Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 57-year-old man with a 15-year history of type 2 diabetes mellitus is evaluated for bilateral burning sensation in his feet for the last 6 to 12 months. The sensation worsens at night. His HbA1c levels have remained less than 7.0% for the last 2 years but were between 8.0% and 9.0% before implementing significant lifestyle changes and transitioning to insulin therapy from metformin therapy 2 years ago.

His medical history includes coronary artery disease, first-degree atrioventricular block, nonproliferative diabetic retinopathy, hypertension, and hyperlipidemia.

Medications are regular insulin, neutral protamine Hagedorn (NPH) insulin, aspirin, metoprolol, atorvastatin, and lisinopril.

On physical examination, findings are compatible with distal polyneuropathy.

A review of the patient’s laboratory studies shows a normal complete blood count including erythrocyte indices.

Which of the following is the most appropriate management of this patient’s neuropathy?

A. Amitriptyline
B. Duloxetine
C. Nerve conduction study
D. Vitamin B₁₂ measurement

MKSAP Answer and Critique

The correct answer is B. Duloxetine.

Duloxetine is a reasonable initial option for this patient’s painful peripheral neuropathy. The typical presentation for distal symmetric polyneuropathy is a bilateral “stocking-glove” distribution. Damage to the small nerve fibers can result in pain, numbness, burning, and tingling. It can also impair light touch and temperature sensation. Damage to the large nerve fibers leads to abnormal vibration sensation and proprioception. Diminished or loss of ankle reflexes is commonly seen early with diabetic polyneuropathy. Motor weakness can occur as the polyneuropathy progresses. Several classes of drugs are frequently used for symptomatic pain relief, including the tricyclic antidepressants (amitriptyline), other classes of antidepressants (duloxetine, venlafaxine), anticonvulsants (pregabalin, gabapentin, valproate), and capsaicin cream. There are few head-to-head comparison trials for these classes of drugs for distal symmetric polyneuropathy, thus selection must take into consideration the potential risks and benefits associated with each drug for an individual patient. Duloxetine has fewer risks than amitriptyline for this patient given his cardiac history.

Tricyclic antidepressants, such as amitriptyline, should be used cautiously in patients with known cardiac disease due to an association between this class of drugs and arrhythmias, heart block, and sudden death. The patient’s history of cardiac disease and a first-degree atrioventricular block may increase his risk of side effects from amitriptyline.

A nerve conduction study is not routinely required for diagnosis or management in patients with diabetes with a typical presentation of symmetric distal polyneuropathy. Atypical clinical features should prompt additional work-up, including electrophysiologic testing.

Vitamin B₁₂ deficiency has been associated with long-term use of metformin and can present with peripheral neuropathy. It is also commonly seen in the setting of megaloblastic anemia. It is unlikely that vitamin B₁₂ deficiency is the cause of this patient’s peripheral neuropathy as he has a classic presentation for symmetric distal polyneuropathy, discontinued metformin 2 years ago, and has a normal complete blood count.

Key Point

• Treatment options for diabetic polyneuropathy include the tricyclic antidepressants, other classes of antidepressants (duloxetine, venlafaxine), anticonvulsants (pregabalin, gabapentin, valproate), and capsaicin cream.

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