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Expert Opinion on Pharmacotherapy Jan 2021The global epidemic of diabetes has led to an epidemic of diabetes complications. Diabetic neuropathy is the most common microvascular complication, of which diabetic... (Review)
Review
INTRODUCTION
The global epidemic of diabetes has led to an epidemic of diabetes complications. Diabetic neuropathy is the most common microvascular complication, of which diabetic peripheral neuropathy (DPN) and autonomic neuropathy (AN) are the most prevalent, affecting ~50% of patients. DPN results in pain with a poor quality of life and a loss of sensation with an increased risk of foot ulceration. Autonomic neuropathy can cause significant morbidity in a minority and is associated with increased mortality. The cornerstone of treatment to prevent or limit the progression of DPN/AN is multifactorial risk factor modification including treatment of glycemia, lipids and blood pressure. Whilst, there are no FDA-approved disease-modifying therapies, there are a number of therapies to relieve symptoms in DPN and AN.
AREAS COVERED
The authors discuss current approved therapies for painful diabetic neuropathy and autonomic neuropathy. They also address the potential role of improving risk factors to limit the development and progression of diabetic neuropathy and new pathogenetic and pain-relieving treatments.
EXPERT OPINION
The FDA-approved Pregabalin and Duloxetine over 25 years ago and Tapentadol, 6 years ago for painful diabetic neuropathy. There are currently no FDA-approved disease-modifying treatments for diabetic neuropathy which has been attributed to inappropriate models of the disease with limited translational capacity and major limitations of trial designs and endpoints in clinical trials.
Topics: Diabetic Neuropathies; Humans; Pain; Quality of Life; Risk Factors; Tapentadol
PubMed: 32866410
DOI: 10.1080/14656566.2020.1812578 -
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 -
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 -
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 -
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 -
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 -
Diabetes Research and Clinical Practice Jul 2023Diabetic neuropathy is associated with increased risk of morbidity and all-cause mortality. It is unclear whether these outcomes differ in patients with diabetic...
Morbidity and mortality of patients with diabetic neuropathy treated with pathogenetically oriented alpha-lipoic acid versus symptomatic pharmacotherapies - A nationwide database analysis from Hungary.
AIMS
Diabetic neuropathy is associated with increased risk of morbidity and all-cause mortality. It is unclear whether these outcomes differ in patients with diabetic neuropathy treated with pathogenetically oriented vs symptomatic pharmacotherapies.
METHODS
We performed a retrospective (2009-2019) database analysis of patients treated with pathogenetically oriented alpha-lipoic acid (ALA) or symptomatic pharmacotherapies for diabetic neuropathy. We investigated clinical outcomes in propensity score matched patients in Hungary. Changes in hazard ratios and annualized event rates were assessed and sensitivity analyses performed.
RESULTS
Hazard ratios favored treatment with ALA vs symptomatic pharmacotherapies regarding acute myocardial infarction (HR 0.73, 95% CI: 0.60-0.89, p = 0.0016), stroke (HR 0.71, 95% CI: 0.62-0.82, p < 0.0001), hospitalization for heart failure (HR 0.72, 95% CI: 0.66-0.78, p < 0.0001), cancer events (HR 0.83, 95% CI: 0.76-0.92, p = 0.0002) and all-cause mortality (HR 0.55, 95% CI: 0.49-0.61, p < 0.0001), but not for lower limb amputation (HR 1.05, 95% CI: 0.89-1.25, p = 0.5455). This association was supported by results of evaluating annual event rates and sensitivity analyses.
CONCLUSIONS
This retrospective database analysis revealed a lower occurrence of cardio- and cerebrovascular morbidity, cancer events and all-cause mortality in patients with diabetic neuropathy treated with pathogenetically oriented ALA vs symptomatic pharmacotherapies. This hypothesis-generating result requires further investigations.
Topics: Humans; Thioctic Acid; Diabetic Neuropathies; Retrospective Studies; Hungary; Antioxidants; Diabetes Mellitus
PubMed: 37257759
DOI: 10.1016/j.diabres.2023.110734 -
Molecular Neurobiology Mar 2022Accelerating cases of diabetes worldwide have given rise to higher incidences of diabetic complications. MiRNAs, a much-explored class of non-coding RNAs, play a... (Review)
Review
Accelerating cases of diabetes worldwide have given rise to higher incidences of diabetic complications. MiRNAs, a much-explored class of non-coding RNAs, play a significant role in the pathogenesis of diabetes mellitus by affecting insulin release, β-cell proliferation, and dysfunction. Besides, disrupted miRNAs contribute to various complications, diabetic retinopathy, nephropathy, and neuropathy as well as severe conditions like diabetic foot. MiRNAs regulate various processes involved in diabetic complications like angiogenesis, vascularization, inflammations, and various signaling pathways like PI3K, MAPK, SMAD, and NF-KB signaling pathways. Diabetic neuropathy is the most common diabetic complication, characterized mainly by pain and numbness, especially in the legs and feet. MiRNAs implicated in diabetic neuropathy include mir-9, mir-106a, mir-146a, mir-182, miR-23a and b, miR-34a, and miR-503. The diabetic foot is the most common diabetic neuropathy, often leading to amputations. Mir-203, miR-23c, miR-145, miR-29b and c, miR-126, miR-23a and b, miR-503, and miR-34a are associated with diabetic foot. This review has been compiled to summarize miRNA involved in initiation, progression, and miRNAs affecting various signaling pathways involved in diabetic neuropathy including the diabetic foot. Besides, potential applications of miRNAs as biomarkers and therapeutic targets in this microvascular complication will also be discussed.
Topics: Diabetes Mellitus; Diabetic Neuropathies; Diabetic Retinopathy; Humans; Insulin; MicroRNAs; Signal Transduction
PubMed: 35023058
DOI: 10.1007/s12035-021-02662-w -
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 -
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