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Molecular Medicine (Cambridge, Mass.) Jul 2023Diabetic peripheral neuropathy (DPN) is a major complication of diabetes. This study aimed to investigate the therapeutic effects and molecular mechanisms of Compound...
BACKGROUND
Diabetic peripheral neuropathy (DPN) is a major complication of diabetes. This study aimed to investigate the therapeutic effects and molecular mechanisms of Compound Qiying Granules (CQYG) for DPN.
METHODS
Rats and RSC96 cells of DPN models were established to evaluate the therapeutic effects of CQYG. Then the morphology and apoptotic changes of sciatic nerves were detected. Further, tandem mass tag based quantitative proteomics technology was used to identify differentially expressed proteins (DEPs) and the underlying molecular mechanisms. Protein expression of key signaling pathways was also detected.
RESULTS
CQYG treatment significantly improved blood glucose and oxidative stress levels, and further reduced nerve fiber myelination lesions, denervation, and apoptosis in DPN rats. Further, 2176 DEPs were found in CQYG treated DPN rats. Enrichment analysis showed that protein processing in the endoplasmic reticulum (ER), and apoptosis were all inhibited after CQYG treatment. Next, CQYG treatment reduced inflammatory factor expression, mitochondrial damage, and apoptosis in RSC96 cells which induced by high glucose. Transmission electron microscopy results found that CQYG treatment improved the morphology of nerve myelin, mitochondria, and ER. CQYG treatment decreased ER stress and apoptosis pathway proteins that were highly expressed in DPN models. In addition, we also predicted the potential targets of CQYG in DEPs.
CONCLUSIONS
CQYG exerts neuroprotective effects in experimental diabetic neuropathy through anti-ER stress and anti-apoptosis.
Topics: Rats; Animals; Diabetic Neuropathies; Rats, Sprague-Dawley; Endoplasmic Reticulum Stress; Myelin Sheath; Signal Transduction; Sciatic Nerve; Diabetes Mellitus
PubMed: 37464341
DOI: 10.1186/s10020-023-00698-3 -
Biomedicine & Pharmacotherapy =... Jan 2022Diabetes has become more common in recent years worldwide, and this growth is projected to continue in the future. The primary concern with diabetes is developing... (Review)
Review
Diabetes has become more common in recent years worldwide, and this growth is projected to continue in the future. The primary concern with diabetes is developing various complications, which significantly contribute to the disease's mortality and morbidity. Over time, the condition progresses from the pre-diabetic to the diabetic stage and then to the development of complications. Years and enormous resources are required to evaluate pharmacological interventions to prevent or delay the progression of disease or complications in humans. Appropriate screening models are required to gain a better understanding of both pathogenesis and potential therapeutic agents. Different species of animals are used to evaluate the pharmacological potentials and study the pathogenesis of the disease. Animal models are essential for research because they represent most of the structural, functional, and biochemical characteristics of human diseases. An ideal screening model should mimic the pathogenesis of the disease with identifiable characteristics. A thorough understanding of animal models is required for the experimental design to select an appropriate model. Each animal model has certain advantages and limitations. The present manuscript describes the animal models and their diagnostic characteristics to evaluate microvascular diabetic complications.
Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Disease Progression; Humans; Species Specificity
PubMed: 34872802
DOI: 10.1016/j.biopha.2021.112305 -
Communications Biology Dec 2021Diabetic neuropathy is one of the most prevalent chronic complications of diabetes, and up to half of diabetic patients will develop diabetic neuropathy during their... (Review)
Review
Diabetic neuropathy is one of the most prevalent chronic complications of diabetes, and up to half of diabetic patients will develop diabetic neuropathy during their disease course. Notably, emerging evidence suggests that glycemic variability is associated with the pathogenesis of diabetic complications and has emerged as a possible independent risk factor for diabetic neuropathy. In this review, we describe the commonly used metrics for evaluating glycemic variability in clinical practice and summarize the role and related mechanisms of glycemic variability in diabetic neuropathy, including cardiovascular autonomic neuropathy, diabetic peripheral neuropathy and cognitive impairment. In addition, we also address the potential pharmacological and non-pharmacological treatment methods for diabetic neuropathy, aiming to provide ideas for the treatment of diabetic neuropathy.
Topics: Blood Glucose; Diabetic Neuropathies; Humans
PubMed: 34876671
DOI: 10.1038/s42003-021-02896-3 -
Wiener Klinische Wochenschrift Jan 2023These are the guidelines for diagnosis and treatment of diabetic neuropathy and diabetic foot.The position statement summarizes characteristic clinical symptoms and...
These are the guidelines for diagnosis and treatment of diabetic neuropathy and diabetic foot.The position statement summarizes characteristic clinical symptoms and techniques for diagnostic assessment of diabetic neuropathy, including the complex situation of the diabetic foot syndrome. Recommendations for the therapeutic management of diabetic neuropathy, especially for the control of pain in sensorimotor neuropathy, are provided. The needs to prevent and treat diabetic foot syndrome are summarized.
Topics: Humans; Diabetic Neuropathies; Diabetic Foot; Pain; Syndrome; Diabetes Mellitus
PubMed: 37101039
DOI: 10.1007/s00508-023-02167-7 -
Journal of Diabetes Research 2021Currently, diabetic peripheral neuropathy (DPN) is one of the most severe complications of diabetes mellitus (DM). Despite the seriousness of this problem, limited... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Currently, diabetic peripheral neuropathy (DPN) is one of the most severe complications of diabetes mellitus (DM). Despite the seriousness of this problem, limited evidence is available on the prevalence of diabetic peripheral neuropathy among patients with diabetes mellitus in Ethiopia. In Ethiopia, there were no updated studies that estimate the national prevalence of DPN. Hence, this systematic review and meta-analysis provided a national prevalence of diabetic peripheral neuropathy among patients with diabetes mellitus in Ethiopia.
METHODS
This study was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) in March 2020 and accepted with the registration number CRD42020173831. Different database searching engines were searched online to retrieve related articles, including PubMed, Scopus, Google Scholar, African Journals Online, World Health Organization (WHO) Afro Library, and Cochrane Review. The reviewers used the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline in the reviewing process. In this systematic review and meta-analysis, all published and unpublished articles were analyzed. The reviewers used the random effects model to estimate the pooled prevalence of diabetic peripheral neuropathy among diabetes mellitus patients. The reviewers conducted the statistical analysis using the R version 3.5.3 and RStudio version 1.2.5033 software for Windows. The reviewers evaluated the heterogeneity across the included studies by the inconsistency index ( ). The reviewers examined the publication bias by the funnel plot.
RESULTS
The search of the databases produced 245 papers. After checking the inclusion and exclusion criteria, 38 articles with 14029 total patients with diabetes mellitus were found suitable for the review. Except for three (retrospective cohort study), all studies were cross-sectional. The overall pooled prevalence of diabetic peripheral neuropathy was 22% (95% CI 18% to 26%). The subgroup analysis of diabetic peripheral neuropathy among patients with diabetes in the different regions was 23% (95% CI 17% to 29%) in Addis Ababa, 27% (95% CI 16% to 38%) in Oromia, 16% (95% CI 14% to 18%) in South nation and nationalities, and 15% (95% CI 6% to 24%) in Amhara.
CONCLUSIONS
More than one-fifth of patients with diabetes have diabetic peripheral neuropathy. According to this study, the prevalence of diabetic peripheral neuropathy in Ethiopia is considerably high. This evidence suggests that attention should be given to patients with diabetes in monitoring patients' blood glucose.
Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Ethiopia; Humans; Prevalence
PubMed: 33628833
DOI: 10.1155/2021/5304124 -
Diabetes Care Oct 2022Different waveforms of spinal cord stimulation (SCS) have now been evaluated for the management of painful diabetic neuropathy (PDN). However, no direct or indirect... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Different waveforms of spinal cord stimulation (SCS) have now been evaluated for the management of painful diabetic neuropathy (PDN). However, no direct or indirect comparison between SCS waveforms has been performed to date.
PURPOSE
To conduct a systematic review and network meta-analysis to evaluate the effectiveness of SCS for PDN.
DATA SOURCES
MEDLINE, CENTRAL, Embase, and WikiStim were searched from inception until December 2021.
STUDY SELECTION
Randomized controlled trials (RCTs) of SCS for PDN were included.
DATA EXTRACTION
Pain intensity, proportion of patients achieving at least a 50% reduction in pain intensity, and health-related quality of life (HRQoL) data were extracted.
DATA SYNTHESIS
Significant reductions in pain intensity were observed for low-frequency SCS (LF-SCS) (mean difference [MD] -3.13 [95% CI -4.19 to -2.08], moderate certainty) and high-frequency SCS (HF-SCS) (MD -5.20 [95% CI -5.77 to -4.63], moderate certainty) compared with conventional medical management (CMM) alone. There was a significantly greater reduction in pain intensity on HF-SCS compared with LF-SCS (MD -2.07 [95% CI -3.26 to -0.87], moderate certainty). Significant differences were observed for LF-SCS and HF-SCS compared with CMM for the outcomes proportion of patients with at least 50% pain reduction and HRQoL (very low to moderate certainty). No significant differences were observed between LF-SCS and HF-SCS (very low to moderate certainty).
LIMITATIONS
Limited number of RCTs and no head-to-head RCTs conducted.
CONCLUSIONS
Our findings confirm the pain relief and HRQoL benefits of the addition of SCS to CMM for patients with PDN. However, in the absence of head-to-head RCT evidence, the relative benefits of HF-SCS compared with LF-SCS for patients with PDN remain uncertain.
Topics: Diabetes Mellitus; Diabetic Neuropathies; Humans; Network Meta-Analysis; Pain; Pain Measurement; Spinal Cord Stimulation
PubMed: 36150057
DOI: 10.2337/dc22-0932 -
Acta Diabetologica Nov 2021The first reports of a link between thiamine and diabetes date back to the 1940s. Some years later, a role for thiamine deficiency in diabetic neuropathy became evident,...
The first reports of a link between thiamine and diabetes date back to the 1940s. Some years later, a role for thiamine deficiency in diabetic neuropathy became evident, and some pilot studies evaluated the putative effects of thiamine supplementation. However, the administration of thiamine and its lipophilic derivative benfotiamine for the treatment of this complication gained consensus only at the end of the '90 s. The first evidence of the beneficial effects of thiamine on microvascular cells involved in diabetic complications dates to 1996: from then on, several papers based on in vitro and animal models have addressed the potential use of this vitamin in counteracting diabetic microangiopathy. A few pilot studies in humans reported beneficial effects of thiamine administration on diabetic nephropathy, but, despite all promising proofs-of-concept, the possible role of thiamine in counteracting development or progression of retinopathy has not been addressed until now. Thiamine is a water-soluble vitamin, rapidly expelled from the body, with no issues of over-dosage or accumulation; unfortunately, it is non-patentable, and neither industry nor independent donors are interested in investing in large-scale randomized controlled clinical trials to investigate its potential in diabetes and its complications. Consequently, science will not be able to disprove a promising hypothesis and, more importantly, diabetic people remain deprived of a possible way to ameliorate their condition.
Topics: Animals; Diabetes Complications; Diabetes Mellitus; Diabetic Nephropathies; Diabetic Neuropathies; Humans; Thiamine
PubMed: 34091762
DOI: 10.1007/s00592-021-01752-4 -
Journal of Diabetes Oct 2022Metformin is a hypoglycemic drug widely used in the treatment of type 2 diabetes. It has been proven to have analgesic and neuroprotective effects. Metformin can reverse... (Review)
Review
Metformin is a hypoglycemic drug widely used in the treatment of type 2 diabetes. It has been proven to have analgesic and neuroprotective effects. Metformin can reverse pain in rodents, such as diabetic neuropathic pain, neuropathic pain caused by chemotherapy drugs, inflammatory pain and pain caused by surgical incision. In clinical use, however, metformin is associated with reduced plasma vitamin B12 levels, which can further neuropathy. In rodent diabetes models, metformin plays a neuroprotective and analgesic role by activating adenosine monophosphate-activated protein kinase, clearing methylgloxal, reducing insulin resistance, and neuroinflammation. This paper also summarized the neurological adverse reactions of metformin in diabetic patients. In addition, whether metformin has sexual dimorphism needs further study.
Topics: Adenosine Monophosphate; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Hypoglycemic Agents; Metformin; Neuroprotective Agents; Pain; Protein Kinases; Vitamin B 12
PubMed: 36117320
DOI: 10.1111/1753-0407.13310 -
Nutrients Jan 2020Unhealthy dietary habits are major modifiable risk factors for the development of type 2 diabetes mellitus, a metabolic disease with increasing prevalence and serious... (Review)
Review
Unhealthy dietary habits are major modifiable risk factors for the development of type 2 diabetes mellitus, a metabolic disease with increasing prevalence and serious consequences. Microvascular complications of diabetes, namely diabetic peripheral neuropathy (DPN), retinopathy (DR), and nephropathy (DN), are associated with high morbidity rates and a heavy social and economic burden. Currently, available therapeutic options to counter the evolution of diabetic microvascular complications are clearly insufficient, which strongly recommends further research. Animal models are essential tools to dissect the molecular mechanisms underlying disease progression, to unravel new therapeutic targets, as well as to evaluate the efficacy of new drugs and/or novel therapeutic approaches. However, choosing the best animal model is challenging due to the large number of factors that need to be considered. This is particularly relevant for models induced by dietary modifications, which vary markedly in terms of macronutrient composition. In this article, we revisit the rodent models of diet-induced DPN, DR, and DN, critically comparing the main features of these microvascular complications in humans and the criteria for their diagnosis with the parameters that have been used in preclinical research using rodent models, considering the possible need for factors which can accelerate or aggravate these conditions.
Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Blood Glucose; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Diet, High-Fat; Dietary Carbohydrates; Disease Models, Animal; Humans; Species Specificity
PubMed: 31963709
DOI: 10.3390/nu12010250 -
Biomedicine & Pharmacotherapy =... Apr 2024Painful diabetic neuropathy (PDN) is a common chronic complication of diabetes that causes neuropathic pain and negatively affects the quality of life. The management of... (Review)
Review
Painful diabetic neuropathy (PDN) is a common chronic complication of diabetes that causes neuropathic pain and negatively affects the quality of life. The management of PDN is far from satisfactory. At present, interventions are primarily focused on symptomatic treatment. Ion channel disorders are a major cause of PDN, and a complete understanding of their roles and mechanisms may provide better options for the clinical treatment of PDN. Therefore, this review summarizes the important role of ion channels in PDN and the current drug development targeting these ion channels.
Topics: Humans; Diabetic Neuropathies; Quality of Life; Neuralgia; Drug Development; Diabetes Mellitus
PubMed: 38490158
DOI: 10.1016/j.biopha.2024.116417