The classic model of the neuropathic foot is most frequently associated with diabetes. Diabetes is a commonly encountered comorbidity in the population of patients with wounds. While many comorbidities have the potential to impact wound healing, this is especially true with diabetes. Therefore, the health care professional needs to understand the diabetes disease process, its implications on the general health of the patient, and its impact on wound healing specifically. The wound care clinician does not manage the diabetes—this responsibility belongs to another provider, usually a primary care physician or an endocrinologist who coordinates the overall diabetes plan of care.

However, it is the responsibility of the wound care clinician to (1) review the patient’s blood glucose values to ensure there is adequate control of the disease to support effective wound healing and (2) recognize when the disease may be negatively affecting a patient’s wound healing potential.

This chapter provides an overview of the epidemiology of diabetes, its effects on wound healing, clinical challenges that the comorbidity of diabetes poses to the form and function of the foot, and considerations for clinical interventions when a diabetic foot ulcer (DFU) is present. For comprehensive information on the pathophysiology and treatment of diabetes, the reader should consult other sources, including the standards of care from the American Diabetes Association¹ and American Association of Clinical Endocrinologists’ comprehensive diabetes management algorithm—2018.² This chapter also provides an overview of treatment strategies necessary for patients to control their diabetes in order to assist in optimal treatment of chronic wounds, including diabetic foot ulcers.

Epidemiology and Health Care Implications

The prevalence of diabetes has been rising steadily and dramatically over the past several decades and is currently considered to be at epidemic proportions worldwide.^1,3 In 2017 the global prevalence for diabetes is estimated to be 425 million individuals, projecting growth to 629 million in 2045.³ The Centers for Disease Control and Prevention (CDC) estimates that as of 2017 the United States had 30 million people diagnosed with diabetes, or roughly 9.4% of the population, plus another 7 million that are undiagnosed with type 2 diabetes (T2DM).⁴ In addition to this number, over 80 million people have the condition of prediabetes, adding up to over 100 million people living with diabetes or prediabetes in the United States. The number of people at risk for or with diabetes continues to increase despite significant efforts to screen and educate the general population about the controllable risks associated with acquiring diabetes: obesity, lack of exercise and physical activity, lack of access to good nutrition, and/or poor dietary choices. These are the major risk factors for T2DM for 90% of the individuals with diabetes, in addition to the strong genetic predisposition to T2DM.

The burden of diabetes has profound implications for public health and health care systems both nationally and internationally. The number of people with diabetes in the United States is growing so rapidly that the U.S. health care system is severely challenged financially by this one disease (FIGURE 7-1).⁴ Currently one in four health care dollars is spent on the management of diabetes and its associated complications.^5,6

Diabetes has a profound impact on health as a result of secondary complications such as heart disease, kidney disease, retinopathy, neuropathy, chronic wounds, and lower-limb amputation. In addition, people are acquiring T2DM at younger ages than ever before in the United States.⁴ Therefore, T2DM is no longer a disease for only the over 40 age group. Accordingly, providers are seeing younger people with diabetes-related complications, including issues related to foot pathology and wound healing challenges. Furthermore, the older population is being affected the most from a number perspective, with the largest prevalence of diabetes in the over 65-year-old age group (TABLE 7-1).⁴

Health care professionals who care for people with chronic wounds who also have diabetes are challenged to achieve wound closure and optimal wound healing outcomes. Diabetes management strategies and wound/foot care are both necessary to provide an environment in which wound closure can occur.

Effects of Diabetes on Wound Healing

Faulty wound healing is a well-recognized complication of diabetes. Current evidence confirms that diabetes inhibits all phases of wound healing via impaired function of the primary cells responsible for wound repair (i.e., neutrophils, macrophages, and fibroblasts), frequently resulting in delayed healing or chronic non-healing wounds. In addition, there is decreased efficacy of cytokines and growth factors in people with diabetes and accompanying hyperglycemia. The accumulation of advanced glycosylation end products (AGEs, also referred to as advanced glycated end products), nitric oxide dysfunction, decreased insulin availability or increased insulin resistance, and altered homocysteine levels also contribute to the complex healing impairments for people with diabetes. Micro- and macrovascular disease, neuropathy, immune dysfunction, and biochemical and hormonal abnormalities all contribute to the altered tissue repair processes in people with diabetes and hyperglycemia (TABLE 7-2).⁷

One example of a diabetes-mediated impairment in wound healing is susceptibility to infection. Under normal conditions, during the hemostasis healing phase there is immediate fibrin plug formation as platelets aggregate at the wound site. The platelets release various growth factors and cytokines, which then recruit inflammatory cells; however, in a hyperglycemic environment, there is a delay in fibrin plug formation, leaving the wound open to contaminants. In addition, there is a delay (or decrease) in the release of growth factors and cytokines, causing impaired recruitment of the inflammatory cells. With this delay, the individual is at risk for infection. In fact, people with diabetes have more frequent infections than patients without diabetes.⁷ On the other side, infection will increase the stress-related hormones needed to fight illness, which in turn increases the blood glucose levels. Therefore, high glucose levels in an individual whose blood sugars are usually well controlled may be a sign of localized infection.

Research in human and animal models has identified many of the changes that contribute to delayed wound healing at the molecular level; however, more research is needed to completely understand how diabetes contributes to faulty tissue repair.⁸

Extensive research has focused on the causes of and interventions for diabetic (also referred to as neuropathic) foot wounds; however, the impairments related to diabetes are much more far-reaching than just the foot, affecting healing of all types of wounds regardless of etiology (eg, pressure ulcers, vascular ulcers, and surgical wounds). In summary, diabetes profoundly impairs the four overlapping phases of wound healing. The underlying mechanisms of the effects of diabetes on wound healing have been extensively investigated over the past few decades; however, complete understanding of the complex and multifaceted pathophysiologic relationship between DM and defective healing continues to elude the scientific community.

Medical Management and Team Care of Diabetes

Diabetes care is complex and multifaceted, requiring a team approach to patient-centered care, with the patient being an integral member of the team (FIGURE 7-9). While the medical team leader is the physician or advanced practice nurse (who uses input, education services, and treatments from other health care providers), the management that occurs on a daily basis is provided by the patient (or by caregivers when the patient is too impaired to perform adequate self-management).⁸ The ability of the patient to adequately manage the diabetes depends on extensive and ongoing training, education, and feedback from the health care team for reaching individualized goals for each patient.

Effective wound care includes a review of the patient’s diabetes management strategies. Without good glucose control, the patient will have difficulty reaching or sustaining wound closure.

The American Association of Diabetes Educators (AADE) is a multidisciplinary professional organization that empowers diabetes educators as well as other team members responsible for ensuring patients have the knowledge they need to self-manage their disease. Without adequate diabetes self-management education, patients are lost as to how to change their lifestyle and habits to ensure acute and chronic complications are delayed or averted (TABLE 7-7). The following list provides the basic elements of a well-rounded diabetes management education program for patients with diabetes, consisting of seven core self-care behaviors that patients should learn in order to delay or avoid complications from diabetes⁹:

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  Healthy Eating: Patients are taught which foods to eat in a manner that assists with blood glucose control. The different types of macronutrients are described including carbohydrates, protein, and fats. Many people with diabetes think the diet issue is related to ingesting sugar, not understanding that every type of carbohydrate influences blood glucose and that not all carbohydrates are created equal, meaning some cause the glucose to go high, while other have less effects on the overall blood glucose levels. Diabetes educators teach the person how to count carbohydrates, read food labels, measure each serving, develop an eating plan, prevent high or low blood glucose levels, and set goals for healthy eating.⁹

  
  
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  Being Active: Being active is part of being healthy in general and is a necessary component for optimal health when a person has diabetes. Physical activity (including exercise) is a powerful modality for the person with diabetes and must be coordinated with the individual’s medication and nutrition regimes. The effects of physical activity include lowering blood glucose, lowering cholesterol, improving blood pressure, lowering stress and anxiety, and improving mood. Depending on the associated complications (eg, diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy), certain precautions and contraindications may be implemented to avoid physical activity-induced damage to already-compromised tissues and organs. For example, patients who have severe foot deformities or a history of diabetic foot ulcers need to be instructed in an activity program that does not cause friction and shear to the plantar foot structures. A referral to a physical therapist knowledgeable about exercises and diabetes is recommended for establishing an appropriate exercise program for the patient with diabetes. Individuals will adhere to activity programs more readily when doing activities they enjoy such as dancing, bike riding, or walking the dog. The activity plan must be customized and embraced by the patient for long-term adherence to take place.⁹

Exercises in a standing position that result in the foot being planted while the body moves (eg, squats, the elliptical, rowing) will produce shear between the subcutaneous tissue and the bony prominences of the plantar foot. Bicycling or using an upper extremity cycle ergometer is advised for cardiopulmonary conditioning if the individual has any risk factors for (or a history of) foot ulceration.

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  Glucose Monitoring: Glucose monitoring helps patients determine the day-to-day control of their disease. Monitoring gives patients a tool to determine objectively if their blood glucose is too high or too low. This information helps them with self-management decisions on a day-to-day basis related to food choices and amounts and types of activities they can do, and helps guide the patients regarding when and whether to see a medical professional. The patient who monitors consistently will discover abnormal glucose excursions and can get help as soon as possible to remedy the higher glucose levels. When monitoring blood glucose, the patient will need the following basic supplies:

  
  
  
  
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    Lancet—thin needle to prick skin for small sample of blood;

    
    
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    Test strips—small pieces of specially prepared paper that absorbs the blood from the lancet prick;

    
    
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    Meter (aka glucometer)—small electronic device that reads the test strip and gives glucose readings;

    
    
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    Log book—to record the numbers from the blood glucose meter and to share with the health care team managing the diabetes.⁹

  
  
  
  
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  Medications: The drug armamentarium for glycemic control for people with diabetes is large and growing as the impairments related to diabetes are better understood. The different drugs and combination therapies address different pathophysiological mechanisms and different organs involved in blood glucose control. The management of T1DM and T2DM is completely different, as these are different diseases with the similar outcome of hyperglycemia.⁸ Medications can be oral and/or injectable for T2DM; however, T1DM requires injectable insulin. Inhaled insulin, a new delivery method for insulin, was approved by the FDA in June 2014 for use in both T1DM and T2DM. Inhaled insulin may take the place of short-acting insulins, but do not replace the intermediate and long-acting forms of insulin.⁹ See TABLE 7-6.

  
  
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  Problem Solving: Preparation and planning are critical components of a well-designed diabetes management program. Patients should monitor their blood glucose levels, looking for too high (hyperglycemia) and too low (hypoglycemia) numbers. However, even the patient who is trying the best to plan well for managing the disease will sometimes find it difficult. Life has all kinds of ups and downs, and no matter how well patients plan, blood glucose can and will go in the wrong direction at some point. An example would be the patient whose blood glucose has been running 180–230 mg/dL for several days, when the random glucose readings are usually between 125 and 145 mg/dL. The patient knows these are higher than normal readings, but may not know why. This person needs professional help to determine if the diabetes management program is still working. There are several reasons the readings may be increasing, eg, illness, a wound infection (if a wound is present), failing beta cells in the pancreas requiring adding insulin to the medication regime, or the glucose strips are out of date. On the other hand, blood glucose can go low, particularly when patients are on oral or injectable diabetes medications. Examples of situations that cause glucose to go low is lack of sufficient food when diabetes medications are taken, too strenuous of an exercise or activity session, or the most common cause—diabetes medications. A bit of health care detective work is necessary when situations such as these arise.⁹

  
  
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  Reducing Risks: Patients who take responsibility for their day-to-day diabetes management can prevent or delay the devastating complications of this disease. Some of the major complications include heart disease, stroke, nephropathy (kidney disease), retinopathy (eye disease), neuropathy, foot abnormalities, and non-healing wounds. In addition to controlling their blood glucose levels, patients with diabetes should reduce other risk factors that work in tandem with diabetes and cause the complications to be more severe. Healthy habits to help prevent complications from diabetes include not smoking, seeing the health care practitioner who helps manage the diabetes on a regular basis, annual eye exams, dental care, foot screens, and proper care of the feet and nails.⁹

  
  
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  Healthy Coping: Increased stress in one’s life increases blood glucose levels. There are the daily types of stress (eg, traffic and getting the kids off to school), and the more serious issues such as divorce or money problems. Adding life stresses to the strain that the disease state of diabetes causes can be almost overwhelming for some patients. When there are high levels of stress in the diabetes patient’s life, it is important that the patient turns to healthy coping methods rather than harmful habits such as smoking, overeating, and excessive alcohol consumption. Some of the recommendations for handling stress for people with diabetes include the following: having a support system with people the patient trusts, physical activity which increases brain endorphins and in turn softens the stress response, thinking positive, and being good to one’s self. Sometimes the person is in depression, a common issue for people with diabetes. Some of the signs that a patient with diabetes is depressed include lack of interest or pleasure in personal or social activities, not wanting to discuss their diabetes issues with family or friends, sleeping for long periods each day, and not providing daily self-care from a personal and/or diabetes perspective. Some people get so depressed they decide to give up on themselves and stop with their good diabetes management. Recognizing patient depression is a health care assessment activity and should be done for all people with diabetes, both those with and without complications from their disease.⁹

Challenges in Caring for the Patient with Diabetes

Education

There are many challenges in providing care for individuals with diabetes. Education is required not only for self-management of diabetes, but also for self-management of the wound. Many people with chronic wounds and diabetes do not have the necessary information to adequately manage the disease, especially in the presence of a chronic wound that causes both psychological and physiological stress. The standard of care for individuals with diabetes is referral to a comprehensive diabetes education program upon diagnosis of the disease⁸; however, many do not have access to a diabetes education center. Such individuals thus present to the wound care clinic with a critical deficiency in their ability to manage the disease. This deficiency itself could be a contributing factor to both the development of the wound and the impaired wound healing.

Depression and Burnout

As mentioned previously many people with diabetes have varying levels of depression,⁸ which can mildly or severely compromise self-management, depending on their coping abilities. If the individual’s diabetes management strategies are compromised by depression, the provider can expect more challenges for wound healing. Diabetes alone conveys psychological, social, and financial burdens on the affected individual; a wound creates additional psychological, social, and financial burdens.

Burnout is a potential problem for everyone concerned—the patient can become burned out from living with diabetes and its associated complications continuously, with no respite, and the wound care team can become burned out by the impact of diabetes on wound healing and the perception that the patient is not optimally self-managing the disease or the wound, thereby “sabotaging” the wound care plan. The psychosocial impact of diabetes is life altering, especially with the addition of chronic complications that frequently accompany diabetes, including unsightly, odiferous, and difficult-to-manage wounds. There are no easy answers or rote formulas for these challenges; providers must do their best to provide comprehensive support to these patients and their families.⁸

Adherence

The patient’s adherence to the overall disease management plan is critical. However, before placing the term non-compliant or non-adherent on the person with diabetes, the wound care clinician should assess whether the patient has the best diabetes management plan individualized to his or her needs. The clinician must assess the patient’s ability to self-manage the diabetes and provide an appropriate referral as needed to address deficiencies where they exist. The status of the patient’s diabetes control is prerequisite knowledge in order for the wound care clinician to help the patient create an environment for wound closure and healing. TABLE 7-8 lists helpful strategies for the clinician who is working with a patient who is having difficulty with adherence.

The Wound Care Clinician’s Role

The initial examination of the patient with a wound includes a basic assessment of the patient’s diabetes management plan to ensure that the disease is under control. TABLE 7-9 is a suggested list of intake components to consider, and TABLE 7-10 lists the diagnostic criteria for diabetes.

A typical case scenario may present as follows: a patient with diabetes presents with a wound with signs and symptoms of infection. The blood glucose level is 345 mg/dL. The clinician needs to determine which came first: chronic hyperglycemia, which made the patient more susceptible to infection, or the infection, which caused the blood glucose levels to increase. A comparison of the capillary blood glucose levels with a current hemoglobin A1C test can help make this determination. If the A1C value is high, then the blood glucose has been out of control for at least several months and diabetes management strategies are of paramount importance. If the A1C shows adequate control, then the diabetes has been well managed, and the infection has caused the elevated blood glucose levels. At this point, the patient may require the addition of insulin to the diabetes medication regime—at least temporarily—to help control the infection-instigated elevated blood glucose. The wound care clinician can make this recommendation to the provider who manages the patient’s diabetes. Thus, object glycemic tests can be used to help manage wound healing, remembering that diabetes is ever present and must be managed at all times to help create the best wound closure and healing outcomes.

Conclusion (Diabetes)

The wound care team needs a working knowledge of the diagnosis of diabetes, diabetes management strategies (including the most commonly associated complications and the effects of diabetes on wound healing), as well as proficiency in performing a thorough assessment of the patient and the wound. While it is not the responsibility of the wound care team to manage the person’s diabetes—that duty belongs to the patient and the practitioner responsible for the medical management—the wound care team should assess if the disease is being managed as successfully as possible and recognize when other diabetes interventions and counseling need to be considered for optimal wound closure and healing outcomes.^10,11

The diabetic foot is a complicated pathological entity suffering from varying degrees of physiological and biomechanical balance and imbalance. Prolonged exposure to slowly elevating blood glucose leads to glycosylation of multiple organ systems and progressively advancing neurovascular crises triggered by the loss of system homeostasis. The “perfect storm” of intrinsic and extrinsic stressors associated with diabetes causes a system collapse that results in a breakdown of the foot’s ability to manage the combination of individual stressors, thereby leading to a breakdown sufficient to cause ulceration and/or neuroarthropathy of the diabetic foot.¹²

Once the skin has broken and exposed the underlying tissues to the risk of infection, the patient and the practitioner have a relatively short period of time within which to address the component problems and restore balance to the system, otherwise complications such as osteomyelitis or amputation may ensue. Carlyle Begay, in a presentation delivered to the National Indian Health Bureau in January 2012, referred to this time period as “the golden hour for the diabetic foot,” a concept coined from the emergency management of cardiovascular and cerebrovascular accidents (FIGURE 7-10).¹³

From the onset of the wound, there are approximately 30 days or 4 weeks to restore homeostasis and thereby prevent further tissue breakdown, infection, and progression to amputation. Standard of care requires the introduction of definitive care before 4 weeks; advanced therapies to heal the wound can be initiated at that time if 50% wound closure has not occurred. Dr Peter Sheehan conducted a large, prospective, multicenter trial of 203 diabetic patients that assessed the ability of the 4-week healing rate to predict complete healing at 12 weeks. He concluded that “patients in whom ulcer size fails to reduce by half over the first 4 weeks of treatment are unlikely to achieve wound healing over a reasonable period.”¹⁴

There is a fivefold increase in the risk of infection in wounds that progress beyond 4 weeks of therapy and a 155 times greater risk of amputation once an infection develops.¹⁵

A panel created for the American Diabetes Association Consensus Development Conference on Diabetic Foot Wound Care in April 1999 concluded, “Any wound that remains unhealed after 4 weeks is cause for concern, as it is associated with worse outcomes, including amputations.”¹⁶ It is evident from these studies that a wound on a diabetic foot is a very serious event and must be treated as such from day one. Early interventions such as risk assessment, educational initiatives, and aggressive treatment interventions can literally be life saving for many patients with diabetes.

Diabetes and the Effects on the Systems of the Foot

Foot problems are common in patients with diabetes and 25% of them, or approximately 6.8 million people, will develop a foot ulcer during their lifetime.^17,18 Once an ulcer has developed, the 5-year survival rate for a patient with diabetes is approximately 45%, a figure that is lower than that for both prostate and breast cancer. Despite the dangers and the risks associated with ulceration in the diabetic population, the problem has received very little press in comparison to other more politically interesting diseases.¹⁹ For many years, foot complications have been the leading cause of hospitalization for patients with diabetes.²⁰ Almost 30% of diabetics aged 40 years or older have impaired sensation in the feet (ie, at least one area that lacks feeling), or approximately 8 million individuals (60–70% of people with diabetes) have mild-to-severe forms of nervous system damage affecting both sensory and motor systems.²¹ The major system failure in diabetics leading to the development of an ulcer is the loss of protective sensation in the lower extremity. Combined with intrinsic muscle loss and extrinsic muscle imbalance, this leads to increasing biomechanical stress in areas of high pressure and eventual tissue loss. The skin breakdown is a combination of pressure ischemia, reperfusion injury, expanding sublesional microhemorrhage and micronecrosis, and shearing injury, all of which lead to an accumulation of coalescing blood and transudate within or beneath the skin. The skin eventually ruptures, opening the subcutaneous tissues to bacterial invasion from the skin surface (FIGURES 7-11 and 7-12).

Diabetic dyshidrosis or dry skin secondary to the loss of normal skin perspiring (a result of autonomic nervous dysfunction) is documented, and patient education about the daily use of an emollient is included in the care plan, along with consultation with a podiatric or allopathic physician for a prescription hydrating cream (FIGURE 7-13). Neurologic assessment includes the Semmes–Weinstein monofilament test, reflexes, biothesiometer testing, muscle strength and function, visual gait and posture analysis, and some quantification of plantar pressures (FIGURE 7-8). FIGURE 7-14 illustrates the 10 sites that are tested with the monofilaments. The PressureStat device is an excellent tool for obtaining a quick quantifiable assessment of plantar pressures (FIGURE 7-15).