ARTICLE IN BRIEF
Among recommendations, a new consensus guideline on diabetic neuropathy suggests that a clinical exam is sufficient and cost-effective in diagnosing and managing diabetic neuropathy and could avoid expensive referrals for electrophysiological tests and the added cost and wait times for a neurological consultation.
New guidelines on the prevention, diagnosis, and treatment of diabetic neuropathy could help primary care physicians and neurologists better manage the common and complicated condition, according to a position statement by the American Diabetes Association published in January in Diabetes Care.
The position statement, developed by neurologists and endocrinologists from North America and Europe, updated a much more brief consensus statement by the American Diabetes Association that was published in 2004.
“There is a diabetes epidemic, and there are far too many patients for specialists to manage,” said Rodica Pop-Busui, MD, PhD, professor of internal medicine, metabolism, endocrinology and diabetes, and associate chair of clinical research at the University of Michigan, who led the panel of experts. “There has been a lot of conflicting information and confusion among practitioners. Diabetic neuropathy is very complex and has multiple forms.”
Among the conclusions, the guidelines stated that a clinical exam, which is outlined in a step-by-step algorithm, is sufficient and cost-effective in diagnosing and managing neuropathy and could avoid expensive referrals for electrophysiological tests and the added cost and wait times for a neurological consultation.
Another important section of the statement provides an organized assessment for the treatment of pain associated with peripheral neuropathy, pointing to treatments that could be used in lieu of more addictive substances like opioids.
The report highlights the recognition and treatment of autonomic neuropathy, particularly cardiovascular autonomic neuropathy. Treating these neuropathies could reduce symptoms and improve quality of life, the experts said. Distal symmetric polyneuropathy (DSPN) and autonomic neuropathy are the most common forms seen in practice and the statement goes into detail on each one.
“While all authors agreed on the definitions of neuropathy, regardless if they were neurologists or endocrinologists, there were lengthy discussions on how to best diagnose neuropathy and the role of quantitative assessments, such as nerve conduction studies, in diagnosis and treatment,” said Eva L. Feldman, MD, PhD, FAAN, the Russell N. DeJong professor of neurology and director of the A. Alfred Taubman Medical Research Institute and director of the program for neurology research and discovery at the University of Michigan, who was one of the report authors.
“Peripheral neuropathy is a clinical diagnosis, and unless there are atypical features, it does not require more sophisticated assessments, such as nerve conduction studies. Neurologists agree with endocrinologists on this point.”
Dr. Feldman said that the current guideline provides more detailed definitions of different types of diabetic neuropathy along with more detailed guidelines on treatment.
“Compared to [the document developed by the ADA in] 2004, we now know that patients with prediabetes develop early neuropathy that is indistinguishable from diabetic neuropathy; this emphasizes the need for early diagnosis and treatment of type 2 diabetes,” she said. “A second important component is our increased awareness of the differences between small and large fiber neuropathy, and how frequently small fiber neuropathy is present secondary to prediabetes or new-onset diabetes.”
She said that there were unresolved issues as well. “Diagnostic tools, such as corneal confocal microscopy or sudometry, require more research to confirm their role in the diagnosis and assessment of diabetic peripheral neuropathy. Of course, the pivotal issue that is not resolved is our lack of understanding, despite decades of research, of exactly how diabetes results in peripheral nervous system injury.”
EXPERTS WEIGH IN
“This is an important position statement because it was generated by an international panel of experts in diabetes and in neurology, and it is extensively referenced,” said Peter J. Dyck, MD, FAAN, director of the Peripheral Nerve Research Laboratory at the Mayo Clinic in Rochester, MN.
Dr. Dyck said that he agrees with the panel on the need for “adequate surveillance for diabetic polyneuropathy of patients at risk for diabetes, that is, patients with pre-diabetes and of patients with diabetes.”
Anne Louise Oaklander, MD, PhD, FAAN, associate professor of neurology at Harvard's Massachusetts General Hospital and a member of the Neurology Today editorial advisory board, said the guideline statement that prediabetes can lead to neuropathy does not reflect a “unified belief,” however, and is controversial.
“It is important for physicians to understand peripheral neuropathies and identify and manage these problems early,” she said, adding: “The single most important change in the guideline is the inclusion of small fiber neuropathy.”
Still, she added, the consensus guideline is “helpful for me and I manage peripheral neuropathies every day.”
Dr. Dyck noted that he also believes that most patients need not be referred to neurologists, as suggested by the guideline. He also agreed that the referral be made “when motor involvement is greater than sensory involvement; when symptoms begin abruptly, and involvement is asymmetric.”
Dr. Dyck said he agrees with the three evaluations (symptoms, monofilament testing of the foot, and assessment of pin prick and vibration sensation), but said that he is concerned about making all three assessments mandated without knowing whether such assessments are worthwhile in preventing or reducing foot ulcers and neurogenic arthropathy.
“What if it simply results in a perfunctory set of examinations, increases overall costs, and doesn't prevent foot complications? Are the evaluations of physicians sufficiently proficient to do these evaluations? We recently assessed the proficiency and test-retest reproducibility of clinical examinations in diabetes patients and found that expert diabetologists and neurologists overestimated polyneuropathy quite markedly and were excessively variable in their examination/re-examinations.”
“With training and emphasis on being more specific in their judgments, proficiency and reproducibility were markedly improved,” Dr. Dyck continued. “Therefore, I would urge health care agencies to explore use and improved quantitative and referenced methods to do these evaluations before mandating these specific evaluations.”
Dr. Oaklander said a consensus by experts in the field is something that all neurologists will follow. “The AAN guideline offers a narrow view of treatments, and this is a more comprehensive report on prevention, diagnosis, and management,' she said. “This will also set the tone for general practitioners. Diabetes is one of the few causes of neuropathy that we have treatments for.”
ADA CONSENSUS GUIDELINE ON DIABETIC NEUROPATHY
The expert panel recommends screening for symptoms and signs of diabetic neuropathy to intervene early and prevent further complications. Prevention focuses on glucose control and lifestyle modifications, Dr. Pop-Busui said.
They point to well-designed studies that demonstrated that optimizing glucose control early in patients with type 1 diabetes can prevent or delay distal symmetric polyneuropathy (DSPN) — studies have shown a 78 percent risk reduction — and cardiovascular autonomic neuropathy (CAN).
Tight regulation of glucose can only modestly prevent or slow DSPN (studies show a 5 to 9 percent relative risk reduction) or CAN in patients with type 2 diabetes, likely because patients with type 2 diabetes present with multiple other risk factors. However, the consensus is that managing glucose levels may not be enough to prevent DSPN and CAN in type 2 patients, and multifactorial interventions that include lifestyle changes (exercise and diet) are recommended to reduce theses risks.
The report includes signs, symptoms and pathogenesis of the most common types of diabetic neuropathies and recommendations for screening and diagnosis. For example, “all patients should be assessed for distal symmetric polyneuropathy starting at diagnosis of type 2 diabetes and five years after the diagnosis of type 1 diabetes,” and the assessment should be done at least once a year.
The panel recommends screening for patients with prediabetes who have symptoms of peripheral neuropathy. The assessment should include a history and either “temperature or pinprick sensation (small-fiber function) and vibration sensation using a 128-Hz tuning fork (large-fiber function). All patients should have annual 10-g monofilament testing to assess for feet at risk for ulceration and amputation.”
“Electrophysiological testing or referral to a neurologist is rarely needed for screening, except in situations where the clinical features are atypical, the diagnosis is unclear, or a different etiology is suspected,” the panel said. “Atypical features include motor greater than sensory neuropathy, rapid onset, or asymmetrical presentation.”
They also recommended yearly assessments to test for DSPN in patients with type 1 diabetes for five or more years and all patients with type 2 diabetes. This can be done with a medical history and simple office-based clinical tests, including pinprick and temperature sensation, proprioception, 10-g monofilament and ankle reflex tests to assess light-touch perception and a 128-Hz tuning fork test to assess vibration perception. This is important to pick up disease in the 50 percent of people who are asymptomatic.
Tests to rule out diabetes as a cause of the neuropathy include a detailed family and medication history and tests to measure serum B12, folic acid, thyroid function, complete blood count, metabolic panel, and a serum protein immunoelectrophoresis.
The report includes the three-minute diabetic foot exam to identify diabetes-related complications and education of the patient on foot care. (This can be carried out by other health professionals following the diabetic exam.)
The report briefly mentions disease-modifying therapies since there are a lack of treatment options and little scientific evidence that there are medicines to slow or reverse the nerve damage.
The panel emphasized non-opioid pain management for neuropathies, including pregabalin or duloxetine (or gabapentin) as a first-line approach, and then trying tricyclic antidepressants that may also work to reduce neuropathic pain in diabetes. (The tricyclics should be used cautiously “given the higher risk of serious side effects,” they said.)
“Given the high risks of addiction and other complications, the use of opioids, including tapentadol or tramadol, is not recommended as first- or second-line agents for treating the pain associated with DSPN,” the experts wrote.