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Nutrients Oct 2020To investigate the efficacy of Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine, and Vitamin B12 (B12) in one tablet in Diabetic Neuropathy (DN). (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
To investigate the efficacy of Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine, and Vitamin B12 (B12) in one tablet in Diabetic Neuropathy (DN).
PATIENTS-METHODS
In this prospective, double-blind, placebo-controlled study, 85 patients with Diabetes Mellitus Type 2 (DMT2) were randomly assigned, either to receive the combination of four elements (active group, = 43), or placebo ( = 42) for 12 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured the vibration perception threshold (BIO), and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Pain (PS) and quality of life (QL) questionnaires were administered.
RESULTS
At follow-up, BIO, MNSIQ, QL, PAIN, and SNCV, SNAP, and B12 levels had significantly improved inactive group ( <0.001, <0.001, <0.001, <0.001, = 0.027, = 0.031, and <0.001 respectively), whereas the inplacebo group MCR (mean circular resultant) and PAIN deteriorated ( <0.001, <0.001). The changes in MNSIQ, QL, SNCV, BIO, and PAIN differed significantly between groups ( <0.001, <0.001, = 0.031, <0.001, and <0.001 respectively).
CONCLUSIONS
The combination of the four elements in one tablet for 12 months in patients with DMT2 improved all indices of peripheral neuropathy, including SNAP and SNCV, pain, and Quality of Life perception, except CARTs and MNSIE.
Topics: Aged; Carnitine; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Neural Conduction; Pain Measurement; Prospective Studies; Quality of Life; Reflex; Superoxide Dismutase; Thioctic Acid; Treatment Outcome; Vitamin B 12
PubMed: 33114210
DOI: 10.3390/nu12113254 -
BMC Endocrine Disorders Feb 2021Advanced glycation end-products (AGEs) are heterogeneous molecules produced by the non-enzymatic glycation of proteins, lipids, or nucleic acids during hyperglycaemia.... (Review)
Review
Advanced glycation end-products (AGEs) are heterogeneous molecules produced by the non-enzymatic glycation of proteins, lipids, or nucleic acids during hyperglycaemia. Accumulation of AGEs in the peripheral nerves has recently been proposed as an additional risk factor for the development of diabetic neuropathy (DN). The gold standard for measurement of tissue-bound AGEs is tissue biopsy. However, their assessment with the newer, fast and simple method of skin autofluorescence (sAF) has recently gained special interest by virtue of its non-invasive, highly reproducible nature and its acceptable correlation with the reference method of skin biopsy. Accumulation of tissue AGEs evaluated by sAF has been shown to independently correlate with DN. Importantly, increasing evidence underscores their potential value as early biomarkers of the latter. Further important associations include diabetic nephropathy, diabetic retinopathy and cardiovascular autonomic neuropathy. However, the value of the implementation of screening with skin AGEs for DN remains unclear. The aim of the present review is to critically summarise current evidence on the association between skin AGEs and diabetic microvascular complications, with a particular emphasis on diabetic neuropathy, and to note the most important limitations of existing knowledge. Longer follow-up studies are also highly anticipated to clarify its role and provide data on patient selection and cost-effectiveness.
Topics: Diabetic Angiopathies; Diabetic Neuropathies; Glycation End Products, Advanced; Humans; Optical Imaging; Skin
PubMed: 33622304
DOI: 10.1186/s12902-021-00697-7 -
Current Opinion in Lipidology Aug 2021Hyperlipidaemia is associated with the development of neuropathy. Indeed, a mechanistic link between altered lipid metabolism and peripheral nerve dysfunction has been... (Review)
Review
PURPOSE OF REVIEW
Hyperlipidaemia is associated with the development of neuropathy. Indeed, a mechanistic link between altered lipid metabolism and peripheral nerve dysfunction has been demonstrated in a number of experimental and clinical studies. Furthermore, post hoc analyses of clinical trials of cholesterol and triglyceride-lowering pharmacotherapy have shown reduced rates of progression of diabetic neuropathy. Given, there are currently no FDA approved disease-modifying therapies for diabetic neuropathy, modulation of lipids may represent a key therapeutic target for the treatment of diabetic nerve damage. This review summarizes the current evidence base on the role of hyperlipidaemia and lipid lowering therapy on the development and progression of peripheral neuropathy.
RECENT FINDINGS
A body of literature supports a detrimental effect of dyslipidaemia on nerve fibres resulting in somatic and autonomic neuropathy. The case for an important modulating role of hypertriglyceridemia is stronger than for low-density lipoprotein cholesterol (LDL-C) in relation to peripheral neuropathy. This is reflected in the outcomes of clinical trials with the different therapeutic agents targeting hyperlipidaemia reporting beneficial or neutral effects with statins and fibrates. The potential concern with the association between proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy and cognitive decline raised the possibility that extreme LDL-C lowering may result in neurodegeneration. However, studies in murine models and data from small observational studies indicate an association between increased circulating PCSK9 levels and small nerve fibre damage with a protective effect of PCSK9i therapy against small fibre neuropathy. Additionally, weight loss with bariatric surgery leads to an improvement in peripheral neuropathy and regeneration of small nerve fibres measured with corneal confocal microscopy in people with obesity with or without type 2 diabetes. These improvements correlate inversely with changes in triglyceride levels.
SUMMARY
Hyperlipidaemia, particularly hypertriglyceridemia, is associated with the development and progression of neuropathy. Lipid modifying agents may represent a potential therapeutic option for peripheral neuropathy. Post hoc analyses indicate that lipid-lowering therapies may halt the progression of neuropathy or even lead to regeneration of nerve fibres. Well designed randomized controlled trials are needed to establish if intensive targeted lipid lowering therapy as a part of holistic metabolic control leads to nerve fibre regeneration and improvement in neuropathy symptoms.
Topics: Animals; Diabetic Neuropathies; Humans; Hyperlipidemias; Lipids
PubMed: 34101657
DOI: 10.1097/MOL.0000000000000770 -
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 -
Endocrine, Metabolic & Immune Disorders... 2020Alpha-lipoic acid (ALA) was used in the treatment of diabetic peripheral neuropathy (DPN) using different routes, doses and treatment durations. The aim of this work is... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Alpha-lipoic acid (ALA) was used in the treatment of diabetic peripheral neuropathy (DPN) using different routes, doses and treatment durations. The aim of this work is to assess the efficacy of oral 600mg ALA twice daily over 6 months in the treatment of patients with DPN.
METHODS
This is a prospective, single-center, double-blinded, placebo-controlled study conducted at the outpatient clinic of Mansoura Specialized Hospital, Mansoura University. A total of 200 patients with DPN were randomly assigned to add on treatment with either oral 600mg twice daily ALA (n=100) or placebo (n=100) for 6 months. Treatment outcome was assessed using vibration perception threshold (VPT), neurological symptom score (NSS), neurological disability score (NDS), and visual analog scale (VAS) for pain at baseline and at each visit (1, 3 and 6 months) after the start of treatment.
RESULTS
Comparison between the study groups regarding the baseline data revealed no statistically significant differences. with respect to the outcome parameters, no significant differences were found between the studied groups at baseline. However, in subsequent visits, ALA-treated patients had significantly better results regarding almost all the outcome parameters (NSS, NDS, VAS, VPT). Mild nausea was reported in 6 patients. None of the studied patients discontinued treatment.
CONCLUSION
Oral 600mg ALA twice-daily treatment for DPN over 6 months is effective, safe and tolerable.
Topics: Administration, Oral; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Female; Humans; Male; Middle Aged; Prospective Studies; Thioctic Acid; Treatment Outcome
PubMed: 32370731
DOI: 10.2174/1871530320666200506081407 -
Archives of Physiology and Biochemistry Apr 2023The prevalence of diabetic neuropathy is drastically increasing in the world. To halt the progression of diabetic neuropathy, there is an unmet need to have potential...
CONTEXT
The prevalence of diabetic neuropathy is drastically increasing in the world. To halt the progression of diabetic neuropathy, there is an unmet need to have potential biomarkers for the diagnosis and new drug discovery.
OBJECTIVE
To study various biomarkers involved in the pathogenesis of diabetic neuropathy.
METHODS
The literature was searched with the help of various scientific databases and resources like PubMed, ProQuest, Scopus, and Google scholar from the year 1976 to 2020.
RESULTS
Biomarkers of diabetic neuropathy are categorised as inflammatory biomarkers such as MCP-1, VEGF, TRPV1, NF-κB; oxidative biomarkers such as adiponectin, NFE2L2; enzyme biomarkers like NADPH, ceruloplasmin, HO-1, DPP-4, PARP α; miscellaneous biomarkers such as SIRT1, caveolin 1, MALAT1, and microRNA. All biomarkers have a significant role in the pathogenesis of diabetic neuropathy.
CONCLUSION
These biomarkers have a potential role in the progression of diabetic neuropathy and can be considered as potential targets for new drug discovery.
Topics: Humans; Diabetic Neuropathies; NF-kappa B; Biomarkers; Diabetes Mellitus
PubMed: 33186087
DOI: 10.1080/13813455.2020.1837183 -
Current Diabetes Reviews 2022
Topics: Diabetes Mellitus; Diabetic Neuropathies; Humans
PubMed: 35545970
DOI: 10.2174/157339981805220407104606 -
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 -
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