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Reviews in Endocrine & Metabolic... Aug 2023Emerging evidence suggests that treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) could be an interesting treatment strategy to reduce neurological... (Review)
Review
Emerging evidence suggests that treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) could be an interesting treatment strategy to reduce neurological complications such as stroke, cognitive impairment, and peripheral neuropathy. We performed a systematic review to examine the evidence concerning the effects of GLP-1 RAs on neurological complications of diabetes. The databases used were Pubmed, Scopus and Cochrane. We selected clinical trials which analysed the effect of GLP-1 RAs on stroke, cognitive impairment, and peripheral neuropathy. We found a total of 19 studies: 8 studies include stroke or major cardiovascular events, 7 involve cognitive impairment and 4 include peripheral neuropathy. Semaglutide subcutaneous and dulaglutide reduced stroke cases. Liraglutide, albiglutide, oral semaglutide and efpeglenatide, were not shown to reduce the number of strokes but did reduce major cardiovascular events. Exenatide, dulaglutide and liraglutide improved general cognition but no significant effect on diabetic peripheral neuropathy has been reported with GLP-1 RAs. GLP-1 RAs are promising drugs that seem to be useful in the reduction of some neurological complications of diabetes. However, more studies are needed.
Topics: Humans; Hypoglycemic Agents; Liraglutide; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide 1; Cardiovascular Diseases; Stroke; Diabetes Complications
PubMed: 37231200
DOI: 10.1007/s11154-023-09807-3 -
Nutrients Aug 2023Alpha-lipoic acid (ALA) was found to improve the symptoms in patients with diabetic sensorimotor peripheral neuropathy (DSPN) by reducing oxidative stress and... (Meta-Analysis)
Meta-Analysis Review
Alpha-lipoic acid (ALA) was found to improve the symptoms in patients with diabetic sensorimotor peripheral neuropathy (DSPN) by reducing oxidative stress and ameliorating microcirculation. Our meta-analysis is aimed at evaluating the effects of oral-administered ALA versus a placebo in patients with DSPN and determining the optimal dosage for this treatment. We systematically reviewed randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to determine the efficacy of oral ALA for patients with DSPN. The primary outcome was total symptoms' score (TSS), and secondary outcomes were the neurological disability score (NDS), neuropathy impaired score (NIS), NIS-lower limb (NIS-LL), vibration perception threshold (VPT), nerve conduction study (NCS) results, and global satisfaction. A subgroup analysis of the ALA dosage (600, 1200, and 1800 mg/day) was also conducted. Ten RCTs (1242 patients) were included. ALA treatment produced favorable results for TSS (a dose-related trend was observed), NDS, and the global satisfaction score. For VAS, VPT, NIS-LL, and NCS results, ALA did not produce favorable results. ALA treatment had favorable effects on DSPN by reducing sensory symptoms, and it resulted in a dose-dependent response relative to the placebo for TSS and the global satisfaction score. The use of ALA to prevent neurological symptoms should be further researched.
Topics: Humans; Diabetic Neuropathies; Thioctic Acid; Administration, Oral; Databases, Factual; Lower Extremity; Diabetes Mellitus
PubMed: 37630823
DOI: 10.3390/nu15163634 -
Frontiers in Neurology 2023Painful Diabetic Peripheral Neuropathy (PDPN) is a common complication of diabetes, it severely affects the quality of life of patients. Acupuncture has been shown to be...
BACKGROUND
Painful Diabetic Peripheral Neuropathy (PDPN) is a common complication of diabetes, it severely affects the quality of life of patients. Acupuncture has been shown to be effective in the treatment of PDPN. To evaluate the efficacy and safety of acupuncture for pain relief in patients diagnosed with diabetic peripheral neuropathy, we conducted a systematic review and meta-analysis.
METHOD
We thoroughly searched specific databases, which included PUBMED, EMBASE, Web of Science, the Cochrane Library, the Chinese Biomedical Literature Database, the Chinese National Knowledge Infrastructure, China Science and Technology Journal Database and the Wanfang Data. All randomized controlled trials of acupuncture therapy for PDPN with pain change scales were included. Included studies were assessed for methodological quality according to the risk of bias from the Cochrane handbook. Meta-analyses were carried out to analyze the outcomes, subgroup analyses, sensitivity analyses, and funnel plot analyses were undertaken.
RESULTS
This systematic review evaluated a total of 25 trials of acupuncture therapy in combination with conventional treatment, involving a total of 1,561 patients with PDPN. According to the results, among 16 trials using VAS scores with a total of 1,552 patients, 2 acupoint injection trials (MD -2.38, 95% CI: -2.76 to -2.01, < 0.00001), 12 acupuncture trials (MD -1. 31, 95% CI: -1.60 to -1.02, < 0.00001) and 2 moxibustion trials showed that acupuncture therapy combined with conventional treatment improved pain better than conventional treatment (MD -2.50, 95% CI: -2.76 to -2.24, < 0.00001). In the subgroup analysis of the acupuncture group, the results of the 5 trials in which the location of acupuncture was only in the limbs (MD -1.27, 95% CI: -1.54 to -1.01, < 0.00001) and the 7 trials both in limbs and torso (MD -1.38, 95% CI: -1.81 to -0.95, < 0.00001) also demonstrated that acupuncture was effective in pain improvement.
CONCLUSION
This meta-analysis analyzed the possible efficacy of acupuncture in combination with conventional treatment for pain in diabetic peripheral neuropathy, particularly when acupoints are located in the limbs. However, there are limitations to this meta-analysis and future clinical studies are needed to confirm these findings.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023449447, identifier (CRD42023449447).
PubMed: 38046594
DOI: 10.3389/fneur.2023.1281485 -
Pain Practice : the Official Journal of... Jan 2024Dietary interventions, vitamins, and nutritional supplementation are playing an increasingly important role in the management of neuropathic pain. Current... (Review)
Review
BACKGROUND/IMPORTANCE
Dietary interventions, vitamins, and nutritional supplementation are playing an increasingly important role in the management of neuropathic pain. Current pharmacological treatments are poorly tolerated and ineffective in many cases.
OBJECTIVE
This systematic review aims to study the efficacy of dietary interventions, vitamins, and nutritional supplementation in the management of chronic neuropathic pain in adults.
EVIDENCE REVIEW
The review followed PRISMA guidelines and was registered with PROSPERO (#CRD42022300312). Ten databases and gray literature, including Embase.com, MEDLINE and Web of Science, were systematically searched using a combination of keywords and controlled vocabulary related to chronic neuropathic pain and oral non-pharmacological supplements. Studies on adult humans published between 2000 and 2021 were considered for inclusion. The Cochrane Handbook was used to assess risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation was used to determine overall quality of evidence.
FINDINGS
Forty studies were included in the final review, and results were categorized according to pain type including pain related to chemotherapy-induced peripheral neuropathy (CIPN, 22 studies, including 3 prospective cohorts), diabetic peripheral neuropathy (DPN, 13 studies, including 2 prospective), complex regional pain syndrome (CRPS-I, 3 studies, including 1 prospective), and other (2 studies, both RCT). The CIPN studies used various interventions including goshajinkigan (4 studies), vitamin E (5), vitamin B12 (3), glutamine (3), N-acetyl-cysteine (2), acetyl-l-carnitine (2), guilongtonluofang (1), ninjin'yoeito (1), alpha-lipoic acid (1), l-carnosine (1), magnesium and calcium (1), crocin (1), and antioxidants (1), with some studies involving multiple interventions. All CIPN studies involved varying cancers and/or chemotherapies, advising caution for generalizability of results. Interventions for DPN included alpha-lipoic acid (5 studies), vitamin B12 (3), acetyl-l-carnitine (3), vitamin E (1), vitamin D (2), and a low-fat plant-based diet (1). Vitamin C was studied to treat CRPS-I (3 studies, including 1 prospective). Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies.
CONCLUSIONS
Based on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N-acetyl-cysteine, l-carnosine, crocin, and magnesium is warranted. Acetyl-l-carnitine was found to be likely ineffective or harmful. Alpha-lipoic acid was not found effective. Studies with goshajinkigan, vitamin B12, vitamin E, and glutamine had conflicting results regarding efficacy, with one goshajinkigan study finding it harmful. Guilongtonluofang, ninjin'yoeito, and antioxidants showed various degrees of potential effectiveness. Regarding DPN, our review supports the use of alpha-lipoic acid, acetyl-l-carnitine, and vitamin D. The early use of vitamin C prophylaxis for the development of CRPS-I also seems promising. Further research is warranted to confirm these findings.
Topics: Humans; Adult; Acetylcarnitine; Magnesium; Thioctic Acid; Carnosine; Glutamine; Cysteine; Prospective Studies; Dietary Supplements; Vitamins; Neuralgia; Vitamin E; Ascorbic Acid; Diet; Antioxidants; Vitamin B 12; Complex Regional Pain Syndromes; Vitamin D
PubMed: 37654090
DOI: 10.1111/papr.13291 -
Diabetes/metabolism Research and Reviews Mar 2024Principles of wound management, including debridement, wound bed preparation, and newer technologies involving alternation of wound physiology to facilitate healing, are...
AIMS
Principles of wound management, including debridement, wound bed preparation, and newer technologies involving alternation of wound physiology to facilitate healing, are of utmost importance when attempting to heal a chronic diabetes-related foot ulcer. However, the rising incidence and costs of diabetes-related foot ulcer management necessitate that interventions to enhance wound healing of chronic diabetes-related foot ulcers are supported by high-quality evidence of efficacy and cost effectiveness when used in conjunction with established aspects of gold-standard multidisciplinary care. This is the 2023 International Working Group on the Diabetic Foot (IWGDF) evidence-based guideline on wound healing interventions to promote healing of foot ulcers in persons with diabetes. It serves as an update of the 2019 IWGDF guideline.
MATERIALS AND METHODS
We followed the GRADE approach by devising clinical questions and important outcomes in the Patient-Intervention-Control-Outcome (PICO) format, undertaking a systematic review, developing summary of judgements tables, and writing recommendations and rationale for each question. Each recommendation is based on the evidence found in the systematic review and, using the GRADE summary of judgement items, including desirable and undesirable effects, certainty of evidence, patient values, resources required, cost effectiveness, equity, feasibility, and acceptability, we formulated recommendations that were agreed by the authors and reviewed by independent experts and stakeholders.
RESULTS
From the results of the systematic review and evidence-to-decision making process, we were able to make 29 separate recommendations. We made a number of conditional supportive recommendations for the use of interventions to improve healing of foot ulcers in people with diabetes. These include the use of sucrose octasulfate dressings, the use of negative pressure wound therapies for post-operative wounds, the use of placental-derived products, the use of the autologous leucocyte/platelet/fibrin patch, the use of topical oxygen therapy, and the use of hyperbaric oxygen. Although in all cases it was stressed that these should be used where best standard of care was not able to heal the wound alone and where resources were available for the interventions.
CONCLUSIONS
These wound healing recommendations should support improved outcomes for people with diabetes and ulcers of the foot, and we hope that widescale implementation will follow. However, although the certainty of much of the evidence on which to base the recommendations is improving, it remains poor overall. We encourage not more, but better quality trials including those with a health economic analysis, into this area.
Topics: Pregnancy; Female; Humans; Diabetic Foot; Placenta; Foot Ulcer; Wound Healing; Diabetes Mellitus
PubMed: 37232034
DOI: 10.1002/dmrr.3644 -
Diabetes/metabolism Research and Reviews Mar 2024This is the 2023 International Working Group on the Diabetic Foot guideline on the prevention of foot ulcers in persons with diabetes, which updates the 2019 guideline....
AIMS
This is the 2023 International Working Group on the Diabetic Foot guideline on the prevention of foot ulcers in persons with diabetes, which updates the 2019 guideline. This guideline is targeted at clinicians and other healthcare professionals.
MATERIALS AND METHODS
We followed the Grading of Recommendations, Assessment, Development and Evaluations methodology to devise clinical questions and critically important outcomes in the PICO format, to conduct a systematic review of the medical-scientific literature including, where appropriate, meta-analyses, and to write recommendations and their rationale. The recommendations are based on the quality of evidence found in the systematic review, expert opinion where (sufficient) evidence was not available, and a weighing of the desirable and undesirable effects of an intervention, as well as patient preferences, costs, equity, feasibility and applicability.
RESULTS
We recommend screening a person with diabetes at very low risk of foot ulceration annually for the loss of protective sensation and peripheral artery disease, and screening persons at higher risk at higher frequencies for additional risk factors. For preventing a foot ulcer, educate persons at-risk about appropriate foot self-care, educate not to walk without suitable foot protection, and treat any pre-ulcerative lesion on the foot. Educate moderate-to-high risk people with diabetes to wear properly fitting, accommodative, therapeutic footwear, and consider coaching them to monitor foot skin temperature. Prescribe therapeutic footwear that has a demonstrated plantar pressure relieving effect during walking, to help prevent plantar foot ulcer recurrence. Consider advising people at low-to-moderate risk to undertake a, preferably supervised, foot-ankle exercise programme to reduce ulcer risk factors, and consider communicating that a total increase in weight-bearing activity of 1000 steps/day is likely safe with regards to risk of ulceration. In people with non-rigid hammertoe with pre-ulcerative lesion, consider flexor tendon tenotomy. We suggest not to use a nerve decompression procedure to help prevent foot ulcers. Provide integrated foot care for moderate-to-high-risk people with diabetes to help prevent (recurrence of) ulceration.
CONCLUSIONS
These recommendations should help healthcare professionals to provide better care for persons with diabetes at risk of foot ulceration, to increase the number of ulcer-free days and reduce the patient and healthcare burden of diabetes-related foot disease.
Topics: Humans; Diabetic Foot; Foot Ulcer; Risk Factors; Evidence-Based Medicine; Diabetes Mellitus
PubMed: 37302121
DOI: 10.1002/dmrr.3651 -
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 -
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 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