presence/extent of ischemia and neuropathy.⁹ Once the DFU has been classified, a care plan can be established. A multidisciplinary team of specialists including wound care experts, endocrinologists, podiatrists, surgeons, hospitalists, infectious disease specialists, and orthotists is recommended as part of a care plan by the International Working Group on the Diabetic Foot.⁹

Initial treatment for DFUs typically begins with debridement to convert the chronic wound to an acute wound by removing dead tissue. Debridement also decreases bacterial presence and inflammatory cytokines.⁹ Following removal of dead tissue, the wound is dressed appropriately, and the patient is fitted with offloading footwear to decrease pressure on the ulcer.⁹ Offloading is a crucial aspect of DFU treatment and can be accomplished using footwear modifications, braces, walkers and total-contact casting. However, patient compliance can be a significant barrier to success with offloading, as research has shown that patients with removable-cast walkers only wear them for 28% of their total daily activity time. For patients who are non-compliant with removable offloading supports, nonremovable orthoses may achieve better results.⁹ Patients should be educated on foot care, appropriate footwear recommendations to reduce pressure points, proper wound dressing changing techniques, and may also be asked to play a role in their treatment journey by improving their nutritional intake, and quitting smoking.⁹ At reassessment, if there is less than a 50% reduction in wound size after 4 weeks with appropriate offloading and wound care, the chances of spontaneous healing are low and may require additional care and/or surgical intervention.^8,9

Given the morbidity and mortality risks associated with DFUs and infections, more attention should be focused on the prevention of these ailments. The International Working Group on the Diabetic Foot recommends adequate patient education, close follow-up and assessments of lower extremities, and clear communication between multidisciplinary team members as components of a successful plan to prevent the development of DFUs and associated infections.⁹

In our September blog post, we discussed the risk of amputations associated with PAD and actions clinicians and patients can take to improve patient outcomes and prevent disease progression. While improvements in treatment innovation are certainly important for patient care and patient outcomes, it is clear education on disease states and preventative measures are key in providing confidence to clinicians and patients in managing these complex diseases and reducing severity of disease.

For the latest updates on StimLabs, information on disease states that may create risk factors for chronic wounds and non-medicinal educational patient tips, please follow StimLabs Unprocessed.

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1. U.S. Department of Health and Human Services; Centers for Disease Control and Prevention. (2020). National Diabetes Statistics Report 2020: Estimates of Diabetes and Its Burden in the United States. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf. Accessed 2021, September 13. 2. Artasensi, A., Pedretti, A., Vistoli, G., & Fumagalli, L. (2020). Type 2 Diabetes Mellitus: A Review of Multi-Target Drugs. Molecules (Basel, Switzerland), 25(8), 1987. https://doi.org/10.3390/molecules25081987 3. Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K. B., Ostolaza, H., & Martín, C. (2020). Pathophysiology of Type 2 Diabetes Mellitus. International journal of molecular sciences, 21(17), 6275. https://doi.org/10.3390/ijms21176275 4. Poznyak, A., Grechko, A. V., Poggio, P., Myasoedova, V. A., Alfieri, V., & Orekhov, A. N. (2020). The Diabetes Mellitus-Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation. International journal of molecular sciences, 21(5), 1835. https://doi.org/10.3390/ijms21051835 5. Sapra, A., & Bhandari, P. (2021). Diabetes Mellitus. In StatPearls. StatPearls Publishing. 6. Rachdaoui N. (2020). Insulin: The Friend and the Foe in the Development of Type 2 Diabetes Mellitus. International journal of molecular sciences, 21(5), 1770. https://doi.org/10.3390/ijms21051770 7. Hoogwerf B. J. (2020). Type of diabetes mellitus: Does it matter to the clinician?  Cleveland Clinic journal of medicine, 87(2), 100–108. https://doi.org/10.3949/ccjm.87a.19020 8. Aumiller, W. D., & Dollahite, H. A. (2015). Pathogenesis and management of diabetic foot ulcers. JAAPA : official journal of the American Academy of Physician Assistants, 28(5), 28–34. https://doi.org/10.1097/01.JAA.0000464276.44117.b1 9. Del Core, M. A., Ahn, J., Lewis III, R. B., Paspovic, K. M., Lalli, T. A. J., Wukich, D. K. (2018). The Evaluation and Treatment of Diabetic Foot Ulcers and Diabetic Foot Infections. Foot & Ankle Orthopaedics, 3(3), 1-11. https://doi.org/10.1177/2473011418788864.