-
Stem Cells Translational Medicine Apr 2023Diabetic neuropathy is a major complication of diabetes mellitus that occurs during the early stages of the disease. Many pathogenic mechanisms are related and induced...
Diabetic neuropathy is a major complication of diabetes mellitus that occurs during the early stages of the disease. Many pathogenic mechanisms are related and induced by hyperglycemia. However, even if these factors improve, diabetic neuropathy cannot go into remission and progresses slowly. Furthermore, diabetic neuropathy often progresses even with proper glycemic control. Recently, bone marrow-derived cells (BMDCs) were reported to be involved in the pathogenesis of diabetic neuropathy. BMDCs expressing proinsulin and TNFα migrate to the dorsal root ganglion and fuse with neurons, and this neuronal-hematopoietic cell fusion induces neuronal dysfunction and apoptosis. The CD106-positive lineage-sca1+c-kit+ (LSK) stem cell fraction in the bone marrow is strongly involved in cell fusion with neurons, leading to diabetic neuropathy. Surprisingly, when CD106-positive LSK stem cells obtained from diabetic mice were transplanted into nondiabetic mice, they fused with dorsal root ganglion neurons and induced neuropathy in non-hyperglycemic normal mice. The transplanted CD106-positive LSK fraction inherited the trait even after transplantation; this "progeny effect" may explain the irreversibility of diabetic neuropathy and is a significant finding for determining the target of radical treatments and provides new directions for developing therapeutic methods for diabetic neuropathy.
Topics: Mice; Animals; Bone Marrow Transplantation; Diabetic Neuropathies; Bone Marrow Cells; Diabetes Mellitus, Experimental; Cell Fusion; Neurons; Hematopoietic Stem Cell Transplantation; Mice, Inbred C57BL
PubMed: 36976582
DOI: 10.1093/stcltm/szad015 -
International Journal of Molecular... Aug 2021Diabetic retinopathy is a major retinal disease and a leading cause of blindness in the world. Diabetic retinopathy is a neurovascular disease that is associated with... (Review)
Review
Diabetic retinopathy is a major retinal disease and a leading cause of blindness in the world. Diabetic retinopathy is a neurovascular disease that is associated with disturbances of the interdependent relationship of cells composed of the neurovascular units, i.e., neurons, glial cells, and vascular cells. An impairment of these neurovascular units causes both neuronal and vascular abnormalities in diabetic retinopathy. More specifically, neuronal abnormalities including neuronal cell death and axon degeneration are irreversible changes that are directly related to the vision reduction in diabetic patients. Thus, establishment of neuroprotective and regenerative therapies for diabetic neuropathy in the retina is an emergent task for preventing the blindness of patients with diabetic retinopathy. This review focuses on the pathogenesis of the neuronal abnormalities in diabetic retina including glial abnormalities, neuronal cell death, and axon degeneration. The possible molecular cell death pathways and intrinsic survival and regenerative pathways are also described. In addition, therapeutic approaches for diabetic neuropathy in the retina both in vitro and in vivo are presented. This review should be helpful for providing clues to overcome the barriers for establishing neuroprotection and regeneration of diabetic neuropathy in the retina.
Topics: Animals; Combined Modality Therapy; Diabetic Neuropathies; Diabetic Retinopathy; Humans; Molecular Targeted Therapy; Nerve Regeneration; Neuroprotection; Neuroprotective Agents
PubMed: 34445756
DOI: 10.3390/ijms22169050 -
Biochimica Et Biophysica Acta.... Jun 2023Western lifestyle contributes to an overt increase in the prevalence of metabolic anomalies including diabetes mellitus (DM) and obesity. Prevalence of DM is rapidly... (Review)
Review
Western lifestyle contributes to an overt increase in the prevalence of metabolic anomalies including diabetes mellitus (DM) and obesity. Prevalence of DM is rapidly growing worldwide, affecting many individuals in both developing and developed countries. DM is correlated with the onset and development of complications with diabetic nephropathy (DN), diabetic cardiomyopathy (DC) and diabetic neuropathy being the most devastating pathological events. On the other hand, Nrf2 is a regulator for redox balance in cells and accounts for activation of antioxidant enzymes. Dysregulation of Nrf2 signaling has been shown in various human diseases such as DM. This review focuses on the role Nrf2 signaling in major diabetic complications and targeting Nrf2 for treatment of this disease. These three complications share similarities including the presence of oxidative stress, inflammation and fibrosis. Onset and development of fibrosis impairs organ function, while oxidative stress and inflammation can evoke damage to cells. Activation of Nrf2 signaling significantly dampens inflammation and oxidative damage, and is beneficial in retarding interstitial fibrosis in diabetic complications. SIRT1 and AMPK are among the predominant pathways to upregulate Nrf2 expression in the amelioration of DN, DC and diabetic neuropathy. Moreover, certain therapeutic agents such as resveratrol and curcumin, among others, have been employed in promoting Nrf2 expression to upregulate HO-1 and other antioxidant enzymes in the combat of oxidative stress in the face of DM.
Topics: Humans; Diabetic Nephropathies; NF-E2-Related Factor 2; Antioxidants; Diabetic Neuropathies; Diabetes Complications; Cardiomyopathies; Fibrosis; Inflammation; Diabetes Mellitus
PubMed: 37028606
DOI: 10.1016/j.bbadis.2023.166714 -
Pediatric Diabetes Mar 2021Pediatric neuropathy attributed to metabolic dysfunction is a well-known complication in children and youth with type 1 diabetes. Moreover, the rise of obesity and in... (Review)
Review
Pediatric neuropathy attributed to metabolic dysfunction is a well-known complication in children and youth with type 1 diabetes. Moreover, the rise of obesity and in particular of type 2 diabetes may cause an uptick in pediatric neuropathy incidence. However, despite the anticipated increase in neuropathy incidence, pathogenic insights and strategies to prevent or manage neuropathy in the setting of diabetes and obesity in children and youth remain unknown. Data from adult studies and available youth cohort studies are providing an initial understanding of potential diagnostic, management, and preventative measures in early life. This review discusses the current state of knowledge emanating from these efforts, with particular emphasis on the prevalence, clinical presentation, diagnostic approaches and considerations, and risk factors of neuropathy in type 1 and type 2 diabetes in children and youth. Also highlighted are current management strategies and recommendations for neuropathy in children and youth with diabetes. This knowledge, along with continued and sustained emphasis on identifying and eliminating modifiable risk factors, completing randomized controlled trials to assess effectiveness of strategies like weight loss and exercise, and enhancing awareness to support early detection and prevention, are pertinent to addressing the rising incidence of neuropathy associated with diabetes and obesity in children and youth.
Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Incidence; Prevalence; Risk Factors; Young Adult
PubMed: 33205601
DOI: 10.1111/pedi.13153 -
Frontiers in Endocrinology 2023Diabetes sensory polyneuropathy (DSPN) is a significant complication of diabetes affecting up to 50% of patients in their lifetime and approximately 20% of patients... (Review)
Review
Diabetes sensory polyneuropathy (DSPN) is a significant complication of diabetes affecting up to 50% of patients in their lifetime and approximately 20% of patients suffer from painful diabetes neuropathic pain. DSPN - both painless and painful - leads to considerable morbidity including reduction of quality of life, increased lower limb amputations and is associated with worsening mortality. Significant progress has been made in the understanding of pathogenesis of DSPN and the last decade has seen newer techniques aimed at its earlier diagnosis. The management of painful DSPN remains a challenge despite advances made in the unravelling the pathogenesis of pain and its transmission. This article discusses the heterogenous clinical presentation of DSPN and the need to exclude key differential diagnoses. Furthermore, it reviews in detail the current diagnostic techniques involving both large and small neural fibres, their limitations and advantages and current place in the diagnosis of DSPN. Finally, the management of DSPN including newer pharmacotherapies are also discussed.
Topics: Humans; Quality of Life; Diabetic Neuropathies; Pain; Nerve Fibers; Diabetes Mellitus
PubMed: 37274325
DOI: 10.3389/fendo.2023.1165505 -
Oxidative Medicine and Cellular... 2020Diabetic neuropathy is one of the clinical syndromes characterized by pain and substantial morbidity primarily due to a lesion of the . The burden of diabetic neuropathy... (Review)
Review
Diabetic neuropathy is one of the clinical syndromes characterized by pain and substantial morbidity primarily due to a lesion of the . The burden of diabetic neuropathy is related not only to the complexity of diabetes but also to the poor outcomes and difficult treatment options. There is no specific treatment for diabetic neuropathy other than glycemic control and diligent foot care. Although various metabolic pathways are impaired in diabetic neuropathy, enhanced cellular oxidative stress is proposed as a common initiator. A mechanism-based treatment of diabetic neuropathy is challenging; a better understanding of the pathophysiology of diabetic neuropathy will help to develop strategies for the new and correct diagnostic procedures and personalized interventions. Thus, we review the current knowledge of the pathophysiology in diabetic neuropathy. We focus on discussing how the defects in metabolic and vascular pathways converge to enhance oxidative stress and how they produce the onset and progression of nerve injury present in diabetic neuropathy. We discuss if the mechanisms underlying neuropathy are similarly operated in type I and type II diabetes and the progression of antioxidants in treating diabetic neuropathy.
Topics: Diabetic Neuropathies; Humans; Oxidative Stress; Reactive Oxygen Species
PubMed: 32832011
DOI: 10.1155/2020/9524635 -
Frontiers in Endocrinology 2024
Topics: Humans; Diabetic Neuropathies; Early Diagnosis; Drug Therapy, Combination
PubMed: 38868745
DOI: 10.3389/fendo.2024.1422734 -
Diabetes Research and Clinical Practice Dec 2023Painful Diabetic Peripheral Neuropathy (PDN) is common, affecting around a quarter of patients with both type 1 and type 2 diabetes, and can lead to significant...
Painful Diabetic Peripheral Neuropathy (PDN) is common, affecting around a quarter of patients with both type 1 and type 2 diabetes, and can lead to significant curtailment of functionality and quality of life. Patients may present with unremitting burning, aching or "electric-shock" type pains in their feet, legs and later, in the hands. Conventional management approaches must focus not only on pain relief, but also on concurrent sleep problems, mood disorders and functionality. The mainstay of treatment is pharmacotherapy. Most current international guidelines recommend a choice of four drugs: amitriptyline, duloxetine, pregabalin or gabapentin, as initial treatment for PDN. Recent evidence from the OPTION-DM trial demonstrated that these drugs and their combinations have equivalent efficacy. Moreover, combination treatment provided significant pain relief to patients with inadequate response to the maximum tolerated dose of monotherapy. PDN refractory to pharmacotherapy can be treated with capsaicin 8% or high frequency spinal cord stimulation.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Quality of Life; Duloxetine Hydrochloride; Pain
PubMed: 38245323
DOI: 10.1016/j.diabres.2023.110765 -
Psychiatria Polska 2016Diabetes itself, by its nature, can aggravate the symptoms of depression. One of its main complications is peripheral diabetic neuropathy (PDN). Based on the literature... (Review)
Review
Diabetes itself, by its nature, can aggravate the symptoms of depression. One of its main complications is peripheral diabetic neuropathy (PDN). Based on the literature the presence of the relationship between the PDN and depression is confirmed. The symptoms connected with instability while walking and reduction of everyday activities were the strongest predictors of the intensification of depression symptoms. The relationship between the neuropathic ulcers and depression is considered as ambiguous. Additional problems in diagnosis and evaluation is the polyetiologic character of the disease, damage to the nerve fibers of different thickness, variety of methods of the diagnosis and differences in the prevalence of diabetic neuropathy (26%-50%). The presence of the described differences may be connected with diagnostic methods and the fact of the modification of perceived symptoms such as pain by the depression itself. One of the results of difficulties in describing the relationships and diagnosis are problems, described in the literature, with the selection of patients requiring treatment of PDN.
Topics: Adaptation, Psychological; Adult; Aged; Depression; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Prevalence; Self Report; Sex Factors
PubMed: 27288684
DOI: 10.12740/PP/OnlineFirst/42352 -
The Korean Journal of Internal Medicine Sep 2020Neuropathy is the most prevalent microvascular complication of diabetes mellitus; it encompasses distal symmetric polyneuropathy, autonomic neuropathy, radiculoplexus... (Review)
Review
Neuropathy is the most prevalent microvascular complication of diabetes mellitus; it encompasses distal symmetric polyneuropathy, autonomic neuropathy, radiculoplexus neuropathy, mononeuropathy, and treatment-induced neuropathy. The prevalence rate of diabetic neuropathy in Korea was reported to be approximately 43%, which is similar to rates in other countries. However, the precise pathogenic mechanism underlying diabetic neuropathy is still obscure, and many clinical trials have failed to develop methods to prevent or reduce the progression of diabetic neuropathy. Nevertheless, early diagnosis and proper management of diabetic neuropathy are essential to alleviate disabling symptoms and to improve the quality of life of patients. This review discusses clinical manifestations and classification of diabetic neuropathies, bedside neurological examination, and electrophysiological tests.
Topics: Diabetes Mellitus; Diabetic Neuropathies; Humans; Prevalence; Quality of Life; Republic of Korea
PubMed: 32921007
DOI: 10.3904/kjim.2020.202