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Diabetic Neuropathy Treatment Guidelines 2020

Aan Updates Treatment Guidance On Painful Diabetic Neuropathy

Diabetic Neuropathy Problems, Causes and Solutions

Megan Brooks

PDN is very common and can greatly affect an individual’s quality of life, guideline author Brian Callaghan, MD, University of Michigan in Ann Arbor, noted in a news release.

“So this guideline aims to help neurologists and other doctors provide the highest quality patient care based on the latest evidence,” Callaghan said.

The recommendations update the 2011 AAN guideline on the treatment of PDN. The new guidance was December 27 in Neurology and has been endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine.

Update Of Guidelines Recommends Fda

The American Diabetes Association has updated its guidelines on the management of diabetic peripheral neuropathy in patients with diabetes.

The guidelines,¹ which were last updated in 2005, recommend pregabalin or duloxetine as first-line for managing symptoms of DPN. Both agents are approved by the US Food and Drug Administration for this indication. Gabapentin also is considered a possible initial approach to therapy, and tricyclic antidepressants, while currently not approved approved for this indication, also have evidence of efficacy for the treatment of neuropathic pain. However, the ADA also stressed the importance of practicing caution given the higher risk of serious side effects.¹

The ADA also has updated its clinical position concerning the use of opioids to treat DPNit now recommends opioids should be used only in the event all other medications fail to adequately treat symptoms. Even in patients who are unresponsive to other medications and may benefit from an add-on opioid, “those patients first should be referred to specialized pain clinics,” according to the ADA.

The primary strategy for combating DPN is still prevention, according to Gary Jay, MD. Writing in , Dr. Jay and co-author Grazia Allepo, MD, noted that maintaining glycemic control is essential. “But because diabetic neuropathy has multifactorial pathogenesis, additional therapies should be aimed at controlling hypertension, normalizing dyslipidemia, smoking cessation, and weight reduction.”

What Causes Diabetic Neuropathy

Although the exact causes of diabetic neuropathy are unknown, several factors may contribute to the disorder, including:

  • High blood sugar . High blood glucose causes chemical changes in nerves and impairs the nerves ability to transmit signals. It can also damage blood vessels that carry oxygen and nutrients to the nerves.
  • Metabolic factors. In addition to glucose levels, high triglyceride and cholesterol levels are also associated with increased risk of neuropathy. Patients who are overweight or obese are also at increased risk of developing neuropathy.
  • Inherited factors. There are some genetic traits that may make some people more susceptible to nerve disease than others.

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Improving Other Risk Factors

Although getting blood glucose under control is important, it might not be enough. It is also important to control other risk factors such as high triglycerides or cholesterol, treat high blood pressure and quit smoking. Daily aerobic exercises are shown to protect the nerves and improve neuropathy outcomes. Losing weight is also important if a patient is obese or overweight.

Corneal And Retinal Innervation

Diabetic Neuropathy

A number of different ophthalmic measures of neuronal integrity have been proposed as surrogate measures of DPN and other neurological diseases, including corneal confocal microscopy , retinal nerve fiber layer thickness, and pupil responsiveness . CCM is a rapid and non-invasive modality for the study of corneal innervation and has emerged as a technique for diagnosing DPN . It has a high sensitivity and a specificity of 4064% to diagnose DPN . Furthermore, CCM measures correlate with IENFD on skin biopsy . Pritchard et al. demonstrated that a reduced corneal nerve fiber length was predictive of incident DPN . Moreover, Dehghani et al. found that corneal nerve parameters rapidly declined prior to the development of foot complications .

Optical coherence tomography has been used to identify the loss of retinal nerve fibers in a number of neurological disease, including DPN . Retinal nerve fiber layer loss is observed in patients with diabetes and correlates with the stage of diabetic retinopathy . However, reports have shown that RNFL loss in patients with diabetes without diabetic retinopathy . Indeed, two recent studies have found that measures of RNFL loss are associated with DPN . OCT and CCM measures hold promise as a reliable and repeatable non-invasive measure which may be used to detect early DPN in the clinical and research setting. However, they are not currently widely available as they require specialist expertise and expensive equipment to perform .

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The Classification And Definition Of Diabetic Neuropathies

Diabetic neuropathies are heterogenous in their clinical presentation, risk factors and pathophysiology. The neuropathic syndromes may be classified according to the nerve type affected , site of nerve injury , and disease time course . The neuropathic syndromes may broadly be divided into typical DPN and atypical diabetic neuropathies, the latter of which are outside the scope of this review . The American Diabetes Association has recently developed a simplified classification schema for diabetic neuropathies, reproduced in Table 1 . Typical DPN is by far the most prevalent form of neuropathy in diabetes and characteristically affects both sensory and motor nerves in a peripheral distribution . However, the relative impact on small and large sensory fibers, and motor fibers varies among individuals. The Toronto Diabetic Neuropathy Expert Group defined DPN as a symmetrical, length dependent sensorimotor polyneuropathy attributable to metabolic and microvessel alterations as a result of chronic hyperglycemia exposure and cardiovascular risk covariates .

Table 1. Classification for diabetic neuropathies.

Overview Of Diabetic Neuropathy And Review Of Fda

The Foot and Ankle Online Journal 13 : 2

Keywords: diabetic neuropathy, gabapentin, duloxetine, cymbalta, FDA warning for gabapentinoids

ISSN 1941-6806

1 Clinical Associate Professor Temple University School of Podiatric Medicine, Medicine Department , Philadelphia, PA.2 Podiatric Student Temple University School of Podiatric Medicine3 Clinical Professor Temple University School of Podiatric Medicine, Biomechanics and Medicine Department* Corresponding author: elove@temple.edu

Diabetic neuropathy is the most common complication of uncontrolled and chronic diabetes. Neuropathy is the result of a compromised somatosensory system leaving patients with irreversible nerve damage . The progression of this neuropathic pain may lead to disorders such as insomnia, depression, anxiety, and impaired quality of life . This common complication of diabetes is correlated to increase doctor visits and increase prescription of medication . Currently, treatment management for diabetic neuropathic pain focuses on treating the symptoms due to the irreversible nerve damage .

Our goal was to provide an overview of diabetic neuropathy and oral treatment options including a recent update of the new FDA warnings on gabapentinoids.


Thorough research of literature via PubMed concerning the etiology of diabetic neuropathy symptom presentation FDA approved oral medications for patients with neuropathic pain was reviewed.


Epidemiology of Diabetic Neuropathy


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New Perspective In Diabetic Neuropathy: From The Periphery To The Brain A Call For Early Detection And Precision Medicine

  • 1Endocrinology Department, Renmin Hospital of Wuhan University, Wuhan, China
  • 2Diabetes Research Unit, Sheffield Teaching Hospitals, Royal Hallamshire Hospital, Sheffield, United Kingdom

Diabetic peripheral neuropathy is a common chronic complication of diabetes mellitus. It leads to distressing and expensive clinical sequelae such as foot ulceration, leg amputation, and neuropathic pain . Unfortunately, DPN is often diagnosed late when irreversible nerve injury has occurred and its first presentation may be with a diabetic foot ulcer. Several novel diagnostic techniques are available which may supplement clinical assessment and aid the early detection of DPN. Moreover, treatments for DPN and painful-DPN are limited. Only tight glucose control in type 1 diabetes has robust evidence in reducing the risk of developing DPN. However, neither glucose control nor pathogenetic treatments are effective in painful-DPN and symptomatic treatments are often inadequate. It has recently been hypothesized that using various patient characteristics it may be possible to stratify individuals and assign them targeted therapies to produce better pain relief. We review the diagnostic techniques which may aid the early detection of DPN in the clinical and research environment, and recent advances in precision medicine techniques for the treatment of painful-DPN.

Treatment Of Painful Diabetic Neuropathy

New Guidelines for Type 1 Diabetes in Adults: An Overview

The most disabling symptom of neuropathy is often neuropathic pain, which is experienced by about a quarter of individuals with the disorder . Treatment of neuropathic pain does not alter the natural history of neuropathy, but is still important to improve the quality of life of patients. There are few head-to-head trials comparing the efficacy of neuropathic pain medications, all of which were originally developed for other therapeutic reasons. Very few patients experience a complete improvement in pain, and a pain reduction of 3050% should be considered significant . Both the American Academy of Neurology and the European Federation of Neurological Societies have published guidelines on treating neuropathic pain . These guidelines and multiple other systematic reviews demonstrate consistent evidence for the efficacy of tricyclic antidepressants , gabapentinoids , serotoninnoradrenaline reuptake inhibitors and opioids . The TCAs and gabapentin and venlafaxine have the lowest out-of-pocket costs of the oral medications used for treating neuropathic pain and should be considered before more expensive options .

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Updates 2022 Treatment Guidance On Painful Diabetic Neuropathy Aan

Kategori: Nyheter
Publicerad 05 januari 2022

Updated guidelines from the American Academy of Neurology advise against prescribing opioids for painful diabetic neuropathy but note that several other oral and topical therapies may help ease pain.

PDN is very common and can greatly affect an individual’s quality of life, guideline author Brian Callaghan, MD, University of Michigan in Ann Arbor, noted in a news release.

“So this guideline aims to help neurologists and other doctors provide the highest quality patient care based on the latest evidence,” Callaghan said.

The recommendations update the 2011 AAN guideline on the treatment of PDN. The new guidance was December 27 in Neurology and has been endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine.

How Is Diabetic Neuropathy Diagnosed

Early diagnosis of diabetic neuropathy gives patients the best chance of effective treatment. But since not all foot or limb pain means diabetic neuropathy, accurate diagnosis is important to ensure appropriate treatment.

Diagnosis of diabetic neuropathies is based on history, clinical examination and supporting laboratory tests. Your doctor may:

  • Check muscle strength and reflexes.
  • Check muscle sensitivity to position, vibration, temperature and light touch.
  • Request additional tests, such as:
    • Ultrasound to determine how parts of the urinary tract are functioning.
    • Electromyography to determine how muscles respond to electrical impulses.
    • Nerve conduction studies to check flow of electrical current through a nerve.
    • Skin biopsies to evaluate cutaneous nerve innervation.
    • Nerve and muscle biopsies for histopathological evaluation.

A comprehensive evaluation including a review of blood pressure, cholesterol and blood glucose screenings combined with more advanced screening, helps the doctor rule out other causes and identify the core problem.

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Assessment Of Albuminuria And Estimated Glomerular Filtration Rate

Screening for albuminuria can be most easily performed by urinary albumin-to-creatinine ratio in a random spot urine collection . Timed or 24-h collections are more burdensome and add little to prediction or accuracy. Measurement of a spot urine sample for albumin alone without simultaneously measuring urine creatinine is less expensive but susceptible to false-negative and false-positive determinations as a result of variation in urine concentration due to hydration.

Normal UACR is defined as < 30 mg/g Cr, and high urinary albumin excretion is defined as 30 mg/g Cr. However, UACR is a continuous measurement, and differences within the normal and abnormal ranges are associated with renal and cardiovascular outcomes . Furthermore, because of high biological variability of > 20% between measurements in urinary albumin excretion, two of three specimens of UACR collected within a 3- to 6-month period should be abnormal before considering a patient to have high or very high albuminuria . Exercise within 24 h, infection, fever, congestive heart failure, marked hyperglycemia, menstruation, and marked hypertension may elevate UACR independently of kidney damage .

Diagnosis Of The Underlying Lesion Or Disease Of The Somatosensory System

Coach Beverly

The previously mentioned methods have focused on the detection of damage to the nociceptive system, in particular the afferent C- and A-delta-fibers, as the cause of neuropathic pain. The basis for further diagnostics is a complete neurological examination. Further apparatus- based examinations , laboratory or cerebral spinal fluid examinations should be performed depending on the patients medical history and clinical findings. For details we refer to the guidelines for the corresponding diseases.

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Aan: Painful Diabetic Neuropathy Treatment Guidelines Updated

The American Academy of Neurology has issued updated recommendations for the treatment of painful diabetic polyneuropathy.

According to the new guidelines, several pharmacotherapies have been shown to reduce pain in patients with painful diabetic neuropathy, a condition that can greatly affect quality of life. Four classes of oral medications that have demonstrated efficacy in clinical trials include tricyclic antidepressants , serotonin-norepinephrine reuptake inhibitors , gabapentinoids , and sodium channel blockers .

New studies on sodium channel blockers published since the last guideline have resulted in these drugs now being recommended and considered as effective at providing pain relief as the other drug classes recommended in this guideline, said guideline author Brian C. Callaghan, MD, MS, of the University of Michigan in Ann Arbor and a Fellow of the American Academy of Neurology.

As all of these treatments were found to be relatively similar with respect to efficacy, other factors such as side effects, patient preferences, comorbidities, and cost should be considered when making treatment decisions.

Following titration to an effective dose, if a treatment fails to reduce pain or if the side effects of the drug outweigh its benefits after approximately 12 weeks, it can be considered a failure, according to the guidelines. When meaningful improvement is not demonstrated with the initial therapy, a trial of a different class of medication may be offered.

Controlling Blood Glucose Levels

Getting blood glucose levels under control cant reverse nerve damage but can prevent further damage from occurring. Your doctor will give you specific blood sugar goals. Managing these levels includes eating a healthy diet high in protein and low in carbs. When you eat carbs, try to choose food with a higher fiber content, avoiding chips and soda.

Regular exercise can help keep blood sugar levels manageable by increasing insulin sensitivity, meaning youll need to take less insulin each day. Getting enough sleep is also important, as we often crave high-carb foods when overly tired.

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Selective Serotonin Reuptake Inhitibors

The efficacy of selective serotonin reuptake inhibitors in neuropathic pain has not be proven beyond doubt . The studies conducted have been very small, not randomized and controlled or have shown no relevant effect .

Recommendation: SSRI such as citalopram/escitalopram, fluoxetine, fluvoxamine or sertraline should not be used in the treatment of neuropathic pain.

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Diabetic Neuropathy: New Treatment Guidelines

Diabetic neuropathy refers to nerve damage due to diabetes and it may lead to pain and numbness, most often in the hands and feet. To help neurologists and other doctors determine the best treatment for people with diabetic neuropathy, the American Academy of Neurology has issued a guideline on oral and topical treatments for painful diabetic neuropathy.

The guideline is published in the December 27, 2021, online issue of Neurology®, the medical journal of the AAN, and is endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine. This guideline updates the 2011 AAN guideline on the treatment of painful diabetic neuropathy.

The guideline states that there are many oral and topical medications that are effective in reducing nerve pain. Before prescribing a treatment, it says a doctor should first determine if a person also has mood or sleep problems since treatment for these conditions is also important.

To reduce nerve pain, the guideline recommends that doctors may offer treatments from the following drug classes: tricyclic antidepressants such as amitriptyline, nortriptyline and imipramine serotonin-norepinephrine reuptake inhibitors such as duloxetine, venlafaxine or desvenlafaxine gabapentinoids such as gabapentin or pregabalin and/or sodium channel blockers such as carbamazepine, oxcarbazepine, lamotrigine, or lacosamide. Evidence shows these medications may all reduce nerve pain.

Comparison Of Amitriptyline Supplemented With Pregabalin Pregabalin Supplemented With Amitriptyline And Duloxetine Supplemented With Pregabalin For The Treatment Of Diabetic Peripheral Neuropathic Pain : A Multicentre Double

  • AffiliationsDiabetes Research Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UKSchool of Health and Related Research, and Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
  • Uazman AlamAffiliationsDepartment of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UKLiverpool University Hospital NHS Foundation Trust, Liverpool, UK
  • Edward B JudeAffiliationsDepartment of Diabetes and Endocrinology, Tameside and Glossop Integrated Care NHS Foundation Trust, Ashton under Lyne, UKDivision of Diabetes, Endocrinology & Gastroenterology, University of Manchester, Manchester, UK
  • School of Medicine, University of Liverpool, Liverpool, UKDepartment of Diabetes and Endocrinology, Countess of Chester Hospital NHS Foundation Trust, Chester, UK
  • Dinesh SelvarajahAffiliationsSchool of Health and Related Research, and Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
  • on behalf of theOPTION-DM trial group

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Treatment Of Foot Complications

Detailed treatment of foot ulceration and CN is beyond the scope of this statement, and the reader is referred to a relevant review . Effective off-loading that prevents patients with plantar neuropathic ulcers to walk on the lesions is the key to successful management . Off-loading, usually with casting, and careful follow-up and repeated investigations are also key components for the management of CN . Ongoing education and regular podiatry follow-up can reduce the incidence of foot complications in those found to be at high risk. Early intervention for foot lesions and CN or suspected CN can slow or reverse progression.

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