Diabetic Peripheral Neuropathy Patients Research Articles

Combination therapy is it in the future for successfully treating peripheral diabetic neuropathy?

In 2022, the Center for Disease Control and Prevention reported that 11.3% of the United States population, 37.3 million people, had diabetes and 38% of the population had prediabetes. A large American study conducted in 2021 and supported by many other studies, concluded that about 47% of diabetes patients have peripheral neuropathy and that diabetic neuropathy was present in 7.5% of patients at the time of diabetes diagnosis. In subjects deemed to be pre-diabetes and impaired glucose tolerance there was a wide range of prevalence estimates (interquartile range (IQR): 6%-34%), but most studies (72%) reported a prevalence of peripheral neuropathy ≥10%. There is no recognized treatment for diabetic peripheral neuropathy (DPN) other than good blood glucose control. Good glycemic control slows progression of DPN in patients with type 1 diabetes but for patients with type 2 diabetes it is less effective. With obesity and type 2 diabetes at epidemic levels the need of a treatment for DPN could not be more important. In this article I will first present background information on the “primary” mechanisms shown from pre-clinical studies to contribute to DPN and then discuss mono- and combination therapies that have demonstrated efficacy in animal studies and may have success when translated to human subjects. I like to compare the challenge of finding an effective treatment for DPN to the ongoing work being done to treat hypertension. Combination therapy is the recognized approach used to normalize blood pressure often requiring two, three or more drugs in addition to lifestyle modification to achieve the desired outcome. Hypertension, like DPN, is a progressive disease caused by multiple mechanisms. Therefore, it seems likely as well as logical that combination therapy combined with lifestyle adjustments will be required to successfully treat DPN.

Clinical effect of acupuncture combined with medication on diabetic peripheral neuropathy and its influence on serum lipid metabolism

To observe the clinical effect on diabetic peripheral neuropathy (DPN) treated with acupuncture combined with medication and explore its effect mechanism. Sixty-two patients of DPN were randomly divided into a combined therapy group (31 cases) and a medication group (31 cases, 2 cases dropped out); besides, 20 healthy subjects were recruited as a normal group. On the base of routine intervention, in the medication group, thioctic acid capsules were administrated orally, 0.2 g each time, 3 times a day. In the combined therapy group, besides the medication as the medication group, acupuncture was performed on bilateral Quchi (LI 11), Waiguan (TE 5), Hegu (LI 4), Tianshu (ST 25), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3) and the needles were retained for 30 min, acupuncture was delivered once daily, 6 times a week. The duration of treatment was 4 weeks in the two groups. The score of Toronto clinical scoring system (TCSS), the nerve conduction velocity of median nerve (MN) and common peroneal nerve (CPN) were observed before and after treatment in the two intervention groups; and the serum lipid metabolism was detected before and after treatment in the two intervention groups and the normal group. Compared with that before treatment, the scores of TCSS were reduced in the combined therapy group and the medication group (P<0.05) after treatment, and the score decrease in the combined therapy group was larger than that of the medication group (P<0.001). The motor nerve conduction velocity and the sensory nerve conductive velocity of MN and CPN after treatment all increased in the combined therapy group and the medication group compared with those before treatment (P<0.05), and the improvements in the combined therapy group were larger than those of the medication group (P<0.001). Before treatment DPN patients had 365 differential lipid metabolites, including sphingosine (SPH, d18:0), involved in the inositol phosphate metabolism, compared with the subjects of the normal group. There were 103 differential lipid metabolites in the medication group before and after treatment, including lysophosphatidyl ethanolamine (LPE, 18:1/0:0), participated in glycerophospholipid metabolism. In the combined therapy group, before and after treatment, there were 99 differential lipid metabolites, including lysophosphatidylcholine (LPC, 18:0/0:0), participated in the neuroactive ligand-receptor interaction. Acupuncture greatly affected 50 lipid metabolites such as lysophosphatidic acid (LPA, 0:0/22:6), LPA(0:0/18:2) and LPC(O-18:0), which was mainly involved in glycerophospholipid metabolism. Acupuncture combined with medication ameliorates the symptoms and the nerve conduction velocity in DPN patients, which may be related to the regulation of serum lipid metabolism.

Decreased glucagon in diabetic peripheral neuropathy patients with long duration type 2 diabetes.

The aim of this study was to investigate the association of fasting C-peptide and glucagon with diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2DM). A comprehensive evaluation was conducted on 797 patients with T2DM to assess the various risk factors affecting DPN. The subjects were categorized into short duration and long duration group according to the duration of diabetes with a threshold of 10years. Logistic regression analysis was employed to examine the association between DPN and islet function, as well as other parameters. Receiver operating characteristic curve analysis was performed to evaluate the predictive capability of glucagon. The fasting C-peptide levels were significantly lower in the DPN patients with short duration of diabetes, but lost significance in the long duration group. Conversely, a decreased level of glucagon was only observed in DPN patients with long duration of diabetes. For the group with long duration of diabetes, glucagon was the sole risk factor associated with DPN. The receiver operating characteristic curve analysis revealed that glucagon in the long duration group exhibited a moderate area under the curve of 0.706. The serum glucagon levels in T2DM patients with DPN exhibited bidirectional changes based on the duration of diabetes. Decreased glucagon was associated with DPN in T2DM patients with long duration of diabetes.

Severity of Peripheral Neuropathy in Diabetic Patients

Introduction: Diabetes mellitus is a chronic degenerative disease that can significantly impact both life expectancy and quality of life among affected populations, primarily by disrupting metabolic control and exacerbating disease complications. Objective: To assess the severity of neuropathy across four domains (pain, loss of sensation, postural instability, and depression) in individuals with diabetes mellitus. Materials and Methods: This was a cross-sectional, descriptive-correlational, and qualitative study The study population comprised diabetic individuals attending outpatient clinics for diabetic foot care at Hospital de S. João - Unidade de Valongo and Centro Hospitalar do Alto Ave in Guimarães. Variables included gender, age, type and duration of diabetes, neuropathic characteristics, balance, dependency/independence, and depression. Results: Regarding neuropathy severity, most diabetic patients exhibited loss of sensation and moderate pain, with no apparent postural instability or depression. However, both instability and depression were observed when neuropathic signs were present. Conclusions: The presence of neuropathic signs was associated with increased postural instability, reduced functionality, and a higher prevalence of depressive symptoms. Furthermore, a positive relationship was observed between pain severity and depressive symptomatology.

Early Detection of Diabetic Peripheral Neuropathy in Diabetic Patients: A Cross-Sectional Study.

Diabetic Peripheral Neuropathy (DPN) is a chronic complication in Type 2 Diabetes Mellitus (T2DM) patients and is characterized by paresthesia, pain, and hypoesthesia of the extremities. The Diabetic Neuropathy Symptom-Score (DNS) is a quick, inexpensive, and easy-to-perform tool to detect DPN in clinical practice. Biochemical markers like Nitric Oxide (NO) and Vascular Endothelial Growth Factor (VEGF) play a role in the early detection of DPN. This study aims to investigate the relationship between risk factors and these biomarkers. So, it is expected to improve the prevention and treatment of diabetic neuropathy more effectively. A cross-sectional method was used for this study. The sample size was 85 patients with T2DM who visited several primary healthcare in Medan, selected by consecutive sampling method based on eligibility criteria. Data collected included DNS, assessment of NO, VEGF, Glycated Hemoglobin (HbA1C), plasma blood glucose (PBG), and lipid profile. The collected data were analyzed using an independent T-test. The results showed that most T2DM patients, namely 73 people (85.9%), experienced DPN. From the bivariate analysis results, the risk factors associated with the prevalence of DPN in T2DM patients were found to be increased levels of total cholesterol, HbA1c, NO, and VEGF (p < 0.05). Meanwhile, blood pressure, fasting BGL, HDL-C, LDL-C, and triglycerides were not related to the occurrence of DPN in this study (p> 0.05). DNS can be used as a quick and easy initial screening tool implemented in clinical practice for screening DPN. Diabetic patients with DPN tend to have lower NO and increased VEGF; besides, NO levels are also associated with the progression of DPN. Furthermore, education, blood sugar control, and physical exercise, especially leg exercises, can prevent progressive DPN.

Association of serum NF-κB levels with peripheral neuropathy in type 2 diabetes mellitus patients: a pilot study.

Hyperglycaemia-induced inflammation plays a vital role in the development of diabetic peripheral neuropathy (DPN). Recent evidences had reported the involvement of the transcription factor nuclear factor kappa-light-chain-enhancer of activated Bcell (NF-κB) in diabetic experimental models. So, this pilot study aimed to evaluate serum NF-κB levels in DPN patients. We recruited 50 T2DM patients, of which 25 were T2DM with neuropathy and 25 were T2DM without neuropathy. In all the participants peripheral neuropathy was diagnosed based on Total neuropathy score (TNS). Serum NF-κB levels were measured by ELISA. We observed that the serum NF-κB levels were higher in DPN patients in comparison to T2DM patients without neuropathy. On spearman correlation, a positive correlation was found between serum NF-κB levels and TNS in the DPN group (r=0.741, p<0.001). The regression model shows the TNS to be an independent determinant of serum NF-κB levels after adjustment for potential confounders like age, duration of diabetes, and HbA1C (B=81.34; p<0.001). NF-κB activation plays a key role in promoting inflammation which is associated with the progression of DPN. In this respect, the study of NF-κB levels in serum may be an additional diagnostic marker for DPN.

Effect of Exercises for Strengthening the Intrinsic Muscles of the Foot and Improving Ankle Mobility on Patients of Diabetic Peripheral Neuropathy.

Background and objectives The study aimed to compare the efficacy of standard home care versus structured ankle mobility exercises in enhancing ankle and foot joint range of motion (ROM) among individuals with diabetes mellitus (DM). Additionally, it investigated the impact of foot intrinsic muscle strengthening exercises on hallux grip force in those with Diabetic Peripheral Neuropathy (DN). Materials and methods In a study of 200 patients with Diabetic Neuropathy (DN), selected from 345 screened diabetics with stable glucose levels and routine monitoring at a tertiary care facility, the efficacy of structured exercises versus standard care was evaluated. Participants, aged 40-70 years with mild neuropathic symptoms (neuropathy disability score of 3 to 5), were divided into two groups. Group 1 received standard care per International Diabetic Foot guidelines, while Group 2 performed targeted foot intrinsic muscle strengthening and ankle mobility exercises over eight weeks. The range of motion (ROM) for ankle and first metatarsophalangeal (MTP) joints and hallux grip force were measured, showing significant improvements in Group 2. Analysis was done using IBM SPSS. Results The average age of the individuals in group 1 (n=100) was 53.87±5.42 years, whereas the average age of the subjects in group 2 (n=100) was 54.23±4.69 years. The study included a total of 97 male participants, with 48 in group 1 and 49 in group 2. The groups exhibited homogeneity in terms of age, gender, duration of DM, and BMI (p>,0.05). When comparing the ROM for ankle dorsiflexion between the groups, it was shown that subjects in group 2 had a substantially higher ROM following exercise for both the right (27.97°±5.3° Vs 19.24°±2.54°) and left (28.55°±4.61° Vs 18.22°±1.14°) ankles compared to the patients in group 1 (p<,0.01). Nevertheless, there were statistically insignificant differences (p>,0.05) observed within the groups, both before and after the exercises, for all the variables examined except for right and left ankle dorsiflexion, and right ankle plantarflexion in group 2. Group 2 subjects exhibited a considerably greater hallux grip force compared to group 1 subjects. The mean enhanced paper grip strength for the right and left big toe of group 2 was 44±3.58 N and 43.2±2.62 N respectively. The mean enhanced paper grip force for the right and left big toe of group 1 was 38±3.11 N and 37.92±2.13 N respectively. A statistically highly significant difference was observed for hallux grip force between the groups (p<,0.01). Conclusion The findings of this study suggest that performing the foot intrinsic muscle strengthening and ankle mobility exercises on the foot and ankle joints can potentially enhance ROM and hallux grip force in patient groups with DN.

Exploring the role of mitochondrial-associated and peripheral neuropathy genes in the pathogenesis of diabetic peripheral neuropathy

BackgroundDiabetic peripheral neuropathy (DPN) is a prevalent and serious complication of diabetes mellitus, impacting the nerves in the limbs and leading to symptoms like pain, numbness, and diminished function. While the exact molecular and immune mechanisms underlying DPN remain incompletely understood, recent findings indicate that mitochondrial dysfunction may play a role in the advancement of this diabetic condition.MethodsTwo RNA transcriptome datasets (codes: GSE185011 and GSE95849), comprising samples from diabetic peripheral neuropathy (DPN) patients and healthy controls (HC), were retrieved from the Gene Expression Omnibus (GEO) database hosted by the National Center for Biotechnology Information (NCBI). Subsequently, differential expression analysis and gene set enrichment analysis were performed. Protein–protein interaction (PPI) networks were constructed to pinpoint key hub genes associated with DPN, with a specific emphasis on genes related to mitochondria and peripheral neuropathy disease (PND) that displayed differential expression. Additionally, the study estimated the levels of immune cell infiltration in both the HC and DPN samples. To validate the findings, quantitative polymerase chain reaction (qPCR) was employed to confirm the differential expression of selected genes in the DPN samples.ResultsThis research identifies four hub genes associated mitochondria or PN. Furthermore, the analysis revealed increased immune cell infiltration in DPN tissues, particularly notable for macrophages and T cells. Additionally, our investigation identified potential drug candidates capable of regulating the expression of the four hub genes. These findings were corroborated by qPCR results, reinforcing the credibility of our bioinformatics analysis.ConclusionsThis study provides a comprehensive overview of the molecular and immunological characteristics of DPN, based on both bioinformatics and experimental methods.

Dosing time-dependent difference in the suppressive effect of empagliflozin on the development of mechanical pain hypersensitivity in diabetic mice.

A problem for patients with diabetes is the rise of complications, such as peripheral neuropathy, nephropathy and retinopathy. Among them, peripheral neuropathy, characterized by numbness and/or hypersensitivity to pain in the extremities, is likely to develop in the early stages of diabetes. Empagliflozin (EMPA), a sodium-glucose cotransporter-2 inhibitor, exerts hypoglycemic effects by preventing glucose reabsorption in proximal tubular cells. EMPA can improve cardiovascular and renal outcomes in diabetic patients, but its suppressive effect on the development of diabetic neuropathy remains unclear. In this study, we demonstrated that optimizing the dosing schedule of EMPA suppressed the development of pain hypersensitivity in streptozotocin (STZ)-induced diabetic model mice maintained under standardized light/dark cycle conditions. A single intraperitoneal administration of STZ to mice induced hyperglycemia accompanied by pain hypersensitivity. Although EMPA did not exert anti-hypersensitivity effect on STZ-induced diabetic mice after the establishment of neuropathic pain, the development of pain hypersensitivity in the diabetic mice was significantly suppressed by daily oral administration of EMPA at the beginning of the dark phase. On the other hand, the suppressive effect was not observed when EMPA was administered at the beginning of the light phase. The hypoglycemic effect of EMPA and its stimulatory effect on urinary glucose excretion were also enhanced by the administration of the drug at the beginning of the dark phase. Nocturnal mice consumed their food mainly during the dark phase. Our results support the notion that morning administration of EMPA may be effective in suppressing the development of peripheral neuropathy in diabetic patients. Significance Statement Empagliflozin, a sodium-glucose cotransporter-2 inhibitor suppressed the development of neuropathic pain hypersensitivity in streptozotocin-induced diabetic model mice in a dosing time-dependent manner.

Sensorimotor training improves gait, ankle joint proprioception, and quality of life in patients with diabetic peripheral neuropathy: A single-blinded randomized controlled trial.

To investigate the effect of Sensorimotor Training (SMT) on gait, ankle joint proprioception, and quality of life in Diabetic Peripheral Neuropathy (DPN) patients. A prospective, single-blind, randomized controlled experiment was performed. Forty patients with DPN aged 50 to 65 yrs were distributed randomly into two groups, the SMT group (n = 20) and the control group (n = 20). Both groups attended awareness sessions about diabetes and foot care for 30 minutes, every two weeks. Moreover, the SMT group received 6wk (3 days/week) of SMT. Spatiotemporal gait parameters, proprioception accuracy of the ankle joint, and quality of life were measured before and after 6 weeks of intervention. Regarding baseline data, no significant differences were identified among groups (p > 0.05). After 6wk intervention, the SMT group exhibited significant improvements in all outcome variables (p < 0.001), while the control group showed significant changes in quality of life only (p = 0.03). Comparing groups after intervention reveals statistically significant differences in all measured variables in favor of the SMT group (p < 0.001). Sensorimotor training may improve spatiotemporal gait parameters, ankle joint proprioception, and quality of life of patients with DPN.

Effects of Balance Training Versus Aerobic Exercise with Stretching to Improve Postural Stability and Walking Performance in Diabetic Peripheral Neuropathy Patients

Effects of Balance Training Versus Aerobic Exercise with Stretching to Improve Postural Stability and Walking Performance in Diabetic Peripheral Neuropathy Patients

A study on prevalence of diabetic peripheral neuropathy in diabetic patients attending a rural health and training centre.

Diabetic neuropathy is a common complication, affecting up to half the diabetics. Diabetic peripheral neuropathy (DPN) predominantly affects the hands and lower limbs. It leads to loss of protective sensation, resulting in continuous injury to insensitive feet. The early detection of DPN using an objective screening test followed by its appropriate management is important, as up to 50% of diabetic peripheral neuropathies may be asymptomatic. To screen diabetic patients attending a Rural Health and Training Centre of a medical college in Tamil Nadu for DPN. To assess the association between DPN and sociodemographic factors, duration of diabetes, glycemic control, physical activity, body mass index, smoking and habit of alcohol consumption. The study was conducted among 206 diabetic patients attending a Rural Health and Training Centre. Participants were assessed using the Michigan Neuropathy Screening Instrument (MNSI), which involves using a questionnaire followed by a physical examination. Of the 206 patients, 61.2% were male, and 38.8% were female. The mean age was 50.86 years (standard deviation [SD] = 12.26 years). The mean duration of diabetes was 8.3 years (SD = 5.5 years). The proportion of diabetics who were screened positive for peripheral neuropathy was 16.5% and 21.8% using the MNSI questionnaire and examination, respectively. Age of 60 years and above was significantly associated with DPN.(OR = 3.982, P value = 0.0001). Duration of more than 5 years of diabetes was also significantly associated with DPN.(OR = 6.01, P value = 0.003). A high proportion of diabetics were screened positive for peripheral neuropathy, and many of them were unaware of having the complication. Many risk factors associated with DPN were reported in this study. Thus, early diagnosis and management with MNSI or any other validated screening tool in health care institutions is essential.

Association of Hematological Parameters and Diabetic Neuropathy: A Retrospective Study.

Diabetic neuropathy (DN) is a common complication of type 2 diabetes (T2DM) and is characterized by persistent inflammation. Hematological parameters have emerged as a novel marker for detecting chronic inflammatory conditions, including diabetes. We aim to examine the association between HbA1c levels, which can indicate the presence of diabetic neuropathy, and hematological parameters to explore the possibility of using hematological parameters as a new indicator for DN in T2DM patients. This was a retrospective study of 768 (483 males and 284 females) medical records of adult T2DM patients with or without neuropathy who attending the outpatient neuromuscular clinic at King Abdul-Aziz University Hospital from January 2016 to December 2021. The results showed significant increases in HbA1c levels (p=0.000), lymphocyte levels (p=0.028), and the neutrophil-lymphocyte ratio (NLR) (p=0.011). In the T2DM group, HBA1C levels were found to be positively correlated with age (r=0.306, p=0.000), neutrophil (NEUT) (r=0. 287, p=0.000), platelet (PLT) (r=0. 148, p=0.039), and neutrophil-lymphocyte ratio (NLR) (r=0.306193, p=0.0007), and negatively correlated with gender (r=-0.306193, p=0.0007). In the T2DMN group, HBA1C levels showed a positive correlation with hemoglobin (HB) (r=0.084, p=0.045), PLT (r=0.087, p=0.037), and PLT/mean corpuscular hemoglobin (MCH) ratio (PLT/MCH ratio) (r=0.12, p=0.004), and a negative correlation with age (r=-0.204, p=0.000), gender (r=-0.086, p=0.041), weight (WT) (r=-0.113, p=0.007), Body Surface Area (BSA) (r=-0.09, p=0.031), mean corpuscular volume (MCV) (r=-0.292, p=0.000), and MCH (r=-0.186, p=0.000). Our study found a significant association between HbA1c, a biomarker for diabetic neuropathy, and various hematological parameters (HB, MCV, MCH, PLT, PLT/MCH ratio) in T2DMN patients. By effectively controlling and monitoring these variables, it may be feasible to prevent or delay the progression of peripheral neuropathy in diabetic patients. However, further research is needed to validate these findings.

Effect of Sensory Re-Education with Aerobic Training on Sensation and Balance among Diabetic Peripheral Neuropathy Patients: A Pilot Study

Background: People with diabetes have 10 to 30 times higher risk of lower limb amputation than people without thedisease. 85% of non-traumatic amputations in diabetic patients begin with a foot ulcer. Therefore, early interventionis necessary to control the symptoms of diabetic peripheral neuropathy and improve balance. Resistance andaerobic training reduce diabetic symptoms by lowering HbA1C levels. In order to restore functional sensibility,improve adaptive functioning, and improve balance, sensory re-education and aerobics are combined. Therefore,the aim of this study is to find out the effect of Sensory re-education and aerobics on sensation and balance amongdiabetic peripheral neuropathy patients.Purpose: The Purpose of the study is to determine the effects of sensory re-education with aerobic training onsensory perception and balance in Diabetic peripheral neuropathy patients.Material and Method: This study included diabetic individuals of both genders between the ages of 45-60, lowPAR-Q risk scores and Toronto clinical neuropathy scores (TCNS) between 6 and 11. A total of 20 participantswere randomly selected and received sensory re-education with aerobics for six weeks.Results: Individuals with diabetic peripheral neuropathy experienced statistically significant improvement inTCNS from 9.3±1.25 to 4.5± 1.3, in BBS 48.5 ± 2.70 to 41.7±1.41, in TUG 8.12±1.28 to 6.95 ±1.30, with a P value of &lt;0.01.Conclusion: Sensory re-education with aerobic training for 6 weeks of duration reported improvement in sensoryperception and balance among people with diabetic peripheral neuropathy patients.

The effectiveness of neurodynamic techniques in patients with diabetic peripheral neuropathy: Study protocol for a randomized sham-controlled trial

Abstract Background: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus (DM). DPN is the primary risk factor for diabetic foot ulcers that can cause amputation. Although several observational studies have investigated the morphological and biomechanical characteristics of peripheral nerves in DPN, interventional studies regarding the effectiveness of neurodynamic techniques (NDT) in DPN patients are confined to a handful. The effects of NDT on neuropathy severity, nerve conduction parameters, quality of life (QoL), and mechanosensitivity have not been explored yet in this population. Materials and Methods: Forty type 2 DPN (T2DPN) patients, diagnosed based on an electrodiagnosis study, will be recruited into two groups. The experimental group will receive the tibial nerve’s real proximal and distal slider techniques in addition to DPN standard treatment as a basic treatment, and the control group will receive the tibial nerve’s sham proximal and distal slider techniques along with the basic treatment for eight sessions twice a week. Baseline and post-intervention assessments will be based on the Michigan diabetic neuropathy score (MDNS) (primary outcome), tibial nerve conduction parameters, neuropathy-specific quality of life (Neuro QoL) questionnaire, and straight leg raising range of motion (SLR ROM) (secondary outcomes). Results: This study is expected to last approximately seven months, depending on recruitment. The results of the study will be published in a peer-reviewed journal. Conclusions: The present study will evaluate the efficacy of NDT on the primary and secondary outcome measurements in DPN patients.

Vitamin D Deficiency Participates in Depression of Patients with Diabetic Peripheral Neuropathy by Regulating the Expression of Pro-Inflammatory Cytokines.

Vitamin D deficiency is associated with patients with diabetic peripheral neuropathy (DPN), and low levels of vitamin D are common in patients with depression. Depression is common in DPN patients and the definite pathogenesis remains unclear. This study aimed to determine vitamin D deficiency in the onset of depression in DPN and evaluate the effect of vitamin D supplementation on depression. A total of 192 patients with DPN were enrolled in this study. Clinical and laboratory information was collected. Chemiluminescent immunoassay was used to measure the level of 25(OH)D. Enzyme-linked immunosorbent assay was employed to measure the concentrations of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-17A. Subjects with low 25(OH)D received 5000IU vitamin D daily for 12 weeks. Depression scores and levels of 25(OH)D, IL-1β, TNF-α, and IL-17A were re-evaluated after supplementation. The incidence of vitamin D deficiency and depression was high in DPN patients. Compared with vitamin D sufficient participants, Hamilton Depression Rating Scale (HAMD) scores and the levels of inflammatory markers IL-1β, TNF-α, and IL-17A were significantly higher in insufficient group (all p<0.05). HAMD score, IL-1β, TNF-α, and IL-17A were negatively correlated with 25(OH)D (all p<0.05). A linear relationship existed among IL-1β, TNF-α, IL-17A, and 25(OH)D (p<0.05). HAMD scores, IL-1β, TNF-α, and IL-17A were all reduced significantly after supplementation of vitamin D (p<0.05). Binary logistic analysis revealed that vitamin D insufficiency was an independent risk factor for depression in patients with DPN. Receiver operating characteristic (ROC) curve analysis showed a high sensitivity (87.20%) of 25(OH)D in discriminating DPN patients with depression. Vitamin D deficiency participated in occurrenceof depression in DPN patients and could be mediated, at least in part, by upregulation of pro-inflammatory cytokines. Vitamin D supplementation may be effective in improving depressive symptoms in DPN patients.

Phytocannabinoids for the Treatment of Neuropathic Pain: A Scoping Review of Randomised Controlled Trials Published Between 2012 and 2023.

Neuropathic pain (NP) remains a challenge to treat, with 50% of patients experiencing limited efficacy from current treatments. Medicinal cannabis, which contains tetrahydrocannabinol (THC), cannabidiol (CBD) and other minor cannabinoids, is garnering attention as an alternative treatment for NP. This paper reviews the clinical evidence for phytocannabinoid treatment of NP. Seventeen randomised controlled trials (RCT) were identified for inclusion in this review. Of these, ten studies using phytocannabinoid preparations containing THC alone had the most evidence for pain relief. Four studies investigating THC/CBD combinations showed some reductions in pain scores, although not all findings were statistically significant, whereas studies investigating CBD (two studies) or cannabidivarin (one study) showed no analgesic effect over placebo. However, CBD studies were of small sample size when compared to other studies in the review and short duration. Results for treatment of diabetic peripheral neuropathy patients with THC showed better improvements over those for NP induced by chemotherapy and multiple sclerosis, with these trials using vaporised whole plant cannabis. This formulation may have trace amounts of other minor cannabinoids, compared with synthetic cannabinoids such as dronabinol or nabilone that were investigated in other studies. This review provides an overview of RCTs that have investigated phytocannabinoid use for the treatment of NP. There appears to be evidence to necessitate further high quality RCTs into novel formulations of phytocannabinoids for the treatment of NP.

Physical training and activity in people with diabetic peripheral neuropathy: A case report

Background: Diabetes mellitus (DM) is the most common endocrine disorder affecting more than 100 million people worldwide, around 6% of the population. This matter characterized by hyperglycemia (high glucose levels in blood) caused by a lack or ineffective production of insulin by the pancreas which results in an increase or decrease in the concentration of glucose in the blood. Diabetic peripheral neuropathy (DPN) or what is called diabetic peripheral neuropathy is the most common complication in cases of diabetes mellitus. DPN is a disease of loss of motor, sensory and autonomic nerve function, which can affect the peripheral nervous system. Sensorimotor training is considered a technique that can improve balance. This emphasizes the function of the sensorimotor system as a unit that works to increase sensory input and motor recruitment patterns in maintaining joint stability and regulating movement through the central nervous system (CNS). Aerobic exercise is a type of physical activity that can prevent and reduce DPN. Aerobic exercise such as treadmill can train balance. Balance training shows a high positive effect on improving motor and sensory symptoms in peripheral neuropathyPurpose: To examine the effects of sensorimotor training and lower limb muscle activity in DPN patients using treadmill.Method: The research uses a case study design, namely a research method that uses various data sources that can be used as research material, describing and explaining comprehensively various aspects of an individual, group, program, organization or event systematically. Participants in this study were patients aged 64 years, female, diagnosed diabetes mellitus type 2 (T2DM) for 10 years by a doctor. This research uses an aspect identification questionnaire instrument. DPN is screened using Michigan Neuropathy Screening Instrument (MNSI). Static balance is determined by romberg test and for dynamic balance it is measured by timed up and go test. Functional lower limb muscle strength is checked using tests Five Time Sit to Stand (5xSST).Results: The data for the respondent is a housewife aged 64 years, last education is junior high school with status as a housewife. The patient suffered from T2DM for 10 years with a hemoglobin 1AC level of 6.8 mg/dl, was overweight as indicated by the patient's BMI of 26 kg/m2. Often feels pain in both legs, when the patient walks and does strenuous activities with a score of 9, and the pain decreases when resting with a score of 3. Apart from that, the patient also has vision problems with a score of 20/40, meaning the patient can only see letters. at a distance of 20 feet. Even though normally letters can be seen clearly, namely 40 feet, this visual disturbance can cause the patient's balance to be disturbed. Providing treatment for 6 weeks can significantly improve the patient's quality of life as seen from the initial WHO QoL score of 58 to 86.Conclusion: Providing treadmill training for 6 weeks carried out 3 times a week showed significant results in reducing hemoglobin levels and DPN scores in T2DM patients.

Unraveling the Role of Tumor Necrosis Factor-Alpha in Diabetic Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

Diabetic peripheral neuropathy (DPN) is a prevalent and debilitating complication of diabetes mellitus, leading to sensory abnormalities, decreased balance, and increased risk of foot problems. Although tumor necrosis factor-alpha (TNF-α) has emerged as a potential factor in the pathogenesis of DPN, its role remains contested. This study intends to thoroughly analyze the association between TNF-α and DPN by combining data from various global studies. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and included 23 articles investigating TNF-α levels in DPN patients for systematic review and 11 articles for meta-analysis. Data were extracted, and heterogeneity was examined. A random-effect model was chosen due to high heterogeneity. The major outcome measure across studies was serum TNF-α levels. The meta-analysis found a significant mean difference of 15.2464 (95% confidence interval = 4.4963; 25.9965) under the random-effect model due to the substantial heterogeneity (I2 = 98.1%) among included studies. The meta-analysis indicates a consistent elevation in TNF-α levels in individuals with DPN compared to those without neuropathy. This underlines the potential of TNF-α as a biomarker and contributor to diabetic neuropathy. Despite heterogeneity, the study's extensive scope and systematic approach enhance the trustworthiness and generalizability of the findings.

Effect of glycemic control on clinical manifestations of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus

Effect of glycemic control on clinical manifestations of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus