Current And Emerging Options For Treating Diabetic Neuropathy

By Stephanie Wu, DPM

   Neuropathy is a common and debilitating complication of diabetes mellitus. According to data compiled by the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) and the American Diabetes Association (ADA), roughly 60 to 70 percent of the 18.2 million Americans with diabetes will develop some form of diabetic neuropathy and about 3 million patients with diabetes will experience painful neuropathy.

   There are three broad types of neuropathy (sensory, motor and autonomic) associated with diabetes. Sensory neuropathy is the most prevalent of the three and is often simply referred to as diabetic neuropathy. Symptoms usually begin distally at the base of the toes and ascend proximally up the lower leg as the disease progresses. These symptoms can often be described as burning, tingling, stabbing, and a “pins and needles” sensation in a stocking and glove distribution. The paresthesias often result in the loss of pain perception. This loss of protective sensation can lead to the formation of foot ulcerations, infections, even amputations, and cause significant morbidity and mortality.

   The pathogenesis of diabetic neuropathy is believed to be multifactorial with hyperglycemia being the primary risk factor.1,2 The exact sequence of physiological events that results in this loss of pain perception is poorly understood and is the focus of current research. Researchers have suggested several theories about the possible etiopathogeny of diabetic neuropathy. These theories include: abnormalities of protein glycation; sorbitol accumulation; polyol pathway flux; protein kinase C activation; advanced glycation endproducts (AGE); receptor for advanced glycation end products (RAGE); a decrease in neuronal nitric oxide synthase (nNOS) protein; and microvascular hypoxia resulting in oxidative stress.2-8

   The goals of treating diabetic neuropathy are preventing and possibly reversing the progression of nerve damage, and reducing the symptoms. Currently, there is no available pharmacologic agent in the United States that repairs the underlying nerve damage. Although current medical treatment algorithms stress the importance of delaying the onset of diabetic neuropathy, these algorithms are primarily geared toward alleviating the symptoms. The recent resurgence of interest in the pathogenic mechanisms of diabetic neuropathy has inspired new avenues of investigation for therapeutic intervention with some promising results.

   With this in mind, let us take a closer look at current and emerging treatments for diabetic neuropathy.

Emphasizing Glycemic Control

   In general, researchers note that diabetic neuropathy results from chronic nerve damage secondary to hyperglycemia. Rigid glycemic control is of fundamental importance to help delay the onset and slow the progression of neuropathy.9 The diabetes control and complications trial (DCCT) has shown that good glycemic control can decrease the risk of diabetic neuropathy by over 50 percent. It is recommended that people with diabetes ideally maintain their hemoglobin A1c readings at 7.0 or below.

   One may combine good glycemic control with the myriad of pharmaceutical agents available for symptom management. These agents include the use of selective serotonin and norepinephrine reuptake inhibitors (SSNRI), anticonvulsants, tricyclic antidepressants (TCAs), antiarrhythmics and topical therapy. Non-narcotic analgesics, such as acetaminophen, tramadol and nonsteroidal antiinflammatories, have been advocated as adjunctive treatments. Opioid analgesics are not very efficacious in the treatment of neuropathic type pain, can lead to addiction and are therefore generally not recommended.

Assessing The Effectiveness Of SSNRI Agents

   Both serotonin and norepinephrine have been characterized to help regulate emotions as well as sensitivity to pain. SSNRIs represent a class of antidepressant agents that help regulate and treat depressive disorders and neuropathic pain by sustaining levels of the two neurotransmitters in a balanced fashion.

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