Current And Emerging Tools For Assessing Diabetic Peripheral Neuropathy

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Maria K. Piemontese, DPM, and Andrew J. Meyr, DPM

An international study of patients with diabetes presenting with incident foot ulceration identified the “critical triad” of peripheral neuropathy, trauma and foot deformity in the pathogenesis of approximately 63 percent of patients.1 The most common component was peripheral neuropathy, which was present in nearly 80 percent of the patients in this study.

   Podiatric physicians are generally well aware of both the prevalence and potential complications associated with diabetic peripheral neuropathy.2 We are also fairly quick to recognize and diagnose the sensory component of this sequela. What we may be guilty of, however, is neither appreciating the breadth of diabetic neuropathy nor quantifying our examination of the patient with diabetic neuropathy.

   The effect of diabetes and hyperglycemia on patient outcomes is well established. The Portland Diabetic Project shows results that are simply staggering with respect to patient morbidity and mortality following cardiovascular interventions.3 Further investigations into orthopedic-specific postoperative outcomes have also shown that diabetes contributes to adverse patient morbidity, length of hospital stay, cost of hospital admission and infection rates among other variables.4-7

   What we have recently been learning, however, is the interesting effect that neuropathy may specifically have on these outcomes.

   Wukich and colleagues recently published a study that highlights this concept.8 The retrospective chart review focused on over 1,000 patients who had elective orthopedic foot and ankle surgery. The authors found that patients with diabetes were five times as likely to experience a severe infection requiring hospitalization in comparison to non-diabetic patients.

   Interestingly, though, there was no significant difference when researchers removed neuropathy from the analysis. In other words, diabetic patients without neuropathy were as likely to have a significant postoperative infection in comparison to non-diabetic patients. Further, neuropathy as a single factor demonstrated an odds-ratio analysis of 9.32 as a predictor for postoperative infection. This means a patient with neuropathy was more than nine times as likely to develop a postoperative infection in this cohort.8

A Closer Look At The Pathogenesis Of Diabetic Neuropathy

Diabetic peripheral neuropathy most commonly occurs as a symmetric distal polyneuropathy affecting large and small fibers. Although the cause is multifactorial, the most accepted theories involve direct axonal injury secondary to metabolic abnormalities and inadequate microvasculature.9,10 This theory involves the accumulation of sorbitol, which is the product formed from glucose by the aldose reductase enzyme. For those with hyperglycemia, elevated levels of sorbitol result in the swelling of cells, increased activity of protein kinase C and decreased intracellular levels of myo-inositol and taurine. These processes in turn lead to limited intracellular metabolism and damage to blood vessels.

   Additionally, glycosylation of axon and microvessel proteins may cause reduction of endoneural blood flow and nerve ischemia, causing nerve and ganglia hypoxia with oxidative stress.11,12

   Regardless of the cause, we understand the effects.9-12 The three main types of neuropathy that we generally encounter are sensory, motor and autonomic in nature.

   Sensory neuropathy presents with an insidious onset and has a stocking and glove distribution in the distal extremities. The disease first affects smaller unmyelinated fibers. This in turn compromises the patient’s ability to detect thermal and mechanical pain. With continued exposure to hyperglycemia, the larger fibers become affected and influence the sensation of sharp pain, proprioception and pressure. Although the importance and impact of this sensory neuropathy are clear, the motor and autonomic components may be just as damaging from a pathogenesis perspective.

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