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Current Molecular Medicine 2023Diabetic mellitus is a worldwide endocrine and metabolic disorder with insulin insensitivity or deficiency or both whose prevalence could rise up to 592 million by 2035.... (Review)
Review
Diabetic mellitus is a worldwide endocrine and metabolic disorder with insulin insensitivity or deficiency or both whose prevalence could rise up to 592 million by 2035. Consistent hyperglycemia leads to one of the most common comorbidities like Diabetic Peripheral Neuropathy (DPN). DPN is underlined with unpleasant sensory experience, such as tingling and burning sensation, hyperalgesia, numbness, etc. Globally, 50-60% of the diabetic population is suffering from such symptoms as microvascular complications. Consistent hyperglycemia during DM causes activation/inhibition of various pathways playing important role in the homeostasis of neurons and other cells. Disruption of these pathways results into apoptosis and mitochondrial dysfunctions, causing neuropathy. Among these, pathways like Polyol and PARP are some of the most intensively studied ones whereas those like Wnt pathway, Mitogen activated protein kinase (MAPK), mTOR pathway are comparatively newly discovered. Understanding of these pathways and their role in pathophysiology of DN underlines a few molecules of immense therapeutic value. The inhibitors or activators of these molecules can be of therapeutic importance in the management of DPN. This review, hence, focuses on these underlying molecular mechanisms intending to provide therapeutically effective molecular targets for the treatment of DPN.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus
PubMed: 34397329
DOI: 10.2174/1566524021666210816093111 -
Current Diabetes Reports Oct 2017Treatment-induced neuropathy of diabetes (TIND) is an under-recognized iatrogenic painful sensory and autonomic neuropathy. This review highlights the clinical symptoms... (Review)
Review
PURPOSE OF REVIEW
Treatment-induced neuropathy of diabetes (TIND) is an under-recognized iatrogenic painful sensory and autonomic neuropathy. This review highlights the clinical symptoms and signs, raises awareness of the cause, and provides education about prevention of TIND.
RECENT FINDINGS
TIND may be triggered by a rapid decline in the blood glucose levels following the use of insulin, oral hypoglycemic medications, or even diet only to control diabetes. This may be seen in up to 10% of patients with diabetic neuropathy and has the potential for significant long-term complications that could be avoided through careful disease management. Based on the available evidence, a decrease in the glycosylated hemoglobin A1C of more than 3 points in 3 months in individuals with chronic hyperglycemia increases the risk of developing TIND. TIND is more common than previously suspected, and is tied to rates of glycemic control. Slower changes to glucose control are suggested, although there is no prospective data on disease prevention. Future research is necessary to guide treatment recommendations.
Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Follow-Up Studies; Glycated Hemoglobin; Humans; Insulin; Microvessels; Risk Factors
PubMed: 29064042
DOI: 10.1007/s11892-017-0960-6 -
The Journal of the Royal College of... Sep 2020Diabetic autonomic neuropathy is an under-recognised complication of diabetes and the prediabetic state. A wide range of manifestations can be seen due to involvement of... (Review)
Review
Diabetic autonomic neuropathy is an under-recognised complication of diabetes and the prediabetic state. A wide range of manifestations can be seen due to involvement of cardiovascular, gastrointestinal, genitourinary, sudomotor and neuroendocrine systems. Cardiac autonomic neuropathy is the most dreaded complication carrying significant mortality and morbidity. Early detection and control of diabetes and other cardiovascular risk factors is the key to treat and prevent progression of autonomic neuropathy. Recently, a new entity of treatment-induced neuropathy (TIND) of diabetes mellitus causing autonomic neuropathy is being increasingly recognised.
Topics: Diabetes Mellitus; Diabetic Neuropathies; Humans
PubMed: 32936100
DOI: 10.4997/JRCPE.2020.310 -
International Journal of Molecular... May 2021Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients' quality of life. DN could be present... (Review)
Review
Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients' quality of life. DN could be present as peripheral, autonomous or, clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of "metabolic memory" in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.
Topics: Animals; Diabetic Neuropathies; Epigenesis, Genetic; Epigenomics; Genetic Predisposition to Disease; Humans; Inflammation; Peripheral Nervous System
PubMed: 34063061
DOI: 10.3390/ijms22094887 -
Revue Medicale Suisse Jun 2022Diabetic neuropathy is a heterogeneous entity, grouping multiple disorders, of which the most classic form is distal symmetric polyneuropathy (DSPN). Its diagnosis is... (Review)
Review
Diabetic neuropathy is a heterogeneous entity, grouping multiple disorders, of which the most classic form is distal symmetric polyneuropathy (DSPN). Its diagnosis is based in most cases on a compatible history and clinical examination. Screening for DSPN, to allow the implementation of preventive measures against its complications, remains the cornerstone of management, in the absence of specific treatment. In this article, we propose a review of the different forms of diabetic neuropathy and their management.
Topics: Diabetes Mellitus; Diabetic Neuropathies; Humans; Physical Examination; Polyneuropathies
PubMed: 35647748
DOI: 10.53738/REVMED.2022.18.784.1106 -
Diabetes/metabolism Research and Reviews Jan 2019Diabetes impairs the bone marrow (BM) architecture and function as well as the mobilization of immature cells into the bloodstream and number of potential regenerative... (Review)
Review
Diabetes impairs the bone marrow (BM) architecture and function as well as the mobilization of immature cells into the bloodstream and number of potential regenerative cells. Circadian regulation of bone immature cell migration is regulated by β-adrenergic receptors, which are expressed on haematopoietic stem cells, mesenchymal stem cells, and osteoblasts in the BM. Diabetes is associated with a substantially lower number of sympathetic nerve terminal endings in the BM; thus, diabetic neuropathy plays a critical role in BM dysfunction. Treatment with mesenchymal stem cells, BM mononuclear cells, haematopoietic stem cells, and stromal cells ameliorates the dysfunction of diabetic neuropathy, which occurs, in part, through secreted neurotrophic factors, growth factors, adipokines, and polarizing macrophage M2 cells and inhibiting inflammation. Inflammation may be a therapeutic target for BM stem cells to improve diabetic neuropathy. Given that angiogenic and neurotrophic effects are two major barriers to effective diabetic neuropathy therapy, targeting BM stem cells may provide a novel approach to develop these types of treatments.
Topics: Bone Marrow; Bone Marrow Cells; Diabetic Neuropathies; Humans; Inflammation
PubMed: 30289199
DOI: 10.1002/dmrr.3083 -
Presse Medicale (Paris, France : 1983) Jun 2024Diabetic neuropathy is a frequent and severe degenerative complication of diabetes. The diagnosis is easily performed in painful symptomatic patients. Sensitivity... (Review)
Review
Diabetic neuropathy is a frequent and severe degenerative complication of diabetes. The diagnosis is easily performed in painful symptomatic patients. Sensitivity disorders responsible for numbness, tingling, and loss of feeling are part and parcel of diabetic foot syndrome and require investigation in view of preventing trophic ulcers. To date, there exists no specific treatment for diabetic neuropathy possibly preventable by careful control of metabolic disorder. Effective management of diabetic patients would make it possible to limit the dramatic consequences of diabetic neuropathy while at the same time acting on other complications.
Topics: Humans; Diabetic Neuropathies; Diabetic Foot
PubMed: 38663725
DOI: 10.1016/j.lpm.2024.104236 -
Diabetes Research and Clinical Practice Dec 2023Diabetic neuropathy is a common complication of diabetes that affects up to 50% of patients during the course of the disease; 20-30% of the patients also develop...
Diabetic neuropathy is a common complication of diabetes that affects up to 50% of patients during the course of the disease; 20-30% of the patients also develop neuropathic pain. The mechanisms underlying neuropathy are not known in detail, but both metabolic and vascular factors may contribute to the development of neuropathy. The development of the most common type of neuropathy is insidious, often starting distally in the toes and feet and gradually ascending up the leg and later also involving fingers and hands. The symptoms are mainly sensory with either sensory loss or positive symptoms with different types of paresthesia or painful sensations. In more advanced cases motor dysfunction may occur, causing gait disturbances and falls. The diagnosis of neuropathy is based on history and a careful examination, which includes a sensory examination of both large and small sensory nerve fiber function, as well as an examination of motor function and deep tendon reflexes of the lower limbs. Attention needs to be paid to the feet including examination of the skin, joints, and vascular supply. Nerve conduction studies are rarely needed to make a diagnosis of neuropathy. In patients with clear motor deficit or with an asymmetrical presentation, additional electrophysiological examination may be necessary. Early detection of diabetic neuropathy is important to avoid further irreversible injury to the peripheral nerves.
Topics: Humans; Diabetic Neuropathies; Neural Conduction; Peripheral Nerves; Neuralgia; Hand; Diabetes Mellitus
PubMed: 38245319
DOI: 10.1016/j.diabres.2023.110753 -
Current Pain and Headache Reports Jun 2022Many Americans cope with painful diabetic neuropathy (DN) as a sequela of high rates of diabetes mellitus in the US population. Appropriate management of this complex,... (Review)
Review
PURPOSE OF REVIEW
Many Americans cope with painful diabetic neuropathy (DN) as a sequela of high rates of diabetes mellitus in the US population. Appropriate management of this complex, debilitating chronic pain condition requires thorough evaluation through a biopsychosocial framework. This review aims to synthesize findings from original research studies and analyze the psychological factors that influence the experience of, and treatments for, DN pain.
RECENT FINDINGS
Existing clinical literature suggests a wide breadth of psychological factors impacting DN pain. One research study detailed the demographic characteristics of DN patients most likely to have significant anxiety or depressive symptoms, and have emotional distress adversely impacting their response to therapies. A retrospective study demonstrated a correlation between patients' mindfulness-based stress reduction and improvement in DN pain severity. In addtion, a small-scale, randomized controlled pilot study supported cognitive-behavioral therapy as a superior intervention to conventional medical treatments in reducing DN patients' pain severity and pain interference, even when not accompanied by significant improvement in depressive symptoms. This review of investigations into psychological factors implicated in DN pain suggests that diagnosable mental health conditions as well as discrete, adverse thinking processes both exert significant influences on DN pain. This review further brings attention to the beneficial impact that psychotherapeutic modalities can have on DN pain.
Topics: Chronic Disease; Chronic Pain; Cognitive Behavioral Therapy; Diabetes Mellitus; Diabetic Neuropathies; Humans; Neuralgia; Randomized Controlled Trials as Topic; Retrospective Studies
PubMed: 35380405
DOI: 10.1007/s11916-022-01040-y -
International Review of Neurobiology 2016The study of diabetic neuropathy has relied primarily on the use of streptozotocin-treated rat and mouse models of type 1 diabetes. This chapter will review the creation... (Review)
Review
The study of diabetic neuropathy has relied primarily on the use of streptozotocin-treated rat and mouse models of type 1 diabetes. This chapter will review the creation and use of other rodent models that have been developed in order to investigate the contribution of factors besides insulin deficiency to the development and progression of diabetic neuropathy as it occurs in obesity, type 1 or type 2 diabetes. Diabetic peripheral neuropathy is a complex disorder with multiple mechanisms contributing to its development and progression. Even though many animal models have been developed and investigated, no single model can mimic diabetic peripheral neuropathy as it occurs in humans. Nonetheless, animal models can play an important role in improving our understanding of the etiology of diabetic peripheral neuropathy and in performing preclinical screening of potential new treatments. To date treatments found to be effective for diabetic peripheral neuropathy in rodent models have failed in clinical trials. However, with the identification of new endpoints for the early detection of diabetic peripheral neuropathy and the understanding that a successful treatment may require a combination therapeutic approach there is hope that an effective treatment will be found.
Topics: Animals; Antibiotics, Antineoplastic; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Disease Models, Animal; Humans; Neural Conduction; Rodentia; Streptozocin
PubMed: 27133146
DOI: 10.1016/bs.irn.2016.03.002