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Muscle & Nerve Mar 2021Diabetic peripheral neuropathy and metabolic syndrome (MetS) are both global health challenges with well-established diagnostic criteria and significant impacts on... (Review)
Review
Diabetic peripheral neuropathy and metabolic syndrome (MetS) are both global health challenges with well-established diagnostic criteria and significant impacts on quality of life. Clinical observations, epidemiologic evidence, and animal models of disease have strongly suggested MetS is associated with an elevated risk for cryptogenic sensory peripheral neuropathy (CSPN). MetS neuropathy preferentially affects small unmyelinated axons early in its course, and it may also affect autonomic and large fibers. CSPN risk is linked to MetS and several of its components including obesity, dyslipidemia, and prediabetes. MetS also increases neuropathy risk in patients with established type 1 and type 2 diabetes. In this review we present animal data regarding the role of inflammation and dyslipidemia in MetS neuropathy pathogenesis. Several studies suggest exercise-based lifestyle modification is a promising treatment approach for MetS neuropathy.
Topics: Bariatric Surgery; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diet Therapy; Disease Progression; Dyslipidemias; Exercise; Humans; Hypoglycemic Agents; Metabolic Syndrome; Obesity; Peripheral Nervous System Diseases; Prediabetic State; Risk Factors; Small Fiber Neuropathy; Topiramate
PubMed: 33098165
DOI: 10.1002/mus.27086 -
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 -
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 -
International Journal of Molecular... Jun 2016Diabetic foot ulceration is a serious complication of diabetes mellitus worldwide and the most common cause of hospitalization in diabetic patients. The etiology of... (Review)
Review
Diabetic foot ulceration is a serious complication of diabetes mellitus worldwide and the most common cause of hospitalization in diabetic patients. The etiology of diabetic foot ulcerations is complex due to their multifactorial nature; in the pathophysiology of diabetic foot ulceration polyneuropathy is important. Proper adherence to standard treatment strategies and interdisciplinary cooperation can reduce the still high rates of major amputations.
Topics: Diabetic Foot; Diabetic Neuropathies; Evidence-Based Medicine; Humans; Interprofessional Relations; Standard of Care; Treatment Outcome; Wound Healing
PubMed: 27294922
DOI: 10.3390/ijms17060917 -
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 -
Pain Sep 2020Neuropathy is a common complication of long-term diabetes that impairs quality of life by producing pain, sensory loss and limb amputation. The presence of neuropathy in... (Review)
Review
Neuropathy is a common complication of long-term diabetes that impairs quality of life by producing pain, sensory loss and limb amputation. The presence of neuropathy in both insulin-deficient (type 1) and insulin resistant (type 2) diabetes along with the slowing of progression of neuropathy by improved glycemic control in type 1 diabetes has caused the majority of preclinical and clinical investigations to focus on hyperglycemia as the initiating pathogenic lesion. Studies in animal models of diabetes have identified multiple plausible mechanisms of glucotoxicity to the nervous system including post-translational modification of proteins by glucose and increased glucose metabolism by aldose reductase, glycolysis and other catabolic pathways. However, it is becoming increasingly apparent that factors not necessarily downstream of hyperglycemia can also contribute to the incidence, progression and severity of neuropathy and neuropathic pain. For example, peripheral nerve contains insulin receptors that transduce the neurotrophic and neurosupportive properties of insulin, independent of systemic glucose regulation, while the detection of neuropathy and neuropathic pain in patients with metabolic syndrome and failure of improved glycemic control to protect against neuropathy in cohorts of type 2 diabetic patients has placed a focus on the pathogenic role of dyslipidemia. This review provides an overview of current understanding of potential initiating lesions for diabetic neuropathy and the multiple downstream mechanisms identified in cell and animal models of diabetes that may contribute to the pathogenesis of diabetic neuropathy and neuropathic pain.
Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Glucose Intolerance; Humans; Neuralgia; Pain; Pain Measurement; Quality of Life
PubMed: 32999525
DOI: 10.1097/j.pain.0000000000001922 -
Current Diabetes Reports Aug 2019Diabetic peripheral neuropathy eventually affects nearly 50% of adults with diabetes during their lifetime and is associated with substantial morbidity including pain,... (Review)
Review
PURPOSE OF REVIEW
Diabetic peripheral neuropathy eventually affects nearly 50% of adults with diabetes during their lifetime and is associated with substantial morbidity including pain, foot ulcers, and lower limb amputation. This review summarizes the epidemiology, risk factors, and management of diabetic peripheral neuropathy and related lower extremity complications.
RECENT FINDINGS
The prevalence of peripheral neuropathy is estimated to be between 6 and 51% among adults with diabetes depending on age, duration of diabetes, glucose control, and type 1 versus type 2 diabetes. The clinical manifestations are variable, ranging from asymptomatic to painful neuropathic symptoms. Because of the risk of foot ulcer (25%) and amputation associated with diabetic peripheral neuropathy, aggressive screening and treatment in the form of glycemic control, regular foot exams, and pain management are important. There is an emerging focus on lifestyle interventions including weight loss and physical activity as well. The American Diabetes Association has issued multiple recommendation statements pertaining to diabetic neuropathies and the care of the diabetic foot. Given that approximately 50% of adults with diabetes will be affected by peripheral neuropathy in their lifetime, more diligent screening and management are important to reduce the complications and health care burden associated with the disease.
Topics: Amputation, Surgical; Cost of Illness; Diabetic Foot; Diabetic Neuropathies; Humans; Lower Extremity; Mass Screening; Risk Factors
PubMed: 31456118
DOI: 10.1007/s11892-019-1212-8 -
Acta Neurologica Scandinavica Oct 2022Traditionally, neurophysiology is the primary diagnostic and prognostic biomarker in peripheral neuropathy clinical practice; however, it may lack responsiveness in the... (Review)
Review
Traditionally, neurophysiology is the primary diagnostic and prognostic biomarker in peripheral neuropathy clinical practice; however, it may lack responsiveness in the context of slowly progressive neuropathies and where there is significant axonal damage. The development of ultrasensitive platforms for measuring serum proteins at the lower limit of detection of traditional ELISA techniques has transformed the field of blood biomarkers of peripheral neuropathy. A variety of blood biomarkers have been identified from inflammatory cytokines and apokines in diabetic neuropathy through to neuron-specific proteins such as neurofilament light chain, Schwann cell-specific proteins such as TMPRSS5 and microRNAs in other acquired and hereditary neuropathies. In this article, we review blood biomarkers of disease activity for the common subtypes of peripheral neuropathy including inflammatory demyelinating neuropathies, vasculitic neuropathy, diabetic neuropathy, chemotherapy-induced neuropathy and Charcot-Marie-Tooth disease and related disorders including TTR amyloidosis.
Topics: Antineoplastic Agents; Biomarkers; Charcot-Marie-Tooth Disease; Cytokines; Humans; MicroRNAs
PubMed: 35611606
DOI: 10.1111/ane.13650 -
Methodist DeBakey Cardiovascular Journal 2018Cardiovascular autonomic neuropathy (CAN) is a severely debilitating yet underdiagnosed condition in patients with diabetes. The prevalence can range from 2.5% (based on... (Review)
Review
Cardiovascular autonomic neuropathy (CAN) is a severely debilitating yet underdiagnosed condition in patients with diabetes. The prevalence can range from 2.5% (based on the primary prevention cohort in the Diabetes Control and Complications Trial) to as high as 90% of patients with type 1 diabetes. Clinical manifestations range from orthostasis to myocardial infarction. The diagnosis is made using multiple autonomic function tests to assess both sympathetic and parasympathetic function. The pathophysiology of CAN is complex, likely multifactorial, and not completely understood. Treatment is limited to symptomatic control of orthostatic hypotension, which is a late complication, and current strategies to reverse CAN are limited. This review explores the epidemiology, pathophysiology, clinical manifestations, diagnosis, and complications of CAN as well as current treatment options.
Topics: Autonomic Nervous System; Autonomic Nervous System Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Heart; Humans; Predictive Value of Tests; Risk Factors; Treatment Outcome
PubMed: 30788010
DOI: 10.14797/mdcj-14-4-251