The Diabetic Foot and Neuroarthropathy

Metabolic Control

Diabetes is a metabolic disease resulting from inadequate insulin production, decreased end-organ responsiveness, or a combination of both. Historically, diabetes mellitus has been categorized as either Type I disease where patients cannot produce insulin, or Type II disease where patients either cannot produce sufficient insulin to support their body mass or have end-organ nonresponsiveness. Experts now appreciate a spectrum of disease that ranges from an inability to produce virtually any insulin to a progressive inter-relationship of inability to produce sufficient insulin to support increased body mass combined with end-organ responsiveness.

The modern treatment of diabetes is multifactorial. Medical management starts with dietary intervention focused on regulating the amount of glucose and glucose equivalents derived from protein and fat. Standardizing the amount of glucose intake attempts to minimize the stress on the pancreas to produce increasing amounts of insulin. Medical treatment then combines medications to increase the affected individual's ability to maximize the production of endogenous insulin combined with bioengineered insulin and medications designed to improve the effectiveness of the native and exogenous insulin. At the same time that an effort is made to control blood sugar levels, a concerted effort is made to control the parallel cardiovascular risk associated with low density lipoproteins.

The effectiveness of treatment is guided by monitoring the serum level of glycosylated hemoglobin (HbA1c). The HbA1c test is a simple blood test that measures the average blood sugar level over the past 3 months. It is also the standard screening test to diagnose prediabetes and diabetes. Higher HbA1c levels are linked to diabetes complications, so reaching and maintaining an individual HbA1c level below 6% is the goal of modern therapy. The current American Diabetes Association defines a normal HbA1c as under 5.7%. Prediabetics have serum levels between 5.7% and 6.4%. One is officially diagnosed with a diagnosis of diabetes when their HbA1c is 6.5% or higher.

Diabetic Organ System Disease

Diabetes associated organ disease is a consequence of increased circulating blood glucose. The increased circulating blood glucose covalently binds to hemoglobin, forming glycosylated hemoglobin, that is hemoglobin A1c. This glycosylated hemoglobin stimulates the formation of free radicals within red blood cells. Through a complex mechanism, these free radicals interact with low-density lipoproteins to cause damage to the basement membranes of blood vessels, leading to the development of atherosclerotic blood vessel disease. The multiple organ system impairment so characteristic of longstanding diabetes develops secondary to this thickening and damage at the basement membrane of small blood vessels at the vascular bed and capillary level of targeted organs. Any process that inhibits product exchange will impair the homeostasis of the tissue containing the vascular bed. While macro blood flow may be adequate, the actual micro-perfusion of target organs is impaired. It is this systemic microvascular disease process, related to increased circulating glycosylated hemoglobin, that is responsible for the development of a similar disease level in so many different organs over time. This phenomena explains why patients develop similar increasing pathologic levels of cardiac, renal, vascular, and neuropathic organ system disease at approximately the same period of disease progression ( Fig. 32-2 ).

Peripheral Neuropathy

It is well accepted that the presence of sensory neuropathy, as measured by insensitivity to the Semmes-Weinstein 5.07 (10 g) monofilament, is the primary risk factor associated with the development of diabetic foot ulcers or foot infections ( Fig. 32-3 ). It has long been held that the loss of protective sensation in these patients allows externally applied trauma through pressure or shear, to cause failure of the soft tissue envelope and the development of ulcers or wounds. The pathophysiology of diabetic foot ulcers is actually far more complex. Cancer patients often develop a similar level of sensory peripheral neuropathy as a consequence of chemotherapy. On examination, these patients will often have an objective loss of sensation. They frequently complain of burning neuropathic pain, yet they rarely develop foot ulcers, infection, or Charcot foot deformity. We need to explore the unique environment associated with diabetes that is responsible for this epidemic.

Longstanding diabetic patients develop motor and vasomotor peripheral neuropathy in addition to the sensory neuropathy, both of which contribute to the pathologic process. The motor neuropathy is responsible for the development of structural deformities, creating bony prominences that serve as pressure points for the application of direct pressure or shearing forces. Historically, it was thought that diabetic patients developed the typical claw and hammertoe deformities secondary to idiopathic contracture of the intrinsic muscles of the foot ( Fig. 32-4 ). Our modern appreciation for the development of organ system disease provides a much more reasonable explanation. Peripheral neuropathy develops as a consequence of the basement membrane disease process within the vessels of the target organ, that is peripheral nerves. Dorsiflexor muscles are fast twitch muscles, much smaller in cross-sectional diameter than their antagonist plantar flexor muscles. The associated motor nerves to the smaller dorsiflexor muscles are also smaller in diameter and, thus, are affected earlier in the pathologic disease process than the larger nerves responsible for innervating the postural plantar flexor muscles. This leads to a relative dynamic muscle imbalance that only worsens with time. With time, the flexible dynamic deformity, through collagen cross-linking, leads to the development of static joint contracture. The end result is the development of the clearly recognizable fixed structural deformity (see Figs. 32-4 and 32-5 ).

Autonomic neuropathy produces dysfunction within the sweat glands of the foot. This leads to the development of stiff, dry, scaly skin that cracks easily because of its inflexible qualities. Cracks in the thickened stiff skin, especially between the toes and in exposed areas overlying bony prominences, lead to skin breakdown and create an entry portal for bacteria ( Fig. 32-6 ). These three components of peripheral neuropathy lead to chronic soft tissue swelling, leathery connective tissue with increased collagen cross-linking, and stiffness of the periarticular tissues (see Figs. 32-4–32-6 ).

Angiopathy

The characteristics of peripheral vascular disease in diabetic patients carries both similarities and substantial differences from the idiopathic atherosclerotic peripheral vascular disease observed in the nondiabetic. Both develop narrowing of arterial vessels secondary to the development of atheromatous plaque. The pathologic component specific to diabetic vascular disease is the injury observed at the basement membrane level of vessels within the heart and extremities. This injury impairs the ability of oxygen and nutrients to be transferred from arterial blood through the small vessel vascular bed of the targeted end organ tissues. This end organ pathology, similar to all other affected end organs, leads to progressive dysfunction and irreversible damage within the small vessels of the targeted arterial tree. When this basement membrane disease occurs within the heart, the expression is coronary artery disease. When in the kidney, one observes the development of renal failure. When in the arterial tree, one observes the so-called small vessel peripheral vascular disease associated with diabetes.

Structural Changes

The human foot is a uniquely adapted terminal end organ of weight bearing. Important structural changes observed within the soft tissue envelope of the plantar weight-bearing skin and the joints of the toes are crucial factors in the development of diabetic foot disease. Stiffness and callus formation within the skin have been found to be important factors associated with breakdown in the soft tissue envelope and ulcer formation. It has been demonstrated that the plantar skin of the diabetic patient is thicker with a very stiff elastic modulus more prone to form thick calluses. Whether these characteristics are a true independent variable secondary to the vasomotor neuropathy, or simply a response to the application of pressure and shear forces, are topics for discussion (see Fig. 32-6 ).

The typical clawing of the toes has long been thought to be simply secondary to intrinsic muscle contracture within the foot. As discussed earlier, the typical forefoot deformities are likely secondary to longstanding peripheral neuropathy, dynamic muscle imbalance and secondary joint contracture. The ensuing static changes are likely worsened by the associated vasomotor neuropathy, leading to diminished range of motion and the development of joint flexion contractures (see Figs. 32-4–32-6 ). The observed deformities are initially dynamic but become static and fixed structural deformities over time. A secondary consequence of the clawing of the toes is the distal retraction of the soft tissue padding underneath the metatarsal heads. The combination of the muscle imbalanced clawing of the toes, retraction of the plantar sub-metatarsal head soft tissue padding, and dorsally applied pressure from standard footwear makes the metatarsal heads more prominent on the plantar surface and prone to injure the overlying soft tissue envelope.

Immune Deficiency

The mechanical and structural changes within the foot of the longstanding diabetic patient that appear responsible for the development of failure of the protective soft tissue envelope are compounded by the associated immune deficiency seen in this complex patient population. This is expressed by deficiency in both T- and B-cell immune systems. This systematic inability to fend off even low virulent pathogens makes this patient population even more prone to opportunistic infection and rapid clinical deterioration.

Infections in the diabetic patient are often polymicrobial. T- and B-cell dysfunction have long been thought to be the major cause of the impaired immunity. This is compounded by the basement membrane disease that actually impairs local perfusion of infected tissues, impairing the ability of the patient’s immune system to both attack local infection and deliver antibiotic therapy. This explains the seemingly paradoxical presence of bounding pulses and profuse bleeding, combined with the inability to actually perfuse and resolve infection in the end organ.

Morbid Obesity

The United States Centers for Disease Control (CDC) estimated that there were between 16 and 18 million diabetics in the United States in the mid 1980s. The CDC now estimates that there are more than 34 million diabetics, or almost 10% of our population. During the same period of time, the incidence of morbid obesity has also skyrocketed. There is a question of whether we are now better at making the diagnosis of diabetes, or whether there is an important association of an increasing rate of both morbid obesity and the incidence of diabetes. The importance of this question becomes apparent when we appreciate that the presence of morbid obesity amplifies the pathophysiologic effects of the disease process by the application of increased force to a terminal organ of weight bearing that has been compromised in so many ways. The presence of morbid obesity negatively affects cardiovascular function and aerobic functioning of this population, in addition to being responsible for the application of increased biomechanical loads on an already impaired terminal organ of weight bearing.

Central Neuropathy and Judgment Deficits

Many clinicians are lulled into thinking that these individuals develop foot ulcers or infections due to poor health choices, because they are in denial, or they are simply noncompliant . One should appreciate that, in addition to peripheral neuropathy, these patients have a central neuropathy secondary to the same pathologic processes that led to the development of peripheral neuropathy. When objectively studied, these individuals often have cognitive and judgment deficits when compared to healthy controls. Because of this inability to process important information, diabetic educators use frequent patient care encounters and constant educational re-enforcement. It is not that these patients are in denial; they are simply not able to adequately process the information. One must be cognizant of these cognitive deficits when planning treatment.

A secondary important impact of the central neuropathy is the presence of increasing gait instability in the longstanding diabetic population, leading to an increased potential for falls and further trauma. The gait instability is secondary to a combination of both central neuropathy affecting the balance centers in the brain, and the inability to feel the floor , a proprioceptive consequence of the peripheral neuropathy. This instability of gait is largely responsible for the frequent falls observed in this patient population. It also is partially responsible for the abnormal loading applied to the feet of these complex individuals. Treatment is difficult due to poor levels of comprehension, often requiring the use of canes or other assistive walking devices. Physical therapy and gait training can be beneficial.

Preventive Strategies

The most effective methodology of successfully addressing the epidemic of diabetic foot ulcers, infection, and eventual lower extremity amputation is the development of a health system strategy. This starts with the identification of patients at risk and creates a patient care algorithm, based on the expression of the disease in the individual patient. The identification of at risk patients has historically fallen on the primary care physician. This methodology allows too many patients who would benefit from intervention to go undetected. Whether the medical management of diabetes is provided by the primary care physician or endocrinologist, most organizations employ the diabetic educator as a key conduit to provide a continuum of patient education, well-patient monitoring, and the identification of treatable disease expression. Most best practice organizations take advantage of this relationship and assign the task of diabetic foot risk stratification to the diabetic educator. This allows selective referral to the appropriate specialists, based on the disease expression of the individual patient. Incorporating diabetic foot screening into the domain of the diabetic educator ensures making diabetic foot care an essential component of overall diabetic disease management. An important by-product is the creation of a methodology to identify disease expression at an earlier stage of development, when morbidity is more easily reversible and treatment is less invasive.

Risk Stratification

The treatment of the diabetic foot is based on risk stratification. Diabetics that have previously had a foot ulcer or infection, or have previously undergone an ipsilateral or contralateral partial or whole foot amputation, are the highest risk group for the development of diabetic foot ulcers or infection. The most predictive clinical finding is the presence of peripheral neuropathy, as measured by insensitivity to the Semmes-Weinstein 5.07 (10 g) monofilament ( Figs. 32-3 and 32-7 ). The presence of normal pedal pulses is indicative of adequate vascular inflow. The absence of palpable pedal pulses should be noted, but further testing is not necessary, as intervention is not generally advised until the patient either has a nonhealing wound or complains of pain at rest .

Structural bony deformity, in the form of hammer or claw toes, hallux valgus or deformity associated with Charcot foot arthropathy, create identifiable geographic locations for the development of diabetic foot ulcers ( Figs. 32-4, 32-8 , and 32-9 ). Other important risk factors include advanced trophic skin changes, including decreased hair growth, abnormal toe nails, discoloration or atrophy of the skin, history of claudication with walking, and venous insufficiency, especially in morbidly obese patients.

Many grading systems have been developed in the attempt to develop a scoring system capable of predicting the risk for the development of diabetic foot ulcers. Most are cumbersome, not necessarily statistically accurate, and are difficult to correlate with individual patient care. Understanding the spectrum of risk allows the clinician to develop a simple methodology. At the low end of risk stratification is the diabetic patient with no structural deformity, protective sensation (as measured by the Semmes-Weinstein 5.07, 10 g monofilament), and palpable pedal pulses. The opposite end of the spectrum is characterized by the patient with structural deformity, peripheral neuropathy and absent pedal pulses ( Fig. 32-10 ).

Patient Education

Individual patient education is the cornerstone of a multidisciplinary health system strategy for the treatment of the diabetic foot epidemic. Unlike the joint arthroplasty patient who has high patient education retention following a single class prior to joint replacement surgery, the longstanding diabetic patient at risk for the development of foot-associated pathology often has cognitive and judgment deficits secondary to their central neuropathy. While physicians have long held the mistaken opinion that longstanding diabetics are in denial, and/or simply noncompliant, the actual barrier to successful patient education are the cognitive and judgment deficits that makes information retention so difficult. A successful patient education program in this unique patient population requires frequent patient encounters with the diabetic educator for reinforcement of the principles of care and reassessment.

The essential first step is the reinforcement of daily self-examination. Problems identified early are easier to treat and have more favorable outcomes than pathologic conditions that have progressed. The barriers to successful daily self-examination are poor vision secondary to retinal disease, joint stiffness and arthritis that impairs bending and accessing feet, and morbid obesity that physically blocks the ability to view feet. Overcoming these barriers can often be achieved by training a spouse or other caregiver. Patients are provided mirrors and magnifying glasses to improve access ( Box 32-1 ). The relationship between the diabetic educator and the patient often allows the earlier identification of pathology, when treatment is more reversible and less invasive.