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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 -
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 -
International Journal of Molecular... Dec 2021Diabetes mellitus (DM) leads to complications, the majority of which are nephropathy, retinopathy, and neuropathy. Redox imbalance and inflammation are important... (Review)
Review
Diabetes mellitus (DM) leads to complications, the majority of which are nephropathy, retinopathy, and neuropathy. Redox imbalance and inflammation are important components of the pathophysiology of these complications. Many studies have been conducted to find a specific treatment for these neural complications, and some of them have investigated the therapeutic potential of melatonin (MEL), an anti-inflammatory agent and powerful antioxidant. In the present article, we review studies published over the past 21 years on the therapeutic efficacy of MEL in the treatment of DM-induced neural complications. Reports suggest that there is a real prospect of using MEL as an adjuvant treatment for hypoglycemic agents. However, analysis shows that there is a wide range of approaches regarding the doses used, duration of treatment, and treatment times in relation to the temporal course of DM. This wide range hinders an objective analysis of advances and prospective vision of the paths to be followed for the unequivocal establishment of parameters to be used in an eventual therapeutic validation of MEL in neural complications of DM.
Topics: Animals; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Diabetic Retinopathy; Humans; Melatonin
PubMed: 35008523
DOI: 10.3390/ijms23010100 -
Annual Review of Medicine Jan 2024Diabetic neuropathy is a highly prevalent complication of diabetes. It consists of a broad range of neuropathic conditions, such as distal symmetric polyneuropathy and... (Review)
Review
Diabetic neuropathy is a highly prevalent complication of diabetes. It consists of a broad range of neuropathic conditions, such as distal symmetric polyneuropathy and various forms of autonomic neuropathies involving the cardiovascular, gastrointestinal, and urogenital systems. Prevention or diagnosis in early stages of disease is crucial to prevent symptomatic onset and progression, particularly in the absence of current disease-modifying therapies. In this review, we describe the four main types of diabetic neuropathy. We review current understanding with respect to diagnosis and treatment while highlighting knowledge gaps and future directions.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus
PubMed: 38285516
DOI: 10.1146/annurev-med-043021-033114 -
Biomedicine & Pharmacotherapy =... Jun 2022Diabetic neuropathy, also called peripheral diabetic neuropathy (PDN), is among the most significant diabetes health consequences, alongside diabetic nephropathy,... (Review)
Review
Diabetic neuropathy, also called peripheral diabetic neuropathy (PDN), is among the most significant diabetes health consequences, alongside diabetic nephropathy, diabetic cardiomyopathy and diabetic retinopathy. Diabetic neuropathy is the existence of signs and indications of peripheral nerve damage in patients with diabetes after other causes have been governed out. Diabetic neuropathy is a painful and severe complication of diabetes that affects roughly 20% of people. The development of diabetic neuropathy is regulated by blood arteries that nourish the peripheral nerves and metabolic problems such as increased stimulation of polyol pathway, loss of myo-inositol and enhanced non-enzymatic glycation. It's divided into four types based on where neurons are most affected: autonomic, peripheral, proximal, and focal, with each kind presenting different symptoms like numbing, gastrointestinal disorders, and heart concerns. Pharmacotherapy for neuropathic pain is complex and for many patients, effective treatment is lacking; as a result, scientific proof recommendations are crucial. As a result, the current demand is to give the most vital medications or combinations of drugs that work directly on the nerves to help diabetic neuropathy patients feel less pain without causing any adverse effects. In diabetic neuropathy research, animal models are ubiquitous, with rats and mice being the most typically chosen for various reasons. This review covers the epidemiology, clinical features, pathology, clinical symptom, mechanism of diabetic neuropathy development, diagnosis, screening models of animals, diabetic neuropathy pharmacotherapy.
Topics: Animals; Autonomic Nervous System; Diabetes Mellitus; Diabetic Nephropathies; Diabetic Neuropathies; Humans; Mice; Neuralgia; Rats; Treatment Outcome
PubMed: 35658222
DOI: 10.1016/j.biopha.2022.113025