diabetic neuropathies

A review of the causes and treatment of the symptoms of peripheral neuropathy. Figure 2 and Table 1 may be particularly helpful. James W. Mold, MD, MPH

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Importance Peripheral neuropathy, defined as damage to peripheral nerves, affects approximately 1% of adults worldwide. More than 200 causes of peripheral neuropathy exist, with symptoms ranging in severity from mild toe numbness to debilitating symptoms that can require a wheelchair. Diabetes is the most common cause of neuropathy, affecting approximately 206 million people worldwide.

Observations Peripheral neuropathy is typically length-dependent, which means that symptoms appear in the longest nerve axons (toes) and progress proximally over time. Peripheral neuropathy is typically symmetric and affects sensory axons more than motor axons. Diabetic neuropathy, which is often associated with both sensory symptoms, such as pain, tingling, or numbness; mild weakness; and autonomic symptoms, such as orthostatic hypotension, accounts for more than 50% of peripheral neuropathy in Western populations. Other causes of neuropathy include hereditary causes, such as Charcot-Marie-Tooth disease, toxic neuropathy from medications (chemotherapies [eg, cisplatin, paclitaxel, vincristine], amiodarone, or HIV nucleotide reverse transcriptase inhibitors [eg, stavudine, zalcitabine]); alcohol; vitamin deficiencies such as vitamin B12; and monoclonal gammopathies. Up to 27% of adults with neuropathy have no identifiable etiology for their neuropathy after diagnostic testing. Recommended initial testing includes blood glucose (for diabetes), serum B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein electrophoresis with immunofixation (for monoclonal gammopathies). First-line medications for neuropathic pain are the α2-δ calcium channel subunit ligands, such as gabapentin and pregabalin; serotonin norepinephrine reuptake inhibitors, such as duloxetine and venlafaxine; and tricyclic antidepressants, such as amitryptyline and nortriptyline. Pain often persists despite medical management. At least a 50% reduction in pain was observed in 38% of those with painful diabetic peripheral neuropathy receiving 1200 mg of gabapentin daily. Combination drug therapies for neuropathic pain may provide added benefit. The prognosis of peripheral neuropathy depends on its underlying cause, but complete reversal of nerve damage is uncommon even in cases for which there are available treatments.

Conclusions and Relevance Peripheral neuropathy affects approximately 1% of adults worldwide and may cause sensory, motor, and autonomic symptoms. Diabetes is the most common cause of peripheral neuropathy in Western countries. First-line therapies for neuropathic pain include gabapentin, pregabalin, duloxetine, and amitriptyline.

Author/s:

Michelle L. Mauermann, Nathan P. Staff

Diagnosis and management of patients with polyneuropathy

Aubrey Delammermore — Wed, 15 Feb 2023 06:00:00 +0000

Date Added:

February 15, 2023

Journal/Publication:

CMAJ

Publisher:

CMA Impact Inc

Publication Date:

February 13, 2023

Issue:

Volume:

195

Pages:

E227-E233

URL:

Diagnosis and management of patients with polyneuropathy

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1503/cmaj.220936

Keywords

PMID (1):

36781195

MeSH

Polyneuropathies* / diagnosis

Polyneuropathies* / therapy

Humans

diabetic neuropathies

Neurologic Examination

A general review of polyneuropathy syndromes noting red flags and a diagnostic algorithm. James W. Mold, MD, MPH

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Polyneuropathy is a common neurologic condition with an overall prevalence in the general population of about 1%–3%, increasing to roughly 7% among people older than 65 years. Polyneuropathy has many causes, and can present in many different ways; thus, it requires a logical clinical approach for evaluation, diagnosis and management. We review the approach to evaluating a patient with polyneuropathy by highlighting important aspects of the history and neurologic examination. We focus on the role of diagnostic investigations for distal symmetric polyneuropathy (DSP), the most common subtype, and an approach to the symptomatic treatment of painful diabetic polyneuropathy (PDN). We draw on practice based guidelines, meta-analyses and systematic reviews, where
possible, as they represent the highest levels of evidence (Box 1).

Author/s:

Mirian, A., Aljohani, Z., Grushka, D., Florendo-Cumbermack, A.

The relationship between exacerbated diabetic peripheral neuropathy and metformin treatment in type 2 diabetes mellitus

Devin Evans — Wed, 03 Mar 2021 06:00:00 +0000

Date Added:

March 3, 2021

Journal/Publication:

Scientific Reports

Publication Date:

January 21, 2021

Issue:

Volume:

URL:

The relationship between exacerbated diabetic peripheral neuropathy and metformin treatment in type 2 diabetes mellitus

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1038/s41598-021-81631-8

Keywords

PMID (1):

33479439

MeSH

Metformin

diabetic neuropathies

This study suggests that prolonged treatment with metformin is associated with reduced Vitamin B12 levels and an increased incidence of distal peripheral neuropathy. James W. Mold, MD, MPH

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Metformin-treated diabetics (MTD) showed a decrease in cobalamin, a rise in homocysteine, and methylmalonic acid, leading to accentuated diabetic peripheral neuropathy (DPN). This study aimed to determine whether or not metformin is a risk factor for DPN. We compared MTD to non-metformin-treated diabetics (NMTD) clinically using the Toronto Clinical Scoring System (TCSS), laboratory (methylmalonic acid, cobalamin, and homocysteine), and electrophysiological studies. Median homocysteine and methylmalonic acid levels in MTD vs. NMTD were 15.3 vs. 9.6 µmol/l; P < 0.001 and 0.25 vs. 0.13 µmol/l; P = 0.02, respectively with high statistical significance in MTD. There was a significantly lower plasma level of cobalamin in MTD than NMTD. Spearman's correlation showed a significant negative correlation between cobalamin and increased dose of metformin and a significant positive correlation between TCSS and increased dose of metformin. Logistic regression analysis showed that MTD had significantly longer metformin use duration, higher metformin dose > 2 g, higher TCSS, lower plasma cobalamin, and significant higher homocysteine. Diabetics treated with metformin for prolonged duration and higher doses were associated with lower cobalamin and more severe DPN.

Author/s:

Hashem, Manal Mohammed, Esmael, Ahmed, Nassar, Abdelfattah Kasem, El-Sherif, Mohammed

Ameliorative Effects Of N-Acetylcysteine As Adjunct Therapy On Symptoms Of Painful Diabetic Neuropathy

Brian Desmarais — Tue, 03 Mar 2020 14:28:42 +0000

Date Added:

March 3, 2020

Journal/Publication:

Journal of Pain Research

Publication Date:

November 19, 2019

Volume:

Pages:

3147-3159

URL:

Ameliorative Effects Of N-Acetylcysteine As Adjunct Therapy On Symptoms Of Painful Diabetic Neuropathy

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.2147/JPR.S228255

Keywords

N-acetylcysteine

oxidative stress

painful diabetic neuropathy

pregabalin

MeSH

diabetic neuropathies

Adjuvants, Pharmaceutic

Biomarkers

N-acetyl cysteine at 600mg BID may be worth trying in patients with painful neuropathy, but patients may have to wait at least two months to see benefit. James W. Mold, MD, MPH

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PURPOSE:

Painful diabetic neuropathy (PDN) is a variant of diabetic peripheral neuropathy which is highly prevalent and distressing in diabetic patients. Despite its high burden, the optimal treatment of PDN has remained a clinical challenge. To explain the emergence and maintenance of PDN, increasing attention has been focused on dimensions of inflammation and oxidative toxic stress (OTS). Accordingly, the aim of this study was to investigate the effects of oral N-acetylcysteine (NAC), an agent with known anti-oxidant and anti-inflammatory effects, as an adjunct therapy in patients suffering from PDN.

PATIENTS AND METHODS:

113 eligible patients with type 2 diabetes suffering from PDN were randomly assigned to either the pregabalin + placebo or pregabalin + NAC group for 8 weeks (pregabalin at a dose of 150 mg per day, NAC and matched placebo at doses of 600 mg twice a day). Mean pain score was evaluated at baseline, week 1, 2, 4, 6, and 8 of the study based on the mean 24 hr average pain score, using an 11-point numeric rating scale (NRS). As secondary efficacy measures, mean sleep interference score (SIS) resulting from PDN, responder rates, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and safety were also assessed. Additionally, serum levels of total antioxidant capacity (TAC), total thiol groups (TTG), catalase activity (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), nitric oxide (NO), and malondialdehyde (MDA) were assessed at baseline and at the end of the study.

RESULTS:

Ninety patients completed the eight-week course of the study. The decrease in mean pain scores and mean sleep interference score in pregabalin + NAC group was greater in comparison with pregabalin + placebo group (p value<0.001 in both conditions). Moreover, more responders (defined as ≥50% reduction in mean pain score from baseline to end-point) were observed in the pregabalin + NAC group, in comparison with pregabalin + placebo group (72.1% vs 46.8%). More improvement in PGIC and CGIC from baseline to the end of the study was reported in pregabalin + NAC group. Oral NAC had minimal adverse effects and was well tolerated in almost all patients. Furthermore, in respect to OTS biomarkers, adjuvant NAC significantly decreased serum level of MDA and significantly increased serum levels of SOD, GPx, TAC, and TTG.

CONCLUSION:

The pattern of results suggests that compared to placebo and over a time period of 8 weeks, adjuvant NAC is more efficacious in improving neuropathic pain associated with diabetic neuropathy than placebo. Ameliorative effects of NAC on OTS biomarkers demonstrated that NAC may alleviate painful symptoms of diabetic neuropathy, at least in part by its antioxidant effects.

Author/s:

Heidari, N., Sajedi, F., Mohammadi, Y., Mirjalili, M., Mehrpooya, M.

Duloxetine: Painful Diabetic Neuropathy and Fibromyalgia

Jeffrey Wilson — Wed, 31 Oct 2018 14:30:36 +0000

Date Added:

October 31, 2018

Journal/Publication:

Bandolier Journal

Publisher:

Bandolier

URL:

Duloxetine: painful diabetic neuropathy and fibromyalgia

Type:

Meta-analyses, Reviews, and Guidelines

Keywords

duloxetine hydrochloride

Fibromyalgia

diabetic neuropathies

MeSH

duloxetine hydrochloride

Fibromyalgia

diabetic neuropathies

There is good evidence that duloxetine helps some patients with either chronic neuropathic pain or fibromyalgia; 60mg/day worked just as well as 120mg/day.

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Clinical bottom line

There is good evidence that duloxetine at doses of 60 or 120 mg daily helps some people with painful diabetic neuropathy or fibromyalgia. The NNT for one person to have at least 50% pain relief is about 6. Nausea, somnolence constipation and reduced appetite are common adverse events.

Author/s:

Sultan, Asquad, Gaskell, Helen, Derry, Sheena, Moore, R. Andrew