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Neurologic Clinics May 2013Diabetic neuropathies consist of a variety of syndromes resulting from different types of damage to peripheral or cranial nerves. Although distal symmetric... (Review)
Review
Diabetic neuropathies consist of a variety of syndromes resulting from different types of damage to peripheral or cranial nerves. Although distal symmetric polyneuropathy is the most common type of diabetic neuropathy, many other subtypes have been defined since the 1800s, including proximal diabetic, truncal, cranial, median, and ulnar neuropathies. Various theories have been proposed for the pathogenesis of these neuropathies. The treatment of most requires tight and stable glycemic control. Spontaneous recovery is seen in most of these conditions with diabetic control. Immunotherapies have been tried in some of these conditions however are controversial.
Topics: Diabetes Mellitus; Diabetic Neuropathies; Humans; Phenotype; Polyneuropathies
PubMed: 23642718
DOI: 10.1016/j.ncl.2013.02.003 -
Annals of Medicine Feb 2000The incidence of diabetes and its complications is increasing to staggering proportions. Presently the WHO estimates an overall prevalence of 130 million, but by 2025... (Review)
Review
The incidence of diabetes and its complications is increasing to staggering proportions. Presently the WHO estimates an overall prevalence of 130 million, but by 2025 there will be 300 million individuals with diabetes mellitus. The incidence of diabetic neuropathy approaches 50% in most diabetic populations; there is no treatment, and its consequences in the form of foot ulceration and amputation are financially punishing for health care providers. Attempts to develop treatments have faltered for want of an understanding of the aetiology of diabetic neuropathy. As a consequence, 1999 saw the demise of two further compounds: recombinant growth factor by Roche-Genentech and the aldose reductase inhibitor zopolrestat, by Pfizer, both had reached phase III clinical trials. They joined an impressive list of at least 30 other compounds which have reached phase III clinical trials and failed to establish efficacy. The need to establish a viable treatment for human diabetic neuropathy is absolutely paramount. To provide a rational answer as to whether angiotensin-converting enzyme (ACE) inhibitors can prevent human diabetic neuropathy, two major issues need addressing: 1) Does vascular dysfunction cause human diabetic neuropathy? 2) Can ACE inhibitors ameliorate diabetic vascular dysfunction and hence neuropathy? Epidemiological studies support a strong association between neuropathy, retinopathy and nephropathy. Microangiopathy is deemed as the root cause of both nephropathy, and retinopathy and mounting evidence provides support for a vascular basis of diabetic neuropathy. ACE inhibitors appear to correct many of the abnormalities associated with the vascular dysfunction found in diabetes. Thus effective ACE inhibition impacts very positively on cardiovascular outcomes in patients with ischaemic heart disease, particularly in diabetic patients. ACE inhibition also prevents the development and progression of incipient and established diabetic nephropathy and delays progression of background retinopathy. Quinapril improves measures of diabetic autonomic neuropathy. Our recent study has demonstrated a significant improvement in peripheral neuropathy following 12 months of treatment with the ACE inhibitor trandolapril.
Topics: Angiotensin-Converting Enzyme Inhibitors; Clinical Trials as Topic; Diabetic Neuropathies; Disease Progression; Humans; Isoquinolines; Quinapril; Tetrahydroisoquinolines
PubMed: 10711571
DOI: 10.3109/07853890008995903 -
American Family Physician Dec 1996Diabetic neuropathy affects up to 60 percent of the estimated 13 million Americans who have diabetes mellitus. Foot and ankle complications are responsible for more... (Review)
Review
Diabetic neuropathy affects up to 60 percent of the estimated 13 million Americans who have diabetes mellitus. Foot and ankle complications are responsible for more hospital admissions than all other complications of diabetes mellitus combined. Neuropathy is more likely to affect patients who have higher degrees of hyperglycemia and a longer history of diabetes, and those who are older, taller and male. Diabetic neuropathy is usually diagnosed by the loss of ankle reflexes and distal vibratory sensation, but these signs may not always be present. Electromyography is useful in establishing a diagnosis. Treatment is directed toward alleviating the symptoms and correcting the underlying pathogenesis. Strict glycemic control is key in the ultimate prevention of diabetic neuropathy. The family physician can play a significant role in preventing this complication by emphasizing the importance of strict glycemic control.
Topics: Diabetic Neuropathies; Humans; Risk Factors
PubMed: 8961847
DOI: No ID Found -
Brain and Nerve = Shinkei Kenkyu No... May 2024Diabetes stands as the predominant cause of peripheral neuropathy, and diabetic neuropathy (DN) is an early-onset and most frequent complication of diabetes. Distal... (Review)
Review
Diabetes stands as the predominant cause of peripheral neuropathy, and diabetic neuropathy (DN) is an early-onset and most frequent complication of diabetes. Distal symmetric polyneuropathy is the major form of DN; however, various patterns of nerve injury can manifest. Growing evidence suggests that hyperglycemia-related metabolic disorders in neurons, Schwann cells, and vascular endothelial cells play a major role in the development and progression of DN; however, its pathogenesis and development of disease-modifying therapies warrant further investigation. Herein, recent studies regarding the possible pathogenic factors of DN (polyol and other collateral glycolysis pathways, glycation, oxidative stress, Rho/Rho kinase signaling pathways, etc.) and therapeutic strategies targeting these factors are introduced.
Topics: Humans; Diabetic Neuropathies; Oxidative Stress; Animals; Signal Transduction
PubMed: 38741511
DOI: 10.11477/mf.1416202658 -
Current Opinion in Endocrinology,... Apr 2007Diabetic neuropathies comprise a number of conditions affecting somatic or autonomic nerves and are the most common of the long-term diabetic complications. This review... (Review)
Review
PURPOSE OF REVIEW
Diabetic neuropathies comprise a number of conditions affecting somatic or autonomic nerves and are the most common of the long-term diabetic complications. This review considers recent developments in the classification and noninvasive assessment of somatic neuropathy, and describes new approaches to the management of painful neuropathic symptoms.
RECENT FINDINGS
Classification of the diabetic neuropathies needs modifying to include the recently described 'prediabetic neuropathy' or 'neuropathy of impaired glucose tolerance'. There is increasing evidence to support the use of minimally invasive skin biopsies for evaluating small fibre neuropathies, and more recently, the noninvasive corneal confocal microscopy, which enables direct visualization of peripheral nerve in vivo. For those with painful neuropathic symptoms, a number of evidence-based therapies are now available.
SUMMARY
Patients with 'idiopathic neuropathy' should be screened for evidence of impaired glucose tolerance and considered for lifestyle management. Future trials of potential therapies will benefit from more relevant surrogate endpoints. Those with painful neuropathy should only be prescribed therapies whose efficacy has been confirmed by independent randomized controlled trials.
Topics: Biopsy; Cornea; Diabetic Neuropathies; Endocrinology; Glucose Tolerance Test; Humans; Life Style; Microscopy, Confocal; Minimally Invasive Surgical Procedures; Pain; Palliative Care; Peripheral Nervous System Diseases
PubMed: 17940432
DOI: 10.1097/MED.0b013e328014979e -
Journal of Diabetes Research 2021Despite the high prevalence of diabetic neuropathy, its early start, and its impact on quality of life and mortality, unresolved clinical issues persist in the field... (Review)
Review
Despite the high prevalence of diabetic neuropathy, its early start, and its impact on quality of life and mortality, unresolved clinical issues persist in the field regarding its screening implementation, the understanding of its mechanisms, and the search for valid biomarkers, as well as disease-modifying treatment. Genetics may address these needs by providing genetic biomarkers of susceptibility, giving insights into pathogenesis, and shedding light on how to select possible responders to treatment. After a brief summary of recent studies on the genetics of diabetic neuropathy, the current review focused mainly on microRNAs (miRNAs), including the authors' results in this field. It summarized the findings of animal and human studies that associate miRNAs with diabetic neuropathy and explored the possible pathogenetic meanings of these associations, in particular regarding miR-128a, miR-155a, and miR-499a, as well as their application for diabetic neuropathy screening. Moreover, from a genetic perspective, it examined new findings of polymorphisms of miRNA genes in diabetic neuropathy. It considered in more depth the pathogenetic implications for diabetic neuropathy of the polymorphism of MIR499A and the related changes in the downstream action of miR-499a, showing how epigenetic and genetic studies may provide insight into pathogenetic mechanisms like mitochondrial dysfunction. Finally, the concept and the data of genotype-phenotype association for polymorphism of miRNA genes were described. In conclusion, although at a very preliminary stage, the findings linking the genetics and epigenetics of miRNAs might contribute to the identification of exploratory risk biomarkers, a comprehensive definition of susceptibility to specific pathogenetic mechanisms, and the development of mechanism-based treatment of diabetic neuropathy, thus addressing the goals of genetic studies.
Topics: Animals; Diabetic Neuropathies; Epigenesis, Genetic; Genetic Predisposition to Disease; Humans; MicroRNAs; Phenotype; Polymorphism, Genetic; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors
PubMed: 34660810
DOI: 10.1155/2021/5593608 -
Journal of the American Podiatric... Mar 1993Angiopathy, immunopathy, and neuropathy are the key components responsible for diabetic foot complications. The authors report on the current theories of metabolic and... (Review)
Review
Angiopathy, immunopathy, and neuropathy are the key components responsible for diabetic foot complications. The authors report on the current theories of metabolic and structural causes of diabetic neuropathy.
Topics: Diabetic Neuropathies; Humans
PubMed: 8468696
DOI: 10.7547/87507315-83-3-149 -
Current Opinion in Neurology Oct 2002This review will focus on recent advances in the field of diabetic neuropathy, with an emphasis on distal symmetric sensory and sensorimotor polyneuropathy. Some new... (Review)
Review
PURPOSE OF REVIEW
This review will focus on recent advances in the field of diabetic neuropathy, with an emphasis on distal symmetric sensory and sensorimotor polyneuropathy. Some new information in the areas of diabetic amyotrophy and diabetic autonomic neuropathy will also be reviewed.
RECENT FINDINGS
The pathogenesis of diabetic neuropathy is multifactorial. There is increasing evidence to link abnormalities in the polyol pathway to the pathogenesis of diabetic neuropathy. In addition, there appear to be abnormalities of nerve regeneration and of sodium and calcium channels. Aldose reductase inhibitors have shown promise in animal models for reversing neuropathy if started early and used for a sufficient time, but those used to date in human trials are probably not of sufficient potency. Neurotrophic factors and vascular endothelial growth factor both also show promise. Specific recommendations and pathways for diabetic foot care have been devised. Lamotrigine and bupropion represent new treatments for neuropathic pain. The role of impaired glucose tolerance is being explored as it relates to polyneuropathy.
SUMMARY
An increasing understanding of the pathogenetic mechanisms holds out promise for the effective treatment of diabetic neuropathy. The early detection of abnormal glucose metabolism is particularly important, as treatments will probably be most effective if administered early in the course of the neuropathy, when abnormalities of peripheral nerves are more likely to be reversible.
Topics: Diabetic Foot; Diabetic Neuropathies; Glucose Intolerance; Humans; Pain
PubMed: 12352003
DOI: 10.1097/00019052-200210000-00010 -
The Journal of Pharmacy and Pharmacology Sep 2009This is a review of emerging interventions from the recent preclinical and clinical literature that demonstrate the potential for effectiveness in the therapy of... (Review)
Review
OBJECTIVES
This is a review of emerging interventions from the recent preclinical and clinical literature that demonstrate the potential for effectiveness in the therapy of diabetic neuropathy (DN). DN is the most common complication of diabetes mellitus and up to 50% of patients with type 1 and type 2 forms have some or other form of neuropathy. The pathology of DN is characterized by progressive nerve fibre loss that gives rise to positive and negative clinical signs and symptoms such as pain, paraesthesiae and loss of sensation.
KEY FINDINGS
There are very few drugs available to directly treat DN. Those that are clinically indicated provide symptomatic relief but do not repair or reverse underlying nerve damage. However, some agents are in clinical development that may support adult neurons and direct reparative processes after injury stages. Several disease modifying drugs such as aldose reductase inhibitors and protein kinase C inhibitors are in phase III development. Agents on the horizon include neurotrophic factors, growth factors, gene therapy, immunotherapy, poly(ADP-ribose) polymerase inhibitors and non-immunosuppressive immunophilin ligands.
SUMMARY
Progress has been made toward understanding the biochemical mechanisms leading to diabetic neuropathy, and as a result, new treatment modalities are being explored. The pathogenesis, types and approaches for treating DN together with the newer therapeutic interventions on the horizon are discussed.
Topics: Animals; Antioxidants; Clinical Trials as Topic; Diabetic Neuropathies; Enzyme Inhibitors; Genetic Therapy; Humans; Immunophilins; Immunotherapy; Intercellular Signaling Peptides and Proteins; Models, Biological
PubMed: 19703362
DOI: 10.1211/jpp/61.09.0002 -
Angiology Jan 2016Damage of small nerve fibers may lead to a large variety of clinical symptoms. Small-fiber neuropathy underlies the symptoms of painful diabetic neuropathy, which may... (Review)
Review
Damage of small nerve fibers may lead to a large variety of clinical symptoms. Small-fiber neuropathy underlies the symptoms of painful diabetic neuropathy, which may decrease quality of life. It also contributes to the poor prognosis of diabetic neuropathy because it plays a key role in the pathogenesis of foot ulceration and autonomic neuropathy. Impairment of small nerve fibers is considered the earliest alteration in the course of diabetic neuropathy. Therefore, assessment of functional and morphological abnormalities of small nerve fibers may enable timely diagnosis. The definition, symptoms, and clinical significance of small-fiber neuropathy are considered in the present review. An apparently more complex interaction between small-fiber impairment and microcirculation is extensively discussed. Diagnostic modalities include morphometric and functional methods. Corneal confocal microscopy and punch skin biopsy are considered gold standards, but noninvasive functional tests are also diagnostically useful. However, in routine clinical practice, small-fiber neuropathy is diagnosed by its typical clinical presentation. Finally, prompt treatment should be initiated following diagnosis.
Topics: Biopsy; Diabetic Angiopathies; Diabetic Neuropathies; Humans; Microscopy, Confocal; Nerve Fibers; Prognosis; Skin
PubMed: 25957257
DOI: 10.1177/0003319715583595