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Abstract

American Diabetes Association (ADA), Diabetes Canada (DC) published updates to the management of Diabetic peripheral neuropathy (DPN) in 2017 and 2018. National Institute of Healthcare and excellence (NICE) also updated their guidelines for management of neuropathic pain in 2018. This article aims to review the topic given those updates and to highlight similarities as well as differences in management. The authors will focus on implications and their clinical application in everyday practice.
Arch Gen Intern Med 2018 Volume 2 Issue 4
1
http://www.alliedacademies.org/archives-of-general-internal-medicine/Review Article
American Diabetes Association (ADA), Diabetes Canada (DC) published updates to the
management of Diabetic peripheral neuropathy (DPN) in 2017 and 2018. National Institute of
Healthcare and excellence (NICE) also updated their guidelines for management of neuropathic
pain in 2018.
This article aims to review the topic given those updates and to highlight similarities as well as
differences in management. The authors will focus on implications and their clinical application
in everyday practice.
Abstract
Introduction and Background
Diabetic peripheral neuropathy (DPN) is common with
prevalence ranging from 40% to 50% of all patients with long-
standing diabetes [1]. DPN term refers to peripheral nerve
dysfunction and damage in diabetic patients after exclusion of
other causes [2]. The denition encompasses a heterogeneous
group of presentations.
Clinical presentation of DPN could be asymptomatic, typical
neuropathic pain, atypical neuropathic pain, altered or decreased
sensations. Motor or sensorimotor symptoms may present early
on in the form of weakness and wasting. Asymptomatic DPN is
not uncommon. Typical neuropathic pain refers to the typical
presentation of stocking and gloves pain. Atypical neuropathic
pain covers many forms of peripheral neuropathic pain that
varies in site and character. Pain could be refractory to treatment
and affects patient quality of life. Lastly, sensory symptoms
may present in the form of altered or decreased sensations. Both
of which are a risk factor for diabetes complications such as
diabetic foot, ulcers and amputations. Complications of DPN
are signicant causes of morbidity and mortality in the diabetic
population [3].
The mainstay of treatment should remain on prevention rather
than reversibility. To date, once DPN developed no treatment is
available to reverse the condition or to alter the progression course.
Tight Glycaemic control may be an effective intervention to prevent
or delay the development of the condition in type 1 diabetes. It
may help reduce the clinical neuropathy symptoms and signs in
both types of diabetes [2,4,5]. The focus of treatment of DPN is
currently on improving quality of life and preventing complications
through effective screening, pain control and foot care.
Subclinical and clinical DPN and other classications
Subclinical DPN refers to patients with no symptoms but denite
signs and positive nerve conduction studies. Symptoms of
DPN are absent in up to 50% of diabetic peripheral neuropathy
patients [6]. Clinical DPN refers to patients with both symptoms
and signs.
Classication of DPN according to nerve distribution includes
polyneuropathy, mononeuropathy, mononeuropathy multiplex
among other presentations. Also, peripheral nerve dysfunction
could be sensory, motor or both if classied according to
function.
Symptoms and signs
In clinic settings, symptoms and signs are both crucial for
screening for and assessing the severity of DPN.
The most frequent presentation of DPN is the symmetrical
sensory pain/impairment that affects lower limbs sooner than
the upper limbs in a classic stocking and gloves’ appearance
[7]. Other symptoms to suggest DPN include atypical pain,
altered sensation, numbness, pins and needles, hot or burning
sensations. More interestingly, painful symptoms could happen
in diabetic patients with or without neuropathy [8]. Neuropathic
motor dysfunction symptoms include muscle weakness, poor
balance and falls.
Signs of neuropathy tested at the bedside include vibration
sensation and altered proprioception, which reect large-bre
function. Also, impairment of pain, light touch, and temperature
which reects small bres’ functions, Any of which could
present as an early sign of neuropathy [9]. Motor signs include
wasting and decreased reexes. Motor and sensorimotor
neuropathy symptoms and signs are all reported and recognised
complications of diabetes.
Both symptoms and signs carry subjective elements and could
be nonspecic. 10 g Monolament and tuning fork had low
and variable diagnostic accuracies with the former sensitivity
reported from 19% to 73% in one systematic review [10].
Several scoring systems are in place for identication of DPN
cases. The United Kingdom screening test (UKST) [11] and the
Michigan Neuropathy Screening Instrument (MNSI) [12] are
among the commonly used tools. The 2 part diagnostic screening
tools consist of simple symptoms and physical examination
scores (Table 1).
A review of diabetic peripheral neuropathy management given recent guidelines
updates.
Ehab Hamed*, Mohalall Abdel Monem
Department of Family Medicine, Al Khor Health Centre, Primary Health Care Corporation, Qatar
Accepted on August 28, 2018
Keywords: Diabetes peripheral neuropathy, Neuropathic pain, Diabetes complications.
ISSN: 2591-7951
2
Citation: Hamed E, Monem MA. A review of diabetic peripheral neuropathy management given recent guidelines updates. Arch Gen Intern
Med. 2018;2(4):1-5. DOI: 10.4066/ 2591-7951.1000060
Arch Gen Intern Med 2018 Volume 2 Issue 4
Either could serve as a gold standard history taking and
examination tools. Both screening tools have better specicity
and sensitivity but are time-consuming. It is not clear though
that these complex systems have benecial outcomes compared
to the simplied screening [1].
Nerve conduction study and a validated measure of small bre
neuropathy are the gold standards to establish the diagnosis of
typical DPN and to monitor the severity. They are not readily
available in the community and many clinic settings, but they
could play an essential role in at least epidemiological and
research purposes [13].
Generally, the diagnosis of DPN remains clinical diagnosis.
More than one symptom or sign at presentation or combination
of both are stronger predictors of diabetic neuropathy. Current
guidance from ADA and DC does not support the usage of more
scoring systems.
Frequency and mode of bedside assessment
In 2017 statement the American Diabetes Association (ADA)
recommended that all type 2 patients should be assessed with
history taking and bedside testing at the time of diagnosis and at
least annually afterwards. Those with type 1 should be assessed
ve years after diagnosis and again annual testing. Diabetes
Canada (DC) 2018 guidelines seem to agree with the frequency
of check. Both reect on the early presentation of DPN in type
2 patients.
On the mode of testing, The ADA recommends bedside testing
with temp or pinprick sensation and tuning fork to test both
small and large nerve bre functions. 10 g monolament
testing is essential in all patients [2]. DC recommends rapid
screening using either monolament or tuning fork annually
in asymptomatic patients (Table 2). More comprehensive
testing, including scoring systems, could be used for those with
symptoms or positive signs and for research purposes [1].
Patient with prediabetes might benet from baseline assessment
at the time of diagnosis. A holistic evaluation of diabetic foot
risk should include reviewing skin integrity, vascular systems,
footwear and cardiovascular risk factors.
Investigations and differential diagnoses
History, examination alongside investigations could help
exclude other causes of neuropathy. Symptoms and signs that
would warrant referral include an asymmetrical presentation,
rapid progression and motor more than sensory signs. In
everyday practice, recommended blood tests include serum
B12, folic acid, thyroid functions, complete blood count and
serum electrophoresis [14].
Patients with diabetes are likely to have B12 and Thyroid-
function abnormalities. B12 deciency is more associated
with malabsorption rather than nutritional deciency [2].
Specically, In type 2 diabetes population, B12 deciency is
more relevant because of long-term metformin use [15]. On the
other hand, The thyroid stimulating hormone (TSH) was higher
in a Chinese population with DPN, and in another systematic
analysis, subclinical hypothyroidism was associated with more
diabetic complications [16,17]. A periodic check of both B12
and TSH is a reasonable approach in all diabetic patients with
or without neuropathy.
Prevention and tight glycemic control
Prevention approach focuses on glycemic control. In type 1
diabetes near-normal glycemic control reduces the occurrence
of DPN, and patient with intensive treatment showed the
benets of primary prevention for more than ten years [18]. In
ADA DC
Asymptomatic patients mode of assessment Temp or Pinprick
+Tuning fork
+monolament
Either Monolament or tuning fork
Symptomatic patients More comprehensive testing
Both Guidelines recommend annual testing of all type 2 patients from diagnosis and type 1 patients 5 years after diagnosis. Healthcare professionals should assess risk
in at least three different sites on each foot.
Table 2: Frequency and mode of assessment.
UKST MNSI
Symptoms (a) What is the sensation felt?
(b) What is the location of symptoms?
(c) Have the symptoms ever woken patient at night?
(d) What is the timing of symptoms?
(e) How are symptoms relieved?
1. Are your legs and/or feet numb?
2. Do you ever have any burning pain in your legs and/or feet?
3. Are your feet too sensitive to touch?
4. Do you get muscle cramps in your legs and/or feet?
5. Do you ever have any prickling feelings in your legs or feet?
6. Does it hurt when the bed covers touch your skin?
7. When you get into the tub or shower, are you able to tell the hot
water from the cold water?
8. Have you ever had an open sore on your foot?
9. Has your doctor ever told you that you have diabetic neuropathy?
10. Do you feel weak all over most of the time?
11. Are your symptoms worse at night?
12. Do your legs hurt when you walk?
13. Are you able to sense your feet when you walk?
14. Is the skin on your feet so dry that it cracks open?
15. Have you ever had an amputation?
Signs (a) What is the Achilles tendon reex?
(b) What is the vibration sense?
(c) What is the pin-prick sensation?
(d) What is the temperature sensation?
1. Appearance of Feet
2. Ulceration
3. Ankle Reexes
4. Vibration perception at great toe
5. Monolament
Table 1: The United Kingdom screening test (UKST) vs Michigan neuropathy screening instrument (MNSI).
Hamed/Monem
3Arch Gen Intern Med 2018 Volume 2 Issue 4
type 2 tight control is reported as a modestly useful measure for
prevention [1,2]. There is no evidence to date that tight glycemic
control reverses DPN course, but it is paramount for managing
patient cardiovascular risk and preventing complications.
Management of diabetic neuropathy pain
Painful diabetic neuropathy affects 25% to 30% of patients
with diabetes in both hospital and clinic settings. Patients are
reluctant to report their symptoms, and many of them do not
take their medications. Few patients report complete relief
of pain, and 30 to 50 % reduction is considered a meaningful
response [19].
Medications fall into three categories, anticonvulsants,
antidepressants and opioids. Antidepressants are further divided
into serotonin-norepinephrine reuptake group and tri-cyclic
antidepressants (TCA) group. All categories have their common
share of side effects and signicant adverse events. Anticonvulsants
and antidepressants are more favourable options compared to
opioids because of their less addictive prole.
American Diabetes Association (ADA) treatment guidance
elected two medicines from each treatment group as possible
rst lines. It favours pregabalin and gabapentin as options from
the anticonvulsants group, duloxetine and venlafaxine from the
serotonin-norepinephrine reuptake inhibitor group and nally
nortriptyline and desipramine from the tri-cyclic antidepressants
group.
The guidelines allow physicians to choose according to patient
comorbidities, side effects, drug interaction and cost. Of this
list, FDA approved only pregabalin and duloxetine for the
management of pain in diabetic neuropathy patients [2].
Canadian Guidelines afrms there is not enough evidence
for comparative effectiveness. It also highlights the same
two medicine as licensed medications in the treatment of the
condition from Health Canada [1].
Pregabalin and duloxetine numbers needed to treat (NNT) range
from 3.3 to 11 for 30 to 50% of pain reduction. TCA group have
better numbers with NNT falls below three but more side effects.
In other words, about two-thirds of patients may not respond
to treatment, and most patients have a partial response. Other
alternatives include topiramate, venlafaxine, amitriptyline,
nortriptyline and desipramine and topical nitrate spray.
Options from the opioid family include tramadol and tapentadol
with the latter gained the license for treatment of the condition.
Both the ADA and Canadian Guidelines suggest that physicians
should not use opioid agents as rst lines of treatment because
of their higher potential for abuse.
National Institute of Health and Care Excellence (NICE)
suggested a choice of amitriptyline, duloxetine, gabapentin or
pregabalin as the rst line. They advise to switch in between
those agents if the patient is not responding or developing side
effects (Table 2).
NICE recommends referral to a pain specialist in case of
treatment poor response or effect on patient quality of life.
Tramadol is suggested for acute therapy and capsaicin cream
for those patients who have localised pain and don’t want oral
medicine [20].
All current guidelines advise a personalised approach with a
low dose start to be tailored to the maximum response with the
least side effects or adverse events. Early rotation or switch to
another agent in treatment failures, side effects or adverse events
(Table 3). Painful diabetic neuropathy (PDN) can be refractory
to conventional pharmacologic therapy [21].
Other options for pain management
Other options for pain management include surgical
decompression and alternative and complementary medicine
approaches.
Surgical decompression is an evolving eld. A recent systematic
review suggests it may be benecial in DPN cases, though the
evidence comes from observational studies and more focused
towards upper limb presentations [22,23].
Alternative and complementary medicine approaches with
promising results from the latest literature systematic reviews
include alpha lipoic acid, acetyl-l-carnitine, spinal cord
stimulation and capsacian [24-27]. Acupuncture and chinese
medicines have less evidence to support its use.
Beyond pain management
NICE recommendations stress following a personalised
approach with an agreed treatment plan that takes into account
patient concerns, expectations and health beliefs. It stresses the
importance of assessing the impact on life, explaining plans for
ADA DC NICE
Pregabalin
Gabapentin
Duloxetine
Venlafaxine
Nortriptyline
Desipramine
Pregabalin
Gabapentin
Valproate
Duloxetine
Venlafaxine
Amitriptyline
Topical nitrate sprays
Topical capsaicin
Pregabalin
Gabapentin
Duloxetine
Amitriptyline
Capsaicin cream
Notes 1. The choice should be patient specic
2. Starting dose should be low and titrate up according to the response.
3. In non-responders, healthcare professionals should switch between agents. DC guidance suggests they may also be used
in combinations.
4. Tramadol and Tapentadol carry risks of tolerance, abuse and dependency. They may be considered in people not responsive
to the above medications.
Table 3: Pain management medications in DPN.
4
Citation: Hamed E, Monem MA. A review of diabetic peripheral neuropathy management given recent guidelines updates. Arch Gen Intern Med.
2018;2(4):1-5
Arch Gen Intern Med 2018 Volume 2 Issue 4
starting, titrating up doses and monitoring. It follows up on other
coping strategies and rehabilitation programmes and referral to
pain specialists when necessary [20].
Multifactorial care includes optimisation of cardiovascular
risk factors such as lifestyle, dyslipidemia, HTN, erectile
dysfunction and stress. It is also essential to assess the effect of
pain on psychological status. It may improve patient responses
and adherence to treatment. Diabetic peripheral neuropathy was
associated with a higher risk of depression and anxiety [2].
Complications
Diabetic foot ulcers, infections, gangrenes and amputations are
associated with higher mortality and poor prognosis. 50% of
patients with amputations and foot ulcers die within ve years
[28]. The classic triad of ischemia, neuropathy and infection
caused a casual sequence of trauma, ulcer, and infection in
nearly 72% of amputation cases. While the primary pathology is
diabetic vasculopathy, a ve-year retrospective study reported
neuropathy as the main etiopathogenetic factor for diabetic foot
[29].
The term foot care encompasses a patient and physician approach
to screen for neuropathy, vasculopathy and infection signs.
Multidisciplinary team urgent intervention may be required in
the event of ulceration and development of diabetic foot.
Conclusion
Diabetic peripheral neuropathy is a clinical diagnosis that is well
researched with recent updates on management. Combination of
symptoms and signs improves the accuracy of screening and
diagnosis. Healthcare professionals should consider referral
in cases with rapid progression, motor more than sensory
and asymmetrical presentations. Current guidelines suggest
routine blood investigations checks with a focus on vitamin
B12, thyroid function tests and serum electrophoresis. Tight
glycaemic control forms a cornerstone in the prevention or
delay of presentation, and it may prevent complications.
Pain control should be patient centred, regularly monitored
and tailored to minimum effective dose with least side effects.
There is a consensus on the usage of pregabalin, gabapentin,
duloxetine and to less extent venlafaxine and amitryptiline. In
many cases, pain could be refractory to medicine.
A more holistic approach should address the impact of diabetic
neuropathy on a patient’s quality of life, psychological status
and assessment of other cardiovascular risk factors. Screening,
early detection and urgent intervention may help decrease
diabetic foot complications and amputation rates.
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*Correspondence to:
Ehab Hamed
Department of Family Medicine
Al Khor Health Centre
Primary Health Care Corporation
Qatar
E-mail: eshamed@phcc.gov.qa
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Glaucoma is considered the leading cause of irreversible blindness worldwide. Patients with diabetes are at risk of different eye complications, mainly retinopathy. Patients with diabetes are also at risk of developing cataract, uveitis and glaucoma. Three systematic reviews examined the associations between diabetes and glaucoma. Pooled analysis from those studies reported different OR 1.37, (95% CI=0.72-2.02), OR=1.36, (95% CI=1.25-1.50) and OR=1.48, (95% CI=1.29-1.71). Although the results seem close and suggest an increased risk in the diabetic population, the systematic reviews report significant heterogenicity and come short in explaining causality. Indeed, in one systematic review where 3 out of 7 studies suggested a non-significant association, the results were skewed to the positive side with a one-record based study that had a population size exceeding 2 million patients, while the rest of the studies had collectively 100 thousand patients. In our view, a case control study design that combines the patient surveys and electronic medical records ensure accurate data and more valid study results to validate or refute the association. This short communication article discusses the condition associations, theories for increased risk in the diabetic population and implications for future research.
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Objective: To systematically assess benefits and harm of non-pharmacologic interventions for diabetic peripheral neuropathy (DPN) symptoms. Methods: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from 1966 to May 24, 2016 for randomized controlled trials. Two reviewers evaluated studies for eligibility, serially abstracted data, evaluated risk of bias, and graded strength of evidence (SOE) for critical outcomes (pain and quality-of-life). Results: Twenty-three trials were included. For pain, alpha-lipoic acid was more effective than placebo (moderate SOE) and frequency-modulated electromagnetic stimulation was more effective than sham (low SOE) in the short-term but not the long-term. Electrical stimulation (including transcutaneous) was not effective for pain (low SOE). Spinal cord stimulation was more effective than usual care for pain (low SOE), but had serious complications, and studies had no sham arm. Evidence for cognitive behavioral therapy and acupuncture was insufficient; no exercise or physical therapy trials met inclusion criteria. No interventions reported sufficient evidence on quality-of-life. Most studies were short-term with unclear risk of bias. Conclusions: Alpha-lipoic acid and spinal cord stimulation were effective for pain; studies were short-term with quality deficits. Spinal cord stimulation had serious adverse events. Further research should address long-term outcomes and other non-pharmacologic treatments.
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Abundant evidence suggests an association between subclinical hypothyroidism (SCH) and type 2 diabetes mellitus (T2DM), but small sample sizes and inconclusive data in the literature complicate this assertion. We measured the prevalence of SCH in T2DM population, and investigated whether T2DM increase the risk of SCH and whether SCH was associated with diabetic complications. We conducted a meta-analysis using PubMed, EMBASE, Web of Science, Wan Fang, CNKI and VIP databases for literature search. We obtained studies published between January 1, 1980 to December 1, 2014. The studies were selected to evaluate the prevalence of SCH in T2DM subjects, compare the prevalence of SCH in T2DM subjects with those non-diabetics, and investigate whether diabetic complications were more prevalent in SCH than those who were euthyroid. Fixed and random effects meta-analysis models were used, and the outcome was presented as a pooled prevalence with 95% confidence interval (95% CI) or a summary odds ratio (OR) with 95% CI. Through literature search, 36 articles met the inclusion criteria and these articles contained a total of 61 studies. Funnel plots and Egger's tests showed no publication bias in our studies, except for the pooled prevalence of SCH in T2DM (P = 0.08) and OR for SCH in T2DM (P = 0.04). Trim and fill method was used to correct the results and five potential missing data were replaced respectively. The adjusted pooled prevalence of SCH in T2DM patients was 10.2%, meanwhile, T2DM was associated with a 1.93-fold increase in risk of SCH (95% CI: 1.66, 2.24). Furthermore, SCH might affect the development of diabetic complications with an overall OR of 1.74 (95% CI: 1.34, 2.28) for diabetic nephropathy, 1.42 (95% CI: 1.21, 1.67) for diabetic retinopathy, 1.85 (95% CI: 1.35, 2.54) for peripheral arterial disease, and 1.87 (95% CI: 1.06, 3.28) for diabetic peripheral neuropathy. T2DM patients are more likely to have SCH when compared with healthy population and SCH may be associated with increased diabetic complications. It is necessary to screen thyroid function in patients with T2DM, and appropriate individualized treatments in addition to thyroid function test should be given to T2DM patients with SCH as well.
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Background Diabetic foot infections are a frequent clinical problem. About 50% of patients with diabetic foot infections who have foot amputations die within five years. Properly managed most can be cured, but many patients needlessly undergo amputations because of improper diagnostic and therapeutic approaches. Discussion The article debates the pros and cons of amputation of the diabetic foot. The thesis is that if the guidelines on the management of the diabetic foot are followed primary amputation is only necessary for the unsalvageable diabetic foot. This approach would reduce the incidence of lower limb amputations in diabetic patients. Summary We favour the argument that a structured clinical and vascular assessment would help clinical decision- making as to which patients to hospitalize, which to send for imaging, or for whom to recommend surgical interventions. Endovascular procedures are the future in the treatment of diabetic arterial disease and hence the diabetic foot. Keywords: Diabetic foot; Infection; Neuropathy; Ischaemia; Treatment; Amputation
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Although guidelines for the management of children with type 1 diabetes include recommendations to screen for diabetic peripheral neuropathies (DPN), the research into the diagnostic utility of screening methods has not been systematically reviewed. The goal of this study was to summarize the findings with regard to the diagnostic accuracy of the Semmes-Weinstein monofilament and the Rydel-Seiffer tuning fork in detecting DPN in children and adolescents compared with the gold standard nerve conduction studies. Based on a PubMed search (conducted on April 26, 2013) and secondary searching, we identified 72 articles for review. We included studies that: (1) assessed DPN with the gold standard nerve conduction studies; (2) used noninvasive screening for DPN (monofilament, tuning fork, or biothesiometer); and (3) were performed in the relevant population (children with diabetes). Five articles met these criteria. Study quality was assessed by using the revised Quality Assessment of Diagnostic Accuracy Studies criteria. Heterogeneous methods precluded a formal meta-analysis of effects. Diagnostic accuracies were heterogeneous for the different screening methods. Sensitivities ranged from 1% to 19% for the tuning fork (3 studies); from 61% to 80% for the biothesiometer (2 studies); and from 19% to 73% for the monofilament (2 studies). Data show extremely low diagnostic utility for standard screening methods (tuning fork and 10-g monofilament) but acceptable utilities for biothesiometry and finer (1 g) monofilaments. Data on the diagnostic utility should be used to inform national and international guidelines on diabetes management.
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Background Over the last decade, surgical decompression procedures have been commonly used in the treatment of diabetic peripheral neuropathy. However, the effectiveness of them remains to be proved. Methods A comprehensive literature search of databases including PubMed-Medline, Ovid-EMBASE, and Cochrane Library was performed to collect the related literatures. The Medical Subject Headings used were “diabetic neuropathy,” “surgical decompression,” and “outcomes.” The methodological index for nonrandomized studies was adopted for assessing the studies included in this review. Analyses were performed with Review Manager (Version 5.3, Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration, 2014). Results A total of 12 literatures (including 8 prospective and 4 retrospective) encompassing 1,825 patients with DPN were included in the final analysis. Only one literature was identified as a randomized controlled trial. The remaining 11 literatures were observational studies; 7 of them were classified as upper-extremity nerve decompression group and 4 of them were classified as lower-extremity nerve decompression group. Meta-analysis shows that Boston questionnaire symptom severity and functional status of upper extremities, and distal motor latency and sensory conduction velocity of median nerve of DPN patients are significantly improved after carpal tunnel release. Besides, visual analog scale and two-point discrimination are considered clinically and statistically significant in lower extremities after operation. Conclusions The findings from our review have shown the efficacy of surgical decompression procedures in relieving the neurologic symptoms and restoring the sensory deficits in DPN patients. As there are few high-quality randomized controlled trials or well-designed prospective studies, more data are needed to elucidate the role of surgical procedures for DPN treatment in the future.
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Painful diabetic peripheral neuropathy occurs in approximately 25% of patients with diabetes mellitus who are treated in the office setting and significantly affects quality of life. It typically causes burning pain, paresthesias, and numbness in a stocking-glove pattern that progresses proximally from the feet and hands. Clinicians should carefully consider the patient’s goals and functional status and potential adverse effects of medication when choosing a treatment for painful diabetic peripheral neuropathy. Pregabalin and duloxetine are the only medications approved by the U.S. Food and Drug Administration for treating this disorder. Based on current practice guidelines, these medications, with gabapentin and amitriptyline, should be considered for the initial treatment. Second-line therapy includes opioid-like medications (tramadol and tapentadol), venlafaxine, desvenlafaxine, and topical agents (lidocaine patches and capsaicin cream). Isosorbide dinitrate spray and transcutaneous electrical nerve stimulation may provide relief in some patients and can be considered at any point during therapy. Opioids and selective serotonin reuptake inhibitors are optional third-line medications. Acupuncture, traditional Chinese medicine, alpha lipoic acid, acetyl-l-carnitine, primrose oil, and electromagnetic field application lack high-quality evidence to support their use.
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Aim: The association between thyroid stimulating hormone (TSH) and type 2 diabetes mellitus (T2DM) is well known. However, whether TSH is related to diabetic peripheral neuropathy (DPN) has not been studied. The aim of this study was to explore the relationship between TSH and DPN in Chinese patients with T2DM. Methods: In this cross-sectional study, 605 patients with T2DM were enrolled. Subclinical hypothyroidism (SCH) was defined as an elevated TSH level (>4.0mIU/L) and a normal free thyroxine level. DPN was evaluated by neurological symptoms, neurological signs, and electromyogram. Results: Serum TSH levels were significantly higher in DPN and signs of DPN compared with non-DPN T2DM patients (both P<0.01).The prevalence of DPN and signs of DPN in SCH subjects was higher than that in euthyroid subjects (both P<0.01). Spearman's correlation analysis showed that the serum TSH level was positively associated with DPN (r=0.172, P<0.01). A significant independent association between TSH and DPN was found by multiple logistic regression analysis after adjusting for potential confounding variables [odds ratio (OR)=1.365, P<0.01]. The patients were sequentially assigned to quartiles according to TSH level. Compared with quartile 1, patients in quartile 2 (P<0.01), quartile 3 (P=0.01), and quartile 4 (P<0.01) had a higher risk of DPN. Receiver-operating characteristic curve analysis revealed that the optimal cutoff point of TSH to indicate DPN was 3.045mIU/L in men and 2.94mIU/L in women. Conclusion: TSH level is independently associated with DPN in Chinese population with T2DM. A high serum TSH level may be a potential risk factor for DPN.
Article
The Diabetes Control and Complications Trial demonstrated that intensive diabetes therapy effectively delays the onset of clinically apparent neuropathy in patients with insulin-dependent diabetes mellitus. A total of 1,441 patients with insulin-dependent diabetes mellitus were randomly assigned to receive intensive treatment or conventional treatment. Of these, 1,290 were randomized at least 4% years or more prior to study termination. Nerve conduction studies were performed at baseline and repeated after approximately 5 years for 1,243 of these patients, 96% of the eligible population. After 5 years of treatment, significant nerve conduction differences were observed between the intensive and conventional treatment groups, all favoring better performance (faster sensory and motor conduction velocities and shorter F-wave latencies) in the intensive treatment group. Moreover, while performance generally deteriorated among the conventionally treated patients, most attributes remained stable or showed modest improvement in the intensively treated group. Treatment group differences were consistent across strata defined by duration of diabetes and the presence of neuropathy at baseline. A nonparametric multivariate test of all ten nerve conduction measures established a strong effect in favor of intensive treatment. These data confirm that the electrophysiological abnormalities associated with diabetic neuropathy are delayed or prevented by intensive diabetes treatment.
Article
To evaluate the effects and safety of 300-600 mg α-lipoic acid (ALA) given i.v. for diabetic peripheral neuropathy (DPN). We searched the databases of Medline, Embase, and Cochrane central register of Controlled Trials and Chinese biological medicine for clinical trials of ALA in the treatment of DPN. Data were extracted to examine methodological quality and describe characteristics of studies. The primary outcomes were efficacy, median motor nerve conduction velocity (MNCV), median sensory nerve conduction velocity (SNCV), peroneal MNCV, and peroneal SNCV. Secondary outcomes were adverse events. Fifteen randomized controlled trials met the inclusion criteria. The treatment group involved the administration of ALA 300-600 mg i.v. per day. And the control group used the same interventions except for ALA. Compared with the control group, nerve conduction velocities increased significantly in the treatment group. The weighted mean differences in nerve conduction velocities were 4.63 (95% confidence interval 3.58-5.67) for median MNCV, 3.17 (1.75-4.59) for median SNCV, 4.25 (2.78-5.72) for peroneal MNCV, and 3.65 (1.50-5.80) for peroneal SNCV in favor of the treatment group. The odds ratio in terms of efficacy was 4.03 (2.73-5.94) for ALA. Furthermore, no serious adverse events were observed during the treatment period. The results of this meta-analysis provide evidence that treatment with ALA (300-600 mg/day i.v. for 2-4 weeks) is safe and that the treatment can significantly improve both nerve conduction velocity and positive neuropathic symptoms. However, the evidence may not be strong because most of the studies included in this meta-analysis have poor methodological quality.