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Frontiers in Endocrinology 2023Vascular endothelial growth factors (VEGFs, including VEGF-A, VEGF-B, VEGF-C, VEGF-D and PLGF) have important roles in the development and function of the peripheral... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Vascular endothelial growth factors (VEGFs, including VEGF-A, VEGF-B, VEGF-C, VEGF-D and PLGF) have important roles in the development and function of the peripheral nervous system. Studies have confirmed that VEGFs, especially VEGF-A (so called VEGF) may be associated with the diabetic peripheral neuropathy (DPN) process. However, different studies have shown inconsistent levels of VEGFs in DPN patients. Therefore, we conducted this meta-analysis to evaluate the relationship between cycling levels of VEGFs and DPN.
METHODS
This study searched 7 databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, WanFang Database, and Chinese Biomedical Literature (CBM), to find the target researches. The random effects model was used to calculate the overall effect.
RESULTS
14 studies with 1983 participants were included, among which 13 studies were about VEGF and 1 was VEGF-B, so only the effects of VEGF were pooled. The result showed that there were obviously increased VEGF levels in DPN patients compared with diabetic patients without DPN (SMD:2.12[1.34, 2.90], <0.00001) and healthy people (SMD:3.50[2.24, 4.75], <0.00001). In addition, increased circulating VEGF levels were not associated with an increased risk of DPN (OR:1.02[0.99, 1.05], <0.00001).
CONCLUSION
Compared with healthy people and diabetic patients without DPN, VEGF content in the peripheral blood of DPN patients is increased, but current evidence does not support the correlation between VEGF levels and the risk of DPN. This suggests that VEGF may play a role in the pathogenesis and repairment of DPN.
Topics: Humans; Diabetes Mellitus; Diabetic Neuropathies; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor B
PubMed: 37251664
DOI: 10.3389/fendo.2023.1169405 -
Geriatrics & Gerontology International Sep 2022The present study comprehensively investigated the relationship between diabetic peripheral neuropathy (DPN) and sarcopenia by identifying all eligible studies and... (Meta-Analysis)
Meta-Analysis
AIM
The present study comprehensively investigated the relationship between diabetic peripheral neuropathy (DPN) and sarcopenia by identifying all eligible studies and summarizing their results.
METHODS
Records were identified through MEDLINE and EMBASE database searching from inception to March 9, 2022. We included all cross-sectional studies investigating the association between DPN and sarcopenia among patients with diabetes. Data from eligible studies, including point estimates and standard errors, were pooled together using the generic inverse variance method.
RESULTS
Of 2989 retrieved articles, five studies met the inclusion criteria and were allowed for meta-analysis. The pooled analysis found a significant association between DPN and sarcopenia with the pooled odds ratio of 1.62 (95% confidence interval: 1.30-2.02; I 0%). The funnel plot was relatively symmetric and was not suggestive of the presence of publication bias.
CONCLUSIONS
The current study discovered a significant association between DPN and sarcopenia in patients with diabetes. However, given summarized data from cross-sectional studies, the temporality between DPN and sarcopenia could not be established. Geriatr Gerontol Int 2022; 22: 785-789.
Topics: Humans; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Sarcopenia
PubMed: 36053982
DOI: 10.1111/ggi.14462 -
Journal of Diabetes and Its... Oct 2021We conducted a systematic review of the literature with meta-analysis to determine whether painful diabetic neuropathy is associated with a specific inflammatory profile. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We conducted a systematic review of the literature with meta-analysis to determine whether painful diabetic neuropathy is associated with a specific inflammatory profile.
METHODS
The study is based on the PRISMA statement for systematic reviews. We performed a search of published studies up until January 2021 in MEDLINE and Web of Science based on heading and free text terms. The search strategy included the phrases: diabetic peripheral neuropathy, painful peripheral neuropathy individually and in combination with the terms: inflammation and inflammatory biomarkers. We screened titles and abstracts and performed data extraction. We also manually searched the article titles in the reference lists of key studies and reviews published in the last 20 years.
DATA EXTRACTION
Data extracted from the studies included study design, inclusion and exclusion criteria, sample type including serum and plasma, source of the sample including patients with peripheral diabetic neuropathy or patients with painful and painless neuropathy of any etiology. Blood concentrations of all measured cytokines were recorded. Whenever possible we calculated the effect size and confidence interval. Non-human studies were excluded from the meta-analysis.
RESULTS
Thirteen studies were included in this meta-analysis. The study design was cross-sectional, case control or cohort type studies. Specific inflammatory mediators are significantly higher in painful than in painless diabetic neuropathy as well as in painful neuropathies of any etiology. Markers of inflammation are also increased in those patients with diabetes mellitus, who suffer from peripheral neuropathy in comparison to patients with diabetes mellitus but no signs of peripheral neuropathy. A proinflammatory state may be the common denominator of pain and peripheral neuropathy in patients with diabetes mellitus but the inflammatory profiles seem to differ.
Topics: Biomarkers; Cross-Sectional Studies; Diabetes Mellitus; Diabetic Neuropathies; Humans; Inflammation; Pain; Peripheral Nervous System Diseases
PubMed: 34389235
DOI: 10.1016/j.jdiacomp.2021.108017 -
The Journal of Pharmacy and Pharmacology Apr 2023Peripheral neuropathy (PN), as an adverse reaction attributed to statin drugs, as well as the beneficial neuroprotective properties of statins, have been widely reported...
OBJECTIVES
Peripheral neuropathy (PN), as an adverse reaction attributed to statin drugs, as well as the beneficial neuroprotective properties of statins, have been widely reported and discussed in the literature. The aim of this study was to systematically review original publications that investigated the association of statin use and PN in diabetic and non-diabetic models, whether determined as a result of laboratory experimentation, or in a clinical setting.
KEY FINDINGS
A comprehensive search of the databases Google Scholar, PubMed/MEDLINE and Scopus was conducted. Sixty-six articles, which evaluated the link between statins and PN in either a clinical or in-vivo/in-vitro condition were included. Statin treatment in neuropathy-induced animal models demonstrates favourable neurological effects in both the morphological and functional aspects of neurons. However, an extended duration of statin treatment is minimally associated with the development of non-diabetic idiopathic neuropathy. Importantly, statins have the potential to regress diabetic PN through anti-inflammatory, anti-oxidant and immunomodulatory properties.
SUMMARY
When interpreting the results from studies that deal with the relationship between statins and PN, it is important to determine the mechanism(s) underlying the development of any potential neuropathies (in the presence or absence of diabetes), the type of model used (human or animal) and the duration of statin treatment.
Topics: Animals; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Diabetic Neuropathies; Diabetes Mellitus
PubMed: 36843566
DOI: 10.1093/jpp/rgac104 -
Complementary Therapies in Medicine Nov 2023To evaluate the effectiveness of acupuncture in relieving diabetic neuropathic pain and to establish a more reliable and efficient foundation for acupuncture practice in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the effectiveness of acupuncture in relieving diabetic neuropathic pain and to establish a more reliable and efficient foundation for acupuncture practice in diabetes care.
METHODS
The Chinese National Knowledge Infrastructure, Wanfang database, Chongqing Weipu, Chinese Biomedical Literature Database, PubMed, Embase, and Cochrane Library were all searched for a randomized controlled trial research of acupuncture for DNP. Two researchers independently performed literature screening, quality evaluation, and data extraction. After selecting studies and extracting data, we conducted the data analysis using RevMan 5.4 and Stata 14.0. The quality was assessed using the Cochrane Risk of Bias Assessment Tool.
RESULTS
An extensive review of 19 studies involving 1276 patients up to April 29, 2023, found that acupuncture was successful in improving pain intensity [MD= -1.09; 95% CI (-1.28, -0.89), P < 0.00001], clinical efficacy indicating pain changes [RR= 1.22; 95% CI (1.15, 1.29), P < 0.00001], and clinical neuropathy [MD= -1.55; 95% CI ( -3.00, -0.09), P = 0.04] in DNP patients. Quality of life was also improved, with few side effects reported.
CONCLUSION
According to this meta-analysis, acupuncture therapy significantly improved the clinical efficacy of pain intensity, pain changes, and clinical neuropathy in patients with DNP, improved the quality of life of patients to a certain extent, and had lower side effects. This discovery provides evidence-based and practical recommendations for the treatment of DNP patients.
Topics: Humans; Quality of Life; Acupuncture Therapy; Diabetic Neuropathies; Treatment Outcome; Neuralgia; Diabetes Mellitus; Randomized Controlled Trials as Topic
PubMed: 37805054
DOI: 10.1016/j.ctim.2023.102992 -
Diabetic Medicine : a Journal of the... Nov 2016To evaluate treatment options for neuropathic pain and sensory symptoms resulting from diabetic peripheral neuropathy of the feet. (Review)
Review
AIM
To evaluate treatment options for neuropathic pain and sensory symptoms resulting from diabetic peripheral neuropathy of the feet.
METHODS
The databases PubMed, Embase and Web-of-Science were searched for randomized controlled trials, published in the period from database inception to 2 July 2015, that evaluated treatments for diabetic peripheral neuropathy of the feet with placebo or standard treatment as comparators. Participants in these trials included people with diabetes mellitus and diabetic peripheral neuropathy who were given any treatment for diabetic peripheral neuropathy. Risk of bias was assessed using the Delphi list of criteria. Data from the trials were extracted using standardized data extraction sheets by two authors independently. All analyses were performed using RevMan 5.2. In case of clinical homogeneity, statistical pooling was performed using a random effects model.
RESULTS
This review included 27 trials on pharmacological, non-pharmacological and alternative treatments. In the meta-analysis of trials of α-lipoic acid versus placebo, total symptom score was reduced by -2.45 (95% CI -4.52; -0.39) with 600 mg i.v. α-lipoic acid (three trials), and was reduced by -1.95 (95% CI -2.89; -1.01) with 600 mg oral α-lipoic acid (two trials). Significant improvements in diabetic peripheral neuropathy symptoms were found with opioids, botulinum toxin A, mexidol, reflexology and Thai foot massage, but not with micronutrients, neurotrophic peptide ORG 2677 and photon stimulation therapy.
CONCLUSION
In this review, we found that α-lipoic acid, opioids, botulinum toxin A, mexidol, reflexology and Thai foot massage had significant beneficial results.
Topics: Complementary Therapies; Diabetic Foot; Diabetic Neuropathies; Humans; Neuralgia; Pain Management; Randomized Controlled Trials as Topic
PubMed: 26822889
DOI: 10.1111/dme.13083 -
The Cochrane Database of Systematic... Jan 2024Diabetic peripheral neuropathy (DPN) is a frequent complication in people living with type 1 or type 2 diabetes. There is currently no effective treatment for DPN.... (Review)
Review
BACKGROUND
Diabetic peripheral neuropathy (DPN) is a frequent complication in people living with type 1 or type 2 diabetes. There is currently no effective treatment for DPN. Although alpha-lipoic acid (ALA, also known as thioctic acid) is widely used, there is no consensus about its benefits and harms.
OBJECTIVES
To assess the effects of alpha-lipoic acid as a disease-modifying agent in people with diabetic peripheral neuropathy.
SEARCH METHODS
On 11 September 2022, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and two clinical trials registers. We also searched the reference lists of the included studies and relevant review articles for additional references not identified by the electronic searches.
SELECTION CRITERIA
We included randomised clinical trials (RCTs) that compared ALA with placebo in adults (aged 18 years or older) and that applied the study interventions for at least six months. There were no language restrictions.
DATA COLLECTION AND ANALYSIS
We used standard methods expected by Cochrane. The primary outcome was change in neuropathy symptoms expressed as changes in the Total Symptom Score (TSS) at six months after randomisation. Secondary outcomes were change in neuropathy symptoms at six to 12 months and at 12 to 24 months, change in impairment, change in any validated quality of life total score, complications of DPN, and adverse events. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
Our analysis incorporated three trials involving 816 participants. Two studies included people with type 1 or type 2 diabetes, while one study included only people with type 2 diabetes. The duration of treatment was between six months and 48 months. We judged all studies at high risk of overall bias due to attrition. ALA compared with placebo probably has little or no effect on neuropathy symptoms measured by TSS (lower score is better) after six months (mean difference (MD) -0.16 points, 95% confidence interval (CI) -0.83 to 0.51; 1 study, 330 participants; moderate-certainty evidence). The CI of this effect estimate did not contain the minimal clinically important difference (MCID) of 0.97 points. ALA compared with placebo may have little or no effect on impairment measured by the Neuropathy Impairment Score-Lower Limbs (NIS-LL; lower score is better) after six months (MD -1.02 points, 95% CI -2.93 to 0.89; 1 study, 245 participants; low-certainty evidence). However, we cannot rule out a significant benefit, because the lower limit of the CI surpassed the MCID of 2 points. There is probably little or no difference between ALA and placebo in terms of adverse events leading to cessation of treatment within six months (risk ratio (RR) 1.48, 95% CI 0.50 to 4.35; 3 studies, 1090 participants; moderate-certainty evidence). No studies reported quality of life or complications associated with DPN.
AUTHORS' CONCLUSIONS
Our analysis suggests that ALA probably has little or no effect on neuropathy symptoms or adverse events at six months, and may have little or no effect on impairment at six months. All the studies were at high risk of attrition bias. Therefore, future RCTs should ensure complete follow-up and transparent reporting of any participants missing from the analyses.
Topics: Adult; Humans; Thioctic Acid; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Lower Extremity; MEDLINE
PubMed: 38205823
DOI: 10.1002/14651858.CD012967.pub2 -
Prosthetics and Orthotics International Feb 2015Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. (Review)
Review
BACKGROUND
Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat.
OBJECTIVE
To discuss current treatment recommendations for painful diabetic peripheral neuropathy.
STUDY DESIGN
Literature review.
METHODS
Systematic review of the literature discussing treatment of painful diabetic peripheral neuropathy. Existing treatment guidelines were studied and compared.
RESULTS
Painful diabetic peripheral neuropathy occurs in about one in six people with diabetes. This condition impairs quality of life and increases healthcare costs. Treatment recommendations exist, but individual patient therapy can require a trial-and-error approach. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. Adequate medication titration and a reasonable trial period should be allowed.
CONCLUSION
The treatment of painful diabetic peripheral neuropathy can be challenging, but effective management can improve patient's quality of life.
CLINICAL RELEVANCE
Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control.
Topics: Analgesics; Cognitive Behavioral Therapy; Diabetic Neuropathies; Electric Stimulation Therapy; Guidelines as Topic; Humans; Pain Management; Quality of Life
PubMed: 25614498
DOI: 10.1177/0309364614542266 -
Frontiers in Endocrinology 2023Diabetic neuropathy (DN) is a prevalent and debilitating complication of diabetes, imposing a significant burden on individuals and healthcare systems worldwide. This...
INTRODUCTION
Diabetic neuropathy (DN) is a prevalent and debilitating complication of diabetes, imposing a significant burden on individuals and healthcare systems worldwide. This study presents a comprehensive analysis of the global research landscape in DN, aiming to provide scientists, funders, and decision-makers with valuable insights into the current state of research and future directions.
METHODS
Through a systematic review of published articles, key trends in DN research, including epidemiology, diagnosis, treatment strategies, and gaps in knowledge, are identified and discussed.
RESULTS
The analysis reveals an increasing prevalence of DN alongside the rising incidence of diabetes, emphasizing the urgent need for effective prevention and management strategies. Furthermore, the study highlights the geographical imbalance in research activity, with a majority of studies originating from high-income countries.
DISCUSSION
This study underscores the importance of fostering international collaboration to address the global impact of DN. Key challenges and limitations in DN research are also discussed, including the need for standardized diagnostic criteria, reliable biomarkers, and innovative treatment approaches. By addressing these gaps, promoting collaboration, and increasing research funding, we can pave the way for advancements in DN research and ultimately improve the lives of individuals affected by this debilitating condition.
Topics: Humans; Diabetic Neuropathies; Forecasting; Prevalence; Diabetes Mellitus
PubMed: 38034004
DOI: 10.3389/fendo.2023.1220896 -
Neurology May 2017To systematically assess the effect of pharmacologic treatments of diabetic peripheral neuropathy (DPN) on pain and quality of life. (Review)
Review
OBJECTIVE
To systematically assess the effect of pharmacologic treatments of diabetic peripheral neuropathy (DPN) on pain and quality of life.
METHODS
We searched PubMed and Cochrane Database of Systematic Reviews for systematic reviews from 2011 to October 12, 2015, and PubMed, Embase, and the Cochrane Central Register of Controlled Trials for primary studies from January 1, 2013, to May 24, 2016. We searched Clinicaltrials.gov on March 9, 2016. Two reviewers independently evaluated studies for eligibility, serially abstracted data, and independently evaluated risk of bias and graded strength of evidence (SOE).
RESULTS
We updated a recently completed systematic review of 57 eligible studies with 24 additional published studies and 25 unpublished studies. For reducing neuropathy-related pain, the serotonin-norepinephrine reuptake inhibitors duloxetine and venlafaxine (moderate SOE), the anticonvulsants pregabalin and oxcarbazepine (low SOE), the drug classes tricyclic antidepressants (low SOE) and atypical opioids (low SOE), and botulinum toxin (low SOE) were more effective than placebo. We could not draw conclusions about quality of life due to incomplete reporting. All studies were short-term (less than 6 months), and all effective drugs had more than 9% dropouts from adverse effects.
CONCLUSIONS
For reducing pain, duloxetine and venlafaxine, pregabalin and oxcarbazepine, tricyclic antidepressants, atypical opioids, and botulinum toxin were more effective than placebo. However, quality of life was poorly reported, studies were short-term, drugs had substantial dropout rates, and opioids have significant risks. Future studies should evaluate longer-term outcomes, use methods and measures recommended by pain organizations, and assess patients' quality of life.
Topics: Analgesics; Diabetic Neuropathies; Humans; Neuralgia; Pain; Peripheral Nervous System Diseases; Quality of Life
PubMed: 28341643
DOI: 10.1212/WNL.0000000000003882