The Management of Diabetic Neuropathy and Glycemic Control in Long-Term Care Facilities (Part III of III)

Tue, 1/13/09 - 3:38pm
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Author(s):

Richard Bedlack, MD, PhD
Activity Medical Director
Associate Professor of Neurology
Duke University School of Medicine
Durham, NC

Pathophysiology

How Does Diabetes Mellitus Cause Nerve Damage?

Although the pathophysiology of diabetic neuropathy is unclear, most experts believe that hyperglycemia is the cause of the nerve damage in DPN.48 Hyperglycemia causes increased levels of intracellular glucose in nerves, leading to saturation of the normal glycolytic pathway.49 Nevertheless, different neuropathies may have different (and perhaps overlapping) mechanisms; for example, with focal or asymmetrical diabetic neuropathy syndromes, vascular injury or autoimmunity may play more important roles. Other factors thought to play a role include activation of the polyol pathway, advanced glycation end products, increases in oxidative stress, altered gene expression with altered cellular phenotypes, changes in cell physiology relating to endoskeletal structure or cellular transport, reduction in neurotropins, and nerve ischemia.

Managing Diabetic Neuropathy Requires Treating the Underlying Disease

Treatment of Neuropathic Pain in Type 2 Diabetes

Optimal management of diabetic neuropathies requires that clinicians understand that long-term control of blood sugars and reduction of cardiovascular risk factors is the cornerstone of treatment, both for diabetes and for diabetic neuropathy.3 Clinicians who properly treat the underlying diabetes have a better chance of reducing neuropathy and its accompanying symptoms, as opposed to regimens that simply address the neuropathy symptoms. Figure 2 presents the ADA and American Association of Clinical Endocrinologists/International Diabetes Federation–recommended goals for patients with type 2 diabetes who are at risk for diabetic neuropathy.4,50-52

Nonpharmacological Treatment Options

Lifestyle Modifications

Diet and exercise have been shown to promote cutaneous reinnervation and improve pain in diabetic neuropathy patients.23,53 Patients should be counseled on the benefits of weight loss, tobacco cessation, and the effects of alcohol on diabetic neuropathy.

The Importance of Foot Care

Once a patient has diabetic neuropathy, foot care becomes crucial for preventing ulceration, infection, and amputation.32 At each visit, the physician should examine the patient’s feet to detect evidence of neuropathy or early lesions, as well as skin breaks, red or callused areas, decreased pedal pulses, delayed capillary refilling, bony deformities, and protective sensation.17

Table 4 provides instructions clinicians should provide patients to foster effective foot care.5,17

Pharmacological Treatment Options

The classes of drugs with the best proven efficacy are antidepressants, anticonvulsants, and opioids.10 Duloxetine, a serotonin noradrenaline reuptake inhibitor (SNRI), and pregabalin are specifically approved by the U.S. Food and Drug Administration (FDA) for the treatment of painful DPN. All other agents must be considered “off-label,” although other considerations, including cost, intolerance of approved agents, comorbidities, and efficacy, may dictate their use.

Antidepressants

Duloxetine has been studied in 2 randomized, double-blind, placebo-controlled trials for relief of pain in patients with painful diabetic neuropathy,54,55 and is approved by the FDA at total dosages of 60 mg/day.56

The first study, published in 2005, was a 12-week, multicenter, double-blind study in which 457 patients experiencing pain due to polyneuropathy caused by type 1 or type 2 diabetes mellitus were randomly assigned to treatment with duloxetine 20 mg/day, 60 mg/day, or 60 mg BID or placebo.54 Duloxetine 60 and 120 mg/day demonstrated statistically significant greater improvement on the 24-hour average pain score compared to placebo. Duloxetine also proved more efficacious than placebo on almost all secondary measures (ie, worst pain severity and mood).

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