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Nature Reviews. Disease Primers Jun 2019The global epidemic of prediabetes and diabetes has led to a corresponding epidemic of complications of these disorders. The most prevalent complication is neuropathy,...
The global epidemic of prediabetes and diabetes has led to a corresponding epidemic of complications of these disorders. The most prevalent complication is neuropathy, of which distal symmetric polyneuropathy (for the purpose of this Primer, referred to as diabetic neuropathy) is very common. Diabetic neuropathy is a loss of sensory function beginning distally in the lower extremities that is also characterized by pain and substantial morbidity. Over time, at least 50% of individuals with diabetes develop diabetic neuropathy. Glucose control effectively halts the progression of diabetic neuropathy in patients with type 1 diabetes mellitus, but the effects are more modest in those with type 2 diabetes mellitus. These findings have led to new efforts to understand the aetiology of diabetic neuropathy, along with new 2017 recommendations on approaches to prevent and treat this disorder that are specific for each type of diabetes. In parallel, new guidelines for the treatment of painful diabetic neuropathy using distinct classes of drugs, with an emphasis on avoiding opioid use, have been issued. Although our understanding of the complexities of diabetic neuropathy has substantially evolved over the past decade, the distinct mechanisms underlying neuropathy in type 1 and type 2 diabetes remains unknown. Future discoveries on disease pathogenesis will be crucial to successfully address all aspects of diabetic neuropathy, from prevention to treatment.
Topics: Diabetic Neuropathies; Humans; Quality of Life; Risk Factors
PubMed: 31197183
DOI: 10.1038/s41572-019-0097-9 -
Journal of Neural Transmission (Vienna,... Apr 2020Neuropathic pain is a frequent condition caused by a lesion or disease of the central or peripheral somatosensory nervous system. A frequent cause of peripheral... (Review)
Review
Neuropathic pain is a frequent condition caused by a lesion or disease of the central or peripheral somatosensory nervous system. A frequent cause of peripheral neuropathic pain is diabetic neuropathy. Its complex pathophysiology is not yet fully elucidated, which contributes to underassessment and undertreatment. A mechanism-based treatment of painful diabetic neuropathy is challenging but phenotype-based stratification might be a way to develop individualized therapeutic concepts. Our goal is to review current knowledge of the pathophysiology of peripheral neuropathic pain, particularly painful diabetic neuropathy. We discuss state-of-the-art clinical assessment, validity of diagnostic and screening tools, and recommendations for the management of diabetic neuropathic pain including approaches towards personalized pain management. We also propose a research agenda for translational research including patient stratification for clinical trials and improved preclinical models in relation to current knowledge of underlying mechanisms.
Topics: Chronic Pain; Diabetic Neuropathies; Humans; Neuralgia
PubMed: 32036431
DOI: 10.1007/s00702-020-02145-7 -
The Lancet. Neurology Jun 2012Diabetic peripheral neuropathy is a prevalent, disabling disorder. The most common manifestation is distal symmetrical polyneuropathy (DSP), but many patterns of nerve... (Review)
Review
Diabetic peripheral neuropathy is a prevalent, disabling disorder. The most common manifestation is distal symmetrical polyneuropathy (DSP), but many patterns of nerve injury can occur. Currently, the only effective treatments are glucose control and pain management. While glucose control substantially decreases the development of neuropathy in those with type 1 diabetes, the effect is probably much smaller in those with type 2 diabetes. Evidence supports the use of specific anticonvulsants and antidepressants for pain management in patients with diabetic peripheral neuropathy. However, the lack of disease-modifying therapies for diabetic DSP makes the identification of new modifiable risk factors essential. Growing evidence supports an association between components of the metabolic syndrome, including prediabetes, and neuropathy. Studies are needed to further explore this association, which has implications for the development of new treatments for this common disorder.
Topics: Diabetic Neuropathies; Humans; Risk Factors
PubMed: 22608666
DOI: 10.1016/S1474-4422(12)70065-0 -
Endocrinology and Metabolism Clinics of... Dec 2013Diabetic neuropathy (DN) is the most common and troublesome complication of diabetes mellitus, leading to the greatest morbidity and mortality and resulting in a huge... (Review)
Review
Diabetic neuropathy (DN) is the most common and troublesome complication of diabetes mellitus, leading to the greatest morbidity and mortality and resulting in a huge economic burden for diabetes care. The clinical assessment of diabetic peripheral neuropathy and its treatment options are multifactorial. Patients with DN should be screened for autonomic neuropathy, as there is a high degree of coexistence of the two complications. A review of the clinical assessment and treatment algorithms for diabetic neuropathy, painful neuropathy, and autonomic dysfunction is provided.
Topics: Autonomic Nervous System Diseases; Cardiovascular Diseases; Diabetic Neuropathies; Guidelines as Topic; Humans; Hyperglycemia; Neuralgia
PubMed: 24286949
DOI: 10.1016/j.ecl.2013.06.001 -
International Journal of Molecular... Aug 2021Diabetic neuropathy, a major complication of diabetes mellitus, refers to a collection of clinically diverse disorders affecting the nervous system that may present with... (Review)
Review
Diabetic neuropathy, a major complication of diabetes mellitus, refers to a collection of clinically diverse disorders affecting the nervous system that may present with pain. Although the number of patients suffering from severe neuropathy is increasing, no optimal treatment method has been developed yet. Acupuncture is well known for its ability to reduce various kinds of pain, and a number of studies have also reported its effect on diabetes mellitus; however, its effect and underlying mechanism against diabetic neuropathy are not yet clearly understood. In this review, ten and five studies performed in humans and animals, respectively, were analyzed. All studies reported that acupuncture significantly relieved diabetic neuropathy. ST36, BL13, BL20, SP6, and SP9 were the most widely used acupoints. Five studies used electro-acupuncture, whereas other studies used manual acupuncture. Furthermore, the effect of acupuncture was shown to be mediated through the various molecules present in the peripheral nerves and spinal cord, such as P65, GPR78, and TRPV1. Five studies reported side effects, such as swelling, numbness, and nausea, but none were reported to be serious. Based on these results, we suggest that acupuncture should be considered as a treatment option for diabetic neuropathy.
Topics: Acupuncture Analgesia; Acupuncture Points; Animals; Diabetic Neuropathies; Endoplasmic Reticulum Chaperone BiP; Humans
PubMed: 34445280
DOI: 10.3390/ijms22168575 -
European Journal of Pharmacology Aug 2018Diabetic neuropathy is regarded as one of the most debilitating outcomes of diabetes mellitus and may cause pain, decreased motility, and even amputation. Diabetic... (Review)
Review
Diabetic neuropathy is regarded as one of the most debilitating outcomes of diabetes mellitus and may cause pain, decreased motility, and even amputation. Diabetic neuropathy includes multiple forms, ranging from discomfort to death. Prognosis of diabetic neuropathy is an uphill task as it remains silent for several years after the onset of diabetes. Hyperglycemia, apart from inducing oxidative stress in neurons, also leads to activation of multiple biochemical pathways which constitute the major source of damage and are potential therapeutic targets in diabetic neuropathy. A vast array of molecular pathways, including polyol pathway, hexosamine pathway, PKCs signaling, oxidative stress, AGEs pathway, PARP pathway, MAPK pathway, NF-κB signaling, hedgehog pathways, TNF-α signaling, cyclooxygenase pathway, interleukins, lipoxygenase pathway, nerve growth factor, Wnt pathway, autophagy, and GSK3 signaling may be accounted for the pathogenesis and progression of diabetic neuropathy. Although symptomatic treatment is available for diabetic neuropathy, few treatment options are available to eliminate the root cause. The immense physical, psychological, and economic burden of diabetic neuropathy highlights the need for cost effective and targeted therapies. The main aim of this review is to highlight the putative role of various mechanisms and pathways involved in the development of diabetic neuropathy and to impart an in-depth insight on new therapeutic approaches aimed at delaying or reversing various modalities of diabetic neuropathy.
Topics: Animals; Diabetic Neuropathies; Disease Progression; Drug Therapy, Combination; Humans; Hyperglycemia; Incidence; Molecular Targeted Therapy; Neurons; Neuroprotective Agents; Oxidative Stress; Prognosis; Signal Transduction; Treatment Outcome
PubMed: 29966615
DOI: 10.1016/j.ejphar.2018.06.034 -
Handbook of Clinical Neurology 2013Diabetes is the most common cause of peripheral neuropathy in the world. Both type 1 (insulin-dependent) and type 2 diabetes are commonly complicated by peripheral nerve... (Review)
Review
Diabetes is the most common cause of peripheral neuropathy in the world. Both type 1 (insulin-dependent) and type 2 diabetes are commonly complicated by peripheral nerve disorders. Two main types of neuropathy are observed: the most common is a nerve fiber length-dependent, distal symmetrical sensory polyneuropathy with little motor involvement but frequent, and potentially life threatening, autonomic dysfunction. Alteration of temperature and pain sensations in the feet is an early manifestation of diabetic polyneuropathy. The second pattern is a focal neuropathy, which more commonly complicates or reveals type 2 diabetes. Poor diabetic control increases the risk of neuropathy with subsequent neuropathic pains and trophic changes in the feet, which can be prevented by education of patients.
Topics: Diabetic Neuropathies; Humans; Neural Conduction
PubMed: 23931803
DOI: 10.1016/B978-0-444-52902-2.00033-3 -
Handbook of Clinical Neurology 2014Neuropathies related to diabetes mellitus can affect 60-70% of patients with diabetes. These can include peripheral polyneuropathies, mononeuropathies, and autonomic... (Review)
Review
Neuropathies related to diabetes mellitus can affect 60-70% of patients with diabetes. These can include peripheral polyneuropathies, mononeuropathies, and autonomic neuropathies. Control of glucose, lipids, and hypertension and cessation of smoking can limit onset and progression of these neuropathies. Besides control of the above listed risk factors, we do not have effective medications to treat the pathophysiologic mechanisms of diabetic neuropathies. Treatment is limited to ameliorating pain and correcting the end organ consequences of the neuropathic processes.
Topics: Diabetic Neuropathies; Humans; Risk Factors
PubMed: 24365351
DOI: 10.1016/B978-0-7020-4087-0.00051-6 -
Current Neurology and Neuroscience... Aug 2014Diabetic neuropathies (DNs) differ in clinical course, distribution, fiber involvement (type and size), and pathophysiology, the most typical type being a... (Review)
Review
Diabetic neuropathies (DNs) differ in clinical course, distribution, fiber involvement (type and size), and pathophysiology, the most typical type being a length-dependent distal symmetric polyneuropathy (DSP) with differing degrees of autonomic involvement. The pathogenesis of diabetic DSP is multifactorial, including increased mitochondrial production of free radicals due to hyperglycemia-induced oxidative stress. Mechanisms that impact neuronal activity, mitochondrial function, membrane permeability, and endothelial function include formation of advanced glycosylation end products, activation of polyol aldose reductase signaling, activation of poly(ADP ribose) polymerase, and altered function of the Na(+)/K(+)-ATPase pump. Hyperglycemia-induced endoplasmic reticulum stress triggers several neuronal apoptotic processes. Additional mechanisms include impaired nerve perfusion, dyslipidemia, altered redox status, low-grade inflammation, and perturbation of calcium balance. Successful therapies require an integrated approach targeting these mechanisms. Intensive glycemic control is essential but is insufficient to prevent onset or progression of DSP, and disease-modifying treatments for DSP have been disappointing. Atypical forms of DN include subacute-onset sensory (symmetric) or motor (asymmetric) predominant conditions that are frequently painful but generally self-limited. DNs are a major cause of disability, associated with reduced quality of life and increased mortality.
Topics: Diabetic Neuropathies; Humans
PubMed: 24954624
DOI: 10.1007/s11910-014-0473-5 -
Experimental and Clinical Endocrinology... Feb 2023
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus
PubMed: 36720239
DOI: 10.1055/a-1946-3813