The American Diabetes Association (ADA) released an updated position statement on the prevention, detection, and management of diabetic neuropathies, which represent the most common chronic complications of the disease.1 Distal symmetric polyneuropathy (DSPN) and autonomic neuropathy, especially cardiovascular autonomic neuropathy (CAN), are the forms most often studied and most frequently observed in clinical practice. The position statement was published in Diabetes Care.
Since the previous ADA position statement on diabetic neuropathy was published in 2005, new evidence on the topic has emerged. “In addition, given the complexity of diabetic neuropathy, there was somewhat contradictory information in the literature, and thus our group of experts was convened by the ADA to condense and clarify the evidence on the subject, come to a consensus, and present it for the daily use of practicing physicians,” explained lead researcher Rodica Pop-Busui, MD, PhD, professor of internal medicine in the Division of Metabolism, Endocrinology, and Diabetes, and associate chair of clinical research at the University of Michigan in Ann Arbor.
“The recommendations reinforce much of what clinicians are already doing — or should be doing — in routine clinical practice,” according to Kevin M. Pantalone, DO, staff endocrinologist and director of clinical research at the Cleveland Clinic in Ohio. “It is important to note that the most effective treatment of diabetic neuropathy is prevention.” In addition, screening is critical to enable early detection and intervention.
The first section of the position statement offers the following recommendations regarding prevention of DSPN and CAN. First, glucose control should be optimized as early as possible to prevent or slow the development of DSPN and CAN in patients with type 1 diabetes. Enhanced glucose control in this patient group has been found to substantially decrease the incidence of DSPN — by 60% (95% CI, 38%-74%) in one study, for example — and to reduce the risk of CAN by up to 45%.2,3
Second, in patients with type 2 diabetes, glucose control should be optimized to prevent or delay the progression of DSPN, and a multifactorial approach targeting glycemia and other risk factors should be considered in order to prevent CAN. In studies in this patient group, enhanced glucose control led to only a modest reduction in DSPN risk (relative risk reduction, 5% to 9%), and it has not been shown to consistently decrease the risk of CAN.4,5 “However, a multifactorial intervention, including a lifestyle component, targeting glucose and cardiovascular disease risk factors reduced the risk of CAN by 60% in people with type 2 diabetes,” the researchers wrote.6 One study observed nerve fiber regeneration in patients with type 2 diabetes who participated in an exercise program, while nerve fiber loss occurred in those who followed usual care.7
DSPN accounts for an estimated 75% of diabetic neuropathies and is a major cause of foot ulceration and prerequisite to Charcot neuroarthropathy (CN), which increases the risk of amputation and predicts mortality.8,9 In addition, DSPN contributes to falls and fractures, which may further influence the pathogenesis of CN.10 It is recommended that the initial assessment in DSPN take place at the time of diagnosis in patients with type 2 diabetes and 5 years following diagnosis in patients with type 1 diabetes. Annual assessments are recommended in both groups thereafter.
Pinprick and temperature sensation may be used to evaluate small-fiber function, while proprioception, 10-g monofilament testing, ankle reflexes, and vibration perception using a 128-Hz tuning fork may be used to assess large-fiber function. Annual 10-g monofilament testing should be conducted in all patients at risk for foot ulceration and amputation.1 “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 guidelines suggest.
In pain treatment, pharmaceutical interventions are the only measures supported by compelling evidence, while glycemic control and lifestyle management are not. Dr Pantalone thinks this point should have been included. “Their hard recommendations, as in routine clinical practice, the false belief of many clinicians that better glycemic control in patients with existing neuropathic pain will help to improve pain control, leads to inappropriate delays in the initiation of pharmacologic therapy and thus delays in improving patient discomfort,” he said.
Recommendations for the management of symptomatic neuropathic pain include pregabalin or duloxetine and possibly gabapentin as an initial treatment approach. Tricyclic antidepressants may also be effective, although they are not approved by the US Food and Drug Administration (FDA) for this indication and carry the risk of serious adverse effects. Opioids should generally not be used as first- or second-line pain treatment strategies in these cases due to the risk of addiction and other adverse effects.1
Diabetic Autonomic Neuropathies
The prevalence of CAN increases with diabetes duration, affecting at least 30% of patients with type 1 diabetes after 20 years and up to 60% of patients with type 2 diabetes after 15 years.11,12CAN is a risk factor for mortality and several types of cardiovascular dysfunction.
The researchers recommended that patients with microvascular and neuropathic pain be evaluated for signs and symptoms of CAN. If detected, tests should be performed to rule out other conditions that could mimic CAN. Since hypoglycemia unawareness may be linked with CAN, clinicians may consider screening patients accordingly.13 “CAN treatment is generally focused on alleviating symptoms and should be targeted to the specific clinical manifestation,” they stated.
“The position statement also reminds clinicians that there are other forms of diabetic neuropathy,” Dr Pantalone added. The recommendations touch on detection and treatment of less common types, including gastrointestinal and urogenital neuropathies, as well as atypical forms such as mononeuropathies and treatment-induced neuropathy.
The researchers offered suggestions to improve the design of future clinical trials in this area, which have yet to produce promising results pertaining to therapies for diabetic neuropathy.
Next steps should include “continued efforts to find effective and safe disease-modifying agents to reverse this complication and improve patients' quality of life and daily function,” said Dr Pop-Busui. “We hope these guidelines bring together primary care physicians, endocrinology specialists, and neurologists to expand the care provided to diabetic patients.”
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