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International Journal of Molecular... Feb 2021Diabetic neuropathy is one of the most common complications of diabetes. This complication is peripheral neuropathy with predominant sensory impairment, and its symptoms... (Review)
Review
Diabetic neuropathy is one of the most common complications of diabetes. This complication is peripheral neuropathy with predominant sensory impairment, and its symptoms begin with hyperesthesia and pain and gradually become hypoesthesia with the loss of nerve fibers. In some cases, lower limb amputation occurs when hypoalgesia makes it impossible to be aware of trauma or mechanical stimuli. On the other hand, up to 50% of these complications are asymptomatic and tend to delay early detection. Therefore, sensitive and reliable biomarkers for diabetic neuropathy are needed for an early diagnosis of this condition. This review focuses on systemic biomarkers that may be useful at this time. It also describes research on the relationship between target gene polymorphisms and pathological conditions. Finally, we also introduce current information on regenerative therapy, which is expected to be a therapeutic approach when the pathological condition has progressed and nerve degeneration has been completed.
Topics: Animals; Biomarkers; Cytokines; Diabetic Neuropathies; Exosomes; Glyoxal; Humans; Inflammation; Lactoylglutathione Lyase; MicroRNAs; Nerve Fibers; Neurons; Polymorphism, Genetic; Pyruvaldehyde; Regenerative Medicine; Toll-Like Receptors
PubMed: 33669048
DOI: 10.3390/ijms22052301 -
The Korean Journal of Internal Medicine Sep 2020Neuropathy is the most prevalent microvascular complication of diabetes mellitus; it encompasses distal symmetric polyneuropathy, autonomic neuropathy, radiculoplexus... (Review)
Review
Neuropathy is the most prevalent microvascular complication of diabetes mellitus; it encompasses distal symmetric polyneuropathy, autonomic neuropathy, radiculoplexus neuropathy, mononeuropathy, and treatment-induced neuropathy. The prevalence rate of diabetic neuropathy in Korea was reported to be approximately 43%, which is similar to rates in other countries. However, the precise pathogenic mechanism underlying diabetic neuropathy is still obscure, and many clinical trials have failed to develop methods to prevent or reduce the progression of diabetic neuropathy. Nevertheless, early diagnosis and proper management of diabetic neuropathy are essential to alleviate disabling symptoms and to improve the quality of life of patients. This review discusses clinical manifestations and classification of diabetic neuropathies, bedside neurological examination, and electrophysiological tests.
Topics: Diabetes Mellitus; Diabetic Neuropathies; Humans; Prevalence; Quality of Life; Republic of Korea
PubMed: 32921007
DOI: 10.3904/kjim.2020.202 -
Irish Journal of Medical Science Feb 2023Diabetic foot neuropathy is one of the complications of diabetes that affects around 50% of diabetic people. Because peripheral neuropathy involves nerve loss around the...
BACKGROUND
Diabetic foot neuropathy is one of the complications of diabetes that affects around 50% of diabetic people. Because peripheral neuropathy involves nerve loss around the foot areas, patients with diabetic neuropathy frequently lose sensation in their feet while walking or standing. Furthermore, since sensory nerves are damaged, the area that holds the majority of the foot pressure and temperature is at high risk of injury. If not diagnosed and treated properly, it can cause foot injury and eventually lead to edema, gangrene, ulcers, amputation, and even death. There are now several techniques of detecting diabetic neuropathy, but they are limited in their availability, cost-effectiveness, and complexity.
AIMS
The primary goal of this research was to develop devices for early detection and treatment of diabetic foot neuropathy.
METHODS
The proposed device combines a foot pressure monitoring method and a foot temperature measurement method to diagnose diabetic neuropathy early on, with red light therapy added as a treatment method. For 2 weeks, the device measures the patient's foot pressure and temperature, and light therapy is provided if a change in pressure or temperature at a specific area is observed.
RESULTS
The device prototype was successfully developed, and numerous tests were carried out in accordance with the design specifications. For pressure measurement and temperature measurement, measurement accuracy of 99.05% and 99.30%, respectively, were attained.
CONCLUSION
The early detection and treatment device developed in this study could be used at home by diabetic patients as well as in hospitals to test for and treat diabetic foot neuropathy at an early stage. The device incorporates two different methods of diabetic foot neuropathy detection with high measurement accuracy which makes it suitable for use in resource-limited areas at low cost. The incorporation of red light therapy together with the two methods of diabetic neuropathy detection gives another unique feature for our device.
Topics: Humans; Diabetic Foot; Diabetic Neuropathies; Foot; Amputation, Surgical; Sensation; Diabetes Mellitus
PubMed: 35195847
DOI: 10.1007/s11845-022-02958-3 -
Journal of Clinical Pharmacy and... Oct 2021B vitamin therapy is a common treatment for diabetic pain and neuropathy, yet its use remains controversial in patients lacking B vitamin deficiencies. The aim of this... (Review)
Review
WHAT IS KNOWN AND OBJECTIVE
B vitamin therapy is a common treatment for diabetic pain and neuropathy, yet its use remains controversial in patients lacking B vitamin deficiencies. The aim of this review was to summarize the current evidence for the efficacy of B vitamin therapy in diabetic patients with neuropathy.
COMMENT
We screened the English literature for clinical studies evaluating B vitamins as a therapy for pain and neuropathy in diabetic patients. We selected 43 relevant studies for qualitative analysis based on our selection criteria. Our survey of the literature revealed substantive heterogeneity with respect to efficacies of reported outcomes, as well as study design. Most beneficial outcomes were reported against baseline measures, with few positive comparisons against placebo. This highlights the need for larger, placebo-controlled studies.
WHAT IS NEW AND CONCLUSION
B vitamins should be considered a plausible therapy for diabetic neuropathy, but its overall efficacy remains uncertain and requires further study.
Topics: Chronic Pain; Diabetic Neuropathies; Drug Combinations; Humans; Vitamin B Complex
PubMed: 33565138
DOI: 10.1111/jcpt.13375 -
Current Diabetes Reviews 2021Painful Diabetic Neuropathy (PDN) is a devastating condition affecting one in three people with diabetes. (Review)
Review
BACKGROUND
Painful Diabetic Neuropathy (PDN) is a devastating condition affecting one in three people with diabetes.
INTRODUCTION
Keeping in mind the unceasingly escalating prevalence of diabetes mellitus worldwide, the number of PDN patients is also expected to rise with a reduced quality of life in patients and a staggering increase in healthcare costs. Despite relentless efforts and continuous research, the commercially available medications for relieving diabetic neuropathy pain are only partially effective with substantial side effects. This is, in part, due to our partial awareness of the underlying complexities causing PDN. The pathogenesis of PDN remains elusive because of the difficulty in obtaining damaged nerve samples and the absence of non-invasive methods to investigate the pathogenesis at different stages of disease progression. The purpose of this review was to describe pathogenesis, clinical manifestations and treatment options for PDN.
METHODS
The keywords relevant to the scope of this paper were put in electronic databases (PubMed and Google Scholar) to fetch the relevant data. The data were then analyzed and compiled.
RESULTS
A simplified overview of PDN for researchers new to the field has been provided in an attempt to clarify common confusions. The changes in skin structure and functions in response to diabetes, diabetic neuropathy and painful diabetic neuropathy are also discussed. The unavailability of an efficacious pain reliever for PDN stresses on the need for identifying the microenvironmental factors that are altered in PDN and manipulate them to tailor targeted theranostics.
CONCLUSION
In the end, we proposed to consider the altered skin structure, function and microenvironmental factors in the diabetic population for devising smart, targeted, stimuli-responsive treatment options to attain maximum pain relief with minimum side effects.
Topics: Diabetes Mellitus; Diabetic Neuropathies; Humans; Pain; Pain Management; Quality of Life
PubMed: 33143631
DOI: 10.2174/1573399816666201103142521 -
Molecular Medicine (Cambridge, Mass.) Jul 2023Diabetic peripheral neuropathy (DPN) is a major complication of diabetes. This study aimed to investigate the therapeutic effects and molecular mechanisms of Compound...
BACKGROUND
Diabetic peripheral neuropathy (DPN) is a major complication of diabetes. This study aimed to investigate the therapeutic effects and molecular mechanisms of Compound Qiying Granules (CQYG) for DPN.
METHODS
Rats and RSC96 cells of DPN models were established to evaluate the therapeutic effects of CQYG. Then the morphology and apoptotic changes of sciatic nerves were detected. Further, tandem mass tag based quantitative proteomics technology was used to identify differentially expressed proteins (DEPs) and the underlying molecular mechanisms. Protein expression of key signaling pathways was also detected.
RESULTS
CQYG treatment significantly improved blood glucose and oxidative stress levels, and further reduced nerve fiber myelination lesions, denervation, and apoptosis in DPN rats. Further, 2176 DEPs were found in CQYG treated DPN rats. Enrichment analysis showed that protein processing in the endoplasmic reticulum (ER), and apoptosis were all inhibited after CQYG treatment. Next, CQYG treatment reduced inflammatory factor expression, mitochondrial damage, and apoptosis in RSC96 cells which induced by high glucose. Transmission electron microscopy results found that CQYG treatment improved the morphology of nerve myelin, mitochondria, and ER. CQYG treatment decreased ER stress and apoptosis pathway proteins that were highly expressed in DPN models. In addition, we also predicted the potential targets of CQYG in DEPs.
CONCLUSIONS
CQYG exerts neuroprotective effects in experimental diabetic neuropathy through anti-ER stress and anti-apoptosis.
Topics: Rats; Animals; Diabetic Neuropathies; Rats, Sprague-Dawley; Endoplasmic Reticulum Stress; Myelin Sheath; Signal Transduction; Sciatic Nerve; Diabetes Mellitus
PubMed: 37464341
DOI: 10.1186/s10020-023-00698-3 -
Diabetes & Metabolic Syndrome 2021Painful diabetic neuropathy significantly affects the quality of life in people with diabetic peripheral neuropathy (DPN). Existing pharmacological agents have limited... (Review)
Review
BACKGROUND AND AIMS
Painful diabetic neuropathy significantly affects the quality of life in people with diabetic peripheral neuropathy (DPN). Existing pharmacological agents have limited efficacy and development of tolerance is a limitation.
METHODS
The present review focuses on novel pharmacological (systemic and topical) and non-pharmacological modalities for the alleviation of pain in people with DPN. We identified English language articles concerning studies with novel agents (animal or human) targeting symptomatic relief of painful diabetic neuropathy.
RESULTS
Though the pathophysiology of pain in DPN is complex, a better understanding of pain pathways (peripheral and central) have helped to identify potential targets for therapeutic success. Studies of pharmacological agents acting on various aspects of pain pathways including μ-opioid receptor agonist- norepinephrine reuptake inhibitor (MONRI), cannabinoid receptor, dual serotonin-nor-adrenergic (SNRI)-and triple dopamine reuptake inhibitor (SNDRI), purinergic receptors and sodium channel v1.7 blockers have undergone trials in humans and shown to improve pain symptoms and quality of life in people with DPN. A few other investigational agents targeting acetylcholine receptor, vanilloid channel, chemokine signaling, micro-RNA or mesenchymal stem cell based therapies (animal studies) have demonstrated promise in alleviation of pain. Topical agents like high-dose lidocaine, capsaicin, clonidine, amitriptyline and ketamine may benefit refractory neuropathic pain.
CONCLUSIONS
Novel MONRI, SNRI and cannabinoid receptor agonists have shown some promise for neuropathic pain relief in human trials, but await regulatory approvals. However, most of the novel pharmacological agents (systemic or topical) require appropriately powered placebo-controlled studies for clinical usage in painful diabetic neuropathy.
Topics: Animals; Diabetic Neuropathies; Humans; Molecular Targeted Therapy
PubMed: 33484985
DOI: 10.1016/j.dsx.2021.01.004 -
Journal of Diabetes Investigation May 2022The most frequent diabetic complication, diabetic neuropathy, lacks accessible objective assessments. The concept and definition of diabetic neuropathy should be...
The most frequent diabetic complication, diabetic neuropathy, lacks accessible objective assessments. The concept and definition of diabetic neuropathy should be rethought to achieve the successful development of diagnostic and therapeutic methods.
Topics: Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Humans
PubMed: 35218156
DOI: 10.1111/jdi.13780 -
Current Diabetes Reviews 2017Diabetic neuropathy is a common complication of diabetes. It adversely affects the lives of most diabetics. It is the leading cause of non-traumatic limb amputation.... (Review)
Review
INTRODUCTION
Diabetic neuropathy is a common complication of diabetes. It adversely affects the lives of most diabetics. It is the leading cause of non-traumatic limb amputation. Diabetic autonomic neuropathy can target any system and increases morbidity and mortality. Treatment begins with adequate glycemic control but despite this, many patients go on to develop neuropathy which suggests there are additional and unidentified, as yet, pathological mechanisms in place. Although several theories exist, the exact mechanisms are not yet established. Disease modifying treatment requires a more complete understanding of the mechanisms of disease. Pathways Involved: This review discusses the potential pathological mechanisms of diabetic neuropathy, including the polyol pathway, hexosamine pathway, protein kinase C, advanced glycation end product formation, polyADP ribose polymerase, and the role of oxidative stress, inflammation, growth factors and lipid abnormalities. Finally it focuses on how possible changes in glutamate signaling pathways fit into the current theories.
CONCLUSION
Insights into the mechanisms involving gene expression in diabetic neuropathy can help pinpoint genes with altered expression. This will help in the development of novel alternative therapeutic strategies to significantly slow the progression of neuropathy in susceptible individuals and perhaps even prevention.
Topics: Animals; Diabetic Neuropathies; Glutamic Acid; Glycation End Products, Advanced; Hexosamines; Humans; Inflammation; Metabolic Networks and Pathways; Oxidative Stress; Polymers; Protein Kinase C
PubMed: 27341846
DOI: 10.2174/1573399812666160624122605 -
The Journal of Pharmacy and Pharmacology Jul 2020This review surveys current pharmacotherapies available for the treatment of diabetic peripheral neuropathy (DPN), emphasising their mechanisms of action. (Review)
Review
OBJECTIVES
This review surveys current pharmacotherapies available for the treatment of diabetic peripheral neuropathy (DPN), emphasising their mechanisms of action.
METHODS
A comprehensive literature review focusing on the 'pharmacotherapy and treatment of diabetic peripheral neuropathy' was conducted. The Database of International Pharmaceutical Abstracts, EMBASE, PubMed, OVID, Scopus, Google and Google Scholar were searched, and reference lists of relevant articles were also included.
KEY FINDINGS
Diabetic peripheral neuropathy is often inadequately treated, and the role of improving glycaemic control specifically in type-2 diabetes remains unclear. It is crucial to explore the mechanisms of action and effectiveness of available therapies. Major international clinical guidelines for the management of DPN recommend several symptomatic treatments. First-line therapies include tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, and anticonvulsants that act on calcium channels. Other therapies include opioids and topical agents such as capsaicin and lidocaine. The objectives of this paper are to review current guidelines for the pharmacological management of DPN and to discuss research relevant to the further development of pharmacological recommendations for the treatment of diabetic neuropathy.
SUMMARY
Diabetic neuropathy is a highly prevalent, disabling condition, the management of which is associated with significant costs. Evidence supports the use of specific anticonvulsants and antidepressants for pain management in patients with diabetic peripheral neuropathy. All current guidelines advise a personalised approach with a low-dose start that is tailored to the maximum response having the least side effects or adverse events.
Topics: Diabetic Neuropathies; Humans; Medication Therapy Management; Practice Guidelines as Topic
PubMed: 32067247
DOI: 10.1111/jphp.13241