Management Of Diabetic Neuropathy Research Articles

Diabetic Neuropathy: A Guide to Pain Management.

Diabetic neuropathy is a common complication of diabetes mellitus (DM) and can affect up to 50% of DM patients during their lifetime. Patients typically present with numbness, tingling, pain, and loss of sensation in the extremities. Since there is no treatment targeting the underlying mechanism of neuropathy, strategies focus on preventative care and pain management. Up to 69% of patients with diabetic neuropathy receive pharmacological treatment for neuropathic pain. The United States Food and Drug Administration (FDA) confirmed four drugs for painful diabetic neuropathy (PDN): pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch. Nonpharmacological treatments such as spinal cord stimulation (SCS) and transcutaneous electrical nerve stimulation (TENS) both show promise in reducing pain in DM patients. Despite the high burden associated with PDN, effective management remains challenging. This update covers the background and management of diabetic neuropathy, including its epidemiology, pathogenesis, preventative care, and current therapeutic strategies.

Diabetic Neuropathy: An Overview of Molecular Pathways and Protective Mechanisms of Phytobioactives.

Diabetic neuropathy (DN) is a common and debilitating complication of diabetes mellitus that affects the peripheral nerves and causes pain, numbness, and impaired function. The pathogenesis of DN involves multiple molecular mechanisms, such as oxidative stress, inflammation, and pathways of advanced glycation end products, polyol, hexosamine, and protein kinase C. Phytochemicals are natural compounds derived from plants that have various biological activities and therapeutic potential. Flavonoids, terpenes, alkaloids, stilbenes, and tannins are some of the phytochemicals that have been identified as having protective potential for diabetic neuropathy. These compounds can modulate various cellular pathways involved in the development and progression of neuropathy, including reducing oxidative stress and inflammation and promoting nerve growth and repair. In this review, the current evidence on the effects of phytochemicals on DN by focusing on five major classes, flavonoids, terpenes, alkaloids, stilbenes, and tannins, are summarized. This compilation also discusses the possible molecular targets of numerous pathways of DN that these phytochemicals modulate. These phytochemicals may offer a promising alternative or complementary approach to conventional drugs for DN management by modulating multiple pathological pathways and restoring nerve function.

Current Concepts in the Molecular Mechanisms and Management of Diabetic Neuropathy by Pharmacotherapeutics and Natural Compounds.

One of the most crippling effects of diabetes mellitus is diabetic neuropathy, which can cause discomfort, loss of movement, and even amputation. Diabetic neuropathy manifests in a variety of ways, ranging from pain to death. Diagnosing diabetic neuropathy can be challenging since it often goes unnoticed for many years following the onset of diabetes. In addition to oxidative stress in neurons, hyperglycemia activates a number of metabolic pathways that are important sources of damage and possible targets for treatment in diabetic neuropathy. Downstream metabolic cascades caused by prolonged hyperglycemia include activation of protein kinase C, increased production of advanced glycation end products, excessive release of cytokines, increased oxidative stress, and injury to peripheral nerves. Despite the fact that these metabolic anomalies are considered the main cause of diabetes-related microvascular issues, the diverse mechanistic processes of neuropathy are characterized by organ-specific histological and biochemical features. Although the symptoms of diabetic neuropathy can be treated, there are few options to correct the underlying problem. Diabetic neuropathy exerts a tremendous financial, psychological, and physical burden on society, emphasizing the need for efficient and focused treatment. The major goal of this review is to shed light on the multiple mechanisms and pathways that contribute to the onset of diabetic neuropathy and to provide readers with a comprehensive understanding of emerging therapeutic strategies to postpone or reverse various forms of diabetic neuropathy. The article discusses available medications and provides the latest guidelines for the treatment of pain and distal symmetric polyneuropathy, including diabetic autonomic neuropathy, which may help the patients control pain well and assess alternatives for treatment that might be more successful in preventing or delaying the course of a disease.

Evaluation and Management of Diabetic Neuropathy from the Perspective of People with Diabetes

Diabetic foot ulcers (DFU) and infections are the most common complications of diabetic foot disease. Mortality and financial burdens for both patients and society on the whole are caused by the prevalence of complications. Peripheral neuropathy, peripheral arterial disease, and immune response dysfunction are just a few of the main contributing factors that must be understood in order to effectively treat the condition. In order to treat diabetic foot disease, you must first get a comprehensive physical examination and a detailed history of your condition. Diabetic neuropathy and peripheral vascular disease, as well as any evidence of diabetic foot ulcers or infection, should be examined during this procedure. Patients with diabetes mellitus were studied to see if there was a link between cognitive impairment and the condition of their feet and whether or not they followed their doctor's recommendations for glycemic control. Using a random sample of diabetes patients, researchers conducted a prospective study to see how many people had the condition. The Mini-Mental State Valuation, the Trail Making Judgments, and the Michigan Screening Instrument were used to assess cognitive abilities. In the one-month follow-up, glycated hemoglobin (HB1Ac >7%) was linked to the MMSE and medication adherence, but no link was seen between cognitive function and neuropathy. According to the results of a ROC curve investigation, HB1Ac and the MNSI score both significantly (p< 0.05) mitigate towards eventual adherence to medicine for foot problems. For the purpose of determining if DFU was associated with cognitive impairment, the Chi square valuation was used in the statistical examination. As a determinant of MMSE and MoCA scores, the researchers used linear regression to come to their conclusion. Diabetic foot issues should be managed with good blood sugar control and less acute neuropathy, and this does not seem to be linked to cognitive dysfunction. More study is required in order to personalize treatments for diseases of the central and peripheral nervous systems appropriately. Cognitive dysfunction should be taken into account by doctors and podiatrists while treating diabetic foot problems

Impact of Resveratrol and Pharmaceutical Care on Type 2 Diabetes Mellitus and Its Neuropathic Complication: A Randomized Placebo Controlled Clinical Trial

Background. Management of diabetic neuropathy (DN) is a challenging issue. Therefore, integration of pharmaceutical care provided by the clinical pharmacists with pharmacotherapy may provide multifaceted approach to target the management of hyperglycemia and diabetic neuropathic complication. This study aimed to evaluate the effects of resveratrol (Resv) and/or pharmaceutical care (PC) on glycemic control and amelioration of diabetes-associated neuropathic complications. Patients and Methods. A four-arm randomized placebo-controlled clinical trial assigned 120 patients from the Diabetes and Endocrinology Center in Sulaymaniyah City, Iraq. The patients were divided into four groups. The Resv group (n = 30) received 500 mg Resv capsules once daily. The Placebo group (n = 30) received placebo capsules. Resv + PC (n = 30) received Resv 500 mg capsules with PC. Placebo + PC (n = 30) received placebo capsule plus PC. The duration of the intervention was 90 days. Drug therapy problems (DTPs) have been utilized as an important domain in PC. Clinical signs, symptoms, and neuropathic abnormalities were assessed using the Michigan Neuropathy Screening Instrument (MNSI), Douleur Neuropathique 4 (DN4) questions, and nerve conduction studies (NCSs) of the lower-limb sensory and motor nerves. Results. 97 patients from all the groups completed the study. At baseline, 84% of the Resv, 87% of the Placebo, and 92% of each of Resv + PC and Placebo + PC groups, respectively, had at least one DTP. The provision of PC resulted in a dramatic reduction in the number of DTP. Resveratrol with PC significantly ameliorated hyperglycemic status, neuropathic signs, and symptoms, as evidenced by a decrease in MNSI and DN4 scores and improvement in electroneurographic parameters. Conclusion. These findings support the integration of the PC concept into a pharmacotherapy intervention; they also encourage supplementation of Resv with conventional diabetes therapy to emphasize on the importance of this herbal medicine with the provision of PC in the management of diabetes and its neuropathic complications. This trial is registered with NCT05172947.

The systematic review on Madhumeha w.r.t. Diabetic Neuropathy and its management: A review article

The world's fastest-growing major illness is diabetes mellitus. It's a metabolic illness that could lead to an insufficiency or malfunction in the production of insulin. Many of the Samhitas contain detailed descriptions of Madhumeha. Diabetic neuropathy is most common complication of Diabetes, approximately 50% of patients with diabetes eventually develop neuropathy. Symptoms of diabetic neuropathy not directly mentioned in Ayurveda but symptoms like Suptata, Chumchumayan, Karpada Daha, seen in Prameha either in Prameha prodomal stage, exhibition stage or in complication stage. As Samprapti of diabetic neuropathy not clearly mentioned in Samhitas so, after reviewing different Samhitas, a Samprapti has been suggested with possible management of Diabetic neuropathy in Ayurveda i.e., Shodhan and Samana Chikitsa and mode of action of Shodhan Chikitsa.

Current advancement in the preclinical models used for the assessment of diabetic neuropathy.

Diabetic neuropathy is one of the prevalent and debilitating microvascular complications of diabetes mellitus, affecting a significant portion of the global population. Relational preclinical animal models are essential to understand its pathophysiology and develop effective treatments. This abstract provides an overview of current knowledge and advancements in such models. Various animal models have been developed to mimic the multifaceted aspects of human diabetic neuropathy, including both type 1 and type 2 diabetes. These models involve rodents (rats and mice) and larger animals like rabbits and dogs. Induction of diabetic neuropathy in these models is achieved through chemical, genetic, or dietary interventions, such as diabetogenic agents, genetic modifications, or high-fat diets. Preclinical animal models have greatly contributed to studying the intricate molecular and cellular mechanisms underlying diabetic neuropathy. They have shed light on hyperglycemia-induced oxidative stress, neuroinflammation, mitochondrial dysfunction, and altered neurotrophic factor signaling. Additionally, these models have allowed for the investigation of morphological changes, functional alterations, and behavioral manifestations associated with diabetic neuropathy. These models have also been crucial for evaluating the efficacy and safety of potential therapeutic interventions. Novel pharmacological agents, gene therapies, stem cell-based approaches, exercise, dietary modifications, and neurostimulation techniques have been tested using these models. However, limitations and challenges remain, including physiological differences between humans and animals, complex neuropathy phenotypes, and the need for translational validation. In conclusion, preclinical animal models have played a vital role in advancing our understanding and management of diabetic neuropathy. They have enhanced our knowledge of disease mechanisms, facilitated the development of novel treatments, and provided a platform for translational research. Ongoing efforts to refine and validate these models are crucial for future treatment developments for this debilitating condition.

Serum uric acid and risk of diabetic neuropathy: a genetic correlation and mendelian randomization study.

Previous observational studies have indicated an association between serum uric acid (SUA) and diabetic neuropathy (DN), but confounding factors and reverse causality have left the causality of this relationship uncertain. Univariate Mendelian randomization (MR), multivariate MR and linkage disequilibrium score (LDSC) regression analysis were utilized to assess the causal link between SUA and DN. Summary-level data for SUA were drawn from the CKDGen consortium, comprising 288,648 individuals, while DN data were obtained from the FinnGen consortium, with 2,843 cases and 271,817 controls. Causal effects were estimated primarily using inverse variance weighted (IVW) analysis, supplemented by four validation methods, with additional sensitivity analyses to evaluate pleiotropy, heterogeneity, and result robustness. The LDSC analysis revealed a significant genetic correlation between SUA and DN (genetic correlation = 0.293, P = 2.60 × 10-5). The primary methodology IVW indicated that each increase of 1 mg/dL in SUA would increase DN risk by 17% (OR = 1.17, 95% CI 1.02-1.34, P = 0.02), while no causal relationship was found in reverse analysis (OR = 1.00, 95% CI 0.98~1.01, P = 0.97). Multivariate MR further identified that the partial effect of SUA on DN may be mediated by physical activity, low density lipoprotein cholesterol (LDL-C), insulin resistance (IR), and alcohol use. The study establishes a causal link between elevated SUA levels and an increased risk of DN, with no evidence for a reverse association. This underscores the need for a comprehensive strategy in DN management, integrating urate-lowering interventions with modulations of the aforementioned mediators.

Digital Nerve Care Forum: Innovative Healthcare Professionals Education on Neuropathy.

Neuropathy is a common complication of diabetes, rarely detected on time, often deprioritized by treating physicians, and hence rarely managed in time, leading to avoidable complications which can be limb and life-threatening. Despite introducing new diagnostic tests, novel potential bio parameters, and a series of relatively small intervention studies utilizing detailed phenotypic profiling, the management of diabetic neuropathy (DN) and painful DN has remained unchanged due to misdiagnosis. The diagnostic complexity of diabetic peripheral neuropathy (DPN), variation in patient response to treatment, and regulatory pressures to meet data-driven quality metrics for diabetes management all likely contributes to the underdiagnosis and treatment of DPN in clinical practice. Educating the primary healthcare providers and diabetic trainers would help improve the number of diagnosed DPN cases as these practitioners lead public health literacy. The digital nerve care forum (NCF) is an educational initiative created by clinical experts and Procter and Gamble (P&G) health academy. Its primary aim is to generate awareness amongst healthcare practitioners (HCPs) about early diagnosis and timely management of DPN. Since its inception in October 2020, NCF has conducted 143 engagements; 39 neuropathy case puzzles, four interactive case-based discussions, two diagnostic workshops, four mentor-mentee nerve talk shows, two intercountry nerve talk shows, two global neuropathy awareness week initiatives, three nerves of steel (Women's Day special engagements), and 17 NCF times (Newsletters). This online forum is hosted on a global HCP education and upskilling platform, MediSage, which offers these educational resources to HCPs worldwide for free. It has helped create a community of 254, 714 HCPs from 86 countries across six continents supported by 30 neuropathy experts from seven countries. With a repeated viewership of 53% of HCPs engaging continuously, NCF empowers this community to improve diabetic patient care. Activities that increase disease awareness and highlight the importance of diabetic nerve health have been the key objectives behind the several educational programs on NCF. To drive this continuum, these digital programs are now becoming more phygital and impactful than ever. Therefore, earlier detection of DPN in at-risk individuals and those with prediabetes or type 2 diabetes is recommended for better management through optimal intervention and lifestyle changes and to prevent future complications of untreated DPN. How to cite this article: Kalra S, Tiwaskar M, Shrestha D, et al. Digital Nerve Care Forum: Innovative Healthcare Professionals Education on Neuropathy. J Assoc Physicians India 2023;71(10):89-92.

Management of diabetic neuropathy with memantine: A randomized clinical trial.

Diabetes patients frequently experience diabetic neuropathy (DN), a microvascular complication that significantly reduces patients' quality of life. Memantine has demonstrated potential benefits for neuropathic pains in preclinical studies. This study aimed to assess the efficacy of memantine in the management of peripheral neuropathy in patients with type 2 diabetes mellitus (T2DM). This randomized clinical trial includes 143 diabetic patients (aged between 18 and 75years) with a confirmed diagnosis of diabetic neuropathy. Patients were randomly assigned to receive memantine 5mg twice daily for 1week, followed by 10mg twice daily plus gabapentin 300 mg daily (n = 72) or just gabapentin 300mg daily (n = 71) for 8weeks. The DN4 questionnaire, monofilament, tuning fork, and Tip-therm tests were used to measure neuropathy at baseline and after the 8-week intervention. The mean score of the DN4 questionnaire in the memantine group was significantly lower than the control group (p. value: .001). The number of patients with diabetic neuropathy remarkably decreased in the memantine group at the end of the study based on the performed tests (p. value: .001). Memantine functions as a beneficial agent in the management of diabetic neuropathy, which would significantly improve the quality of life in diabetic patients.

Nerve conduction parameters and its correlations with glycemic control and duration in type 2 diabetes mellitus − A cross-sectional study

Background: Diabetic neuropathy is one of the most common microvascular complications of diabetes mellitus (DM) and can lead to a wide array of complications, which are concerning as these are considered a leading cause of disability due to foot ulceration, amputation, gait disturbances, and injuries secondary to falls. Nerve conduction studies (NCS) enable the diagnosis of sensory and motor neuropathy even if the dysfunction is subclinical. This study was conducted to assess the correlation between glycated hemoglobin and duration of diabetes with the parameters of NCS among patients of type 2 DM. Methodology: A cross-sectional study was conducted in a tertiary care center in South India. The study was conducted from November 2022 to February 2023. Sixty patients with type 2 DM who presented to the outpatient department with symptoms of neuropathy were included in the study. Detailed clinical history was taken and clinical examination was done. NCS was conducted in them. The parameters of NCS were correlated with HbA1c and duration of diabetes. The statistical analysis was carried out using the SPSS software version 29.0. Results: Sixty patients with type 2 DM were included in the study. The mean age of type 2 DM patients was 60.92 ± 10.9 years. The mean duration of type 2 DM (in years) was 12.8 ± 6.5. Twenty-three participants (38.3%) had solely an axonal pattern of diabetic neuropathy; whereas 20 (33.3%) participants showed a combined axonal and demyelinating pattern of diabetic neuropathy. There was a significant negative correlation between HbA1c and NCS parameters such as nerve conduction velocity, amplitude, and persistence (p < 0.001); and a significant positive correlation between HbA1c and NCS parameters such as latency and F-wave latency (p < 0.001). There was a significant correlation between parameters of NCSs and duration of DM (p < 0.001). Conclusion: Glycemic control and duration of DM have a significant impact on the nerve conduction parameters. Patients with poor glycemic control have decreased NCS parameters such as velocity, amplitude, and persistence; and increased parameters such as latency and F-wave latency. Strict glycemic control can be reinforced for better management of diabetic neuropathy.

Issues and challenges in diabetic neuropathy management: A narrative review.

Diabetic neuropathy (DN) is a devastating disorder with an increasing prevalence globally. This epidemic can pose a critical burden on individuals and com-munities, subsequently affecting the productivity and economic output of a country. With more people living a sedentary lifestyle, the incidence of DN is escalating worldwide. Many researchers have relentlessly worked on ways to combat this devastating disease. Their efforts have given rise to a number of commercially available therapies that can alleviate the symptoms of DN. Unfortunately, most of these therapies are only partially effective. Worse still, some are associated with unfavorable side effects. This narrative review aims to highlight current issues and challenges in the management of DN, especially from the perspective of molecular mechanisms that lead to its progression, with the hope of providing future direction in the management of DN. To improve the approaches to diabetic management, the suggested resolutions in the literature are also discussed in this review. This review will provide an in-depth understanding of the causative mechanisms of DN, apart from the insights to improve the quality and strategic approaches to DN management.

Synergistic role of resveratrol and exercise training in management of diabetic neuropathy and myopathy via SIRT1/NGF/GAP43 linkage

AimsOxidative stress also plays an important role in the pathogenesis of diabetic neuropathy (DN). Both resveratrol (RES) and exercise (EX) have potent anti-oxidative benefits. Low levels of nerve growth factor (NGF) and SIRT1 (a member of sirtuin family) have been reported in patients with DN. The current study has been designed to investigate the role of serum NGF and SIRT1 on DN-induced hyperalgesia and motor incoordination and to evaluate the possible protective role of RES and/or EX. Main methodsA total of 40 male adult albino rats divided into five groups; control, DN, DN + RES, DN + EX, and DN + RES and EX. DN was confirmed by sensorimotor disturbance and diminished nerve conduction velocity (NCV). NGF and SIRT1 levels were measured by western blot. Calcitonin gene-related peptide (CGRP) was measured by PCR. Myofibrillar degeneration and inflammation scores were revealed via H&E microscopic analysis of the gastrocnemius muscle. Immunohistochemical evaluation of caspase3 and TNF-α was performed in the lumber segment of spinal cord and gastrocnemius muscle sections. Ultrastructural evaluation of sciatic nerve axonal degeneration has also been assessed. Key findingsDN group showed decreased SIRT1 level, decreased NGF level and correlated with CGRP level and Na+/K+ ATPase. Treatment with RES and/or EX resulted in improvement of sensorimotor disturbance. DN characterized by reduced SOD level, whereas RES and/or EX could limit oxidative damage by up-regulation Bcl2, Akt and GAP-43 and down-regulation of caspase3 and TNF-α. In conclusion, increased level of SIRT1and NGF by incorporation of RES (natural supplementation) and EX (life style modification) could improve the neuroinflammatory state in DN.

Role of yoga therapy in the management of diabetic neuropathy: a review article

Background: Autonomic Diabetic Neuropathy, the most frequent diabetic consequence, is commonly treated with medicines without success. Diabetes is a chronic disease due to insulin resistance or reduced insulin secretion, India is known as the "diabetic world capital," with a projected growth of 63 %, exceeding 98 million by 2030. The latest diabetes mellitus statistics are worrying, stating that around 150 million individuals globally have diabetes mellitus, with this number expected to doubling by 2025 Objective: The purpose of the study was to conduct a review on role of Yoga in the management of Autonomic Diabetic Neuropathy. Method: A review was conducted using search terms Autonomic Diabetic Neuropathy and Yoga, Autonomic Diabetic Neuropathy and Alternative Therapy, Diabetic Autonomic Neuropathy and Yoga, Diabetic Autonomic Neuropathy and Alternative Therapy, Diabetic Neuropathy and Yoga, Diabetic Neuropathy and Alternative therapy and all the probable term in national and international data repositories such as PubMed, google scholar, in English language. Only 5 studies are selected out of 1493. For this Review article Literature Searched from starting to till April 2022. Conclusion: Studies showing clinical significance of Yoga in the management of Diabetic Neuropathy, but studies are less available and also lack of quality study. New Researchers should create more original evidences by conducting Randomized Controlled Trials in the large sample size.

ViphyllinTM, a Standardized Black Pepper Extract Exerts Antihyperglycemic Effect and Improves Sciatic Nerve Conduction in High Fat Diet/Streptozotocin-Induced Diabetic Model Rats.

PurposeResearch on plant-based formulations has drawn considerable attention in the management of diabetic neuropathy (DN) for having lesser side effects than the synthetic counterparts. Here, we have investigated for the first time the therapeutic effects of a standardized Piper nigrum L., (black pepper) seed extract, ViphyllinTM in mitigating hyperglycemia and neuropathic pain of type 2 diabetes model rats.MethodsType 2 diabetes was induced in male Wistar rats using high fat diet and a single dose of streptozotocin (60 mg/kg i.p.). The diabetic rats were orally administered with Viphyllin containing not less than 30% β-caryophyllene (BCP), at 25 mg, 50 mg and 100 mg/kg/day doses for 6 weeks. Changes in body weight, fasting blood glucose (FBG), glucose tolerance, and blood biochemical parameters were measured. The nociceptive response to thermal stimulus (tail flick test) and sciatic nerve conduction velocity (NCV) were recorded at the end of study.ResultsViphyllin treatment markedly improved the body weight and glucose tolerance in diabetic rats. Also, the extract could significantly reduce the diabetes-induced elevation in FBG, liver and kidney indices. Further, Viphyllin dose-dependently increased the nociception latency in tail flick test compared to untreated diabetic rats (p<0.05). Viphyllin at 100 mg/kg significantly increased the NCV (44.12±1.91*** m/s vs diabetic control 25.80±1.88 m/s). The antioxidant enzyme activities in sciatic nerve tissue were considerably increased in Viphyllin-treated groups compared to diabetic control. A 6-week treatment with Viphyllin markedly reversed the pathological manifestations of diabetes in vital organs such as liver, kidney and pancreas.ConclusionThe study concludes that Viphyllin exerts antidiabetic effects and improves nerve conduction to mitigate neuropathic pain.

Transdermal Delivery of Capsaicin Nanoemulgel: Optimization, Skin Permeation and In Vivo Activity against Diabetic Neuropathy.

Purpose: Diabetic somatic neuropathy is one of the most prevalent complications in type 1 diabetes mellitus (T1D). Many treatments were investigated to alleviate the pain associated with this condition. Capsaicin is a naturally occurring lipophilic alkaloid that proved to be an effective and safe treatment of chronic painful disorders. Despite the known therapeutic benefits of capsaicin, the conventional topical formulations have limited bioavailability. Therefore, the current study aims to develop capsaicin nanoemulgel to increase skin permeation and enhance its activity against neuropathic pain. Methods: Low-energy emulsification method was used to prepare nanoemulsions, using eucalyptus oil as the oily phase, Tween 80 as a surfactant, propylene glycol, ethanol and isopropyl alcohol as co-surfactants. Pseudo-ternary phase diagrams were constructed to investigate and optimize the formulation. Subsequently, the optimum formulation was formulated as a nanoemulgel and investigated for, skin permeation using Franz diffusion cell, and diabetic neuropathy (DN) management using alloxan-induced diabetic mice. Results: The selected nanoemulsion containing 0.05% capsaicin is composed of 8 % oil, 24 % S mix (Tween 80: isopropyl alcohol 2:1 w/w) and 68 % water. It is characterized by nanosized globules (28.15 ± 0.24 nm) with a relatively low polydispersity index (0.27 ± 0.05). The nanoemulgel revealed circa 4-fold increase in capsaicin cumulative permeation when compared to the conventional gel, and an improvement in its antinociceptive properties was observed in the treated diabetic mice (P < 0.05). Conclusion: The selected capsaicin nanoemulgel would be a promising transdermal formulation that may alleviate diabetic neuropathy in T1D patients.

A NOBEL APPROACH OF DIABETIC NEUROPATHY & ITS MANAGEMENT THROUGH AYURVEDA

Diabetes mellitus vis a vis Madhumeha is a multi-factorial metabolic disorder of the 21st century. It is caused by an absolute or a relative lack of insulin. Its manifestations include hyperglycemia, other metabolic derangements, and long-term damage to blood vessels, eyes, nerves, kidneys, and the heart. It is a leading cause of cardiac death, nonfatal MI, heart failure and stroke. It is also the most common cause of adult blindness, end-stage renal disease, non-traumatic leg amputation and neuropathy. Diabetes mellitus is one of the oldest diseases recognized since antiquity. It is amazing that 7 century B.C. Ayurvedic texts like Charaka and Sushruta Samhita have been described high caloric diet and sedentary habits as an important causative factor of Apathyanitmittaja Prameha and genetic/hereditary factors described as Sahaja Prameha. Besides this, more profound Ayurveda have been mentioned different complications of Madhumeha. These two types of diabetics have been described to be treated on two different lines of management. Its aetiopathogenesis, clinical presentation, complications as well as treatment modalities, appear well comparable to the latest knowledge of conventional medicine. Thus, the present concept will be providing a new outlook about the understanding of aetiopathogenesis and as well management of Diabetic neuropathy. Keywords: Ayurveda, Preameha, Madhumeha, Diabetes mellitus, diabetic neuropathy

Therapeutic Potential of Polyphenols in the Management of Diabetic Neuropathy.

Diabetic neuropathy (DN) is a common and serious diabetes-associated complication that primarily takes place because of neuronal dysfunction in patients with diabetes. Use of current therapeutic agents in DN treatment is quite challenging because of their severe adverse effects. Therefore, there is an increased need of identifying new safe and effective therapeutic agents. DN complications are associated with poor glycemic control and metabolic imbalances, primarily oxidative stress (OS) and inflammation. Various mediators and signaling pathways such as glutamate pathway, activation of channels, trophic factors, inflammation, OS, advanced glycation end products, and polyol pathway have a significant contribution to the progression and pathogenesis of DN. It has been indicated that polyphenols have the potential to affect DN pathogenesis and could be used as potential alternative therapy. Several polyphenols including kolaviron, resveratrol, naringenin, quercetin, kaempferol, and curcumin have been administered in patients with DN. Furthermore, chlorogenic acid can provide protection against glutamate neurotoxicity via its hydrolysate, caffeoyl acid group, and caffeic acid through regulating the entry of calcium into neurons. Epigallocatechin-3-gallate treatment can protect motor neurons by regulating the glutamate level. It has been demonstrated that these polyphenols can be promising in combating DN-associated damaging pathways. In this article, we have summarized DN-associated metabolic pathways and clinical manifestations. Finally, we have also focused on the roles of polyphenols in the treatment of DN.

Quercetin Attenuates Diabetic Peripheral Neuropathy by Correcting Mitochondrial Abnormality via Activation of AMPK/PGC-1α Pathway in vivo and in vitro.

The AMPK/PGC-1α pathway-mediated mitochondrial dysfunction has been supposed to play a crucial role in pathogenesis of diabetic peripheral neuropathy (DPN). The present study investigated the neuroprotective potential of quercetin, a natural AMPK activator. Streptozotocin (STZ)-induced diabetic rats that developed DPN phenotype were orally administrated with quercetin (30 and 60 mg/kg per day) for 6 weeks. The morphologic changes in the sciatic nerves (SN), the pathological structure of neurons in dorsal root ganglion (DRG), and the expressions of myelin proteins were assessed. The ATP content and the mitochondrial ultrastructure were measured. Furthermore, key proteins in the AMPK/PGC-1α pathway were determined. As a result, quercetin administration at both doses improved the paw withdrawal threshold, nerve conduction velocity, and the pathologic changes in SN and DRG of DPN rats. The expressions of myelin basic protein and myelin protein zero were also increased by quercetin. The oxidative stress, decreased ATP generation, and morphological changes of mitochondria were corrected by quercetin. In vitro study found that quercetin treatment significantly decreased the high-glucose-induced generation of reactive oxygen species, as well as attenuated the mitochondrial morphologic injuries and oxidative DNA damages of RSC96 cells. Quercetin treatment promoted the expressions of phosphorylated AMPK, PGC-1α, SIRT1, NRF1, and TFAM under hyperglycemic state in vivo and in vitro. This study revealed that the neuroprotective effect of quercetin was mainly related to mitochondrial protection by activation of the AMPK/PGC-1α pathway for the first time and proved quercetin as a potential therapeutic agent in the management of diabetic neuropathy.

Evaluation in Diagnosis and Management of Diabetic Neuropathy

Evaluation in Diagnosis and Management of Diabetic Neuropathy