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Diabetes Research and Clinical Practice Dec 2023Peripheral neuropathic pain, including painful diabetic neuropathy (PDN), is associated with marked negative impact on health-related quality of life (HRQoL). The... (Review)
Review
Peripheral neuropathic pain, including painful diabetic neuropathy (PDN), is associated with marked negative impact on health-related quality of life (HRQoL). The magnitude of reduction of HRQoL experienced by individual PDN patients appears to be strongly associated with their level of pain and disease severity. In spite of the availability of a range of pharmacotherapy, a substantive proportion of PDN patients continue to experience suboptimal HRQoL. Such patients are potential candidates for spinal cord stimulation (SCS) devices. Three randomised controlled trials in over 300 patients with refractory PDN have shown that the addition of SCS to standard of care therapy results in important health gains, including pain reduction and enhancement of HRQoL. Sham-controlled RCTs that enable blinding of patients, clinicians and researchers are needed to confirm the role of SCS in PDN.
Topics: Humans; Diabetes Mellitus; Diabetic Neuropathies; Quality of Life; Spinal Cord Stimulation
PubMed: 38245322
DOI: 10.1016/j.diabres.2023.110826 -
European Review For Medical and... Aug 2023This study aimed to investigate the relationship between serum asprosin level and diabetic peripheral neuropathy (DPN) in community patients with type 2 diabetes...
OBJECTIVE
This study aimed to investigate the relationship between serum asprosin level and diabetic peripheral neuropathy (DPN) in community patients with type 2 diabetes mellitus (T2DM).
PATIENTS AND METHODS
A total of 498 patients with T2DM were recruited from Zhuoma Community Health Service Station and Chengbei West Street Community Health Service Center in Changzhi City of Shanxi Province between November 2019 and July 2021. Their height, weight, and body mass index (BMI), as well as fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), triglyceride (TG), and serum asprosin levels, were analyzed. Patients were divided into the DPN group (n = 329) and the non-DPN group (n = 169) according to the presence or absence of DPN. The t-test, Mann-Whitney U test, and χ² test were used to compare the indicators between the two groups. Pearson or Spearman correlation analysis was used to evaluate the correlation between serum asprosin and other clinical data. Multivariate logistic regression analysis was used to analyze the influencing factors of DPN.
RESULTS
Compared with the non-DPN group, the DPN group had higher serum asprosin (p < 0.05). The prevalence of DPN gradually increased according to the tertiles of asprosin (56%, 67%, and 75%; p < 0.05). Multivariate logistic regression analysis showed that after adjustment for covariates, patients with asprosin concentrations between 295.4-367.0 pg/ml and concentrations > 367.0 pg/ml had a higher risk of diabetic neuropathy compared than those with asprosin levels < 295.4 pg/ml (p < 0.05).
CONCLUSIONS
Serum asprosin was found to be positively correlated with DPN, and it resulted as an influencing factor for DPN in patients with T2DM in the community. With the increase of asprosin, the risk of DPN also increased.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Body Mass Index; Fasting; Glycated Hemoglobin
PubMed: 37667933
DOI: 10.26355/eurrev_202308_33408 -
Frontiers in Endocrinology 2024The mechanism of Nicotinamide Adenine Dinucleotide (NAD+) metabolism-related genes (NMRGs) in diabetic peripheral neuropathy (DPN) is unclear. This study aimed to find...
BACKGROUND
The mechanism of Nicotinamide Adenine Dinucleotide (NAD+) metabolism-related genes (NMRGs) in diabetic peripheral neuropathy (DPN) is unclear. This study aimed to find new NMRGs biomarkers in DPN.
METHODS
DPN related datasets GSE95849 and GSE185011 were acquired from the Gene Expression Omnibus (GEO) database. 51 NMRGs were collected from a previous article. To explore NMRGs expression in DPN and control samples, differential expression analysis was completed in GSE95849 to obtain differentially expressed genes (DEGs), and the intersection of DEGs and NMRGs was regarded as DE-NMRGs. Next, a protein-protein interaction (PPI) network based on DE-NMRGs was constructed and biomarkers were screened by eight algorithms. Additionally, Gene Set Enrichment Analysis (GSEA) enrichment analysis was completed, biomarker-based column line graphs were constructed, lncRNA-miRNA-mRNA and competing endogenouse (ce) RNA networks were constructed, and drug prediction was completed. Finally, biomarkers expression validation was completed in GSE95849 and GSE185011.
RESULTS
5217 DEGs were obtained from GSE95849 and 21 overlapping genes of DEGs and NMRGs were DE-NMRGs. Functional enrichment analysis revealed that DE-NMRGs were associated with glycosyl compound metabolic process. The PPI network contained 93 protein-interaction pairs and 21 nodes, with strong interactions between NMNAT1 and NAMPT, NADK and NMNAT3, ENPP3 and NUDT12 as biomarkers based on 8 algorithms. Expression validation suggested that ENPP3 and NUDT12 were upregulated in DPN samples (P < 0.05). Moreover, an alignment diagram with good diagnostic efficacy based on ENPP3 and NUDT12 were identified was constructed. GSEA suggested that ENPP3 was enriched in Toll like receptor (TLR) pathway, NUDT12 was enriched in maturity onset diabetes of the young and insulin pathway. Furthermore, 18 potential miRNAs and 36 Transcription factors (TFs) were predicted and the miRNA-mRNA-TF networks were constructed, suggesting that ENPP3 might regulate hsa-miR-34a-5p by affecting MYNN. The ceRNA network suggested that XLOC_013024 might regulate hsa-let-7b-5p by affecting NUDT12. 15 drugs were predicted, with 8 drugs affecting NUDT12 such as resveratrol, and 13 drugs affecting ENPP3 such as troglitazone.
CONCLUSION
ENPP3 and NUDT12 might play key roles in DPN, which provides reference for further research on DPN.
Topics: Humans; NAD; Diabetic Neuropathies; MicroRNAs; Biomarkers; RNA, Messenger; Diabetes Mellitus; Nicotinamide-Nucleotide Adenylyltransferase
PubMed: 38464965
DOI: 10.3389/fendo.2024.1309917 -
Diabetes Care Jan 2024Psychological factors and psychosocial care for individuals with diabetic neuropathy (DN), a common and burdensome complication of diabetes, are important but overlooked... (Review)
Review
Psychological factors and psychosocial care for individuals with diabetic neuropathy (DN), a common and burdensome complication of diabetes, are important but overlooked areas. In this article we focus on common clinical manifestations of DN, unremitting neuropathic pain, postural instability, and foot complications, and their psychosocial impact, including depression, anxiety, poor sleep quality, and specific problems such as fear of falling and fear of amputation. We also summarize the evidence regarding the negative impact of psychological factors such as depression on DN, self-care tasks, and future health outcomes. The clinical problem of underdetection and undertreatment of psychological problems is described, together with the value of using brief assessments of these in clinical care. We conclude by discussing trial evidence regarding the effectiveness of current pharmacological and nonpharmacological approaches and also future directions for developing and testing new psychological treatments for DN and its clinical manifestations.
Topics: Humans; Diabetic Neuropathies; Psychiatric Rehabilitation; Accidental Falls; Fear; Anxiety; Diabetes Mellitus
PubMed: 38117989
DOI: 10.2337/dci23-0033 -
Journal of Managed Care & Specialty... Sep 2023Diabetic peripheral neuropathy, a common comorbidity of diabetes, is a neurodegenerative disorder that targets sensory, autonomic, and motor nerves frequently... (Randomized Controlled Trial)
Randomized Controlled Trial
Diabetic peripheral neuropathy, a common comorbidity of diabetes, is a neurodegenerative disorder that targets sensory, autonomic, and motor nerves frequently associated with painful diabetic neuropathy (PDN). PDN carries an economic burden as the result of reduced work and productivity. A recent multicenter randomized controlled trial, SENZA-PDN (NCT03228420), assessed the impact of high-frequency (10 kHz) spinal cord stimulation (SCS) on pain relief. The effects of high-frequency SCS on health care resource utilization and medical costs are not known. To evaluate the effect of high-frequency (10 kHz) SCS on health care resource utilization (HRU) and medical costs in patients with PDN using data from the SENZA-PDN trial. Participants with PDN were randomly assigned 1:1 to receive either 10 kHz SCS plus conventional medical management (CMM) (SCS treatment group) or CMM alone (CMM treatment group). Patient outcomes and HRU up to the 6-month follow-up are reported here. Costs (2020 USD) for each service was estimated based on publicly available Medicare fee schedules, Medicare claims data, and literature. HRU metrics of inpatient and outpatient contacts and costs are reported as means and SDs. Univariate and bivariate analyses were used to compare SCS and CMM treatment groups at 6 months. At 6-month follow up, the SCS arm experienced approximately half the mean rate of hospitalizations per patient compared with the CMM treatment group (0.08 vs 0.15; = 0.066). The CMM treatment group's total health care costs per patient were approximately 51% higher compared with the SCS treatment group (equivalent to mean annual cost per patient of $9,532 vs $6,300). Our analysis of the SENZA-PDN trial indicates that the addition of 10 kHz SCS therapy results in lower rates of hospitalization and consequently lower health care costs among patients with PDN compared with those receiving conventional management alone.
Topics: United States; Humans; Aged; Diabetic Neuropathies; Spinal Cord Stimulation; Medicare; Patient Acceptance of Health Care; Health Care Costs; Diabetes Mellitus
PubMed: 37610114
DOI: 10.18553/jmcp.2023.29.9.1021 -
Journal of Foot and Ankle Research Dec 2023People with diabetic peripheral neuropathy (DPN) and limited joint mobility syndrome (LJMS) can experience increased forefoot peak plantar pressures (PPPs), a known risk... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
People with diabetic peripheral neuropathy (DPN) and limited joint mobility syndrome (LJMS) can experience increased forefoot peak plantar pressures (PPPs), a known risk factor for ulceration. The aim of this study was to investigate whether ankle and 1st metatarsophalangeal (MTP) joint mobilisations and home-based stretches in people with DPN improve joint range of motion (ROM) and reduce forefoot PPPs.
DESIGN AND METHODS
Sixty-one people with DPN (IWGDF risk 2), were randomly assigned to a 6-week programme of ankle and 1 MTP joint mobilisations (n = 31) and home-based stretches or standard care only (n = 30). At baseline (T0); 6-week post intervention (T1) and at 3 months follow-up (T2), a blinded assessor recorded dynamic ankle dorsiflexion range using 3D (Codamotion) motion analysis and the weight bearing lunge test, static 1st MTP joint dorsiflexion ROM, dynamic plantar pressure and balance.
RESULTS
At T1 and T2 there was no difference between both groups in ankle dorsiflexion in stance phase, plantar pressure and balance. Compared to the control group, the intervention group showed a statistically significant increase in static ankle dorsiflexion range (Left 1.52 cm and 2.9cms, Right 1.62 cm and 2.7 cm) at 6 (T1) and 18 weeks (T2) respectively p < 0.01). Between group differences were also seen in left hallux dorsiflexion (2.75°, p < 0.05) at T1 and in right hallux dorsiflexion ROM (4.9°, p < 0.01) at T2 follow up. Further, functional reach showed a significant increase in the intervention group (T1 = 3.13 cm p < 0.05 and T2 = 3.9 cm p < 0.01). Intervention adherence was high (80%).
CONCLUSIONS
Combining ankle and 1 MTP joint mobilisations with home-based stretches in a 6-week programme in people with DPN is effective in increasing static measures of range. This intervention may be useful for improving ankle, hallux joint mobility and anteroposterior stability limits in people with diabetes and neuropathy but not for reducing PPP or foot ulcer risk.
TRIAL REGISTRATION
https://classic.
CLINICALTRIALS
gov/ct2/show/NCT03195855 .
Topics: Humans; Ankle; Diabetic Neuropathies; Ankle Joint; Risk Factors; Foot Ulcer; Range of Motion, Articular; Diabetes Mellitus
PubMed: 38057930
DOI: 10.1186/s13047-023-00690-4 -
Cells Oct 2023Diabetic peripheral neuropathy (DPN) is the prevalent type of peripheral neuropathy; it primarily impacts extremity nerves. Its multifaceted nature makes the molecular...
Diabetic peripheral neuropathy (DPN) is the prevalent type of peripheral neuropathy; it primarily impacts extremity nerves. Its multifaceted nature makes the molecular mechanisms of diabetic neuropathy intricate and incompletely elucidated. Several types of post-translational modifications (PTMs) have been implicated in the development and progression of DPN, including phosphorylation, glycation, acetylation and SUMOylation. SUMOylation involves the covalent attachment of small ubiquitin-like modifier (SUMO) proteins to target proteins, and it plays a role in various cellular processes, including protein localization, stability, and function. While the specific relationship between high blood glucose and SUMOylation is not extensively studied, recent evidence implies its involvement in the development of DPN in type 1 diabetes. In this study, we investigated the impact of SUMOylation on the onset and progression of DPN in a type 2 diabetes model using genetically modified mutant mice lacking SUMOylation, specifically in peripheral sensory neurons (SNS-Ubc9). Behavioural measurement for evoked pain, morphological analyses of nerve fibre loss in the epidermis, measurement of reactive oxygen species (ROS) levels, and antioxidant molecules were analysed over several months in SUMOylation-deficient and control mice. Our longitudinal analysis at 30 weeks post-high-fat diet revealed that SNS-Ubc9 mice exhibited earlier and more pronounced thermal and mechanical sensation loss and accelerated intraepidermal nerve fibre loss compared to control mice. Mechanistically, these changes are associated with increased levels of ROS both in sensory neuronal soma and in peripheral axonal nerve endings in SNS-Ubc9 mice. In addition, we observed compromised detoxifying potential, impaired respiratory chain complexes, and reduced levels of protective lipids in sensory neurons upon deletion of SUMOylation in diabetic mice. Importantly, we also identified mitochondrial malate dehydrogenase (MDH2) as a SUMOylation target, the activity of which is negatively regulated by SUMOylation. Our results indicate that SUMOylation is an essential neuroprotective mechanism in sensory neurons in type 2 diabetes, the deletion of which causes oxidative stress and an impaired respiratory chain, resulting in energy depletion and subsequent damage to sensory neurons.
Topics: Mice; Animals; Reactive Oxygen Species; Diabetic Neuropathies; Diabetes Mellitus, Experimental; Sumoylation; Diabetes Mellitus, Type 2; Sensory Receptor Cells
PubMed: 37947589
DOI: 10.3390/cells12212511 -
Diabetes/metabolism Research and Reviews Nov 2023To evaluate the effects of foot and ankle physical therapy on ankle and first metatarsophalangeal joint range of motion (ROM), peak plantar pressures (PPPs) and balance... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis of the effects of foot and ankle physical therapy, including mobilisations and exercises, in people with diabetic peripheral neuropathy on range of motion, peak plantar pressures and balance.
To evaluate the effects of foot and ankle physical therapy on ankle and first metatarsophalangeal joint range of motion (ROM), peak plantar pressures (PPPs) and balance in people with diabetes. MEDLINE, EBSCO, Cochrane Database of Systematic Reviews, Joanna Briggs Institute Database of Systematic Reviews, PROSPERO, EThOS, Web of Science and Google Scholar were searched in April 2022. Randomised Controlled Trials (RCT), quasi-experimental, pre-post experimental design and prospective cohort studies were included. Participants were people with diabetes, neuropathy and joint stiffness. Interventions included physical therapy such as mobilisations, ROM exercises and stretches. Outcome measures focused on ROM, PPPs and balance. Methodological quality was assessed with Critical Appraisal Skills Programme RCT and Risk-of-Bias 2 tool. Meta-analyses used random-effects models and data was analysed using the inverse variance method. In total, 9 studies were included. Across all studies, participant characteristics were similar; however, type and exercise dosage varied greatly. Meta-analysis was performed with four studies. Meta-analysis showed significant effects of combined exercise interventions in increasing total ankle ROM (3 studies: MD, 1.76; 95% CI, 0.78-2.74; p = 0; I = 0%); and reducing PPPs in the forefoot area (3 studies; MD, -23.34; 95% CI, -59.80 to 13.13; p = 0.21, I = 51%). Combined exercise interventions can increase ROM in the ankle and reduce PPPs in the forefoot. Standardisation of exercise programmes with or without the addition of mobilisations in the foot and ankle joints needs further research.
Topics: Humans; Ankle Joint; Diabetic Neuropathies; Ankle; Exercise Therapy; Range of Motion, Articular; Diabetes Mellitus
PubMed: 37431167
DOI: 10.1002/dmrr.3692 -
CNS Neuroscience & Therapeutics Apr 2024Diabetic peripheral neuropathy (DPN) constitutes a debilitating complication associated with diabetes. Although, the past decade has seen rapid developments in... (Review)
Review
BACKGROUND
Diabetic peripheral neuropathy (DPN) constitutes a debilitating complication associated with diabetes. Although, the past decade has seen rapid developments in understanding the complex etiology of DPN, there are no approved therapies that can halt the development of DPN, or target the damaged nerve. Therefore, clarifying the pathogenesis of DPN and finding effective treatment are the crucial issues for the clinical management of DPN.
AIMS
This review is aiming to summary the current knowledge on the pathogenesis of DPN, especially the mechanism and application of inflammatory response.
METHODS
We systematically summarized the latest studies on the pathogenesis and therapeutic strategies of diabetic neuropathy in PubMed.
RESULTS
In this seminal review, the underappreciated role of immune activation in the progression of DPN is scrutinized. Novel insights into the inflammatory regulatory mechanisms of DPN have been unearthed, illuminating potential therapeutic strategies of notable clinical significance. Additionally, a nuanced examination of DPN's complex etiology, including aberrations in glycemic control and insulin signaling pathways, is presented. Crucially, an emphasis has been placed on translating these novel understandings into tangible clinical interventions to ameliorate patient outcomes.
CONCLUSIONS
This review is distinguished by synthesizing cutting-edge mechanisms linking inflammation to DPN and identifying innovative, inflammation-targeted therapeutic approaches.
Topics: Humans; Diabetic Neuropathies; Insulin; Inflammation; Treatment Outcome; Signal Transduction; Diabetes Mellitus
PubMed: 37795833
DOI: 10.1111/cns.14477 -
Frontiers in Endocrinology 2023With the increasing incidence of diabetes, diabetic foot ulcer(DFU) has become one of the most common and serious complications in people with diabetes. DFU is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
With the increasing incidence of diabetes, diabetic foot ulcer(DFU) has become one of the most common and serious complications in people with diabetes. DFU is associated with significant morbidity and mortality, and can also result in significant economic, social and public health burdens. Due to peripheral neuropathy, peripheral vascular disease, hyperglycemic environment, inflammatory disorders and other factors, the healing of DFU is impaired or delayed, resulting in the formation of diabetic chronic refractory ulcer. Because of these pathological abnormalities in DFU, it may be difficult to promote wound healing with conventional therapies or antibiotics, whereas platelet-rich plasma(PRP) can promote wound healing by releasing various bioactive molecules stored in platelets, making it more promising than traditional antibiotics. Therefore, the purpose of this systematic review is to summarize and analyze the efficacy of PRP in the treatment of DFU.
METHODS
A literature search was undertaken in PubMed, CNKI, EMB-ASE, the Cochrane Library, the WanFang Database and the WeiPu Database by computer. Included controlled studies evaluating the efficacy of PRP in the treatment of diabetic foot ulcers. The data extraction and assessment are on the basis of PRISMA.
RESULTS
Twenty studies were evaluated, and nineteen measures for the evaluation of the efficacy of PRP in DFU treatment were introduced by eliminating relevant duplicate measures. The efficacy measures that were repeated in various studies mainly included the rate of complete ulcer healing, the percentage of ulcer area reduction, the time required for ulcer healing, wound complications (including infection rate, amputation rate, and degree of amputation), the rate of ulcer recurrence, and the cost and duration of hospitalization for DFU, as well as subsequent survival and quality of life scores. One of the most important indicators were healing rate, ulcer area reduction and healing time. The meta-analysis found that PRP was significantly improve the healing rate(OR = 4.37, 95% CI 3.02-6.33, P < 0.001) and shorten the healing time(MD = -3.21, 95% CI -3.83 to -2.59,P < 0.001)of patients with DFU when compared to the conventional treatment, but there was no significant difference in reducing the of ulcer area(MD = 5.67, 95% CI -0.77 to 12.11,P =0.08>0.05 ).
CONCLUSION
The application of PRP to DFU can improve ulcer healing rate and shorten ulcer healing time, but more clinical data are needed to clarify some efficacy measures. At the same time, a standardized preparation process for PRP is essential.
Topics: Humans; Diabetic Foot; Quality of Life; Anti-Bacterial Agents; Platelet-Rich Plasma; Wound Healing; Diabetes Mellitus
PubMed: 38169990
DOI: 10.3389/fendo.2023.1256081