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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 -
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 -
Journal of Personalized Medicine Mar 2021Diabetic neuropathy is defined as the dysfunction of the peripheral nervous system in diabetic patients. It is considered a microvascular complication of diabetes... (Review)
Review
BACKGROUND
Diabetic neuropathy is defined as the dysfunction of the peripheral nervous system in diabetic patients. It is considered a microvascular complication of diabetes mellitus. Its presence is associated with increased morbidity and mortality. Although several studies have found alterations at somatic motor, sensory levels and at the level of autonomic nervous system in diabetic patients, there is not a systematic approach regarding the differences in neuropathy between the major variants of diabetes, e.g., type 1 and 2 diabetes at both neurological and molecular level.
DATA SOURCES
we systematically (Medline, Scopus, and Cochrane databases) evaluated the literature related to the difference of neuropathy in type 1 and 2 diabetes, differences in molecular biomarkers. Study characteristics: seventeen articles were selected based on pre-defined eligibility criteria.
CONCLUSIONS
both superficial sensitivity (primarily thermal sensitivity to cold) and deep sensitivity (such as vibratory sensitivity), have been reported mainly in type 2 diabetes. Cardiac autonomic neuropathy is one of the diabetic complications with the greatest impact at a clinical level but is nevertheless one of the most underdiagnosed. While for type 1 diabetes patients most neuropathy alterations have been reported for the Valsalva maneuver and for the lying-to-standing test, for type 2 diabetes patients, alterations have been reported for deep-breathing test and the Valsalva test. In addition, there is a greater sympathetic than parasympathetic impairment, as indicated by the screening tests for autonomic cardiac neuropathy. Regarding subclinical inflammation markers, patients with type 2 diabetes showed higher blood levels of inflammatory markers such as high-sensitivity C-reactive protein, proinflammatory cytokines IL-6, IL-18, soluble cell adhesion molecules and E-selectin and ICAM-1, than in type 1 diabetes patients. By contrast, the blood levels of adiponectin, an adipocyte-derived protein with multiple paracrine and endocrine activities (anti-inflammatory, insulin-sensitizing and proangiogenic effects) are higher in type 1 than in type 2 diabetic patients. This review provides new insights into the clinical differences in type 1 and 2 diabetes and provide future directions in this research field.
PubMed: 33810048
DOI: 10.3390/jpm11030230 -
Physiotherapy Theory and Practice Jun 2023To evaluate the effects of exercise therapy on neuropathic symptoms, signs, psychosocial aspects, and physical function in people with diabetic neuropathy (DN). (Review)
Review
OBJECTIVE
To evaluate the effects of exercise therapy on neuropathic symptoms, signs, psychosocial aspects, and physical function in people with diabetic neuropathy (DN).
METHODS
A search in PubMed, Web of Science, Physiotherapy Evidence (PEDro), and Cochrane databases was performed from inception to Invalid Date NaN, . Randomized clinical trials (RCTs) were selected in patients with DN comparing exercise therapy with a control group. The studies' methodological quality was assessed with the PEDro scale. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the overall quality.
RESULTS
Eleven RCTs ( = 517 participants) were included. Nine studies showed high methodological quality. Mean (MD) and standardized mean differences (SMD) were observed in favor of exercise therapy for symptoms (MD = -1.05; confidence interval 95% = -1.90 to -0.20), signs (SMD = -0.66; confidence interval 95%= -1 to -0.32), and physical function (SMD = -0.45; confidence interval 95% = -0.66 to -0.24). No changes were found in psychosocial aspects (SMD = -0.37; confidence interval 95% = -0.92 to 0.18). The overall quality of evidence was very low.
CONCLUSION
The quality of evidence suggesting that exercise therapy provides short-term benefits in neuropathic symptoms, signs, and physical function in patients with DN is very low. Furthermore, there were no effects found on psychosocial aspects.
PubMed: 37341684
DOI: 10.1080/09593985.2023.2227975 -
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 -
Pain Jan 2024This preregistered (CRD42021223379) systematic review and meta-analysis aimed to characterize the placebo and nocebo responses in placebo-controlled randomized clinical... (Meta-Analysis)
Meta-Analysis
This preregistered (CRD42021223379) systematic review and meta-analysis aimed to characterize the placebo and nocebo responses in placebo-controlled randomized clinical trials (RCTs) on painful diabetic neuropathy (PDN), updating the previous literature by a decade. Four databases were searched for PDN trials published in the past 20 years, testing oral medications, adopting a parallel-group design. Magnitude of placebo or nocebo responses, Cochrane risk of bias, heterogeneity, and moderators were evaluated. Searches identified 21 studies (2425 placebo-treated patients). The overall mean pooled placebo response was -1.54 change in the pain intensity from baseline [95% confidence interval (CI): -1.52, -1.56, I 2 = 72], with a moderate effect size (Cohen d = 0.72). The pooled placebo 50% response rate was 25% [95% CI: 22, 29, I 2 = 50%]. The overall percentage of patients with adverse events (AEs) in the placebo arms was 53.3% [95% CI: 50.9, 55.7], with 5.1% [95% CI: 4.2, 6] of patients dropping out due to AEs. The year of study initiation was the only significant moderator of placebo response (regression coefficient = -0.06, [95% CI: -0.10, -0.02, P = 0.007]). More recent RCTs tended to be longer, bigger, and to include older patients (N = 21, rs = 0.455, P = 0.038, rs = 0.600, P = 0.004, rs = 0.472, P = 0.031, respectively). Our findings confirm the magnitude of placebo and nocebo responses, identify the year of study initiation as the only significant moderator of placebo response, draw attention to contextual factors such as confidence in PDN treatments, patients' previous negative experiences, intervention duration, and information provided to patients before enrollment.
Topics: Humans; Nocebo Effect; Diabetic Neuropathies; Placebo Effect; Pain Measurement; Diabetes Mellitus
PubMed: 37530658
DOI: 10.1097/j.pain.0000000000003000 -
Frontiers in Endocrinology 2023Diabetic foot ulcers (DFU) are a major complication of diabetes mellitus (DM). Nutrient deficiencies are among the major risk factors in DFU development and healing. In... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic foot ulcers (DFU) are a major complication of diabetes mellitus (DM). Nutrient deficiencies are among the major risk factors in DFU development and healing. In this context, we aimed to investigate the possible association between micronutrient status and risk of DFU.
METHODS
A systematic review (Prospero registration: CRD42021259817) of articles, published in PubMed, Web of Science, Scopus, CINAHL Complete, and Embase, that measured the status of micronutrients in DFU patients was performed.
RESULTS
Thirty-seven studies were considered, of which thirty were included for meta-analysis. These studies reported levels of 11 micronutrients: vitamins B9, B12, C, D, E, calcium, magnesium, iron, selenium, copper, and zinc. DFU, compared to healthy controls (HC) had significantly lower vitamin D (MD: -10.82 14 ng/ml, 95% CI: -20.47, -1.16), magnesium (MD: -0.45 mg/dL, 95% CI: -0.78, -0.12) and selenium (MD: -0.33 µmol/L, 95% CI: -0.34, -0.32) levels. DFU, compared to DM patients without DFU, had significantly lower vitamin D (MD: -5.41 ng/ml, 95% CI: -8.06, -2.76), and magnesium (MD: -0.20 mg/dL, 95% CI: -0.25, -0.15) levels. The overall analysis showed lower levels of vitamin D [15.55ng/ml (95% CI:13.44, 17.65)], vitamin C [4.99µmol/L (95% CI:3.16, 6.83)], magnesium [1.53mg/dL (95% CI:1.28, 1.78)] and selenium [0.54µmol/L (95% CI:0.45, 0.64)].
CONCLUSION
This review provides evidence that micronutrient levels significantly differ in DFU patients, suggesting an association between micronutrient status and risk of DFU. Therefore, routine monitoring and supplementations are warranted in DFU patients. We suggest that personalized nutrition therapy may be considered in the DFU management guidelines.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=259817, identifier CRD42021259817.
Topics: Humans; Diabetic Foot; Selenium; Magnesium; Vitamins; Micronutrients; Vitamin D; Trace Elements; Diabetes Mellitus
PubMed: 37065742
DOI: 10.3389/fendo.2023.1152854 -
Pain and Therapy Dec 2021Painful diabetic neuropathy is a common disease that results in significant pain and disability. Treatment options have traditionally consisted of conservative measures... (Review)
Review
Painful diabetic neuropathy is a common disease that results in significant pain and disability. Treatment options have traditionally consisted of conservative measures including topical and oral medication management as well as transcutaneous electrical stimulation units. These treatments demonstrate various degrees of efficacy, and many times initial treatments are discontinued, indicating low levels of satisfaction or poor tolerability. Spinal cord stimulation has been proposed as an alternative therapy for treatment of painful diabetic neuropathy of the lower extremities. We performed a systematic literature review to evaluate the safety and effectiveness of this procedure. A literature search identified 14 prospective studies. Based on our analysis of the available evidence, there is moderate-quality evidence for the safety and efficacy of spinal cord stimulation for painful diabetic neuropathy. However, further high-quality research, including a large-scale randomized controlled trial is warranted.
PubMed: 34244979
DOI: 10.1007/s40122-021-00282-9 -
Heliyon Mar 2024Many clinical management strategies have been proposed to deal with diabetic foot ulcers. However, the occurrence and recurrence of foot ulcers remain the major problems...
Many clinical management strategies have been proposed to deal with diabetic foot ulcers. However, the occurrence and recurrence of foot ulcers remain the major problems for diabetics. This study aims to identify, visualize, and characterize the meta-analyses on diabetic foot ulcer research. Articles published online were retrieved from the Web of Science core collection database using a search query incorporating MeSH terms and topics related to diabetic foot ulcers and meta-analysis. The publications were then analyzed for basic characteristics, including publication year, countries, topics covered, references, and keywords discussed in the articles. Data visualization was performed using CiteSpace. 334 meta-analyses and systematic reviews on diabetic foot ulcers were identified. The number of publications has experienced rapid growth in recent years (nearly 6-fold since 2016). The United States, China, Netherlands, England, and Australia had a strong collaboration in the contribution of publication. 7 primary topics were summarized from the top 100 highly cited publications: #1 Interventions (proportion: 59%), #2 Risk factors and Prevention (22%), #3 Epidemiology analysis (6%), #4 Cost-effectiveness of interventions (5%), #5 Long-term prognosis (3%), #6 Quality of life analysis (3%), and #7 Economic burden analysis (2%). Footwear and offloading interventions, multidisciplinary care, hyperbaric oxygen, platelet-rich plasma, and negative pressure wound therapies are highly regarded in terms of intervention. Diabetic foot osteomyelitis, peripheral diabetic neuropathy, chronic limb-threatening ischemia, and infections are the main comorbidities. In recent years, offloading interventions, debridement, telemedicine, long-term prognosis, and economic burden analyses have gradually received attention. Individualized treatment, multidisciplinary collaboration, quality of life considerations, and economic burden analyses are the long-term concerns.
PubMed: 38496839
DOI: 10.1016/j.heliyon.2024.e27534