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There are many important physical examination components to consider in the evaluation of a patient with diabetes. According to the American Diabetes Association 2016 Standards of Medical Care in Diabetes,11 patients with type 2 diabetes should undergo screening for peripheral neuropathy at the time of diagnosis, and patients with type 1 diabetes should be screened 5 years after diagnosis. Following the initial screening, all patients with diabetes should be monitored on an annual basis for this condition. Screening should focus on sensory function, including pinprick, temperature, and vibratory perception (128-Hz tuning fork), or pressure sensation (10-g monofilament at distal halluces).12 Two simple screening tests, including the Michigan neuropathy screening instrument and the United Kingdom screening test, are available for routine clinical practice.13 Patients with diabetes should be educated regarding the importance of vigilant examination and care of their lower extremities. They should be taught to perform daily foot checks and note the development of calluses, ulcers, or deformation. Proper footwear, including socks, should be reviewed in an effort to prevent calluses or ulcers. Additionally, these patients should be taught about proper toenail trimming and dry skin management. Referral to a podiatrist should be considered if lower-extremity deformities are present or if assistance with toenail trimming is needed.


A diagnosis of diabetic peripheral neuropathy is commonly considered on the basis of a patient’s presenting signs and symptoms, medical history, and physical examination findings. A diagnosis of diabetic peripheral neuropathy can be confirmed after electrodiagnostic, sensory, and autonomic function testing. Diagnostic tests commonly performed during an evaluation for diabetic peripheral neuropathy are summarized in Table 4.

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Diabetic peripheral neuropathy can be difficult to treat. At the current time, adequate glycemic control and pain management are the only effective treatment strategies.10 Observational studies have shown that neuropathic symptoms are mitigated with glucose optimization but may not necessarily be reversed.12 Diligent adjustment of diabetes medications is vital in the treatment of peripheral neuropathy. To manage the chronic pain associated with diabetic peripheral neuropathy, practitioners should consider a variety of antidepressants and anticonvulsants, including amitriptyline, duloxetine, venlafaxine, gabapentin, valproate, and pregabalin, as well as opioid therapy. The US Food and Drug Administration has approved duloxetine and pregabalin for the treatment of pain associated with diabetic peripheral neuropathy; however, there is no defined treatment of choice. Direct comparisons of agents have not been conducted, and a patient’s therapy should be switched if the pain does not decrease.14 In addition to maintaining glycemic control and managing pain, practitioners should attempt to control factors that may increase the likelihood of peripheral neuropathy. Therefore, patients with diabetes are encouraged to maintain a healthy body weight, exercise as tolerated, eliminate cigarette smoking and alcohol consumption, and treat blood pressure and lipids to goal. The American Academy of Neurology provides guidelines regarding the pharmacologic and nonpharmacologic treatment of painful diabetic neuropathy.15 These level A and level B recommendations for the treatment of painful diabetic neuropathy are summarized in Table 5.

As previously mentioned in the section on pathophysiology, hyperglycemia-related oxidative stress and the production of free radicals can contribute to the development of peripheral neuropathy. Alpha-lipoic acid, an antioxidant, has been shown to be a powerful scavenger of free radicals in peripheral nerves. Studies have examined the use of alpha-lipoic acid in treating the symptoms of diabetic peripheral neuropathy, and some have found that patients with diabetic peripheral neuropathy who were given 600 mg of intravenous alpha-lipoic acid daily for 3 weeks experienced a decrease in pain, numbness, and paresthesia.16-18 More research is needed to determine the efficacy of alpha-lipoic acid in reducing the symptoms of diabetic neuropathy.

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Case Study

History and presentation 

A patient, aged 79 years, was given a diagnosis of type 2 diabetes approximately 20 years ago. Her condition was originally managed with oral agents, but she was transitioned to a regimen of multiple daily injections of insulin glargine and insulin aspart approximately 8 years ago. Her hemoglobin A1c level has ranged from 7.9% to 8.2% over the last few years. Diabetes-related comorbidities and complications include retinopathy, obesity with a body mass index (BMI) of 39, hypertension, hyperlipidemia, chronic kidney disease (stage 3A), sleep apnea, and diabetic peripheral neuropathy. Between visits with her endocrinologist, she has worked closely with a diabetes educator for assistance with adjusting her insulin dose. The patient was not aware of her hypoglycemia condition in the past but notes that since she has been participating in insulin education and having regular contact with her diabetes educator, her episodes of hypoglycemia have become less frequent. Her husband has been educated regarding the use of glucagon. 

The patient’s main concern at today’s visit is increased sensations of burning and pain in her lower extremities, which she notes have worsened in the last 2 to 3 months. Her primary care provider has referred her to a neurologist to confirm the diagnosis of diabetic peripheral neuropathy. Previously, she preferred nonpharmacologic methods, including ice/heat and exercise, to relieve her symptoms. After the pain and burning sensations worsened, she tried topical capsaicin cream at the recommendation of her pharmacist but found that to be of minimal benefit. She denies issues with lower-extremity ulcerations and states that she assesses her feet on a daily basis, using lotion to manage dry skin. Today, she is inquiring about additional treatment options for improving the management of her diabetic peripheral neuropathy. 

Assessment and plan 

For this patient, the importance of glycemic control and adherence to her schedule of multiple daily insulin injections was stressed. She was referred to a diabetes educator, who provided ongoing support and showed her how to adjust her insulin doses to achieve her glycemic goal. It was recommended that the patient initiate gabapentin at a dosage of 300 mg by mouth once daily. She was instructed to take this medication at bedtime because of its common side effect of drowsiness. She also received written instructions to increase the dose gradually to 1800 mg, to be divided into 3 doses taken throughout the day. The patient was reminded that this medication can take up to 12 weeks to take effect.


Diabetic peripheral neuropathy is a prevalent disorder that is hard to treat. It is often underreported and undertreated. The costs associated with diabetic peripheral neuropathy are high. Potentially 25% of the cost of diabetes care in the United States is associated with neuropathy, ranging from $4.6 billion to $13.7 billion annually.10

To improve outcomes, patients with diabetes should be screened for peripheral neuropathy on an annual basis. A diagnosis of diabetic peripheral neuropathy is often suspected on the basis of symptoms, medical history, and physical examination findings. It is important to consider a variety of conditions in the differential diagnosis because a patient’s neuropathy may have an underlying cause other than diabetes. Glycemic control and pain management are the cornerstones of treatment, with several classes of drugs considered effective in the treatment of diabetic peripheral neuropathy.

Jennifer A. Grenell, APRN, CNP, and Anne E. Turner, PA-C, practice in the Department of Endocrinology at the Mayo Clinic in Rochester, Minn., and specialize in diabetes management.


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