Current And Emerging Insights On Treating Diabetic Peripheral Neuropathy

Peter Bregman, DPM, FAENS, FACFAS, and Pasquale Cancelliere, DPM

Given the serious consequences of neuropathy for the millions with diabetes, it is vital for physicians to have a full armamentarium of treatment options. These authors detail the finer points of surgical nerve decompression, pharmacologic agents and other emerging treatments.

Currently, there are 23 million people with diabetes in the United States alone and 50 percent or more will develop peripheral neuropathy.1 Diabetic peripheral neuropathy continues to be the predisposing factor for diabetic foot complications.2-4 Even in the presence of underlying vascular disease, neuropathy is the threshold for development of diabetic foot ulcerations. As diabetes mellitus continues its trend toward being a global pandemic, an understanding of diabetic peripheral neuropathy is paramount for the physician treating patients affected by the disease.

   In the last eight years the lead author has been involved with the Association of Extremity Nerve Surgeons (AENS), he has gained a wider perspective on the different options available for treating peripheral neuropathy. The lead author has had the pleasure to hear lectures from PhDs in the field of biochemistry who have new insights into the treatment of diabetic neuropathy. The lead author also has heard from pain management specialist MDs from esteemed universities such as Stanford University who have a great grasp of what medications work well and what is just good marketing by the pharmaceutical companies. The lead author has even been exposed to the use of peripheral nerve stimulators that are often a last resort. The lead author also has performed hundreds of decompressions on patients who were diagnosed with nerve entrapment to restore sensation and relieve pain.

   Although a complete review of the pathophysiology of diabetic peripheral neuropathy is beyond the scope of this article, the following are the major pathways for the development of neuropathy. They are the polyol, uremic and advanced glycation end product (AGE) pathways.5 Essentially, they are the result of altered glucose metabolism as a consequence of hyperglycemia. This leads to inhibition of nitric oxide production, accelerated Wallerian degeneration of the nerves and deterioration of the nerve sheath.

   Diabetic peripheral neuropathy will present initially with hyperesthesia, defined as “tingling” and hypersensitivity to either temperature or pain, and is followed by painful feelings of burning. The later stages will be defined by anesthesia of the extremities with the feet being affected primarily. All of these manifestations are defined as sensory and primarily affect small nerve fibers.

   Diabetic peripheral neuropathy is a progressive and irreversible disease. Physicians direct treatment at addressing euglycemia and symptomatic treatment.6

   Motor neuropathy is also part of the equation. This will lead to the loss of the motor end plate of the motor nerve fibers, primarily the large nerve fibers. This causes intrinsic muscle atrophy and the classic “intrinsic minus” foot. When this combination is compounded with diminished proprioceptive sensation, it leads to altered gait patterns and abnormal plantar foot pressures that cause stress to the tissues, including skin, ligaments, joint capsules and bones. The results are ulceration, breakdown and finally amputation. Loss of balance also is of consequence.

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