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Journal of Diabetes Investigation Sep 2017Peripheral neuropathy is a major cause of disability worldwide. Diabetes is the most common cause of neuropathy, accounting for 50% of cases. Over half of people with... (Review)
Review
Peripheral neuropathy is a major cause of disability worldwide. Diabetes is the most common cause of neuropathy, accounting for 50% of cases. Over half of people with diabetes develop neuropathy, and diabetic peripheral neuropathy (DPN) is a major cause of reduced quality of life due to pain, sensory loss, gait instability, fall-related injury, and foot ulceration and amputation. Most patients with non-diabetic neuropathy have cryptogenic sensory peripheral neuropathy (CSPN). A growing body of literature links prediabetes, obesity and metabolic syndrome to the risk of both DPN and CSPN. This association might be particularly strong in type 2 diabetes patients. There are no effective medical treatments for CSPN or DPN, and aggressive glycemic control is an effective approach to neuropathy risk reduction only in type 1 diabetes. Several studies suggest lifestyle-based treatments that integrate dietary counseling with exercise might be a promising therapeutic approach to early DPN in type 2 diabetes and CSPN associated with prediabetes, obesity and metabolic syndrome.
Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Metabolic Syndrome; Prediabetic State; Risk Factors
PubMed: 28267267
DOI: 10.1111/jdi.12650 -
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 -
Diabetes & Vascular Disease Research 2023Diabetes patients frequently experience diabetic neuropathy (DN), a microvascular complication that significantly reduces patients' quality of life. Memantine has... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
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).
METHOD
This randomized clinical trial includes 143 diabetic patients (aged between 18 and 75 years) with a confirmed diagnosis of diabetic neuropathy. Patients were randomly assigned to receive memantine 5 mg twice daily for 1 week, followed by 10 mg twice daily plus gabapentin 300 mg daily ( = 72) or just gabapentin 300 mg daily ( = 71) for 8 weeks. The DN4 questionnaire, monofilament, tuning fork, and Tip-therm tests were used to measure neuropathy at baseline and after the 8-week intervention.
RESULTS
The mean score of the DN4 questionnaire in the memantine group was significantly lower than the control group (. 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 (. value: .001).
CONCLUSION
Memantine functions as a beneficial agent in the management of diabetic neuropathy, which would significantly improve the quality of life in diabetic patients.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Diabetic Neuropathies; Gabapentin; Memantine; Diabetes Mellitus, Type 2; Quality of Life
PubMed: 37495223
DOI: 10.1177/14791641231191093 -
JPMA. the Journal of the Pakistan... Aug 2022Pruritis is a common symptom of many systemic and cutaneous localized diseases and diabetes mellitus is a common syndrome with multiple long term complications,...
Pruritis is a common symptom of many systemic and cutaneous localized diseases and diabetes mellitus is a common syndrome with multiple long term complications, including diabetic painful neuropathy. The involvement of small fibre neurons, in diabetic neuropathy, is recognized as the main pathophysiology. While the C fibres that mediate the sensation of pain and pruritus may belong to different neuronal circuits, there is evidence of cross talk between them. We therefore posit that pruritus may be a symptom of diabetic neuropathy. It should be viewed as an equivalent of microvascular disease, with its accompanying clinical significance and therapeutic implications.
Topics: Humans; Diabetic Neuropathies; Pruritus; Pain; Diabetes Mellitus
PubMed: 36280941
DOI: 10.47391/JPMA.22-85 -
Current Diabetes Reviews 2022Animal models have been widely used to investigate the etiology and potential treatments for diabetic peripheral neuropathy. What we have learned from these studies and... (Review)
Review
INTRODUCTION
Animal models have been widely used to investigate the etiology and potential treatments for diabetic peripheral neuropathy. What we have learned from these studies and the extent to which this information has been adapted for the human condition will be the subject of this review article.
METHODS
A comprehensive search of the PubMed database was performed, and relevant articles on the topic were included in this review.
RESULTS
Extensive study of diabetic animal models has shown that the etiology of diabetic peripheral neuropathy is complex, with multiple mechanisms affecting neurons, Schwann cells, and the microvasculature, which contribute to the phenotypic nature of this most common complication of diabetes. Moreover, animal studies have demonstrated that the mechanisms related to peripheral neuropathy occurring in type 1 and type 2 diabetes are likely different, with hyperglycemia being the primary factor for neuropathology in type 1 diabetes, which contributes to a lesser extent in type 2 diabetes, whereas insulin resistance, hyperlipidemia, and other factors may have a greater role. Two of the earliest mechanisms described from animal studies as a cause for diabetic peripheral neuropathy were the activation of the aldose reductase pathway and increased non-enzymatic glycation. However, continuing research has identified numerous other potential factors that may contribute to diabetic peripheral neuropathy, including oxidative and inflammatory stress, dysregulation of protein kinase C and hexosamine pathways, and decreased neurotrophic support. In addition, recent studies have demonstrated that peripheral neuropathy-like symptoms are present in animal models, representing pre-diabetes in the absence of hyperglycemia.
CONCLUSION
This complexity complicates the successful treatment of diabetic peripheral neuropathy, and results in the poor outcome of translating successful treatments from animal studies to human clinical trials.
Topics: Animals; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Hyperglycemia; Models, Animal
PubMed: 33949936
DOI: 10.2174/1573399817666210504101609 -
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 -
Biomedicine & Pharmacotherapy =... Jan 2022Diabetes has become more common in recent years worldwide, and this growth is projected to continue in the future. The primary concern with diabetes is developing... (Review)
Review
Diabetes has become more common in recent years worldwide, and this growth is projected to continue in the future. The primary concern with diabetes is developing various complications, which significantly contribute to the disease's mortality and morbidity. Over time, the condition progresses from the pre-diabetic to the diabetic stage and then to the development of complications. Years and enormous resources are required to evaluate pharmacological interventions to prevent or delay the progression of disease or complications in humans. Appropriate screening models are required to gain a better understanding of both pathogenesis and potential therapeutic agents. Different species of animals are used to evaluate the pharmacological potentials and study the pathogenesis of the disease. Animal models are essential for research because they represent most of the structural, functional, and biochemical characteristics of human diseases. An ideal screening model should mimic the pathogenesis of the disease with identifiable characteristics. A thorough understanding of animal models is required for the experimental design to select an appropriate model. Each animal model has certain advantages and limitations. The present manuscript describes the animal models and their diagnostic characteristics to evaluate microvascular diabetic complications.
Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Disease Progression; Humans; Species Specificity
PubMed: 34872802
DOI: 10.1016/j.biopha.2021.112305 -
Communications Biology Dec 2021Diabetic neuropathy is one of the most prevalent chronic complications of diabetes, and up to half of diabetic patients will develop diabetic neuropathy during their... (Review)
Review
Diabetic neuropathy is one of the most prevalent chronic complications of diabetes, and up to half of diabetic patients will develop diabetic neuropathy during their disease course. Notably, emerging evidence suggests that glycemic variability is associated with the pathogenesis of diabetic complications and has emerged as a possible independent risk factor for diabetic neuropathy. In this review, we describe the commonly used metrics for evaluating glycemic variability in clinical practice and summarize the role and related mechanisms of glycemic variability in diabetic neuropathy, including cardiovascular autonomic neuropathy, diabetic peripheral neuropathy and cognitive impairment. In addition, we also address the potential pharmacological and non-pharmacological treatment methods for diabetic neuropathy, aiming to provide ideas for the treatment of diabetic neuropathy.
Topics: Blood Glucose; Diabetic Neuropathies; Humans
PubMed: 34876671
DOI: 10.1038/s42003-021-02896-3 -
Wiener Klinische Wochenschrift Jan 2023These are the guidelines for diagnosis and treatment of diabetic neuropathy and diabetic foot.The position statement summarizes characteristic clinical symptoms and...
These are the guidelines for diagnosis and treatment of diabetic neuropathy and diabetic foot.The position statement summarizes characteristic clinical symptoms and techniques for diagnostic assessment of diabetic neuropathy, including the complex situation of the diabetic foot syndrome. Recommendations for the therapeutic management of diabetic neuropathy, especially for the control of pain in sensorimotor neuropathy, are provided. The needs to prevent and treat diabetic foot syndrome are summarized.
Topics: Humans; Diabetic Neuropathies; Diabetic Foot; Pain; Syndrome; Diabetes Mellitus
PubMed: 37101039
DOI: 10.1007/s00508-023-02167-7 -
Diabetes Care Oct 2022Different waveforms of spinal cord stimulation (SCS) have now been evaluated for the management of painful diabetic neuropathy (PDN). However, no direct or indirect... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Different waveforms of spinal cord stimulation (SCS) have now been evaluated for the management of painful diabetic neuropathy (PDN). However, no direct or indirect comparison between SCS waveforms has been performed to date.
PURPOSE
To conduct a systematic review and network meta-analysis to evaluate the effectiveness of SCS for PDN.
DATA SOURCES
MEDLINE, CENTRAL, Embase, and WikiStim were searched from inception until December 2021.
STUDY SELECTION
Randomized controlled trials (RCTs) of SCS for PDN were included.
DATA EXTRACTION
Pain intensity, proportion of patients achieving at least a 50% reduction in pain intensity, and health-related quality of life (HRQoL) data were extracted.
DATA SYNTHESIS
Significant reductions in pain intensity were observed for low-frequency SCS (LF-SCS) (mean difference [MD] -3.13 [95% CI -4.19 to -2.08], moderate certainty) and high-frequency SCS (HF-SCS) (MD -5.20 [95% CI -5.77 to -4.63], moderate certainty) compared with conventional medical management (CMM) alone. There was a significantly greater reduction in pain intensity on HF-SCS compared with LF-SCS (MD -2.07 [95% CI -3.26 to -0.87], moderate certainty). Significant differences were observed for LF-SCS and HF-SCS compared with CMM for the outcomes proportion of patients with at least 50% pain reduction and HRQoL (very low to moderate certainty). No significant differences were observed between LF-SCS and HF-SCS (very low to moderate certainty).
LIMITATIONS
Limited number of RCTs and no head-to-head RCTs conducted.
CONCLUSIONS
Our findings confirm the pain relief and HRQoL benefits of the addition of SCS to CMM for patients with PDN. However, in the absence of head-to-head RCT evidence, the relative benefits of HF-SCS compared with LF-SCS for patients with PDN remain uncertain.
Topics: Diabetes Mellitus; Diabetic Neuropathies; Humans; Network Meta-Analysis; Pain; Pain Measurement; Spinal Cord Stimulation
PubMed: 36150057
DOI: 10.2337/dc22-0932