Diabetic Peripheral Neuropathy: Emerging Treatment Options and the Podiatric Practice

Supported by an educational grant from Eli Lilly and Company and Amylin Pharmaceuticals, Inc
Wednesday, August 25, 2004
9:00 am – 11:00 am

Program Faculty:
David G Armstong, DPM, MSc (Chair)
Aaron I Vinik, MD, PhD, FCP, FACP
Lawrence A Lavery, DPM, MPH
Andrew JM Boulton, MD, FRCP

This symposium described the clinical characteristics of distal symmetric diabetic polyneuropathy, the most common type of diabetic neuropathy, its interrelationship with other diabetic neuropathies, and its common pathogenesis with diabetic retinopathy and diabetic nephropathy, which are also diabetic microvascular complications (DMC).   Screening tools for evaluating the risk of future foot ulceration, and diabetic neuropathy management recommendations emphasizing current and emerging pharmacotherapies were also covered.

Dr Vinik reviewed the pathophysiology and clinical presentation of several neuropathies that occur frequently in patients with diabetes. Diabetic neuropathy and the other DMC share a common pathophysiology. Patients who have one DMC are considered to be at risk for the others. Hyperglycemic, metabolic, vascular, and autoimmune mechanisms have been postulated to explain this phenomenon. Hyperglycemia is associated with increased oxidative stress, sorbitol production via the aldose reductase pathway, and protein kinase C β (PKC β) activation, all of which have been associated with the development of DMC.

Multiple types of nerve fibers are affected by diabetes that may lead to loss of sensation in the foot, leaving patients at risk of ulceration and ultimately for amputation. Dr Lavery reviewed some of the screening tools available for diabetic neuropathy. Risk factors for foot ulceration can be reliably identified with 128 Hz tuning forks, a reflex hammer, vibration perception threshold instrumentation, and nerve conduction velocity instrumentation. No single test meets the ideal of simultaneously being noninvasive, inexpensive, sensitive, and specific for predicting foot ulceration. Screening for diabetic neuropathy with a 128 Hz tuning fork and reflex hammer was recommended. However, getting a good patient history and performing a thorough physical exam are considered more important than any screening test.

Dr Boulton reviewed several current and emerging pharmacotherapeutic agents for chronic manifestations of diabetic neuropathy. Clinical management of diabetic neuropathy encompasses control of both glycemia and pain. Stable, near-normoglycemia is currently the only proven treatment for delaying the development of diabetic neuropathy and other DMC. Although there are no FDA-approved treatments for painful symptoms of diabetic neuropathy, tricyclic antidepressants (TCA) are effective, inexpensive, and recommended for first-line treatment of pain symptoms in diabetic neuropathy in several clinical guidelines. Other agents such as gabapentin and tramadol are frequently used in place of TCA to avoid the TCA’s anticholinergic side effects. Several agents to delay the development and progression of diabetic neuropathy are currently in development. To date, the only pathogenetic treatment for diabetic neuropathy is an aldose reductase inhibitor, epalrestat. This drug has been approved only in Japan; it shows minor clinical benefits for all three DMC. Clinical trials are currently underway for an antioxidant, α-lipoic acid, and a PKC β inhibitor, ruboxistaurin mesylate. Both agents have shown symptomatic improvements in diabetic neuropathy. Ruboxistaurin has also shown benefits for nerve conduction velocity and for diabetic macular edema, a manifestation of diabetic retinopathy. Further clinical trial reports are expected for both agents in 2005.