Symptoms Of Diabetic Peripheral Neuropathy Research Articles

Efficacy of electro-acupuncture versus sham acupuncture for diabetic peripheral neuropathy: study protocol for a three-armed randomised controlled trial

IntroductionSpecific treatment for diabetic peripheral neuropathy (DPN) is still lacking, and acupuncture may relieve the symptoms. We intend to investigate the efficacy and safety of electro-acupuncture (EA) in alleviating symptoms...

Pain exacerbation following physical activity in adults with diabetic neuropathy: Ecological momentary assessment of foot symptoms.

People with diabetic peripheral neuropathy (DPN) report fluctuating foot symptoms. This study used ecological momentary assessment to: (1) compare foot symptoms between days, time points and periods with/without preceding physical activity or pain medication; and (2) determine relationships between symptoms and endogenous pain modulation. Ten low-active Australian adults with probable DPN underwent temporal summation of pain (TSP) and conditioned pain modulation (CPM) then completed mobile phone surveys five times daily for seven days, where they recorded the intensity of six foot symptoms and whether they performed physical activity or consumed pain medication in the preceding three hours. RESULTS: All foot symptoms except numbness were greater in periods following physical activity, whereas periods following pain medication showed greater shooting pain. TSP showed very large correlations with sensitivity to touch, burning pain, shooting pain and prickling/tingling. DISCUSSION: General practitioners should be aware that physical activity might exacerbate symptoms of DPN when encouraging their patients to be active.

Effectiveness of platelet rich plasma (PRP) treatment and its comparison with pregabalin in painful diabetic polyneuropathy: A randomized controlled clinical trial

Background & objective: The most common consequence of diabetes mellitus (DM) is diabetic peripheral neuropathy (DPN), and it has serious clinical implications that can affect patients' quality of life. There is an urgent need to to discover new methods of treatment, as the medications currently in use for prevention and treatment of DPN are only partially effective and have frequent adverse effects. We aimed to determine and compare the effect of platelet rich plasma (PRP) injection on acupuncture points and pregabalin in painful DPN.
 Methodology: A randomized controlled trial was conducted at Iffat Anwar Medical Complex. All the clinically diagnosed patients having neuropathic sign and symptoms of DPN, with type 2 DM diagnosed having an HbA1c level greater than 7.5, both genders aged between 40-70 y were enrolled in the study. After the written informed consent, a total of 60 patients were randomly divided into two groups in a 1:1 ratio. Group I received PRP injections on acupuncture points and Group II received 75 mg pregabalin PO twice daily. The PRP injection treatment was given once a month for three months. Follow up of all patients was conducted every month till three months and after one year for final assessment. All the data was entered and analyzed by SPSS 25.0. The difference among pain, SF-36, sleep quality scale among groups was compared by independent sample t test and before and after difference was observed by paired sample t-test. P < 0.05 was considered as significant.
 Results: The VAS scores were significantly decreased in Group I (from 7.47 ± 1.27 to 3.67 ± 1.09; P < 0.05) as compared to Group II (7.30 ± 1.59 to 5.20 ± 1.58, P < 0.05). The neuropathic symptoms scale also showed significant improvement (Group I: 13.50 ± 50 to 8.50 ± 2.30 vs. Group II: 14.93 ± 2.55 to 9.83 ± 2.17, P < 0.05), as well as the quality of life (Group I: 67.77 to 31.50 ± 9.24 vs. Group II:69.37 ± 11.7to 41.20 ± 12.16, P < 0.05) and sleep quality scale (Group I:49.53 ± 12.4 to 27.30 ± 8.03 vs. Group II: 52.13 ± 10.9to 32.60 ± 7.103, P < 0.05).
 Conclusion: We conclude that the treatment of diabetic peripheral neuropathy with platelet rich plasma injections at acupuncture points significantly improves the pain scores, quality of sleep and neuropathic symptoms as compared to conventional treatment with 75 mg pregabalin PO twice daily.
 Abbreviations: DM- Diabetes Mellitus; DPN- Diabetic Polyneuropathy; LANSS- Leeds Assessment of Neuropathic Symptoms and Signs; PRP- Platelet Rich Plasma; QoL- Quality of Life; SQS- Sleep Quality Scale
 Key words: Acupuncture; Diabetic Poly Neuropathy; Pain; PRP injections; Quality of Life
 Citation: Anwar S, Hassan MW, Shaukat GR, Tirmzi F, Saeed MU, Aslam M. Effectiveness of platelet rich plasma (PRP) treatment and its comparison with pregabalin in painful diabetic polyneuropathy: A randomized controlled clinical trial. Anaesth. pain intensive care 2024;28(1):44-49; DOI: 10.35975/apic.v28i1.2280
 Received: August 07, 2023; Reviewed: August 08, 2923; Accepted: December 21, 2023

VGLUT2 and APP family: unraveling the neurobiochemical mechanisms of neurostimulation therapy to STZ-induced diabetes and neuropathy.

Diabetic Peripheral Neuropathy (DPN) poses an escalating threat to public health, profoundly impacting well-being and quality of life. Despite its rising prevalence, the pathogenesis of DPN remains enigmatic, and existing clinical interventions fall short of achieving meaningful reversals of the condition. Notably, neurostimulation techniques have shown promising efficacy in alleviating DPN symptoms, underscoring the imperative to elucidate the neurobiochemical mechanisms underlying DPN. This study employs an integrated multi-omics approach to explore DPN and its response to neurostimulation therapy. Our investigation unveiled a distinctive pattern of vesicular glutamate transporter 2 (VGLUT2) expression in DPN, rigorously confirmed through qPCR and Western blot analyses in DPN C57 mouse model induced by intraperitoneal Streptozotocin (STZ) injection. Additionally, combining microarray and qPCR methodologies, we revealed and substantiated variations in the expression of the Amyloid Precursor Protein (APP) family in STZ-induced DPN mice. Analyzing the transcriptomic dataset generated from neurostimulation therapy for DPN, we intricately explored the differential expression patterns of VGLUT2 and APPs. Through correlation analysis, protein-protein interaction predictions, and functional enrichment analyses, we predicted the key biological processes involving VGLUT2 and the APP family in the pathogenesis of DPN and during neurostimulation therapy. This comprehensive study not only advances our understanding of the pathogenesis of DPN but also provides a theoretical foundation for innovative strategies in neurostimulation therapy for DPN. The integration of multi-omics data facilitates a holistic view of the molecular intricacies of DPN, paving the way for more targeted and effective therapeutic interventions.

Implementing a contextually appropriate foot-ankle exercise programme in primary care for the prevention of modifiable risk factors for ulcers in people with diabetes: protocol for a hybrid type 2 study

IntroductionDiabetes is a highly prevalent disease that negatively impacts people’s health and quality of life. It can result in diabetic peripheral neuropathy (DPN) and foot complications, which in turn lead...

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 <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.

NAD+ Precursors Reverse Experimental Diabetic Neuropathy in Mice.

Abnormal NAD+ signaling has been implicated in axonal degeneration in diabetic peripheral neuropathy (DPN). We hypothesized that supplementing NAD+ precursors could alleviate DPN symptoms through increasing the NAD+ levels and activating the sirtuin-1 (SIRT1) protein. To test this, we exposed cultured Dorsal Root Ganglion neurons (DRGs) to Nicotinamide Riboside (NR) or Nicotinamide Mononucleotide (NMN), which increased the levels of NAD+, the SIRT1 protein, and the deacetylation activity that is associated with increased neurite growth. A SIRT1 inhibitor blocked the neurite growth induced via NR or NMN. We then induced neuropathy in C57BL6 mice with streptozotocin (STZ) or a high fat diet (HFD) and administered NR or NMN for two months. Both the STZ and HFD mice developed neuropathy, which was reversed through the NR or NMN administration: sensory function improved, nerve conduction velocities normalized, and intraepidermal nerve fibers were restored. The NAD+ levels and SIRT1 activity were reduced in the DRGs from diabetic mice but were preserved with the NR or NMN treatment. We also tested the effect of NR or NMN administration in mice that overexpress the SIRT1 protein in neurons (nSIRT1 OE) and found no additional benefit from the addition of the drug. These findings suggest that supplementing with NAD+ precursors or activating SIRT1 may be a promising treatment for DPN.

Novel drugs affecting diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) poses a significant threat, affecting half of the global diabetic population and leading to severe complications, including pain, impaired mobility, and potential amputation. The delayed manifestation of diabetic neuropathy (DN) makes early diagnosis challenging, contributing to its debilitating impact on individuals with diabetes mellitus (DM). This review examines the multifaceted nature of DPN, focusing on the intricate interplay between oxidative stress, metabolic pathways, and the resulting neuronal damage. It delves into the challenges of diagnosing DN, emphasizing the critical role played by hyperglycemia in triggering these cascading effects. Furthermore, the study explores the limitations of current neuropathic pain drugs, prompting an investigation into a myriad of pharmaceutical agents tested in both human and animal trials over the past decade. The methodology scrutinizes these agents for their potential to provide symptomatic relief for DPN. The investigation reveals promising results from various pharmaceutical agents tested for DPN relief, showcasing their efficacy in ameliorating symptoms. However, a notable gap persists in addressing the underlying problem of DPN. The results underscore the complexity of DPN and the challenges in developing therapies that go beyond symptomatic relief. Despite advancements in treating DPN symptoms, there remains a scarcity of options addressing the underlying problem. This review consolidates the state-of-the-art drugs designed to combat DPN, highlighting their efficacy in alleviating symptoms. Additionally, it emphasizes the need for a deeper understanding of the diverse processes and pathways involved in DPN pathogenesis.

Pathogenetic treatments for diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is found in around one third of people with diabetes, but remains inadequately diagnosed and treated. Its management includes three cornerstones: 1) causal treatment with lifestyle modification, intensive diabetes therapy aimed at near-normoglycemia, and multifactorial cardiovascular risk intervention, 2) pathogenesis-oriented pharmacotherapy, and 3) symptomatic pain relief. Since symptomatic analgesic monotherapy only relieves the pain without targeting the underlying neuropathy and both has limited efficacy and is associated with adverse events, there is an unmet need for additional approaches derived from the pathogenetic concepts of DPN. Preclinical studies have suggested that diabetic neuropathy can be prevented or improved through the use of various agents that interfere with the pathophysiology of the underlying condition. Some of these encouraging findings could be translated successfully into the clinical setting. Efficacy and excellent safety were demonstrated in several meta-analyses (α-lipoic acid) and randomized clinical trials (benfotiamine, actovegin, epalrestat) in the treatment of symptomatic DPN. The NATHAN 1 trial demonstrated an improvement of neuropathic signs (deficits, impairments) after four years in asymptomatic DPN. These compounds are currently authorized for treatment of DPN in several countries. Long-term pivotal clinical trials should further establish their value as mono- and combination therapies in DPN.

Evaluating the effect of acupuncture on symptoms of diabetic peripheral neuropathy (DPN) among individuals with diabetic neuropathy: A single-blind, randomized trial study.

This study aimed to investigate the impact of acupuncture on Diabetic peripheral neuropathy (DPN) symptoms among individuals with diabetic neuropathy. In a single-blind, randomized trial conducted between 2019 and 2020, 60 patients diagnosed with diabetic neuropathy were enrolled. These participants were randomly assigned to either the intervention or control group. The intervention group received real acupuncture alongside routine treatment once a week for seven sessions, each lasting 20min. Meanwhile, the control group received sham acupuncture as an adjunct to their routine treatment, following the same schedule. To evaluate treatment efficacy, the study assessed primary outcomes, such as pain intensity measured using the Visual Analogue Scale (VAS). Secondary outcomes included evaluating fatigue severity and diabetic peripheral neuropathy (DPN) side effects, measured using the multidimensional fatigue inventory (MFI-20) and a standard questionnaire after each session. No statistically significant differences in pain and fatigue scores were observed between the two groups throughout all visits, even after adjusting for baseline characteristics, age, sex, type of diabetes, discopathy, and carpal tunnel syndrome parameters (P > 0.05). The findings did not provide strong evidence supporting a significant effect of real acupuncture compared to sham acupuncture on pain and fatigue values (P = 0.267 and 0.634, respectively). However, the 95% confidence interval for pain scores (-0.35, 1.28) was inconclusive, encompassing effect sizes favoring sham acupuncture. Findings suggest that using acupuncture as an adjunctive therapy alongside routine treatment may not lead to a significant reduction in the symptoms of peripheral neuropathy and fatigue severity among individuals with diabetic neuropathy. The online version contains supplementary material available at 10.1007/s40200-023-01314-1.

ID: 211765 Multiple RCTs of SCS Show Consistent Outcomes in the Treatment of Painful Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is the most common neuropathic syndrome seen in patients with diabetes. DPN symptoms include stabbing or burning pain eventually progressing to numbness in the lower extremities resulting in loss of protective sensation. Traditionally, pain associated with DPN has been treated with gabapentin/pregabalin, tri-cycling antidepressants, and serotonin-norepinephrine reuptake inhibitors1. These treatment approaches are often unsuccessful in the long-term, with many DPN patients abandoning initial prescription analgesics within months1. Spinal Cord Stimulation (SCS) has been examined in 3 randomized controlled trials (RCTs)2,3,4 comparing SCS to conventional treatments.

ID: 215433 The History of Spinal Cord Stimulation to Treat Painful Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is the most common neuropathic syndrome seen in patients with diabetes. Roughly 30% of the diabetes patient population1 experience painful DPN symptoms including bilateral stabbing or burning pain in addition to numbness in the feet and lower legs. Traditionally painful DPN symptoms have been treated with conventional medical management (CMM) including glycemic control, general risk factor management, as well as pharmaceutical agents. These treatment approaches are often unsuccessful in the long-term1. Spinal cord stimulation (SCS) has been demonstrated as an effective treatment for painful DPN of the lower extremities with multiple publications dating back to 1996 showing benefits of SCS for pain relief and improved Quality of Life (QoL) in DPN patients (Figure 1)2-18.

Topical capsaicin for the management of painful diabetic neuropathy: a narrative systematic review.

Aim: To investigate the potential benefit of topical capsaicin formulations. Materials& methods: A narrative systematic review was employed. Results: About8% Capsaicin patches were found to significantly reduce symptoms of diabetic peripheral neuropathy. Capsaicin was found to improve sleep quality (p=0.02). Capsaicin patch exposure for 60minshowed significant reduction in symptoms (-32.8%). Capsaicin cream significantly reduced pain at weeks 2 and 6 (p=0.003 andp=0.03, respectively), but not at week 8 in comparative studies. 0.025% Capsaicin gel had an insignificant reduction in pain compared with placebo (p=0.53), however 0.075% was found to be significant (p=0.038). Capsaicin cream did not have superior improvement of pain as compared with clonidine gel (p=0.931). The most common adverse events included application site discomfort, erythemaand burning. Conclusion: Topical capsaicin treatments are a potentially beneficial peripherally acting medication. Further research is needed to determine the best means of ameliorating the side effects of treatments.

Blocking CXC Motif Chemokine Ligand 2 Ameliorates Diabetic Peripheral Neuropathy via Inhibiting Apoptosis and NLRP3 Inflammasome Activation.

Evidence suggests that CXC motif chemokines are involved in neuronal injury and inflammatory processes. Bioinformatics analysis by using data from the Gene Expression Omnibus (GEO) database was performed and identified CXC motif chemokine ligands (CXCLs) as associated with diabetic peripheral neuropathy (DPN). The present study focused on CXC motif chemokine ligand 2 (CXCL2), and the role and potential mechanisms of CXCL2 in DPN were investigated. The DPN rat model was generated by streptozotocin (STZ) injection in vivo, and high-glucose (HG)-stimulated Schwann cell RSC96 was considered a cell model of DPN in vitro. Neuropathic symptoms of DPN were explored by neurological tests and histological examinations. DPN rats showed a decreased level of motor nerve conduction velocity (MNCV) along with typical histological changes. CXCL2 expression was significantly increased in STZ-induced DPN rat sciatic nerve and HG-induced RSC96 cells. Functionally, CXCL2 knockdown inhibited cell apoptosis and inflammation activation under diabetic conditions in vitro and in vivo. CXCL2 knockdown increased cell viability in HG-treated RSC96 cells and reduced apoptosis concerning the decreased expression of cleaved Caspase 3/9. In addition, CXCL2 knockdown protected against NOD-like receptor protein 3 (NLRP3) inflammasome activation and reduced levels of pro-inflammatory cytokines, interleukin (IL)-1β and IL-18. The repressive effects of CXCL2 knockdown on inflammasome activation under HG conditions were significantly abolished by treatment of the NLRP3 activator nigericin. In conclusion, these results indicated that CXCL2 knockdown exhibited amelioration of hyperglycemia-induced DPN by inhibiting cell apoptosis and NLRP3 inflammasome activation, suggesting that targeting CXCL2 might be a potential strategy for DPN treatment.

Comparative Efficacy of East Asian Herbal Formulae Containing Astragali Radix-Cinnamomi Ramulus Herb-Pair against Diabetic Peripheral Neuropathy and Mechanism Prediction: A Bayesian Network Meta-Analysis Integrated with Network Pharmacology.

The Astragali Radix-Cinnamomi Ramulus herb-pair (ACP) has been widely used in the treatment of diabetic peripheral neuropathy (DPN) as part of East Asian herbal medicine (EAHM). Eligible randomized controlled trials (RCTs) were identified by searching 10 databases. The outcomes investigated were response rate, sensory nerve conduction velocity (SNCV), and motor nerve conduction velocity (MNCV) in four regions of the body. The compounds in the ACP and their targets of action, disease targets, common targets, and other relevant information were filtered using network pharmacology. Forty-eight RCTs, with 4308 participants, and 16 different interventions were identified. Significant differences were observed in the response rate, MNCV, and SNCV, as all EAHM interventions were superior to conventional medicine or lifestyle modification. The EAHM formula containing the ACP ranked highest in more than half of the assessed outcomes. Furthermore, major compounds, such as quercetin, kaempferol, isorhamnetin, formononetin, and beta-sitosterol, were found to suppress the symptoms of DPN. The results of this study suggest that EAHM may increase therapeutic efficacy in DPN management, and EAHM formulations containing the ACP may be more suitable for improving treatment response rates to NCV and DPN therapy.

Prevalence of Karapada daha-suptata in Madhumeha with reference to diabetic peripheral neuropathy in type 2 diabetes mellitus patients.

Background: Diabetes mellitus is a major health issue in today's world. Main threat is not the disease itself but its complications like nephropathy, retinopathy and neuropathy etc. Diabetic peripheral neurropathy is the leading cause of foot ulcers, their complications like limb amputation and cost associated with it. Madhumeha which has been described as 'Maharogas' i.e. difficult to treat disease has many similarities with Diabetes mellitus can be understood and studied as same disease. Ayurveda has mentioned the causes, pathophysiology and symptoms of Diabetic Peripheral Neuropathy as 'karapada daha -suptata' in purvarupa lakshanas and upadrava lakshanas but inscattered form. It needs depth study to understand the concept of Karapada daha- suptata (DPN).
 Objective: To study prevalence of Karapada daha-suptata (Diabetic peripheral neuropathy) and the relation of Karapada daha- suptata (DPN) with age, gender, duration of disease Madhumeha, blood sugar level, alcohol and smoking habit etc in Madhumeha patients.
 Method :A cross sectional study was carried out in Tribhuvan University Ayurveda Teaching Hospital,. Madhumeha patients (Type 2 diabetes mellitus) patients were recruited for the study. MNSI (Michigan Neuropathy Screening Instrument) was used to diagnose Karapada daha- suptata (Diabetic peripheral neuropathy).
 Result: Among 100 patients 31% patient had Karapada daha- suptata (DPN). Our study showed that the prevalence of Karapada daha-suptata(DPN) increased with increasing age of the study population. Similarly prevalence of Karapada daha -suptata in patients with disease duration of Madhumeha (DM2) for more than 5 years was 61.29% where as patients having Diabetes for less than 5 year was 38.71%. Prevalence of Karapada daha-suptata (DPN) was very high (43.13%) among uncontrolled fasting blood sugar level (>126mg/dl) and (47.5%) among uncontrolled post prandial blood sugar level (>200mg/dl). In this study mean Fasting blood sugar level was 177.0323 mg/dl in the patients with Karapada daha-suptata(DPN) and mean post prandial blood sugar level in patients with diabetic peripheral neuropathy was 239.1613mg/dl.
 Conclusion: Our study showed Karapada daha-suptata/DPN is highly prevalent and increasing as the duration of disease Madhumeha increses but its not uncommon in newly disagnosed disease too. This study showed significant relation of Karapada daha suptata with disease duration of Madhumeha, level of blood sugar, and increasing age of the patients.Study showed no significant differences in the prevalence of Kara pada daha- suptata in male and female patients and with the smoking habit of the patients.

Self-Care Behavior of Type 2 Diabetes Patients with Symptoms of Peripheral Neuropathy during the Covid-19 Pandemic: A Qualitative Study

Purpose: This study aims to explore the experiences and perceptions of type 2 diabetes patients with symptoms of Diabetic Peripheral Neuropathy (DPN) in managing their self-care behavior during the COVID-19 pandemic. Methods: Qualitative research with a descriptive phenomenological approach reveals diabetes self-care behavior during the COVID-19 pandemic. Individual interviews were conducted at the participants’ homes with a semi-structured interview guide on twelve type 2 diabetes patients. All interviews were transcribed verbatim and analyzed using thematic content analysis. Results: A total of five themes were identified from the interview analysis, namely: 1) Perception of diabetes self-management; 2) Efforts to control blood sugar; 3) Barriers to blood sugar control; 4) Perceived disturbance; 5) Social support. Since its emergence, the Covid-19 pandemic has become a new obstacle in controlling blood glucose in diabetic patients. In addition to the covid-19 pandemic, negative spiritual coping, low self-motivation, and perceived physical effects are inhibiting factors for blood glucose control in type 2 diabetes patients with symptoms of DPN. Conclusions: Obstacles in efforts to control blood glucose in type 2 diabetes patients with symptoms of DPN include physical, psychological, social, and spiritual aspects. The suggestion in this study is that during the COVID-19 pandemic, it is necessary to adjust and modify diabetes self-management for patients with DPN symptoms. The interventions provided should not only focus on the physical aspect but also need holistic attention to the psychosocial and spiritual aspects simultaneously by involving family participation in the management of the patient’s diabetes.

Differences in motor unit behavior during isometric contractions in patients with diabetic peripheral neuropathy at various disease severities.

The aim of this study was to determine whether HD-sEMG is sensitive to detecting changes in motor unit behavior amongst healthy adults and type 2 diabetes mellitus (T2DM) patients presenting diabetic peripheral neuropathy (DPN) at different levels. Healthy control subjects (CON, n=8) and T2DM patients presenting no DPN symptoms (ABS, n=8), moderate DPN (MOD, n=18), and severe DPN (SEV, n=12) performed isometric ankle dorsiflexion at 30% maximum voluntary contraction while high-density surface EMG (HD-sEMG) was recorded from the tibialis anterior muscle. HD-sEMG signals were decomposed, providing estimates of discharge rate, motor unit conduction velocity (MUCV), and motor unit territory area (MUTA). As a result, the ABS group presented reduced MUCV compared to CON. The groups with diabetes presented significantly larger MUTA compared to the CON group (p<0.01), and the SEV group presented a significantly lower discharge rate compared to CON and ABS (p<0.01). In addition, the SEV group presented significantly higher CoVforce compared to CON and MOD. These results support the use of HD-SEMG as a method to detect peripheral and central changes related to DPN.

Is Cerebrolysin effective in reducing symptoms of Diabetic Peripheral Neuropathy?

Aim This is an investigator initiated observational comparative medical program, to test the efficacy of Cerebrolysin® intake for 1 month versus 2 months, in patients clinically diagnosed with type 2 diabetes mellitus (T2DM) and suffering from peripheral neuropathy. Methods Patients aged ≥ 18 years old, clinically diagnosed with mild or moderate painful diabetic polyneuropathy, received Cerebrolysin® for 1 or 2 months according to investigators’ decision. Demographic data, detailed medical history, and laboratory results were collected at baseline. All enrolled patients were evaluated for Toronto Clinical Scoring System (TCSS), Visual Analogue Scale (VAS) and Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (LANSS) at baseline and end of the program (1 month/2 month). Results VAS, TCSS, and LANSS were significantly improved for all 136 enrolled patients at the end of their treatment with Cerebrolysin® for 1 or 2 months, regarding gender, duration since diagnosis of T2DM (more than or less than 10 years) and HbA1c ≤ 9% or ˃ 9%, with a very highly statistically significant difference (p-value ˂ 0.001). They were slightly improved more in patients received Cerebrolysin® for 1 month more than for 2 months. There was no statistically significant difference for gender, duration of diagnosis with diabetes mellitus less or more than 10 years, and HbA1c ≤ 9% &amp; ˃ 9% regarding the change of VAS, TCSS, and LANSS as dependent variables, using Linear stepwise regression. While there was noticed improvement in VAS, TCSS, and LANSS with use of Cerebrolysin® for 1 month more than 2 months, Regression Coefficient (B (95% of Confidence interval)) B=0.794 (0.29-1.29), B=1.472 (0.87-2.074), B=2.143 (0.45-3.83) and p-value = 0.002, p-value ˂ 0.001, p-value = 0.13 respectively. There was no adverse event (AE) or serious adverse event (SAE) reported during the program. Conclusion: Cerebrolysin® is considered effective in the management of peripheral neuropathy in patients with T2DM Abbreviations: Adverse Event (AE), Advanced Glycation End products (AGE), Contract Research Organization (CRO), Diabetic Peripheral Neuropathy (DPN), Diacylglycerol (DAG), estimated Glomerular Filtration (eGFR), Fasting Blood Sugar (FBS), Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (LANSS), Peripheral Vascular Disease (PVD), Pin- Prick Threshold (PPT), Protein Kinase C (PKC), Statistical Analysis Plan (SAP), Serious Adverse Event (SAE), Standard Deviation (SD), Type 1 Diabetes Mellitus (T1DM), Type 2 Diabetes Mellitus (T2DM), Toronto Clinical Scoring System (TCSS), Traumatic Brain Injury (TBI), Visual Analogue Scale (VAS).

Pathogenesis and Treatment of Diabetic Peripheral Neuropathy

Diabetic neuropathy is the most common chronic complication of both type 1 and type 2 diabetes mellitus. Diabetic peripheral neuropathy (DPN), especially, distal symmetric polyneuropathy is the most common form of diabetic neuropathy. Pathogenesis of the DPN is associated with glycemic dysregulation, which results in activation of polyol, aldose reductase, hexosamine, and protein kinase C pathway and leads to downstream inflammation, generation of reactive oxygen species, and decreased blood flow to peripheral nerves. Furthermore, metabolic syndrome components such as obesity, insulin resistance, and dyslipidemia result in mitochondrial dysfunction and endoplasmic reticulum stress, eventually contributing to axonal failure and apoptosis of nerve cells. Despite its high prevalence, DPN is still underdiagnosed. Among DPN symptoms, neuropathic pain is challenging to manage, resulting in increased risk of associated problems such as sleep disturbance, reduced quality of life, and socioeconomic consequences. Therefore, early diagnosis and active multidisciplinary treatment of DPN is needed.