All patients with diabetes are at increased risk for complications affecting the cardiovascular and nervous systems, as well as the kidneys and eyes. Neuropathy is one of the most common comorbidities — affecting about 60% to 70% of patients. Managing glucose levels is the most direct way to prevent nerve damage and alleviate pain.
Diabetic neuropathy arises when glucose levels consistently remain elevated. Smokers, people aged older than 40 years and those with poorly controlled underlying diabetic disease are at highest risk.
Patients may first notice a tingling in the extremities – including the hand, arms, toes, feet, and legs— before a diabetes diagnosis is even made. This form of peripheral neuropathy may involve symptoms including numbness, weakness or pain.
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Another type, autonomic neuropathies, involves the nervous system and affects the patient’s cardiovascular, gastrointestinal and genitourinary systems. Patients who have an autonomic neuropathy may present with dizziness or weakness; indigestion, nausea or vomiting; diarrhea or constipation; and problems with urination.
Diabetic neuropathic pain can be focal or widespread depending on the source and requires different types of management.
Managing glucose levels
Medication, diet and exercise help keep blood glucose levels within a healthy range.
The Diabetes Control and Complications Trial found that tight glucose control reduced the risk of neuropathy by 60%1, and results from other trials, including the UK Prospective Diabetes Study and ADVANCE, show that stringent glucose control minimizes microvascular problems, including neuropathy.2,3
These studies suggest that a target HbA1C level of 6.5% or less is optimal and should be recommended to avoid neuropathic symptoms and damage. American Diabetes Association (ADA) guidelines currently recommend testing HbA1C levels twice a year. Quarterly testing is suggested for patients who have not met treatment target goals or who have changed treatment strategies.
Medications for pain management
Current first-line medications for managing peripheral neuropathic pain include tricyclic antidepressants (TCAs), selective serotonin-norepinephrin reuptake inhibitors (SNRIs) and anticonvulsants. The SNRI, duloxetine, and anticonvulsant, pregabalin, are the only medications currently approved by the FDA with an indication for diabetic neuropathic pain.
In 2004, duloxetine (Cymbalta, Yentreve) was the first FDA-approved medication for managing diabetic peripheral neuropathy. Nearly half of patients in a placebo-controlled trial that were assigned to 60 mg duloxetine twice daily, reported a 50% reduction in pain compared with about 28% of patients assigned to placebo.4
Common duloxetine adverse events include nausea, somnolence, dizziness and constipation that dissipate with use. In very rare cases the medication can cause liver damage, severe allergic reactions, pneumonia and increased risk for suicide.
Another SNRI, venlafaxine (Effexor, Pfizer), has also been shown to help manage diabetic pain, but may put patients at risk for arrhythmia.5 Dosing starts at 37.5 mg per day and can be increased by the same amount per week to a maximum of 300 mg/day. If prescribing this medication clinicians must perform ongoing cardiac monitoring.
Routine use of tricyclic antidepressants, which include amitriptyline, imipramine, nortriptyline and desipramine, are also appropriate for pain management. Results of one study showed that about 30% of patients assigned to a TCA for diabetic nephropathy experienced a 50% reduction in pain.6
For pain relief TCA doses range from 25 to 150 mg per day, lower than those typically prescribed for depression. Keep in mind that some patients are unable to tolerate TCA’s anticholinergic and sedative properties. Avoid prescribing TCAs to patients who take monoamine oxidase inhibitors for depression, those with a history of CVD and patients that are younger than 65 years. Adverse events include dry mouth, constipation, dizziness, blurred vision and urinary retention.
