Diabetes Care

Diagnosis and Management of Diabetic Peripheral Neuropathy in Primary Care

Brian Muegge, MD, and Kim A. Carmichael, MD—Series Editor

Brian Muegge, MD, and Kim A. Carmichael, MD--Series Editor


Q.  What are the neurologic complications of diabetes mellitus?

A.  The most common neurologic symptom among patients with diabetes mellitus is a distal, symmetric, length-dependent sensorimotor polyneuropathy. Depending on the mode of screening, this complication is found in 10% to 50% of patients with diabetes.1 A minority of those patients with polyneuropathy will be symptomatic, with either positive symptoms (burning, tingling) or negative symptoms (numbness, weakness). 

Less common manifestations include autonomic neuropathies, nerve entrapment syndromes, and polyradiculopathies including diabetic amyotrophy.

Q.  How can a patient with diabetes mellitus be screened for peripheral neuropathy?

A.  Primary care providers can perform an evidence-based examination in 2 to 3 minutes that effectively identifies patients at risk.2 Key elements of screening include patient history, palpation of peripheral pulses, visual inspection of foot deformities, and sensory assessment. Recommendations from the American Diabetes Association2 suggest that 2 sensory tests should be employed. All patients with diabetes should be screened with a 10-g monofilament (a Semmes-​Weinstein monofilament). The monofilament tip is pressed into the skin just until the monofilament buckles, and the pressure is held for 1 second. Patients are asked to report sensation of pressure at 4 sites on each foot (first, third, and fifth metatarsal heads, and plantar surface of the great toe). Inability to sense the monofilament is abnormal.

Screening sensitivity is increased with the addition of one other sensory test. The options include a vibrating tuning fork applied to the tip of the great toe; a pinprick sensation applied just proximal to the nail bed of the great toe; ankle reflex tests; or a vibration perception threshold test using a biothesiometer. An abnormal response to either the monofilament or one of the other tests warrants further investigation.

Q.  What medications are most effective for treating the symptoms of painful diabetic neuropathy?

A.  The choice of treatment is hampered by the absence of high-quality, long-term outcomes studies that compare treatment options in a head-to-head design. Anticonvulsants, tricyclic antidepressants, and serotonin and norepinephrine reuptake inhibitors have all been shown to be more effective than placebo at relieving the painful symptoms of diabetic neuropathy.3

The choice of initial agent is largely driven by comorbidities and adverse effect profile. For example, amitriptyline at doses of 25 to 150 mg/d is one of the most effective treatments for painful symptoms, but it may not be tolerated by the elderly, by patients with conduction system abnormalities, or at higher doses. Anticonvulsants such as gabapentin and pregabalin can promote improved sleep at night but also drowsiness during the day. If a patient does not respond to an agent from one class or cannot tolerate its adverse effects, a medication from a different class should be tried.

A number of low-risk adjunctive treatments such as α-lipoic acid, 600 mg daily, or acetyl-l-carnitine, 1000 mg three times daily, have been shown to improve symptom scores in short-term studies.4

Q.  Should any other testing be performed when peripheral neuropathy is detected?

A.  Basic laboratory assessment is designed to identify the common or easily treatable causes of peripheral neuropathy.5 

Vitamin B12 deficiency may be observed with metformin treatment and should also be suspected in patients with a history of bariatric surgery or with a malabsorption syndrome. Hypothyroidism is an uncommon cause of peripheral neuropathy but is easily treatable if identified. Monoclonal gammopathies can also present with neurologic symptoms, so screening with serum protein electrophoresis or serum free light chain assay is indicated in the initial presentation of peripheral neuropathy.

Q.  When should a patient be referred for specialist evaluation?

A.  In patients with diabetic peripheral neuropathy, the lifetime incidence of developing a foot ulcer is as high as 25%.2 In a patient with normal sensory examination findings, no deformities, and no peripheral artery disease, annual screening by a primary care provider is appropriate.

Specialist referral is indicated for close monitoring and intervention when one or more risk factors for foot ulceration are present. Deformities such as bunions, hammer toes, claw toes, and overlapping toes create pressure points that increase the risk of ulceration. Patients with abnormal sensory examination results or with deformities should be provided prescription or accommodative footwear and be followed by the generalist or specialist at least biannually. The presence of Charcot foot, a severe deformity with warmth and swelling, should prompt immediate surgical referral. If diminished or absent dorsalis pedis or tibialis posterior pulses are detected on clinical examination, consider ankle-brachial index testing and vascular surgery consultation.

Any patient with history of ulcer or amputation is considered at high risk for future ulceration, and specialist follow-up is recommended at short intervals.

Brian Muegge, MD, is a clinical fellow in the Department of Medicine, Division of Endocrinology, Metabolism and Lipid Research, at Washington University School of Medicine in St Louis, Missouri.

Kim A. Carmichael, MD, is an associate professor of medicine in the Department of Medicine, Division of Endocrinology, Metabolism and Lipid Research, at Washington University School of Medicine in St Louis, Missouri. He discloses that he is on the speakers bureau for Janssen, which may be relevant to the content of this article.


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  2. Boulton AJM, Armstrong DG, Albert SF, et al. Comprehensive foot examination and risk assessment: a report of the Task Force of the Foot Care Interest Group of the American Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists. Diabetes Care. 2008;31(8):1679-1685.
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  4. Ziegler D, Ametov A, Barinov A, et al. Oral treatment with α-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 2006;29(11):2365-2370.
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