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Vascular Pharmacology Apr 2022Diabetic neuropathy (DN) encompasses a group of clinical or subclinical manifestations involving a dysfunction in the peripheral nervous system. The cause of the... (Review)
Review
Diabetic neuropathy (DN) encompasses a group of clinical or subclinical manifestations involving a dysfunction in the peripheral nervous system. The cause of the dysfunction is the development of microvascular complications related to diabetes, a disease that affects about 381 million people worldwide. Approximately 50% of patients currently diagnosed with diabetes are expected to manifest DN in the next 10 years. The diagnosis can be made clinically by establishing a good patient history and delving into the symptoms to rule out other etiologies. Treatment of DN focuses on glycemic control and the use of medications to reduce pain, including NSAIDs, antidepressants and antiepileptic drugs. The pathogenesis is of multifactorial origin, associated with various metabolic, vascular, inflammatory and neurodegenerative disorders. The three fundamental cellular alterations participating in the development of DN are chronic inflammation, endothelial dysfunction and oxidative stress. Since the combination of all three is capable of giving rise to nerve ischemia and direct axonal injury, these factors play a key role in the development of polyneuropathy. However, neuronal and microvascular changes do not occur in the same way in all patients with DN, some of whom have no detectable blood abnormalities.
Topics: Diabetes Mellitus; Diabetic Neuropathies; Humans; Inflammation; Oxidative Stress
PubMed: 35063655
DOI: 10.1016/j.vph.2022.106954 -
Stem Cells Translational Medicine Apr 2023Diabetic neuropathy is a major complication of diabetes mellitus that occurs during the early stages of the disease. Many pathogenic mechanisms are related and induced...
Diabetic neuropathy is a major complication of diabetes mellitus that occurs during the early stages of the disease. Many pathogenic mechanisms are related and induced by hyperglycemia. However, even if these factors improve, diabetic neuropathy cannot go into remission and progresses slowly. Furthermore, diabetic neuropathy often progresses even with proper glycemic control. Recently, bone marrow-derived cells (BMDCs) were reported to be involved in the pathogenesis of diabetic neuropathy. BMDCs expressing proinsulin and TNFα migrate to the dorsal root ganglion and fuse with neurons, and this neuronal-hematopoietic cell fusion induces neuronal dysfunction and apoptosis. The CD106-positive lineage-sca1+c-kit+ (LSK) stem cell fraction in the bone marrow is strongly involved in cell fusion with neurons, leading to diabetic neuropathy. Surprisingly, when CD106-positive LSK stem cells obtained from diabetic mice were transplanted into nondiabetic mice, they fused with dorsal root ganglion neurons and induced neuropathy in non-hyperglycemic normal mice. The transplanted CD106-positive LSK fraction inherited the trait even after transplantation; this "progeny effect" may explain the irreversibility of diabetic neuropathy and is a significant finding for determining the target of radical treatments and provides new directions for developing therapeutic methods for diabetic neuropathy.
Topics: Mice; Animals; Bone Marrow Transplantation; Diabetic Neuropathies; Bone Marrow Cells; Diabetes Mellitus, Experimental; Cell Fusion; Neurons; Hematopoietic Stem Cell Transplantation; Mice, Inbred C57BL
PubMed: 36976582
DOI: 10.1093/stcltm/szad015 -
Frontiers in Endocrinology 2023
Topics: Humans; Diabetic Neuropathies; Metformin; Diabetes Mellitus
PubMed: 37396189
DOI: 10.3389/fendo.2023.1228101 -
Clinical Autonomic Research : Official... Aug 2019Diabetic neuropathy is a common and disabling disorder, and there are currently no proven effective disease-modifying treatments. Physical activity and dietary... (Review)
Review
PURPOSE
Diabetic neuropathy is a common and disabling disorder, and there are currently no proven effective disease-modifying treatments. Physical activity and dietary interventions in patients with diabetes and diabetic neuropathy have multiple beneficial effects and are generally low risk, which makes lifestyle interventions an attractive treatment option. We reviewed the literature on the effects of physical activity and dietary interventions on length-dependent peripheral neuropathy and cardiac autonomic neuropathy in diabetes.
METHODS
The electronic database PubMed was systematically searched for original human and mouse model studies examining the effect of either dietary or physical activity interventions in subjects with diabetes, prediabetes, or metabolic syndrome.
RESULTS
Twenty studies are included in this review. Fourteen studies were human studies and six were in mice. Studies were generally small with few controlled trials, and there are no widely agreed upon outcome measures.
CONCLUSIONS
Recent research indicates that dietary interventions are effective in modifying diabetic neuropathy in animal models, and there are promising data that they may also ameliorate diabetic neuropathy in humans. It has been known for some time that lifestyle interventions can prevent the development of diabetic neuropathy in type 2 diabetes mellitus subjects. However, there is emerging evidence that lifestyle interventions are effective in individuals with established diabetic neuropathy. In addition to the observed clinical value of lifestyle interventions, there is emerging evidence of effects on biochemical pathways that improve muscle function and affect other organ systems, including the peripheral nerve. However, data from randomized controlled trials are needed.
Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diet, Healthy; Exercise; Humans; Overweight; Risk Reduction Behavior
PubMed: 31076938
DOI: 10.1007/s10286-019-00607-x -
Oxidative Medicine and Cellular... 2020Diabetic neuropathy is one of the clinical syndromes characterized by pain and substantial morbidity primarily due to a lesion of the . The burden of diabetic neuropathy... (Review)
Review
Diabetic neuropathy is one of the clinical syndromes characterized by pain and substantial morbidity primarily due to a lesion of the . The burden of diabetic neuropathy is related not only to the complexity of diabetes but also to the poor outcomes and difficult treatment options. There is no specific treatment for diabetic neuropathy other than glycemic control and diligent foot care. Although various metabolic pathways are impaired in diabetic neuropathy, enhanced cellular oxidative stress is proposed as a common initiator. A mechanism-based treatment of diabetic neuropathy is challenging; a better understanding of the pathophysiology of diabetic neuropathy will help to develop strategies for the new and correct diagnostic procedures and personalized interventions. Thus, we review the current knowledge of the pathophysiology in diabetic neuropathy. We focus on discussing how the defects in metabolic and vascular pathways converge to enhance oxidative stress and how they produce the onset and progression of nerve injury present in diabetic neuropathy. We discuss if the mechanisms underlying neuropathy are similarly operated in type I and type II diabetes and the progression of antioxidants in treating diabetic neuropathy.
Topics: Diabetic Neuropathies; Humans; Oxidative Stress; Reactive Oxygen Species
PubMed: 32832011
DOI: 10.1155/2020/9524635 -
Acta Neurologica Belgica Jun 2023Research suggests that diabetic peripheral neuropathy (DPN) is related to high serum uric acid (SUA) level, although its correlation with low SUA level has not been... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVES
Research suggests that diabetic peripheral neuropathy (DPN) is related to high serum uric acid (SUA) level, although its correlation with low SUA level has not been reported. Here, diabetic patients with hyperuricemia were excluded, and the correlation between low SUA level and DPN was explored.
SUBJECTS AND METHODS
This prospective observational clinical study enrolled 525 type 2 diabetes mellitus (T2DM) patients without hyperuricemia, who were divided into the diabetes with symptomatic neuropathy (150 cases), diabetes with asymptomatic neuropathy (125 cases) and diabetes with no neuropathy (250 cases) groups.
RESULTS
The SUA slightly decreased in subjects with asymptomatic DPN compared with those with no neuropathy and greatly decreased in subjects with symptomatic DPN compared with those without (P < 0.001). The association of the SUA with diabetic neuropathy was independent of the hyperglycemic state and other potential confounders (odds ratio 0.985 [0.981-0.988], P < 0.001). The SUA was closely correlated with the means of motor/sensory nerve amplitude and CV (all P < 0.001). The optimal cut-off point for SUA to distinguish patients with diabetic neuropathy from those without was 324 umol/L, with a sensitivity of 76.0% and a specificity of 79.2% (AUC = 0.806).
CONCLUSIONS
The low SUA level is closely associated with DPN. Future studies are warranted to clarify the relationship.
Topics: Humans; Diabetes Mellitus, Type 2; Uric Acid; Diabetic Neuropathies; Hyperuricemia; Risk Factors
PubMed: 35643885
DOI: 10.1007/s13760-022-01978-1 -
Wiener Klinische Wochenschrift May 2019These are the guidelines for diagnosis and treatment of diabetic neuropathy and diabetic foot. Diabetic neuropathy comprises a number of mono- and polyneuropathies,... (Review)
Review
These are the guidelines for diagnosis and treatment of diabetic neuropathy and diabetic foot. Diabetic neuropathy comprises a number of mono- and polyneuropathies, plexopathies, radiculopathies and autonomic neuropathy.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: Diabetic Foot; Diabetic Neuropathies; Diagnostic Techniques, Neurological; Humans; Neurologic Examination; Pain; Pain Management; Practice Guidelines as Topic; Syndrome
PubMed: 30980143
DOI: 10.1007/s00508-019-1487-4 -
International Review of Neurobiology 2016Neuropathy is the earliest and commonest complication of diabetes. With increasing duration of diabetes, frequency and severity of neuropathy are worsened. Long-term... (Review)
Review
Neuropathy is the earliest and commonest complication of diabetes. With increasing duration of diabetes, frequency and severity of neuropathy are worsened. Long-term hyperglycemia is therefore implicated in the development of this disorder. Nerve tissues require glucose energy to function and survive. Upon excessive glucose entry into the peripheral nerve, the glycolytic pathway and collateral glucose-utilizing pathways are overactivated and initiate adverse effects on nerve tissues. During hyperglycemia, flux through the polyol pathway, formation of advanced glycation end-products, production of free radicals, flux into the glucosamine pathway, and protein kinase C activity are all enhanced to negatively influence nerve function and structure. Suppression of these aberrant metabolic pathways has succeeded in prevention and inhibition of the development of neuropathy in animal models with diabetes. Satisfactory results were not attained, however, in patients with diabetes and further clinical trials are required. In this review, the author summarizes the hitherto proposed theories on the pathogenesis of diabetic neuropathy related to glucose metabolism and future prospects for the effective treatment of neuropathy.
Topics: Animals; Diabetic Neuropathies; Glucose; Humans; Oxidative Stress; Protein Kinase C
PubMed: 27133148
DOI: 10.1016/bs.irn.2016.03.006 -
Journal of Diabetes and Its... Oct 2021We conducted a systematic review of the literature with meta-analysis to determine whether painful diabetic neuropathy is associated with a specific inflammatory profile. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We conducted a systematic review of the literature with meta-analysis to determine whether painful diabetic neuropathy is associated with a specific inflammatory profile.
METHODS
The study is based on the PRISMA statement for systematic reviews. We performed a search of published studies up until January 2021 in MEDLINE and Web of Science based on heading and free text terms. The search strategy included the phrases: diabetic peripheral neuropathy, painful peripheral neuropathy individually and in combination with the terms: inflammation and inflammatory biomarkers. We screened titles and abstracts and performed data extraction. We also manually searched the article titles in the reference lists of key studies and reviews published in the last 20 years.
DATA EXTRACTION
Data extracted from the studies included study design, inclusion and exclusion criteria, sample type including serum and plasma, source of the sample including patients with peripheral diabetic neuropathy or patients with painful and painless neuropathy of any etiology. Blood concentrations of all measured cytokines were recorded. Whenever possible we calculated the effect size and confidence interval. Non-human studies were excluded from the meta-analysis.
RESULTS
Thirteen studies were included in this meta-analysis. The study design was cross-sectional, case control or cohort type studies. Specific inflammatory mediators are significantly higher in painful than in painless diabetic neuropathy as well as in painful neuropathies of any etiology. Markers of inflammation are also increased in those patients with diabetes mellitus, who suffer from peripheral neuropathy in comparison to patients with diabetes mellitus but no signs of peripheral neuropathy. A proinflammatory state may be the common denominator of pain and peripheral neuropathy in patients with diabetes mellitus but the inflammatory profiles seem to differ.
Topics: Biomarkers; Cross-Sectional Studies; Diabetes Mellitus; Diabetic Neuropathies; Humans; Inflammation; Pain; Peripheral Nervous System Diseases
PubMed: 34389235
DOI: 10.1016/j.jdiacomp.2021.108017 -
The Practitioner Mar 2017Diabetic neuropathy is thought to affect 1.9% of the world’s population and 50% of patients with a diagnosis of diabetes mellitus which would equate to 2.25 million... (Review)
Review
Diabetic neuropathy is thought to affect 1.9% of the world’s population and 50% of patients with a diagnosis of diabetes mellitus which would equate to 2.25 million people in the UK. The term diabetic neuropathy includes multiple distinct clinical entities that have been classified under the broad headings of focal and multifocal neuropathies and symmetrical neuropathies. Peripheral diabetic neuropathy, a chronic distal symmetrical predominantly sensory neuropathy, is the most common form of diabetic neuropathy. Most patients describe moderate to severe pain, using neuropathic descriptors such as burning, shooting or electric shocks. The common presentation is of painful symptoms originating in the feet, that then spread to the knees before involving the distal portion of the upper limbs in a ‘glove and stocking’ distribution. There are number of specific neuropathic pain assessment tools that can be readily used in a non-specialist setting in the community, such as the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) questionnaire. This combines five simple questions and two examination findings to give a dimensionless score for the pain out of 24, with a score ≥ 12 suggesting a neuropathic component is likely.
Topics: Diabetic Neuropathies; Humans
PubMed: 29139278
DOI: No ID Found