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Diabetes Research and Clinical Practice Dec 2023Diabetic peripheral neuropathy (DPN) is found in around one third of people with diabetes, but remains inadequately diagnosed and treated. Its management includes three... (Review)
Review
Diabetic peripheral neuropathy (DPN) is found in around one third of people with diabetes, but remains inadequately diagnosed and treated. Its management includes three cornerstones: 1) causal treatment with lifestyle modification, intensive diabetes therapy aimed at near-normoglycemia, and multifactorial cardiovascular risk intervention, 2) pathogenesis-oriented pharmacotherapy, and 3) symptomatic pain relief. Since symptomatic analgesic monotherapy only relieves the pain without targeting the underlying neuropathy and both has limited efficacy and is associated with adverse events, there is an unmet need for additional approaches derived from the pathogenetic concepts of DPN. Preclinical studies have suggested that diabetic neuropathy can be prevented or improved through the use of various agents that interfere with the pathophysiology of the underlying condition. Some of these encouraging findings could be translated successfully into the clinical setting. Efficacy and excellent safety were demonstrated in several meta-analyses (α-lipoic acid) and randomized clinical trials (benfotiamine, actovegin, epalrestat) in the treatment of symptomatic DPN. The NATHAN 1 trial demonstrated an improvement of neuropathic signs (deficits, impairments) after four years in asymptomatic DPN. These compounds are currently authorized for treatment of DPN in several countries. Long-term pivotal clinical trials should further establish their value as mono- and combination therapies in DPN.
Topics: Humans; Combined Modality Therapy; Diabetes Mellitus; Diabetic Neuropathies; Pain; Thioctic Acid
PubMed: 38245327
DOI: 10.1016/j.diabres.2023.110764 -
Diabetes Research and Clinical Practice Dec 2023The diabetic neuropathies represent the commonest long-term complications of diabetes, and may be the presenting feature of Type 2 diabetes. In clinical practice, distal... (Review)
Review
The diabetic neuropathies represent the commonest long-term complications of diabetes, and may be the presenting feature of Type 2 diabetes. In clinical practice, distal symmetrical polyneuropathy (DSPN) and the autonomic neuropathies are the most frequently seen forms of diabetic neuropathy. The 2017 American Diabetes Association classification system for the neuropathies of diabetes are in general use. Treatment challenges remain and the need for revised recommendations and further discussion of management of severely painful DSPN that does not fully respond to conventional medical management is clear, especially in light of the recent opioid crisis in the USA.
Topics: Humans; Autonomic Nervous System; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Pain; Polyneuropathies
PubMed: 38245328
DOI: 10.1016/j.diabres.2023.110758 -
Current Pain and Headache Reports Jun 2024Diabetic neuropathy is a debilitating complication of diabetes mellitus that affects millions of individuals worldwide. It is characterized by nerve damage resulting... (Review)
Review
PURPOSE OF REVIEW
Diabetic neuropathy is a debilitating complication of diabetes mellitus that affects millions of individuals worldwide. It is characterized by nerve damage resulting from prolonged exposure to high blood glucose levels. Diabetic neuropathy may cause a range of symptoms, including pain, numbness, muscle weakness, autonomic dysfunction, and foot ulcers, potentially causing significant impairment to the quality of life for those affected. This review article aims to provide a comprehensive overview of the pathophysiology of diabetic neuropathy. The etiology of diabetic neuropathy will be discussed, including risk factors, predisposing conditions, and an overview of the complex interplay between hyperglycemia, metabolic dysregulation, and nerve damage. Additionally, we will explore the molecular mechanisms and pathways of diabetic neuropathy, including the impact of hyperglycemia on nerve function, abnormalities in glucose metabolism, the role of advanced glycation end products (AGEs), and inflammatory and immune-mediated processes. We will provide an overview of the various nerve fibers affected by diabetic neuropathy and explore the common symptoms and complications associated with diabetic neuropathy in the pain medicine field.
RECENT FINDINGS
This review highlights advances in understanding the pathophysiology of diabetic neuropathy as well as reviews potential novel therapeutic strategies and promising areas for future research. In conclusion, this review article aims to shed light on the pathophysiology of diabetic neuropathy, its far-reaching consequences, and the evolving strategies for prevention and management. In understanding the mechanisms of diabetic neuropathy and the ongoing research in this area, healthcare professionals can better serve patients with diabetes, ultimately improving well-being and reducing complications.
Topics: Humans; Diabetic Neuropathies; Risk Factors; Hyperglycemia
PubMed: 38558164
DOI: 10.1007/s11916-024-01243-5 -
JAMA Dec 2023
Topics: Humans; Diabetes Mellitus; Diabetic Foot; Quality of Life; Wound Healing
PubMed: 37976071
DOI: 10.1001/jama.2023.17291 -
Pain Practice : the Official Journal of... Feb 2024Pain as a symptom of diabetic polyneuropathy (DPN) significantly lowers quality of life, increases mortality and is the main reason for patients with diabetes to seek... (Review)
Review
INTRODUCTION
Pain as a symptom of diabetic polyneuropathy (DPN) significantly lowers quality of life, increases mortality and is the main reason for patients with diabetes to seek medical attention. The number of people suffering from painful diabetic polyneuropathy (PDPN) has increased significantly over the past decades.
METHODS
The literature on the diagnosis and treatment of diabetic polyneuropathy was retrieved and summarized.
RESULTS
The etiology of PDPN is complex, with primary damage to peripheral nociceptors and altered spinal and supra-spinal modulation. To achieve better patient outcomes, the mode of diagnosis and treatment of PDPN evolves toward more precise pain-phenotyping and genotyping based on patient-specific characteristics, new diagnostic tools, and prior response to pharmacological treatments. According to the Toronto Diabetic Neuropathy Expert Group, a presumptive diagnosis of "probable PDPN" is sufficient to initiate treatment. Proper control of plasma glucose levels, and prevention of risk factors are essential in the treatment of PDPN. Mechanism-based pharmacological treatment should be initiated as early as possible. If symptomatic pharmacologic treatment fails, spinal cord stimulation (SCS) should be considered. In isolated cases, where symptomatic pharmacologic treatment and SCS are unsuccessful or cannot be used, sympathetic lumbar chain neurolysis and/or radiofrequency ablation (SLCN/SLCRF), dorsal root ganglion stimulation (DRGs) or posterior tibial nerve stimulation (PTNS) may be considered. However, it is recommended that these treatments be applied only in a study setting in a center of expertise.
CONCLUSIONS
The diagnosis of PDPN evolves toward pheno-and genotyping and treatment should be mechanism-based.
Topics: Humans; Diabetic Neuropathies; Pain Management; Quality of Life; Pain Measurement; Pain; Spinal Cord Stimulation; Diabetes Mellitus
PubMed: 37859565
DOI: 10.1111/papr.13308 -
Diabetes Research and Clinical Practice Dec 2023This article summarizes the latest epidemiology of diabetic autonomic neuropathy (DAN), and provides a brief overview on epidemiology, current outcomes measures for... (Review)
Review
This article summarizes the latest epidemiology of diabetic autonomic neuropathy (DAN), and provides a brief overview on epidemiology, current outcomes measures for screening and diagnosis in research and clinical settings, the latest evidence on effective management, and novel perspectives on the impacts of social determinants of health in development and management of DAN. Among the various forms of diabetic neuropathy, distal symmetric polyneuropathy and diabetic autonomic neuropathies, particularly cardiovascular autonomic neuropathy, are by far the most studied. However, emerging data highlight the impact of other forms of autonomic neuropathies such as gastrointestinal and urogenital autonomic neuropathies, on healthcare and patients' reported outcomes [1].
Topics: Humans; Diabetic Neuropathies
PubMed: 38245325
DOI: 10.1016/j.diabres.2023.110762 -
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 -
Frontiers in Endocrinology 2023Previous observational studies have indicated an association between serum uric acid (SUA) and diabetic neuropathy (DN), but confounding factors and reverse causality...
BACKGROUND
Previous observational studies have indicated an association between serum uric acid (SUA) and diabetic neuropathy (DN), but confounding factors and reverse causality have left the causality of this relationship uncertain.
METHODS
Univariate Mendelian randomization (MR), multivariate MR and linkage disequilibrium score (LDSC) regression analysis were utilized to assess the causal link between SUA and DN. Summary-level data for SUA were drawn from the CKDGen consortium, comprising 288,648 individuals, while DN data were obtained from the FinnGen consortium, with 2,843 cases and 271,817 controls. Causal effects were estimated primarily using inverse variance weighted (IVW) analysis, supplemented by four validation methods, with additional sensitivity analyses to evaluate pleiotropy, heterogeneity, and result robustness.
RESULTS
The LDSC analysis revealed a significant genetic correlation between SUA and DN (genetic correlation = 0.293, P = 2.60 × 10). The primary methodology IVW indicated that each increase of 1 mg/dL in SUA would increase DN risk by 17% (OR = 1.17, 95% CI 1.02-1.34, P = 0.02), while no causal relationship was found in reverse analysis (OR = 1.00, 95% CI 0.98~1.01, = 0.97). Multivariate MR further identified that the partial effect of SUA on DN may be mediated by physical activity, low density lipoprotein cholesterol (LDL-C), insulin resistance (IR), and alcohol use.
CONCLUSION
The study establishes a causal link between elevated SUA levels and an increased risk of DN, with no evidence for a reverse association. This underscores the need for a comprehensive strategy in DN management, integrating urate-lowering interventions with modulations of the aforementioned mediators.
Topics: Humans; Diabetic Neuropathies; Mendelian Randomization Analysis; Uric Acid; Alcohol Drinking; Cholesterol, LDL; Diabetes Mellitus
PubMed: 38034019
DOI: 10.3389/fendo.2023.1277984 -
Molecular Neurobiology Aug 2023Diabetic peripheral neuropathy (DPN) is a major complication of diabetes mellitus with a high incidence. Oxidative stress, which is a crucial pathophysiological pathway... (Review)
Review
Diabetic peripheral neuropathy (DPN) is a major complication of diabetes mellitus with a high incidence. Oxidative stress, which is a crucial pathophysiological pathway of DPN, has attracted much attention. The distortion in the redox balance due to the overproduction of reactive oxygen species (ROS) and the deregulation of antioxidant defense systems promotes oxidative damage in DPN. Therefore, we have focused on the role of oxidative stress in the pathogenesis of DPN and elucidated its interaction with other physiological pathways, such as the glycolytic pathway, polyol pathway, advanced glycosylation end products, protein kinase C pathway, inflammation, and non-coding RNAs. These interactions provide novel therapeutic options targeting oxidative stress for DPN. Furthermore, our review addresses the latest therapeutic strategies targeting oxidative stress for the rehabilitation of DPN. Antioxidant supplements and exercise have been proposed as fundamental therapeutic strategies for diabetic patients through ROS-mediated mechanisms. In addition, several novel drug delivery systems can improve the bioavailability of antioxidants and the efficacy of DPN.
Topics: Humans; Reactive Oxygen Species; Antioxidants; Diabetic Neuropathies; Oxidative Stress; Glycation End Products, Advanced; Diabetes Mellitus
PubMed: 37115404
DOI: 10.1007/s12035-023-03342-7 -
Diabetes/metabolism Research and Reviews Oct 2023Increasing numbers of reports link vitamin D deficiency to diabetic peripheral neuropathy (DPN), yet evidence regarding neurological deficits and electromyogram is...
AIMS
Increasing numbers of reports link vitamin D deficiency to diabetic peripheral neuropathy (DPN), yet evidence regarding neurological deficits and electromyogram is scarce. The present multi-centre study sought to investigate these associations based on objective quantifications.
MATERIALS AND METHODS
Information on DPN-related symptoms, signs, all diabetic microvascular complications, and nerve conduction abilities (quantified by nerve conduction amplitude and velocity, F-wave minimum latency (FML) of peripheral nerves) were collected from a derivation cohort of 1192 patients with type 2 diabetes (T2D). Correlation, regression analysis, and restricted cubic splines (RCS) were used to explore linear and non-linear relationships between vitamin D and DPN, which were validated in an external cohort of 223 patients.
RESULTS
Patients with DPN showed lower levels of vitamin D than those without DPN; patients with vitamin D deficiency (<30 nmol/L) tended to suffer more DPN-related neurological deficits (paraesthesia, prickling, abnormal temperature, ankle hyporeflexia, and distal pall hypoesthesia correlating with MNSI-exam score (Y = -0.005306X + 2.105, P = 0.048). Worse nerve conduction abilities (decreased motor nerve amplitude, sensory nerve amplitude, motor nerve velocity, and increased FML) were also observed in these patients. Vitamin D had a significant threshold association with DPN (adjusted OR = 4.136, P = 0.003; RCS P for non-linearity = 0.003) and correlates with other microvascular complications (diabetic retinopathy and diabetic nephropathy).
CONCLUSIONS
Vitamin D is associated with the conduction ability of peripheral nerves and may have a nerve- and threshold-selective relationship with the prevalence and severity of DPN among patients with T2D.
Topics: Humans; Diabetes Mellitus, Type 2; Vitamin D; Diabetic Neuropathies; East Asian People; Fluorometholone; Nerve Conduction Studies; Neural Conduction; Vitamin D Deficiency
PubMed: 37337761
DOI: 10.1002/dmrr.3679