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BMC Endocrine Disorders Nov 2022Diabetic peripheral neuropathy (DPN), due to its potential for causing morbidity and disability from foot ulcers and amputations, is increasingly becoming a source of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic peripheral neuropathy (DPN), due to its potential for causing morbidity and disability from foot ulcers and amputations, is increasingly becoming a source of concern in Saudi Arabia and worldwide. However, wide variability exists in the prevalence of DPN reported in previous studies in Saudi Arabia, limiting the utility of existing data in national public health policy. Therefore, the aim of this study was to systematically evaluate the magnitude of DPN in patients living with DM in Saudi Arabia in order to inform policymakers during the implementation of appropriate preventive and treatment strategies for DPN.
METHODS
PubMed, Google Scholar, African Journals Online, Scopus, Web of Science, Embase, and Wiley Online Library were searched systematically to acquire relevant articles based on preset criteria. We evaluated heterogeneity and publication bias and employed a random-effects model to estimate the pooled prevalence of DPN from the included studies. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in conducting the meta-analysis. Analysis was performed using the STATA Version 12 software.
RESULTS
Twelve studies with a total of 4,556 participants living with DM, of whom 2,081 were identified as having DPN were included in the meta-analysis. The overall prevalence of DPN was 39% (95% CI [30%, 49%]). Subgroup analysis based on diagnostic method showed that prevalence estimates for DPN using screening questionnaires and clinical examination were 48% (95% CI [46%, 50%]) and 40% (95% CI: [38%, 42%]), respectively, while the estimated prevalence using nerve conduction studies was 26% (95% CI [15%, 36%]).
CONCLUSION
This study showed a high magnitude of DPN in Saudi Arabia (39%), thus highlighting the need for sustained efforts to reduce the prevalence of diabetes mellitus and DPN in the kingdom.
Topics: Humans; Amputation, Surgical; Diabetes Mellitus; Diabetic Neuropathies; Prevalence; Saudi Arabia
PubMed: 36319996
DOI: 10.1186/s12902-022-01167-4 -
Archives of Osteoporosis Aug 2020Many studies have explored the association between neuropathy and osteoporosis in patients with diabetes mellitus. However, the results still remain inconsistent and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Many studies have explored the association between neuropathy and osteoporosis in patients with diabetes mellitus. However, the results still remain inconsistent and controversial. We aimed to estimate the association between diabetic neuropathy and osteoporosis.
METHODS
Databases, including PubMed, Embase, Web of Science, the Cochrane library, Chinese Biomedical Literature Database (CBM), and Wanfang, were screened from inception to 30 March 2020. Studies were selected and data were extracted by two independent reviewers. Study characteristics and quality sections were reviewed independently. Pooled ORs and 95% CIs were calculated using random effects model when evidence of heterogeneity was present; otherwise, fixed effects model was used. Meta-regression and subgroup analyses were performed to explore the source of heterogeneity. Sensitivity analysis and publication bias were also tested.
RESULTS
A total of 11 studies with 27,585 participants were included in this analysis which indicated that there was an increased odd between diabetic neuropathy and osteoporosis (overall OR 2.20, 95% CI 1.71-2.83). In the subgroup analyses and meta-regression, diabetic neuropathy has no significant difference in osteoporosis or fracture (p = 0.532). And osteoporosis also has no significant difference in type 1 or type 2 diabetic neuropathy (p = 0.668).
CONCLUSIONS
This meta-analysis suggests that patients with diabetic neuropathy have a significantly increased chance of developing osteoporosis, even fragility fracture. The clinicians should pay more attention to the patients with diabetic neuropathy. Further studies were still needed to explore the confounding factors among studies and to elucidate the underlying biological mechanisms.
Topics: Diabetes Mellitus; Diabetic Neuropathies; Humans; Osteoporosis
PubMed: 32779030
DOI: 10.1007/s11657-020-00804-6 -
Journal of Foot and Ankle Research Mar 2021For patients with diabetic foot ulcers, offloading is one crucial aspect of treatment and aims to redistribute pressure away from the ulcer site. In addition to...
BACKGROUND
For patients with diabetic foot ulcers, offloading is one crucial aspect of treatment and aims to redistribute pressure away from the ulcer site. In addition to offloading strategies, patients are often advised to reduce their activity levels. Consequently, patients may avoid exercise altogether. However, it has been suggested that exercise induces an increase in vasodilation and tissue blood flow, which may potentially facilitate ulcer healing. The aim of this systematic review was to determine whether exercise improves healing of diabetic foot ulcers.
REVIEW
We conducted a systematic search of MEDLINE, CINAHL and EMBASE between July 6, 2009 and July 6, 2019 using the key terms and subject headings diabetes, diabetic foot, physical activity, exercise, resistance training and wound healing. Randomised controlled trials were included in this review. Three randomised controlled trials (139 participants) were included in this systematic review. All studies incorporated a form of non-weight bearing exercise as the intervention over a 12-week period. One study conducted the intervention in a supervised setting, while two studies conducted the intervention in an unsupervised setting. Two studies found greater improvement in percentage wound size reduction in the intervention group compared with the control group, with one of these studies achieving statistically significant findings (p < 0.05). The results of the third study demonstrated statistically significant findings for total wound size reduction (p < 0.05), however results were analysed within each treatment group and not between groups.
CONCLUSION
This systematic review found there is insufficient evidence to conclusively support non-weight bearing exercise as an intervention to improve healing of diabetic foot ulcers. Regardless, the results demonstrate some degree of wound size reduction and there were no negative consequences of the intervention for the participants. Given the potential benefits of exercise on patient health and wellbeing, non-weight bearing exercise should be encouraged as part of the management plan for treatment of diabetic foot ulcers. Further research is required to better understand the relationship between exercise and healing of diabetic foot ulcers.
Topics: Aged; Diabetic Foot; Exercise; Exercise Therapy; Female; Foot; Humans; Male; Middle Aged; Regional Blood Flow; Treatment Outcome; Vasodilation; Weight-Bearing; Wound Healing
PubMed: 33743791
DOI: 10.1186/s13047-021-00456-w -
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 -
The Cochrane Database of Systematic... Jan 2014Duloxetine is a balanced serotonin and noradrenaline reuptake inhibitor licensed for the treatment of major depressive disorders, urinary stress incontinence and the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Duloxetine is a balanced serotonin and noradrenaline reuptake inhibitor licensed for the treatment of major depressive disorders, urinary stress incontinence and the management of neuropathic pain associated with diabetic peripheral neuropathy. A number of trials have been conducted to investigate the use of duloxetine in neuropathic and nociceptive painful conditions. This is the first update of a review first published in 2010.
OBJECTIVES
To assess the benefits and harms of duloxetine for treating painful neuropathy and different types of chronic pain.
SEARCH METHODS
On 19th November 2013, we searched The Cochrane Neuromuscular Group Specialized Register, CENTRAL, DARE, HTA, NHSEED, MEDLINE, and EMBASE. We searched ClinicalTrials.gov for ongoing trials in April 2013. We also searched the reference lists of identified publications for trials of duloxetine for the treatment of painful peripheral neuropathy or chronic pain.
SELECTION CRITERIA
We selected all randomised or quasi-randomised trials of any formulation of duloxetine, used for the treatment of painful peripheral neuropathy or chronic pain in adults.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We identified 18 trials, which included 6407 participants. We found 12 of these studies in the literature search for this update. Eight studies included a total of 2728 participants with painful diabetic neuropathy and six studies involved 2249 participants with fibromyalgia. Three studies included participants with depression and painful physical symptoms and one included participants with central neuropathic pain. Studies were mostly at low risk of bias, although significant drop outs, imputation methods and almost every study being performed or sponsored by the drug manufacturer add to the risk of bias in some domains. Duloxetine at 60 mg daily is effective in treating painful diabetic peripheral neuropathy in the short term, with a risk ratio (RR) for ≥ 50% pain reduction at 12 weeks of 1.73 (95% CI 1.44 to 2.08). The related NNTB is 5 (95% CI 4 to 7). Duloxetine at 60 mg daily is also effective for fibromyalgia over 12 weeks (RR for ≥ 50% reduction in pain 1.57, 95% CI 1.20 to 2.06; NNTB 8, 95% CI 4 to 21) and over 28 weeks (RR 1.58, 95% CI 1.10 to 2.27) as well as for painful physical symptoms in depression (RR 1.37, 95% CI 1.19 to 1.59; NNTB 8, 95% CI 5 to 14). There was no effect on central neuropathic pain in a single, small, high quality trial. In all conditions, adverse events were common in both treatment and placebo arms but more common in the treatment arm, with a dose-dependent effect. Most adverse effects were minor, but 16% of participants stopped the drug due to adverse effects. Serious adverse events were rare.
AUTHORS' CONCLUSIONS
There is adequate amounts of moderate quality evidence from eight studies performed by the manufacturers of duloxetine that doses of 60 mg and 120 mg daily are efficacious for treating pain in diabetic peripheral neuropathy but lower daily doses are not. Further trials are not required. In fibromyalgia, there is lower quality evidence that duloxetine is effective at similar doses to those used in diabetic peripheral neuropathy and with a similar magnitude of effect. The effect in fibromyalgia may be achieved through a greater improvement in mental symptoms than in somatic physical pain. There is low to moderate quality evidence that pain relief is also achieved in pain associated with depressive symptoms, but the NNTB of 8 in fibromyalgia and depression is not an indication of substantial efficacy. More trials (preferably independent investigator led studies) in these indications are required to reach an optimal information size to make convincing determinations of efficacy.Minor side effects are common and more common with duloxetine 60 mg and particularly with 120 mg daily, than 20 mg daily, but serious side effects are rare.Improved direct comparisons of duloxetine with other antidepressants and with other drugs, such as pregabalin, that have already been shown to be efficacious in neuropathic pain would be appropriate. Unbiased economic comparisons would further help decision making, but no high quality study includes economic data.
Topics: Adult; Analgesics; Chronic Pain; Diabetic Neuropathies; Duloxetine Hydrochloride; Fibromyalgia; Humans; Neuralgia; Randomized Controlled Trials as Topic; Thiophenes
PubMed: 24385423
DOI: 10.1002/14651858.CD007115.pub3 -
Clinical Drug Investigation Dec 2023Painful peripheral neuropathy is a common and challenging complication of diabetes mellitus. Combination therapy is used widely by clinicians, although strong evidence... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Painful peripheral neuropathy is a common and challenging complication of diabetes mellitus. Combination therapy is used widely by clinicians, although strong evidence for efficacy and safety is lacking. The goal of this study is to compare the efficacy and safety of combination versus monotherapy of first-line medications for peripheral diabetic neuropathy.
METHODS
PubMed, Embase, Cochrane Central, and clinicaltrials.gov databases were searched on December 5, 2022, for randomized clinical trials comparing combined therapy with gabapentinoids and either tricyclic antidepressants (TCAs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) versus monotherapy with any of these drugs. Pooled mean differences (MD) with a 95% confidence interval (CI) were computed for pain outcomes, measured on an 11-point numeric rating scale averaging pain scores in the last 7 days. Risk ratios (RRs) were computed for binary endpoints. Risk assessment was performed using the Risk of Bias 2 tool.
RESULTS
A total of five randomized studies and 916 patients were included. Follow-up ranged from 6 to 12 weeks. Mean pain reduction was greater for combination therapy than monotherapy (MD - 0.39; 95% CI - 0.67 to - 0.12; p = 0.005). Similarly, there was an improvement in ≥ 30% reduction in average pain (RR 1.16; 95% CI 1.07-1.26; p < 0.01) with combination therapy. In contrast, there was no significant difference between groups in ≥ 50% reduction in average pain (RR 1.21; 95% CI 0.99-1.49; p = 0.06). When comparing combination therapy versus gabapentinoid monotherapy, there was also a significant reduction in average pain (MD - 0.61; 95% CI - 0.85 to - 0.37; p < 0.01) with combination therapy.
CONCLUSION
In patients with painful diabetic peripheral neuropathy, the combination of gabapentinoids with TCAs or SNRIs is associated with a greater reduction in pain as compared with monotherapy, although this difference may not translate into a clinically important difference.
Topics: Humans; Diabetic Neuropathies; Serotonin and Noradrenaline Reuptake Inhibitors; Selective Serotonin Reuptake Inhibitors; Pain; Diabetes Mellitus; Randomized Controlled Trials as Topic
PubMed: 37940831
DOI: 10.1007/s40261-023-01318-y -
Expert Review of Neurotherapeutics Mar 2022The aim of this study is to improve our knowledge of cognitive function in individuals with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus and with peripheral diabetic... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The aim of this study is to improve our knowledge of cognitive function in individuals with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus and with peripheral diabetic neuropathy (DPN).
METHODS
A systematic review and meta-analysis was performed of publications included in PubMed, Scopus, PsycInfo and Web of Science databases until November 2021. The study was registered in PROSPERO (CRD42021229163).
RESULTS
A total of 832 articles were identified, 19 of which were selected. The presence of DPN was associated with global cognitive impairment in the T1DM persons in two studies (p=0.046;p=0.03) and T2DM persons in four (p<0.00;p<0.02;p=0.011;p≤0.05) . Differences in specific dimensions - memory, attention, and psychomotor speed - were found in both kinds of diabetes. The meta-analysis showed that the individuals with T2DM and DPN presented a lower mean cognitive performance than those without DPN (-1.0448;95%CI:-1.93%;-0.16%). Depression was associated with impaired cognitive function in these diabetic persons (p < 0.01).
CONCLUSION
The review reveals the great variability in instruments and methodologies, while providing results that support the presence of both global and domain-specific cognitive impairment in diabetic persons with DPN.
Topics: Cognition; Cognitive Dysfunction; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans
PubMed: 35232335
DOI: 10.1080/14737175.2022.2048649 -
Systematic Reviews Mar 2023Painful diabetic peripheral neuropathy (PDPN) is a key concern in clinical practice. In this systematic review and meta-analysis, we compared duloxetine and placebo... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Painful diabetic peripheral neuropathy (PDPN) is a key concern in clinical practice. In this systematic review and meta-analysis, we compared duloxetine and placebo treatments in terms of their efficacy and safety in patients with PDPN.
METHODS
Following the PRISMA guidelines, we searched the Cochrane Library, PubMed, and Embase databases for relevant English articles published before January 11, 2021. Treatment efficacy and safety were assessed in terms of pain improvement, patient-reported health-related performance, and patients' quality of life.
RESULTS
We reviewed a total of 7 randomized controlled trials. Regarding pain improvement, duloxetine was more efficacious than placebo (mean difference [MD] - 0.89; 95% confidence interval [CI] - 1.09 to - 0.69; P < .00001). Furthermore, duloxetine significantly improved the patients' quality of life, which was assessed using the Clinical Global Impression severity subscale (MD - 0.48; 95% CI - 0.61 to - 0.36; P < .00001), Patient Global Impression of Improvement scale (MD - 0.50; 95% CI - 0.64 to - 0.37; P < .00001), and European Quality of Life Instrument 5D version (MD 0.04; 95% CI 0.02 to 0.07; P = .0002). Severe adverse events were rare, whereas nausea, somnolence, dizziness, fatigue, constipation, and decreased appetite were common; approximately, 12.6% of all patients dropped out because of the common symptoms.
CONCLUSIONS
Duloxetine is more efficacious than placebo treatments in patients with PDPN. The rarity of severe adverse events indicates that duloxetine is safe. When a 60-mg dose is insufficient, 120 mg of duloxetine may improve PDPN symptoms. Our findings may help devise optimal treatment strategies for PDPN.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021225451.
Topics: Humans; Duloxetine Hydrochloride; Diabetic Neuropathies; Quality of Life; Randomized Controlled Trials as Topic; Pain; Diabetes Mellitus
PubMed: 36945033
DOI: 10.1186/s13643-023-02185-6 -
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 Public Health 2023Early identification and intervention of diabetic peripheral neuropathy is beneficial to improve clinical outcome. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early identification and intervention of diabetic peripheral neuropathy is beneficial to improve clinical outcome.
OBJECTIVE
To establish a risk prediction model for diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM).
METHODS
The derivation cohort was from a meta-analysis. Risk factors and the corresponding risk ratio (RR) were extracted. Only risk factors with statistical significance were included in the model and were scored by their weightings. An external cohort were used to validate this model. The outcome was the occurrence of DPN.
RESULTS
A total of 95,604 patients with T2DM from 18 cohorts were included. Age, smoking, body mass index, duration of diabetes, hemoglobin A1c, low HDL-c, high triglyceride, hypertension, diabetic retinopathy, diabetic kidney disease, and cardiovascular disease were enrolled in the final model. The highest score was 52.0. The median follow-up of validation cohort was 4.29 years. The optimal cut-off point was 17.0, with a sensitivity of 0.846 and a specificity of 0.668, respectively. According to the total scores, patients from the validation cohort were divided into low-, moderate-, high- and very high-risk groups. The risk of developing DPN was significantly increased in moderate- (RR 3.3, 95% CI 1.5-7.2, = 0.020), high- (RR 15.5, 95% CI 7.6-31.6, < 0.001), and very high-risk groups (RR 45.0, 95% CI 20.5-98.8, < 0.001) compared with the low-risk group.
CONCLUSION
A risk prediction model for DPN including 11 common clinical indicators were established. It is a simple and reliable tool for early prevention and intervention of DPN in patients with T2DM.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Risk Factors; Glycated Hemoglobin; Diabetic Retinopathy
PubMed: 36908480
DOI: 10.3389/fpubh.2023.1128069