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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 -
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,... (Review)
Review
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: Analgesics, Opioid; Diabetic Neuropathies; Humans; Hyperglycemia; Hyperlipidemias; Mass Screening; Pain Management; Prevalence; Quality of Life; Risk Factors; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 31197153
DOI: 10.1038/s41572-019-0092-1 -
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 -
Seminars in Neurology Oct 2019Diabetes mellitus is becoming increasingly common worldwide. As this occurs, there will be an increase in the prevalence of known comorbidities from this disorder of... (Review)
Review
Diabetes mellitus is becoming increasingly common worldwide. As this occurs, there will be an increase in the prevalence of known comorbidities from this disorder of glucose metabolism. One of the most disabling adverse comorbidities is diabetic neuropathy. The most common neuropathic manifestation is distal symmetric polyneuropathy, which can lead to sensory disturbances, including diminished protective sense, making patients prone to foot injuries. However, focal, multifocal, and autonomic neuropathies are also common. Diabetic nerve pain and Charcot osteoarthropathy are advanced neuropathic conditions that portend a severe deterioration in quality of life. To combat these symptoms, along with glycemic control and establishment of health care systems to educate and support patients with the complexities of diabetes, there are pharmacologic remedies to ameliorate the neurologic symptoms. Several guidelines and review boards generally recommend the use of tricyclic antidepressants, serotonin/norepinephrine-reuptake inhibitors, α-2-delta ligands, and anticonvulsants as medications to improve painful diabetic neuropathy and quality of life.
Topics: Diabetes Mellitus; Diabetic Neuropathies; Humans; Neuralgia; Polyneuropathies; Quality of Life
PubMed: 31639839
DOI: 10.1055/s-0039-1688978 -
Endocrinology and Metabolism Clinics of... Sep 2021Microvascular complications of diabetes present a significant challenge due to their diverse presentations, significant morbidity, and as strong predictors of... (Review)
Review
Microvascular complications of diabetes present a significant challenge due to their diverse presentations, significant morbidity, and as strong predictors of cardiovascular disease. Prevention and management strategies should focus on lifestyle modification, education and awareness, systematic screening for early complications, and intensive management of modifiable risk factors. This review discusses the microvascular complications of diabetes, including diabetic retinopathy, diabetic kidney disease, and diabetic neuropathy, and provides best practice clinical care recommendations to guide health care professionals to better manage people with these conditions.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Humans; Risk Factors
PubMed: 34399955
DOI: 10.1016/j.ecl.2021.05.005 -
Brain : a Journal of Neurology Jul 2021Peripheral neuropathy is one of the most common complications of both type 1 and type 2 diabetes. Up to half of patients with diabetes develop neuropathy during the... (Review)
Review
Peripheral neuropathy is one of the most common complications of both type 1 and type 2 diabetes. Up to half of patients with diabetes develop neuropathy during the course of their disease, which is accompanied by neuropathic pain in 30-40% of cases. Peripheral nerve injury in diabetes can manifest as progressive distal symmetric polyneuropathy, autonomic neuropathy, radiculo-plexopathies, and mononeuropathies. The most common diabetic neuropathy is distal symmetric polyneuropathy, which we will refer to as DN, with its characteristic glove and stocking like presentation of distal sensory or motor function loss. DN or its painful counterpart, painful DN, are associated with increased mortality and morbidity; thus, early recognition and preventive measures are essential. Nevertheless, it is not easy to diagnose DN or painful DN, particularly in patients with early and mild neuropathy, and there is currently no single established diagnostic gold standard. The most common diagnostic approach in research is a hierarchical system, which combines symptoms, signs, and a series of confirmatory tests. The general lack of long-term prospective studies has limited the evaluation of the sensitivity and specificity of new morphometric and neurophysiological techniques. Thus, the best paradigm for screening DN and painful DN both in research and in clinical practice remains uncertain. Herein, we review the diagnostic challenges from both clinical and research perspectives and their implications for managing patients with DN. There is no established DN treatment, apart from improved glycaemic control, which is more effective in type 1 than in type 2 diabetes, and only symptomatic management is available for painful DN. Currently, less than one-third of patients with painful DN derive sufficient pain relief with existing pharmacotherapies. A more precise and distinct sensory profile from patients with DN and painful DN may help identify responsive patients to one treatment versus another. Detailed sensory profiles will lead to tailored treatment for patient subgroups with painful DN by matching to novel or established DN pathomechanisms and also for improved clinical trials stratification. Large randomized clinical trials are needed to identify the interventions, i.e. pharmacological, physical, cognitive, educational, etc., which lead to the best therapeutic outcomes.
Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Neuralgia
PubMed: 33711103
DOI: 10.1093/brain/awab079 -
Current Drug Safety 2021Diabetic peripheral neuropathy (DPN) is traditionally divided into large and small fibre neuropathy (SFN). Damage to the large fibres can be detected using nerve... (Review)
Review
BACKGROUND
Diabetic peripheral neuropathy (DPN) is traditionally divided into large and small fibre neuropathy (SFN). Damage to the large fibres can be detected using nerve conduction studies (NCS) and often results in a significant reduction in sensitivity and loss of protective sensation, while damage to the small fibres is hard to reliably detect and can be either asymptomatic, associated with insensitivity to noxious stimuli, or often manifests itself as intractable neuropathic pain.
OBJECTIVE
To describe the recent advances in both detection, grading, and treatment of DPN as well as the accompanying neuropathic pain.
METHODS
A review of relevant, peer-reviewed, English literature from MEDLINE, EMBASE and Cochrane Library between January 1st 1967 and January 1st 2020 was used.
RESULTS
We identified more than three hundred studies on methods for detecting and grading DPN, and more than eighty randomised-controlled trials for treating painful diabetic neuropathy.
CONCLUSION
NCS remains the method of choice for detecting LFN in people with diabetes, while a gold standard for the detection of SFN is yet to be internationally accepted. In the recent years, several methods with huge potential for detecting and grading this condition have become available including skin biopsies and corneal confocal microscopy, which in the future could represent reliable endpoints for clinical studies. While several newer methods for detecting SFN have been developed, no new drugs have been accepted for treating neuropathic pain in people with diabetes. Tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors and anticonvulsants remain first line treatment, while newer agents targeting the proposed pathophysiology of DPN are being developed.
Topics: Anticonvulsants; Diabetes Mellitus; Diabetic Neuropathies; Humans; Selective Serotonin Reuptake Inhibitors
PubMed: 32735526
DOI: 10.2174/1574886315666200731173113 -
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