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Khanna S, Kumar S, Sharma P, Daksh R, Nandakumar K, Shenoy RR. Flavonoids regulating NLRP3 inflammasome: a promising approach in alleviating diabetic peripheral neuropathy. Inflammopharmacology 2025:10.1007/s10787-025-01729-7. [PMID: 40205269 DOI: 10.1007/s10787-025-01729-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 01/25/2025] [Indexed: 04/11/2025]
Abstract
A common and serious side effect of diabetes is diabetic peripheral neuropathy (DPN), which is characterised by gradual nerve damage brought on by oxidative stress, chronic inflammation, and prolonged hyperglycemia. Studies identify NLRP3 inflammasome as a key mediator in the pathogenesis of DPN, connecting neuroinflammation and neuronal damage to metabolic failure. Because of their strong anti-inflammatory and antioxidant qualities, flavonoids, a broad class of naturally occurring polyphenols, have drawn interest as potential treatments for DPN. The various ways that flavonoids affect the NLRP3 inflammasome and their potential as a treatment for DPN are examined in this review. It has been demonstrated that flavonoids prevent NLRP3 activation, which lowers the release of pro-inflammatory cytokines including IL-1β and IL-18 and causes neuroinflammation. Flavonoids work mechanistically by reducing oxidative stress, altering important signalling pathways, and blocking the activities of NF-κB and caspase-1, which are both essential for the activation of the NLRP3 inflammasome. Preclinical research has shown that flavonoids have strong neuroprotective benefits, and few clinical evidence also points to the potential of flavonoids to improve nerve function and lessen neuropathic pain in diabetic patients. The current review emphasises how flavonoids may be used as a treatment strategy to target inflammation in DPN caused by the NLRP3 inflammasome. By targeting important inflammatory pathways, flavonoids provide a new way to slow the progression of this debilitating illness. Further investigation into the mechanisms, clinical translation, and novel drug delivery techniques could enhance the therapeutic efficacy of diabetic peripheral neuropathy.
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Affiliation(s)
- Saumya Khanna
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India, 576104
| | - Sachindra Kumar
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India, 576104
| | - Pratyasha Sharma
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India, 576104
| | - Rajni Daksh
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India, 576104
| | - Krishnadas Nandakumar
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India, 576104
| | - Rekha Raghuveer Shenoy
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India, 576104.
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Khurshid S, Saeed A, Kashif M, Nasreen A, Riaz H. Effects of multisystem exercises on balance, postural stability, mobility, walking speed, and pain in patients with diabetic peripheral neuropathy: a randomized controlled trial. BMC Neurosci 2025; 26:16. [PMID: 40016658 PMCID: PMC11869634 DOI: 10.1186/s12868-024-00924-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Accepted: 12/31/2024] [Indexed: 03/01/2025] Open
Abstract
BACKGROUND Diabetic peripheral neuropathy (DPN), a common complication of diabetes mellitus, is associated with peripheral nerve damage, leading to balance impairments, postural instability, and reduced mobility. Addressing these challenges requires comprehensive interventions that target multiple deficits simultaneously. Evidence suggests that exercise programs combining balance, proprioception, strength, and reaction time training can improve postural stability, enhance mobility, and alleviate pain in individuals with DPN. OBJECTIVE The objective of this study was to compare the effects of multisystem exercises and conventional exercises on balance, postural stability, mobility, and walking speed and to reduce pain in patients with diabetic peripheral neuropathy. METHODS This double-blinded, two-arm parallel design randomized controlled trial was conducted at DHQ Hospital, Pakpattan, Pakistan. A total of 50 participants who met the inclusion criteria were recruited using the nonprobability convenience sampling technique. They were randomly assigned to either a multisystem physical exercise (MPE) group (n = 26) and a conventional exercise group (n = 24). The MPE program included balance, proprioception, strength, and reaction time training, while the control group received conventional exercises, consisted of strength, balance, stretching, and range of motion exercises. Both groups underwent 30 min intervention sessions, 3 times per week, for 8 weeks. The outcome measures used for assessing the balance, postural stability, mobility, and pain included the Berg balance scale (BBS), functional reach test (FRT), time up and go test (TUG), 10 min walk test (10-MWT), and numeric pain rating scale (NPRS). The data was analyzed using SPSS version 26. RESULTS Significant group and time interactions were observed for all outcome measures including BBS, FRT, TUG, 10-MWT, and NPRS (p < 0.001). The between-group analysis also revealed significant differences between the multisystem physical exercise group and the conventional exercise group at both the 4th week and 8th week for BBS, FRT, TUG, 10-MWT, and NPRS (p < 0.05). CONCLUSION The study concluded that multisystem exercises resulted in significant improvement in balance, postural stability, mobility, and walking speed, along with reduction in pain, compared to conventional exercises in patients with diabetic peripheral neuropathy. TRIAL REGISTRATION This randomized controlled study was registered prospectively on November 11th, 2023 with the ClinicalTrials.gov (NCT06130917).
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Affiliation(s)
- Sidra Khurshid
- Riphah College of Rehabilitation and Allied Health Sciences, Riphah International University, Lahore Campus, Islamabad, Pakistan
| | - Aruba Saeed
- Faculty of Rehabilitation Sciences, Lahore University of Biological and Applied Sciences, Lahore, Pakistan.
| | - Muhammad Kashif
- Riphah College of Rehabilitation and Allied Health Sciences, Riphah International University, Lahore Campus, Islamabad, Pakistan
| | - Aniqa Nasreen
- Riphah College of Rehabilitation and Allied Health Sciences, Riphah International University, Lahore Campus, Islamabad, Pakistan
| | - Huma Riaz
- Riphah College of Rehabilitation and Allied Health Sciences, Riphah International University, Lahore Campus, Islamabad, Pakistan
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Zheng S, Zhu M, Fan G, Yang X, Bai M. Application value of strain elastography and shear wave elastography in patients with type 2 diabetic peripheral neuropathy: a prospective observational study. Br J Radiol 2025; 98:280-286. [PMID: 39504467 DOI: 10.1093/bjr/tqae227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 08/24/2024] [Accepted: 11/04/2024] [Indexed: 11/08/2024] Open
Abstract
OBJECTIVE To evaluate the value of conventional ultrasound (US), strain elastography (SE), and shear wave elastography (SWE) in detecting diabetic peripheral neuropathy (DPN) of the tibial nerve (TN), and to establish a predictive model for the diagnosis of DPN. METHODS A total of 32 healthy participants, 34 diabetic patients without DPN, and 36 diabetic patients with DPN were recruited for this study. The TN at the ankle and popliteal fossa were selected for examination. US was used to measure the cross-sectional area (CSA) and perimeter of the TN. Additionally, SE was used to measure the strain ratio (SR) between the TN and the surrounding adipose tissue, and SWE was used to measure the shear wave velocity (SWV) of the TN. RESULTS The CSA, perimeter, SR, and SWV of the TN at the ankle were significantly higher in the DPN group compared to both the Non-DPN group and control group (P < .05). Similarly, the TN at the popliteal fossa showed these differences. At the ankle, the CSA, perimeter, SR, and SWV of the TN in patients without DPN were significantly higher than those in the control group (P < .05). At the popliteal fossa, the SR and SWV of the TN in patients without DPN were significantly higher than those in the control group (P < .05). However, the CSA and perimeter of the TN in patients without DPN did not show a statistically significant difference compared to the control group. The area under the curve (AUC) for the diagnosis of DPN using SWE is significantly greater than that of SE and US. CONCLUSION US, SE, and SWE could be used to diagnose DPN, and they also have good diagnostic value for sub-clinical DPN. Among these methods, SWE has demonstrated superior diagnostic efficacy. Compared to examining the TN in the popliteal fossa, the ankle level offers a better site for examination. ADVANCES IN KNOWLEDGE For diabetic peripheral neuropathy, US, SE, and SWE are all promising diagnostic methods with high clinical utility.
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Affiliation(s)
- Siqi Zheng
- Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Miao Zhu
- Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Gaoxiang Fan
- Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Xueting Yang
- Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Min Bai
- Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
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Sango K, Yako H, Niimi N, Takaku S. Immortalized Schwann cell lines as useful tools for pathogenesis-based therapeutic approaches to diabetic peripheral neuropathy. Front Endocrinol (Lausanne) 2025; 15:1531209. [PMID: 39906036 PMCID: PMC11790431 DOI: 10.3389/fendo.2024.1531209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 12/24/2024] [Indexed: 02/06/2025] Open
Abstract
Growing evidence suggests that hyperglycemia-related abnormalities in Schwann cells play a pivotal role in the development and progression of diabetic peripheral neuropathy (DPN). Several immortalized Schwann cell lines have been established in our laboratory and utilized for the study of DPN; IMS32 from normal ICR mice, 1970C3 from normal C57BL/6 mice, IWARS1 and IKARS1 from wild-type and aldose reductase-deficient C57BL/6 mice, and IFRS1 from normal Fischer 344 rats. These cell lines retain biological features of Schwann cells and display high proliferative activities that enable us to perform molecular and biochemical analyses. In addition, these cells have exhibited metabolic alterations under exposure to diabetes-associated conditions, such as hyperglycemia, dyslipidemia, glycative and oxidative stress load. Herein, recent studies with these cell lines regarding the pathogenic factors of DPN (augmentation of the polyol and other collateral glycolysis pathways, glycative and oxidative stress-induced cell injury, autophagic and proteostatic disturbances, etc.) and therapeutic strategies targeting these factors are introduced.
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Affiliation(s)
- Kazunori Sango
- Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
| | - Hideji Yako
- Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
- Laboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Naoko Niimi
- Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
| | - Shizuka Takaku
- Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
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Debash MN, Kumie G, Sisay A, Gedfie S, Abebe W, Ashagre A, Misganaw T, Debash H, Reta MA. Burden of intestinal parasites among diabetic patients in Africa: a systematic review and meta-analysis. BMC Infect Dis 2025; 25:54. [PMID: 39799295 PMCID: PMC11724454 DOI: 10.1186/s12879-025-10441-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 01/02/2025] [Indexed: 01/15/2025] Open
Abstract
BACKGROUND Intestinal parasite infections remain a serious public health concern around the world, particularly in countries with inadequate sanitation. The study aims to ascertain the total magnitude of intestinal parasites in diabetes patients throughout the African countries. OBJECTIVE The aim of this systematic review and meta-analysis was to determine the general burden of intestinal parasites among diabetic patients in Africa. METHODS A systematic search was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol for studies reporting intestinal parasite infections in patients with diabetes through January 01/2000 to August13/2024. The collected data were analyzed using STATA software version 17. Seven case-control studies and nine cross-sectional studies were included in this study. Heterogeneity across studies was assessed using Cochran's Q statistic and I2 statistics. Subgroup analysis was carried out when the I2 value exceeded 50%, indicating substantial heterogeneity. RESULTS In the current systematic review and meta-analysis, the pooled prevalence of intestinal parasites in diabetic patients was 31% (95% CI: 23-38%) with heterogeneity of I2 = 95.94%; P < 0.001. The highest prevalence based on geographical area was in region of the Egypt 39% (95% CI: 26-52%), and based on study design was in case control studies 40% (95% CI: 28-52%). Poor hygiene and sanitation(P < 0.001), as well as diabetes mellitus status (P < 0.001), were statistically significant factors associated with patients who have diabetes. CONCLUSION Patients with diabetes are a high-risk group for intestinal parasitic infections and should be prioritized for screening. Therefore, it is essential to implement preventative measures for these patients.
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Affiliation(s)
- Marye Nigatie Debash
- Department of Medical Laboratory Science, College of Health Sciences, Woldia University, P.O. box 400, Woldia, Ethiopia.
| | - Getinet Kumie
- Department of Medical Laboratory Science, College of Health Sciences, Woldia University, P.O. box 400, Woldia, Ethiopia
| | - Assefa Sisay
- Department of Medical Laboratory Science, College of Health Sciences, Woldia University, P.O. box 400, Woldia, Ethiopia
| | - Solomon Gedfie
- Department of Medical Laboratory Science, College of Health Sciences, Woldia University, P.O. box 400, Woldia, Ethiopia
| | - Wagaw Abebe
- Department of Medical Laboratory Science, College of Health Sciences, Woldia University, P.O. box 400, Woldia, Ethiopia
| | - Agenagnew Ashagre
- Department of Medical Laboratory Science, College of Health Sciences, Woldia University, P.O. box 400, Woldia, Ethiopia
| | - Tadesse Misganaw
- Department of Medical Laboratory Science, College of Health Sciences, Woldia University, P.O. box 400, Woldia, Ethiopia
| | - Habtu Debash
- Department of Medical Laboratory Science, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
| | - Melese Abate Reta
- Department of Medical Laboratory Science, College of Health Sciences, Woldia University, P.O. box 400, Woldia, Ethiopia
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El Souda SS, Ahmed HH, Maamoun AA, Matloub AA, Aglan HA. Chemical Profile and Potential Application of Agri-food Waste Products for Counteracting Diabetes Induced Neuropathy in Rats. Chem Biodivers 2024; 21:e202400843. [PMID: 39140441 DOI: 10.1002/cbdv.202400843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 07/05/2024] [Accepted: 08/01/2024] [Indexed: 08/15/2024]
Abstract
This study aimed to prepare defatted ethanol extract of Abelmoschus esculentus leaves, Morus nigra leaves and Punica granatum peel, to identify the chemical composition of these extracts and to explore their efficacy in counteracting diabetic neuropathy. LC-ESI-MS spectrometry was the hyphenated tool for component identification of these extracts. Behavioral, biochemical, and histopathological investigations were carried out after treatments of diabetic rats. The phenolic contents in the extracts are 16.38, 34.75 and 40.57 mg GAE/g extract regarding A. esculentus leaves, M. nigra leaves and P. granatum peel respectively. Chemodiversity of the phenolic contents was observed from the LC/Mass, where A. esculentus extract contained isoflavonoids and flavanones, M. nigra extract consisted of benzofurans, prenylated flavonoids, stilbenes, and xanthones, and P. granatum extract was rich in ellagitanins, condensed tannins, and anthocyanins. The extracts normalize of blood glucose levels, enhance the explorative behavior of the rats and their response time to thermal pain, restore the oxidant/antioxidant balance, attenuate inflammation, augment brain monoamines levels and modulate MAO-A and Ache enzyme activity. Furthermore, they recovered brain histopathological alterations. Conclusively, this study offers experimental evidence for the neuroprotective impact of studied defatted ethanol extracts against diabetic neuropathy via their hypoglycemic effect, antioxidant activity, and anti-inflammatory potential.
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Affiliation(s)
- Sahar S El Souda
- Chemistry of Natural Compounds Department, National Research Centre, 33 El Buhouth St, Giza, Dokki, P.O.12622 (ID: 60014618), Cairo, Egypt
| | - Hanaa H Ahmed
- Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Dokki, Egypt
| | - Amal A Maamoun
- Pharmacognosy Department, National Research Centre, 33 El Buhouth St, Cairo, Giza, Dokki, P.O.12622 (ID:60014618), Egypt
| | - Azza A Matloub
- Pharmacognosy Department, National Research Centre, 33 El Buhouth St, Cairo, Giza, Dokki, P.O.12622 (ID:60014618), Egypt
| | - Hadeer A Aglan
- Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Dokki, Egypt
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Sriwastawa K, Kumar A. Mitochondrial dysfunction in diabetic neuropathy: Impaired mitophagy triggers NLRP3 inflammasome. Mitochondrion 2024; 79:101972. [PMID: 39362475 DOI: 10.1016/j.mito.2024.101972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 08/28/2024] [Accepted: 09/30/2024] [Indexed: 10/05/2024]
Abstract
Diabetic neuropathy is one of the challenging complications of diabetes and is characterized by peripheral nerve damage due to hyperglycemia in diabetes. Mitochondrial dysfunction has been reported as one of the key pathophysiological factor contributing to nerve damage in diabetic neuropathy, clinically manifesting as neurodegenerative changes like functional and sensorimotor deficits. Accumulating evidence suggests a clear correlation between mitochondrial dysfunction and NLRP3 inflammasome activation. Unraveling deeper molecular aspects of mitochondrial dysfunction may provide safer and effective therapeutic alternatives. This review links mitochondrial dysfunction and appraises its role in the pathophysiology of diabetic neuropathy. We have also tried to delineate the role of mitophagy in NLRP3 inflammasome activation in experimental diabetic neuropathy.
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Affiliation(s)
- Keshari Sriwastawa
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Punjab, India
| | - Ashutosh Kumar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S Nagar, Punjab, India.
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Jali AM, Banji D, Banji OJF, Hurubi KY, Tawhari FY, Alameer AA, Dohal AS, Zanqoti RA. Navigating Preclinical Models and Medications for Peripheral Neuropathy: A Review. Pharmaceuticals (Basel) 2024; 17:1010. [PMID: 39204115 PMCID: PMC11357099 DOI: 10.3390/ph17081010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 07/24/2024] [Accepted: 07/26/2024] [Indexed: 09/03/2024] Open
Abstract
Peripheral neuropathy (PN) is a multifaceted disorder characterised by peripheral nerve damage, manifesting in symptoms like pain, weakness, and autonomic dysfunction. This review assesses preclinical models in PN research, evaluating their relevance to human disease and their role in therapeutic development. The Streptozotocin (STZ)-induced diabetic rat model is widely used to simulate diabetic neuropathy but has limitations in faithfully replicating disease onset and progression. Cisplatin-induced PN models are suitable for studying chemotherapy-induced peripheral neuropathy (CIPN) and closely resemble human pathology. However, they may not fully replicate the spectrum of sensory and motor deficits. Paclitaxel-induced models also contribute to understanding CIPN mechanisms and testing neuroprotective agents. Surgical or trauma-induced models offer insights into nerve regeneration and repair strategies. Medications such as gabapentin, pregabalin, duloxetine, and fluoxetine have demonstrated promise in these models, enhancing our understanding of their therapeutic efficacy. Despite progress, developing models that accurately mirror human PN remains imperative due to its complex nature. Continuous refinement and innovative approaches are critical for effective drug discovery. This review underscores the strengths and limitations of current models and advocates for an integrated approach to address the complexities of PN better and optimise treatment outcomes.
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Affiliation(s)
- Abdulmajeed M. Jali
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia; (D.B.); (K.Y.H.); (F.Y.T.); (A.A.A.); (A.S.D.); (R.A.Z.)
| | - David Banji
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia; (D.B.); (K.Y.H.); (F.Y.T.); (A.A.A.); (A.S.D.); (R.A.Z.)
| | - Otilia J. F. Banji
- Department of Clinical Pharmacy, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia;
| | - Khalid Y. Hurubi
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia; (D.B.); (K.Y.H.); (F.Y.T.); (A.A.A.); (A.S.D.); (R.A.Z.)
| | - Faisal Y. Tawhari
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia; (D.B.); (K.Y.H.); (F.Y.T.); (A.A.A.); (A.S.D.); (R.A.Z.)
| | - Atheer A. Alameer
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia; (D.B.); (K.Y.H.); (F.Y.T.); (A.A.A.); (A.S.D.); (R.A.Z.)
| | - Atyaf S. Dohal
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia; (D.B.); (K.Y.H.); (F.Y.T.); (A.A.A.); (A.S.D.); (R.A.Z.)
| | - Raha A. Zanqoti
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia; (D.B.); (K.Y.H.); (F.Y.T.); (A.A.A.); (A.S.D.); (R.A.Z.)
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Sharma J, Ahmad I, Singh AKC. Effects of exercises and manual therapy on nerve conduction studies of lower limb in patients with diabetes and diabetic peripheral neuropathy: A systematic review. Int J Diabetes Dev Ctries 2024; 44:241-264. [DOI: 10.1007/s13410-023-01258-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 09/25/2023] [Indexed: 01/04/2025] Open
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Dilixiati D, Waili A, Tuerxunmaimaiti A, Tao L, Zebibula A, Rexiati M. Risk factors for erectile dysfunction in diabetes mellitus: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2024; 15:1368079. [PMID: 38638136 PMCID: PMC11024441 DOI: 10.3389/fendo.2024.1368079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 03/19/2024] [Indexed: 04/20/2024] Open
Abstract
Background Previous studies have established that diabetes mellitus (DM) markedly raises the risk of developing erectile dysfunction (ED). Despite extensive investigations, the risk factors associated with ED in diabetic men have yet to be unequivocally determined, owing to incongruent and inconclusive results reported in various studies. Objective The objective of this systematic review and meta-analysis was to assess the risk factors for ED in men with DM. Methods A comprehensive systematic review was conducted, encompassing studies published in the PubMed, Scopus and Embase databases up to August 24th, 2023. All studies examining the risk factors of ED in patients with DM were included in the analysis. To identify significant variations among the risk factors, odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were employed. The risk of bias was evaluated using the Newcastle-Ottawa Scale(NOS) for longitudinal studies and the Agency for Healthcare Research and Quality Scale(AHRQ) for cross-sectional studies. Results A total of 58 studies, including a substantial participant pool of 66,925 individuals diagnosed with DM, both with or without ED, were included in the meta-analysis. Mean age (OR: 1.31, 95% CI=1.24-1.37), smoking status (OR: 1.32, 95% CI=1.18-1.47), HbA1C (OR: 1.44, 95% CI=1.28-1.62), duration of DM (OR: 1.39, 95% CI=1.29-1.50), diabetic neuropathy (OR: 3.47, 95% CI=2.16-5.56), diabetic retinopathy (OR: 3.01, 95% CI=2.02-4.48), diabetic foot (OR: 3.96, 95% CI=2.87-5.47), cardiovascular disease (OR: 1.92, 95% CI=1.71-2.16), hypertension (OR: 1.74, 95% CI=1.52-2.00), microvascular disease (OR: 2.14, 95% CI=1.61-2.85), vascular disease (OR: 2.75, 95% CI=2.35-3.21), nephropathy (OR: 2.67, 95% CI=2.06-3.46), depression (OR: 1.82, 95% CI=1.04-3.20), metabolic syndrome (OR: 2.22, 95% CI=1.98-2.49), and diuretic treatment (OR: 2.42, 95% CI=1.38-4.22) were associated with increased risk factors of ED in men with DM. Conclusion Our study indicates that in men with DM, several risk factors for ED have been identified, including mean age, HbA1C, duration of DM, diabetic neuropathy, diabetic retinopathy, diabetic foot, cardiovascular disease, hypertension, microvascular disease, vascular disease, nephropathy, depression, metabolic syndrome, and diuretic treatment. By clarifying the connection between these risk factors and ED, clinicians and scientific experts can intervene and address these risk factors, ultimately reducing the occurrence of ED and improving patient management.
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Affiliation(s)
- Diliyaer Dilixiati
- Department of Urology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Alapati Waili
- Department of Pancreatic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Aizihaier Tuerxunmaimaiti
- Department of Cardiac Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Liwen Tao
- Department of Pancreatic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Abudureheman Zebibula
- Department of Urology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Mulati Rexiati
- Department of Urology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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Kulkarni A, Thool AR, Daigavane S. Understanding the Clinical Relationship Between Diabetic Retinopathy, Nephropathy, and Neuropathy: A Comprehensive Review. Cureus 2024; 16:e56674. [PMID: 38646317 PMCID: PMC11032697 DOI: 10.7759/cureus.56674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 03/21/2024] [Indexed: 04/23/2024] Open
Abstract
Diabetic retinopathy, nephropathy, and neuropathy are significant microvascular complications of diabetes mellitus, contributing to substantial morbidity and mortality worldwide. This comprehensive review examines the clinical relationship between these complications, focusing on shared pathophysiological mechanisms, bidirectional relationships, and implications for patient management. The review highlights the importance of understanding the interconnected nature of diabetic complications and adopting a holistic approach to diabetes care. Insights gleaned from this review underscore the necessity for early detection, timely intervention, and integrated care models involving collaboration among healthcare professionals. Furthermore, the review emphasizes the need for continued research to elucidate underlying mechanisms, identify novel therapeutic targets, and assess the efficacy of integrated care strategies in improving patient outcomes. By fostering interdisciplinary collaboration and knowledge exchange, future research endeavors hold the potential to advance our understanding and management of diabetic complications, ultimately enhancing patient care and quality of life.
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Affiliation(s)
- Aditi Kulkarni
- Ophthalmology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Archana R Thool
- Ophthalmology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sachin Daigavane
- Ophthalmology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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12
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Salama RAM, Raafat FA, Hasanin AH, Hendawy N, Saleh LA, Habib EK, Hamza M, Hassan ANE. A neuroprotective effect of pentoxifylline in rats with diabetic neuropathy: Mitigation of inflammatory and vascular alterations. Int Immunopharmacol 2024; 128:111533. [PMID: 38271813 DOI: 10.1016/j.intimp.2024.111533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 01/03/2024] [Accepted: 01/09/2024] [Indexed: 01/27/2024]
Abstract
BACKGROUND Treatment of diabetic neuropathic pain does not change the natural history of neuropathy. Improved glycemic control is the recommended treatment in these cases, given that no specific treatment for the underlying nerve damage is available, so far. In the present study, the potential neuroprotective effect of pentoxifylline in streptozotocin (50 mg/kg) induced diabetic neuropathy in rats was investigated. METHODS Pentoxifylline was administered at doses equivalent to 50, 100 & 200 mg/kg, in drinking water, starting one week after streptozotocin injection and for 7 weeks. Mechanical allodynia, body weight and blood glucose level were assessed weekly. Epidermal thickness of the footpad skin, and neuroinflammation and vascular alterations markers were assessed. RESULTS Tactile allodynia was less in rats that received pentoxifylline at doses of 100 and 200 mg/kg (60 % mechanical threshold increased by 48 % and 60 %, respectively). The decrease in epidermal thickness of footpad skin was almost completely prevented by the same doses. This was associated with a decrease in spinal tumor necrosis factor alpha (TNFα) and nuclear factor kappa B levels and a decrease in microglial ionized calcium binding adaptor molecule 1 immunoreactivity, compared to the control diabetic group. In sciatic nerve, there was decrease in TNF-α and vascular endothelial growth factor levels and intercellular adhesion molecule immunoreactivity. CONCLUSION Pentoxifylline showed a neuroprotective effect in streptozotocin-induced diabetic neuropathy, which was associated with a suppression of both the inflammatory and vascular pathogenic pathways that was not associated with a hypoglycemic effect. Thus, it may represent a potential neuroprotective drug for diabetics.
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Affiliation(s)
- Raghda A M Salama
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Fatema Ahmed Raafat
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Amany Helmy Hasanin
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Nevien Hendawy
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; Faculty of Medicine, Galala University, Suez, Egypt
| | - Lobna A Saleh
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Eman K Habib
- Faculty of Medicine, Galala University, Suez, Egypt; Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - May Hamza
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
| | - Ahmed Nour Eldin Hassan
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; Faculty of Medicine, Galala University, Suez, Egypt
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13
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Suzuki M, Kuromi H, Shindo M, Sakata N, Niimi N, Fukui K, Saitoe M, Sango K. A Drosophila model of diabetic neuropathy reveals a role of proteasome activity in the glia. iScience 2023; 26:106997. [PMID: 37378316 PMCID: PMC10291573 DOI: 10.1016/j.isci.2023.106997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 03/31/2023] [Accepted: 05/25/2023] [Indexed: 06/29/2023] Open
Abstract
Diabetic peripheral neuropathy (DPN) is the most common chronic, progressive complication of diabetes mellitus. The main symptom is sensory loss; the molecular mechanisms are not fully understood. We found that Drosophila fed a high-sugar diet, which induces diabetes-like phenotypes, exhibit impairment of noxious heat avoidance. The impairment of heat avoidance was associated with shrinkage of the leg neurons expressing the Drosophila transient receptor potential channel Painless. Using a candidate genetic screening approach, we identified proteasome modulator 9 as one of the modulators of impairment of heat avoidance. We further showed that proteasome inhibition in the glia reversed the impairment of noxious heat avoidance, and heat-shock proteins and endolysosomal trafficking in the glia mediated the effect of proteasome inhibition. Our results establish Drosophila as a useful system for exploring molecular mechanisms of diet-induced peripheral neuropathy and propose that the glial proteasome is one of the candidate therapeutic targets for DPN.
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Affiliation(s)
- Mari Suzuki
- Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan
| | - Hiroshi Kuromi
- Learning and Memory Project, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan
| | - Mayumi Shindo
- Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan
| | - Nozomi Sakata
- Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan
- Department of Bioscience and Engineering, Shibaura Institute of Technology, Saitama 337-8570, Japan
| | - Naoko Niimi
- Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan
| | - Koji Fukui
- Department of Bioscience and Engineering, Shibaura Institute of Technology, Saitama 337-8570, Japan
| | - Minoru Saitoe
- Learning and Memory Project, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan
| | - Kazunori Sango
- Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan
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14
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Fan T, Yu Y, Chen YL, Gu P, Wong S, Xia ZY, Liu JA, Cheung CW. Histone deacetylase 5-induced deficiency of signal transducer and activator of transcription-3 acetylation contributes to spinal astrocytes degeneration in painful diabetic neuropathy. Glia 2023; 71:1099-1119. [PMID: 36579750 DOI: 10.1002/glia.24328] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 11/24/2022] [Accepted: 12/15/2022] [Indexed: 12/30/2022]
Abstract
Diabetes patients with painful diabetic neuropathy (PDN) show severe spinal atrophy, suggesting pathological changes of the spinal cord contributes to central sensitization. However, the cellular changes and underlying molecular mechanisms within the diabetic spinal cord are less clear. By using a rat model of type 1 diabetes (T1D), we noted an extensive and irreversible spinal astrocyte degeneration at an early stage of T1D, which is highly associated with the chronification of PDN. Molecularly, acetylation of astrocytic signal transducer and activator of transcription-3 (STAT3) that is essential for maintaining the homeostatic astrocytes population was significantly impaired in the T1D model, resulting in a dramatic loss of spinal astrocytes and consequently promoting pain hypersensitivity. Mechanistically, class IIa histone deacetylase, HDAC5 were aberrantly activated in spinal astrocytes of diabetic rats, which promoted STAT3 deacetylation by direct protein-protein interactions, leading to the PDN phenotypes. Restoration of STAT3 signaling or inhibition of HDAC5 rescued astrocyte deficiency and attenuated PDN in the T1D model. Our work identifies the inhibitory axis of HDAC5-STAT3 induced astrocyte deficiency as a key mechanism underlying the pathogenesis of the diabetic spinal cord that paves the way for potential therapy development for PDN.
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Affiliation(s)
- Tingting Fan
- Department of Anaesthesiology, Laboratory and Clinical Research Institute for Pain, The University of Hong Kong, Hong Kong, Hong Kong SAR
| | - Ying Yu
- Department of Anaesthesiology, Laboratory and Clinical Research Institute for Pain, The University of Hong Kong, Hong Kong, Hong Kong SAR
| | - Yong-Long Chen
- Department of Anaesthesiology, Laboratory and Clinical Research Institute for Pain, The University of Hong Kong, Hong Kong, Hong Kong SAR
| | - Pan Gu
- Department of Anaesthesiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Stanley Wong
- Department of Anaesthesiology, Laboratory and Clinical Research Institute for Pain, The University of Hong Kong, Hong Kong, Hong Kong SAR
| | - Zheng-Yuan Xia
- Department of Medicine, State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Hong Kong SAR.,Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Jessica Aijia Liu
- Department of Neuroscience, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR
| | - Chi-Wai Cheung
- Department of Anaesthesiology, Laboratory and Clinical Research Institute for Pain, The University of Hong Kong, Hong Kong, Hong Kong SAR.,Department of Anaesthesiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
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15
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Asano-Hayami E, Morishita Y, Hayami T, Shibata Y, Kiyose T, Sasajima S, Hayashi Y, Motegi M, Kato M, Asano S, Nakai-Shimoda H, Yamada Y, Miura-Yura E, Himeno T, Kondo M, Tsunekawa S, Kato Y, Nakamura J, Kamiya H. Clinical parameters correlated with the psoas muscle index in Japanese individuals with type 2 diabetes mellitus. Diabetol Int 2023; 14:76-85. [PMID: 36636163 PMCID: PMC9829932 DOI: 10.1007/s13340-022-00602-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 08/28/2022] [Indexed: 01/16/2023]
Abstract
Aims Muscle atrophy is a diabetic complication, which results in a deterioration in glycemic control in type 2 diabetes mellitus (T2DM) individuals. The psoas muscle mass index (PMI) is a reliable indicator for estimating whole-body muscle mass. We aimed to examine the relationship between clinical parameters and the PMI to clarify the mechanism underlying muscle atrophy in diabetes. Methods This retrospective, cross-sectional study examined 51 patients (31 men and 20 women) with T2DM and a mean HbA1c value of 9.9 ± 1.7%. These patients were admitted to Aichi Medical University Hospital and underwent abdominal computed tomography imaging from July 2020 to April 2021. Multiple clinical parameters were assessed with the PMI. Results In a multiple regression analysis adjusted for age and sex, the PMI was correlated with body weight, body mass index, serum concentrations of corrected calcium, aspartate aminotransferase, alanine aminotransferase, creatine kinase, thyroid-stimulating hormone (TSH), urinary C-peptide concentrations, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, and the young adult mean score at the femur neck. Receiver operating characteristic curves were created using TSH concentrations and the FT3/FT4 ratio for diagnosing a low PMI. The area under the curve was 0.593 and 0.699, respectively. The cut-off value with maximum accuracy for TSH concentrations was 1.491 μIU/mL, sensitivity was 56.1%, and specificity was 80.0%. Corresponding values for the FT3/FT4 ratio were 1.723, 78.0, and 66.7%, respectively. Conclusion TSH concentrations and the FT3/FT4 ratio are correlated with the PMI, and their thresholds may help prevent muscle mass loss in Japanese individuals with T2DM.
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Affiliation(s)
- Emi Asano-Hayami
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Yoshiaki Morishita
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Tomohide Hayami
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Yuka Shibata
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
- Department of Clinical Laboratory, Aichi Medical University Hospital, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Toshiki Kiyose
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Sachiko Sasajima
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Yusuke Hayashi
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Mikio Motegi
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Makoto Kato
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Saeko Asano
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Hiromi Nakai-Shimoda
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Yuichiro Yamada
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Emiri Miura-Yura
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Tatsuhito Himeno
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
- Department of Innovative Diabetes Therapy, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Masaki Kondo
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Shin Tsunekawa
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Yoshiro Kato
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Jiro Nakamura
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
- Department of Innovative Diabetes Therapy, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
| | - Hideki Kamiya
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195 Japan
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Zibaei M, Bahadory S, Saadati H, Pourrostami K, Firoozeh F, Foroutan M. Intestinal parasites and diabetes: A systematic review and meta-analysis. New Microbes New Infect 2022; 51:101065. [PMID: 36654940 PMCID: PMC9841285 DOI: 10.1016/j.nmni.2022.101065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 12/09/2022] [Accepted: 12/09/2022] [Indexed: 12/25/2022] Open
Abstract
Background Investigating the association between infectious agents and non-communicable diseases is an interesting emerging field of research. Intestinal parasites (IPs) are one of the causes of gastrointestinal complications, malnutrition, growth retardation and disturbances in host metabolism, which can play a potential role in metabolic diseases such as diabetes. The aim of the present study was to investigate the prevalence of IPs in diabetic patients and the association between IPs and diabetes. Methods A systematic literature search was conducted from January 2000 to November 2022in published records by using PubMed, Scopus, and Web of Science databases as well as Google scholar search engine; Out of a total of 29 included studies, fourteen cross-sectional studies (2676 diabetic subjects) and 15 case-control studies (5478 diabetic/non-diabetic subjects) were reviewed. The pooled prevalence of IPs in diabetics and the Odds Ratio (OR) were evaluated by CMA V2. Results In the current systematic review and meta-analysis, the pooled prevalence of IPs in diabetic patients was 26.5% (95% CI: 21.8-31.7%) with heterogeneity of I2 = 93.24%; P < 0.001. The highest prevalence based on geographical area was in Region of the Americas (13.3% (95% CI: 9.6-18.0)).There was significant association between the prevalence of intestinal parasites in diabetic cases compared to controls (OR, 1.72; 95% CI: 1.06-2.78). Conclusion In line with the high prevalence of IPs in diabetic patients, significant association was found however, due to the limitations of the study, more studies should be conducted in developing countries and, the prevalence of IPs in diabetics should not be neglected.
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Affiliation(s)
- Mohammad Zibaei
- Department of Parasitology and Mycology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran,Evidence-based Phytotherapy and Complementary Medicine Research Center, Alborz University of Medical Sciences, Karaj, Iran,Corresponding author. Evidence-based Phytotherapy and Complementary Medicine Research Center, Alborz University of Medical Sciences, Karaj, Iran.
| | - Saeed Bahadory
- Department of Parasitology and Mycology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran,Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran,Corresponding author. Department of Parasitology and Mycology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
| | - Hassan Saadati
- Department of Epidemiology and Biostatistics, School of Health, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Kumars Pourrostami
- Department of Pediatrics, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Farzaneh Firoozeh
- Department of Microbiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Masoud Foroutan
- Department of Basic Medical Sciences, Faculty of Medicine, Abadan University of Medical Sciences, Abadan, Iran
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17
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Zhang W, Chen L, Lou M. Association of Elevated Serum Uric Acid with Nerve Conduction Function and Peripheral Neuropathy Stratified by Gender and Age in Type 2 Diabetes Patients. Brain Sci 2022; 12:brainsci12121704. [PMID: 36552164 PMCID: PMC9775627 DOI: 10.3390/brainsci12121704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/05/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
Background: The relationship between serum uric acid (SUA) level and diabetic peripheral neuropathy (DPN) remains controversial. We aimed to investigate the association between SUA level and DPN and evaluate the effects of SUA level on nerve conduction function via electromyography in patients with type 2 diabetes (T2DM), stratified by gender and age. Methods: This cross-sectional study included 647 inpatients with T2DM from the First Affiliated Hospital of Wenzhou Medical University between February 2017 and October 2020. The diagnosis of DPN was confirmed according to the Toronto Expert Consensus. Clinical data, SUA level, and nerve conduction parameters were obtained from electronic medical records. Results: A total of 647 patients with T2DM were included, and 471 patients were diagnosed with DPN. The level of SUA was higher in the DPN group than in the Non-DPN group (330.58 ± 99.67 vs. 309.16 ± 87.04, p < 0.05). After adjustment, a higher SUA level was associated with the presence of DPN [odds ratio (OR) 1.003, 95% confidence interval (CI), 1.001−1.005; p = 0.017]. The area under the curve for the prediction of DPN was 0.558 (95% CI, 0.509−0.608; p = 0.022), and the optimized cut-off of SUA level was 297.5 µmol/L. The SUA > 297.5 µmol/L level was independently associated with DPN in the male subgroup (OR 2.507, 95% CI, 1.405−4.473; p = 0.002) rather than in the female subgroup. Besides, SUA > 297.5 µmol/L was independently associated with DPN in the younger subgroup (age < 65 years) (OR 2.070, 95% CI, 1.278−3.352; p = 0.003) rather than in the older subgroup. In multiple linear regression analysis, SUA was significantly correlated with certain nerve conduction study parameters in the all patients group, and was also observed in the male and younger subgroups. Conclusions: Elevated SUA was independently associated with poorer nerve conduction functions, and hyperuricemia was also significantly associated with a higher risk of developing DPN in T2DM patients, especially in male and younger patients.
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Affiliation(s)
- Wanli Zhang
- Department of Neurology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009, China
| | - Lingli Chen
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Min Lou
- Department of Neurology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009, China
- Correspondence: ; Tel.: +86-571-87784810; Fax: +86-571-87784850
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18
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Mert T, Sahin E, Yaman S, Sahin M. Pulsed magnetic field treatment ameliorates the progression of peripheral neuropathy by modulating the neuronal oxidative stress, apoptosis and angiogenesis in a rat model of experimental diabetes. Arch Physiol Biochem 2022; 128:1658-1665. [PMID: 32633145 DOI: 10.1080/13813455.2020.1788098] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
OBJECTIVE The present study aimed to investigate the possible anti-neuropathic effects of daily pulsed magnetic field treatments (PMF) in streptozotocin (60 mg/kg) induced 4 weeks diabetic (type-1) wistar rats (6-8 months). MATERIALS AND METHODS Body mass, blood glucose and thermal and mechanical sensations were evaluated during the PMF or sham-PMF in diabetic or non-diabetic rats (n = 7/group). After the measurements of motor nerve conduction velocities (MNCV), the levels of several biomarkers for oxidative stress, apoptosis and angiogenesis in spinal cord and sciatic nerve were measured. RESULTS PMF for 4 weeks significantly recovered the MCNV (96.9% and 63.9%) and almost fully (100%) restored to the latency and threshold. PMF also significantly suppressed the diabetes induced enhances in biochemical markers of both neuronal tissues. CONCLUSIONS Findings suggested that PMF might prevent the development of functional abnormalities in diabetic rats due to its anti-oxidative, anti-apoptotic and anti-angiogenic actions in neuronal tissues.
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Affiliation(s)
- Tufan Mert
- Department of Biophysics, Faculty of Medicine, Bolu Abant Izzet Baysal University, Bolu, Turkey
| | - Emel Sahin
- Department of Medical Biology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Selma Yaman
- Department of Biophysics, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey
| | - Mehmet Sahin
- Department of Medical Biology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
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19
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Bangar NS, Gvalani A, Ahmad S, Khan MS, Tupe RS. Understanding the role of glycation in the pathology of various non-communicable diseases along with novel therapeutic strategies. Glycobiology 2022; 32:1068-1088. [PMID: 36074518 DOI: 10.1093/glycob/cwac060] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 08/10/2022] [Accepted: 09/02/2022] [Indexed: 01/07/2023] Open
Abstract
Glycation refers to carbonyl group condensation of the reducing sugar with the free amino group of protein, which forms Amadori products and advanced glycation end products (AGEs). These AGEs alter protein structure and function by configuring a negative charge on the positively charged arginine and lysine residues. Glycation plays a vital role in the pathogenesis of metabolic diseases, brain disorders, aging, and gut microbiome dysregulation with the aid of 3 mechanisms: (i) formation of highly reactive metabolic pathway-derived intermediates, which directly affect protein function in cells, (ii) the interaction of AGEs with its associated receptors to create oxidative stress causing the activation of transcription factor NF-κB, and (iii) production of extracellular AGEs hinders interactions between cellular and matrix molecules affecting vascular and neural genesis. Therapeutic strategies are thus required to inhibit glycation at different steps, such as blocking amino and carbonyl groups, Amadori products, AGEs-RAGE interactions, chelating transition metals, scavenging free radicals, and breaking crosslinks formed by AGEs. The present review focused on explicitly elaborating the impact of glycation-influenced molecular mechanisms in developing and treating noncommunicable diseases.
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Affiliation(s)
- Nilima S Bangar
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune 412115, Maharashtra, India
| | - Armaan Gvalani
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune 412115, Maharashtra, India
| | - Saheem Ahmad
- Department of Medical Laboratory Sciences, University of Hail, Hail City 2440, Saudi Arabia
| | - Mohd S Khan
- Department of Biochemistry, Protein Research Chair, King Saud University, Riyadh 11451, Saudi Arabia
| | - Rashmi S Tupe
- Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune 412115, Maharashtra, India
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20
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Zhu GC, Chen YW, Tsai KL, Wang JJ, Hung CH, Schmid AB. Effects of Neural Mobilization on Sensory Dysfunction and Peripheral Nerve Degeneration in Rats With Painful Diabetic Neuropathy. Phys Ther 2022; 102:pzac104. [PMID: 35913760 PMCID: PMC7613682 DOI: 10.1093/ptj/pzac104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 03/16/2022] [Accepted: 06/07/2022] [Indexed: 11/13/2022]
Abstract
OBJECTIVE This study aims to evaluate the effectiveness of neural mobilization (NM) in the management of sensory dysfunction and nerve degeneration related to experimental painful diabetic neuropathy (PDN). METHODS This is a pre-clinical animal study performed in the streptozocin-induced diabetic rat model. Three groups were included: a treatment group of rats with PDN receiving NM under anesthesia (PDN-NM, n = 10), a sham treatment group of rats with PDN that received only anesthesia (PDN-Sham, n = 9), and a vehicle control group with nondiabetic animals (Vehicle, n = 10). Rats in the PDN-NM and PDN-Sham groups received 1 treatment session on days 10, 12, and 14 after streptozocin injection, with a 48-hour rest period between sessions. Behavioral tests were performed using von Frey and Plantar tests. Evaluation for peripheral nerve degeneration was performed through measuring protein gene product 9.5-positive intra-epidermal nerve fiber density in hind-paw skin biopsies. All measurements were performed by a blinded investigator. RESULTS The behavioral tests showed that a single NM session could reduce hyperalgesia, which was maintained for 48 hours. The second treatment session further improved this treatment effect, and the third session maintained it. These results suggest that it requires multiple treatment sessions to produce and maintain hypoalgesic effects. Skin biopsy analysis showed that the protein gene product 9.5-positive intra-epidermal nerve fiber density was higher on the experimental side of the PDN-NM group compared with the PDN-Sham group, suggesting NM may mitigate the degeneration of peripheral nerves. CONCLUSION This study demonstrated that NM may be an effective method to manage experimentally induced PDN, potentially through mitigation of nerve degeneration. Further studies are needed to develop standardized protocols for clinical use. IMPACT These findings provide neurophysiological evidence for the use of NM in PDN and can form the basis for the development of physical therapy-based programs in clinics.
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Affiliation(s)
- Guan-Cheng Zhu
- Department of Physical Therapy, National Cheng Kung University, Tainan, Taiwan (R.O.C.)
| | - Yu-Wen Chen
- Department of Physical Therapy, China Medical University, Taichung, Taiwan (R.O.C.)
| | - Kun-Ling Tsai
- Department of Physical Therapy, National Cheng Kung University, Tainan, Taiwan (R.O.C.)
| | - Jhi-Joung Wang
- Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan (R.O.C.)
| | - Ching-Hsia Hung
- Department of Physical Therapy, National Cheng Kung University, Tainan, Taiwan (R.O.C.)
| | - Annina B Schmid
- Nuffield Department of Clinical Neuroscience, University of Oxford, John Radcliffe Hospital, Oxford, UK
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21
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Sasajima S, Kondo M, Ohno N, Ujisawa T, Motegi M, Hayami T, Asano S, Asano-Hayami E, Nakai-Shimoda H, Inoue R, Yamada Y, Miura-Yura E, Morishita Y, Himeno T, Tsunekawa S, Kato Y, Nakamura J, Kamiya H, Tominaga M. Thermal gradient ring reveals thermosensory changes in diabetic peripheral neuropathy in mice. Sci Rep 2022; 12:9724. [PMID: 35697861 PMCID: PMC9192750 DOI: 10.1038/s41598-022-14186-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 05/18/2022] [Indexed: 12/03/2022] Open
Abstract
Diabetic peripheral neuropathy (DPN) includes symptoms of thermosensory impairment, which are reported to involve changes in the expression or function, or both, of nociceptive TRPV1 and TRPA1 channels in rodents. In the present study, we did not find changes in the expression or function of TRPV1 or TRPA1 in DPN mice caused by STZ, although thermal hypoalgesia was observed in a murine model of DPN or TRPV1−/− mice with a Plantar test, which specifically detects temperature avoidance. With a Thermal Gradient Ring in which mice can move freely in a temperature gradient, temperature preference can be analyzed, and we clearly discriminated the temperature-dependent phenotype between DPN and TRPV1−/− mice. Accordingly, we propose approaches with multiple behavioral methods to analyze the progression of DPN by response to thermal stimuli. Attention to both thermal avoidance and preference may provide insight into the symptoms of DPN.
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Affiliation(s)
- Sachiko Sasajima
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.,Division of Cell Signaling, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi, 444-8787, Japan
| | - Masaki Kondo
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
| | - Nobuhiko Ohno
- Department of Anatomy, Division of Histology and Cell Biology, School of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.,Division of Ultrastructural Research, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi, 444-8787, Japan
| | - Tomoyo Ujisawa
- Division of Cell Signaling, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi, 444-8787, Japan.,Thermal Biology Group, Exploratory Research Center on Life and Living Systems (ExCELLS), 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi, 444-8787, Japan
| | - Mikio Motegi
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Tomohide Hayami
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Saeko Asano
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Emi Asano-Hayami
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Hiromi Nakai-Shimoda
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Rieko Inoue
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Yuichiro Yamada
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Emiri Miura-Yura
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Yoshiaki Morishita
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Tatsuhito Himeno
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Shin Tsunekawa
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Yoshiro Kato
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Jiro Nakamura
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.,Department of Innovative Diabetes Therapy, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Hideki Kamiya
- Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan
| | - Makoto Tominaga
- Division of Cell Signaling, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi, 444-8787, Japan. .,Thermal Biology Group, Exploratory Research Center on Life and Living Systems (ExCELLS), 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi, 444-8787, Japan. .,Department of Physiological Sciences, Sokendai, Okazaki, Japan.
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22
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Zhao XW, Yue WX, Zhang SW, Chen Q. Correlation between the accumulation of skin glycosylation end products and the development of type 2 diabetic peripheral neuropathy. BMC Endocr Disord 2022; 22:106. [PMID: 35443645 PMCID: PMC9022282 DOI: 10.1186/s12902-022-00997-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 03/09/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND The accumulation of advanced glycation end products (AGEs) occurring in skin tissues can be measured by AGE Reader. Here, we assessed the correlation between AGEs values and the development of type 2 diabetic peripheral neuropathy (DPN). METHODS The basic clinical information of 560 patients with T2DM was collected through an electronic system. AGEs and diabetic complication risk score was measured by AGE Reader, a non-invasive optical signal detector. All of the participants were classified into 4 groups based on Dyck criteria: grade 0 (non-DPN group), grade 1 (early stage group), grade 2 (middle stage group) and grade 3 (advanced group). Pearson correlation analysis and Spearman correlation analysis were used to evaluate the correlation between AGEs and other indexes. The sensitivity and specificity of glycosylated products were evaluated by ROC curve. RESULTS With the increase of DPN severity, the accumulative AGEs showed an increasing trend. Significant differences (P = 0.000) of AGEs were found among grades 0, 1, 2, and 3 of DPN, and significant differences (P = 0.000) of AGEs were found between grades 1 and 3. There were significant differences in DPN risk score between grades 0, 1, 2, and 3, between grades 1, 2, and 3, and between grades 2 and 3 (P < 0.01 or P < 0.05). AGEs were positively correlated with age, blood uric acid, disease course, systolic blood pressure, the risk scores of the four major complications of diabetes, renal function indicators (serum creatinine, Cystatin C, homocysteine, the ratio of urinary albumin and creatinine, urinary microalbumin, α-microglobulin, urinary transferrin, urinary immunoglobulin), inflammatory indicators (white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, C-reactive protein), and TCSS score. However, it was negatively correlated with BMI,fasting insulin, insulin 1-3 h postprandial, lymphocyte count, HOMA insulin resistance index and estimated glomerular filtration rate. The area under the AGEs cumulant and neuropathy risk score curve was 0.769 and 0.743, respectively. The confidence intervals were (71.2-82.6%) and (68.8-79.9%), respectively. The maximum Youden's index of AGEs cumulant was 0.440, and the corresponding AGEs cumulant value was 77.65. The corresponding sensitivity and specificity were 0.731 and 0.709, respectively. Furthermore, the maximum Youden's index of neuropathy risk score was 0.385, and the corresponding neuropathy risk score was 66.25. The corresponding sensitivity and the specificity were 0.676 and 0.709, respectively. CONCLUSION The cumulative amount of skin AGEs can be used as the diagnostic index and the prediction and evaluation index of DPN severity. Moreover, the diabetic peripheral neuropathy risk score can predict the risk of DPN in patients with T2DM.
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Affiliation(s)
- Xing-Wang Zhao
- Jianyang Hospital of Traditional Chinese Medicine, Jianyang, 641400, China
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China
| | - Wan-Xu Yue
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China
| | | | - Qiu Chen
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.
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23
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Chen W, Wu X, Li S, Zhang Y, Huang Y, Zhuang Y, Bai X, Chen X, Lin X. Optical coherence tomography of the retina combined with color Doppler ultrasound of the tibial nerve in the diagnosis of diabetic peripheral neuropathy. Front Endocrinol (Lausanne) 2022; 13:938659. [PMID: 36339439 PMCID: PMC9634106 DOI: 10.3389/fendo.2022.938659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 10/03/2022] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE To investigate the value of the retinal nerve fiber layer (RNFL) thickness in the optic disc and the cross-sectional area (CSA) of lower limb nerves in the diagnosis of diabetic peripheral neuropathy (DPN) separately and in combination. METHODS A total of 140 patients with type 2 diabetes were enrolled, including 51 patients with DPN (DPN group) and 89 patients without DPN (NDPN group). Clinical data and biochemical parameters were collected. Electromyography/evoked potential instrument was performed for nerve conduction study. Optical coherence tomography was performed to measure the RNFL thickness of the optic disc. Color Doppler ultrasound was performed to measure CSA of lower limb nerves. RESULTS The RNFL thickness was lower and the CSA of the tibial nerve (TN) in the DPN group was larger than that in the NDPN group. The album/urine creatinine ratio, diabetic retinopathy, and CSA of TN at 3 cm were positively correlated with DPN. The RNFL thickness in the superior quadrant of the optic disc was negatively correlated with DPN. For RNFL thickness to diagnose DPN, the area under the curve (AUC) of the superior quadrant was the largest, which was 0.723 (95% confidence interval [CI]: 0.645-0.805), and the best cutoff value was 127.5 μm (70.5% sensitivity, 72.1% specificity). For CSA of TN to diagnose DPN, the AUC of the distance of 5 cm was the largest, which was 0.660 (95% CI: 0.575-0.739), and the best cutoff value was 13.50 mm2 (82.0% sensitivity, 41.6% specificity). For the combined index, the AUC was greater than that of the above two indicators, which was 0.755 (95% CI: 0.664-0.846), and the best cutoff value was 0.376 (64.3% sensitivity, 83.0% specificity). CONCLUSIONS Patients with DPN have a reduction of the RNFL thickness and an increase in the CSA of TN, and these two changes are related to DPN. The RNFL thickness of the optic disc and the CSA of TN can be used as diagnostic indicators of DPN, and the combination of the two indicators has a higher diagnostic value.
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Affiliation(s)
- Weimiao Chen
- Department of Clinical Nutrition, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
- *Correspondence: Xiahong Lin, ; ; Weimiao Chen,
| | - Xiaohong Wu
- Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Shilin Li
- Department of Ultrasound, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Yan Zhang
- Department of Ophthalmology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Yinqiong Huang
- Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Yong Zhuang
- Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Xuefeng Bai
- Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Xiaoyu Chen
- Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Xiahong Lin
- Department of Endocrinology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
- Department of Geriatric Medicine, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
- *Correspondence: Xiahong Lin, ; ; Weimiao Chen,
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24
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Jorge-Galarza E, Torres-Tamayo M, Martínez-Alvarado MDR, Peña-Aparicio B, González-Salazar C, Reyes-Barrera J, Sierra-Beltrán M, Fajardo-Flores E, Kostin A, González-Hermosillo JA. Cardiovascular autonomic responses during head-up tilt test in newly diagnosed type 2 diabetes. Ir J Med Sci 2021; 191:2077-2084. [PMID: 34750734 DOI: 10.1007/s11845-021-02825-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 10/21/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Autonomic dysfunction is commonly observed in patients with long-standing type 2 diabetes. Previous studies have confirmed the value of both subjectively assessed symptoms and objective measurements of autonomic nervous system function in diagnosing cardiovascular autonomic neuropathy. However, the head-up tilt test (HUTT) has been rarely used to investigate cardiovascular autonomic responses in subjects with high risk of newly diagnosed type 2 diabetes (nT2D). OBJECTIVE To evaluate autonomic cardiovascular responses through passive orthostatic challenge along the diabetes continuum. METHODS The study population was stratified as normoglycemic (n = 16), prediabetes (n = 20), and nT2D (n = 20). The prevalence of orthostatic intolerance and autonomic cardiovascular responses was evaluated with the Task Force Monitor during a 30-min passive HUTT. Spectral indices of heart rate and blood pressure variability and baroreceptor effectiveness index (BEI) were calculated through the HUTT. BEI was obtained by the sequence method. RESULTS There were no differences in the prevalence of orthostatic intolerance or in the indices of heart rate and blood pressure variability among the three groups of study. The BEI was attenuated in the nT2D group in supine rest and throughout HUTT compared with normoglycemic and prediabetes groups. The multivariable linear regression analysis showed that BEI was associated with fasting glucose (β = - 0.52, p < 0.001) and HbA1c (β = - 0.57, p < 0.001) independently of cardiovascular risk factors. CONCLUSION Cardiovascular autonomic neuropathy, expressed as blunted BEI, is the only abnormal autonomic nervous test detected in nT2D, and it was independently associated with fasting glucose and HbA1c values.
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Affiliation(s)
- Esteban Jorge-Galarza
- Endocrinology Department, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Margarita Torres-Tamayo
- Endocrinology Department, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | | | - Berenice Peña-Aparicio
- Endocrinology Department, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Carmen González-Salazar
- Endocrinology Department, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Juan Reyes-Barrera
- Endocrinology Department, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Manuel Sierra-Beltrán
- Dysautonomic Clinic, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Erika Fajardo-Flores
- Dysautonomic Clinic, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Andrey Kostin
- Dysautonomic Clinic, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - J Antonio González-Hermosillo
- Dysautonomic Clinic, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico. .,, Mexico City, Mexico.
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25
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Pakpahan C, Ibrahim R, William W, Faizah Z, Juniastuti J, Lusida MI, Oceandy D. Stem cell therapy and diabetic erectile dysfunction: A critical review. World J Stem Cells 2021; 13:1549-1563. [PMID: 34786157 PMCID: PMC8567456 DOI: 10.4252/wjsc.v13.i10.1549] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 05/04/2021] [Accepted: 09/23/2021] [Indexed: 02/06/2023] Open
Abstract
Erectile dysfunction (ED) has been identified as one of the most frequent chronic complications of diabetes mellitus (DM). The prevalence of ED is estimated to be about 67.4% in all DM cases worldwide. The pathophysiological process leading to ED involves endothelial, neurological, hormonal, and psychological factors. In DM, endothelial and neurological factors play a crucial role. Damages in the blood vessels and erectile tissue due to insulin resistance are the hallmark of ED in DM. The current treatments for ED include phosphodiesterase-5 inhibitors and penile prosthesis surgery. However, these treatments are limited in terms of just relieving the symptoms, but not resolving the cause of the problem. The use of stem cells for treating ED is currently being studied mostly in experimental animals. The stem cells used are derived from adipose tissue, bone, or human urine. Most of the studies observed an improvement in erectile quality in the experimental animals as well as an improvement in erectile tissue. However, research on stem cell therapy for ED in humans remains to be limited. Nevertheless, significant findings from studies using animal models indicate a potential use of stem cells in the treatment of ED.
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Affiliation(s)
- Cennikon Pakpahan
- Department of Biomedical Sciences, Universitas Airlangga, Surabaya 60132, Indonesia
- Andrology Program, Universitas Airlangga, Surabaya 60132, Indonesia
| | - Raditya Ibrahim
- Andrology Program, Universitas Airlangga, Surabaya 60132, Indonesia
| | - William William
- Andrology Program, Universitas Airlangga, Surabaya 60132, Indonesia
- Department of Medical Biology, School of Medicine and Health Sciences Atma Jaya Catholic University of Indonesia, Jakarta 14440, Indonesia
| | - Zakiyatul Faizah
- Department of Biomedical Sciences, Universitas Airlangga, Surabaya 60132, Indonesia
| | | | - Maria I Lusida
- Institute for Tropical Disease, Universitas Airlangga, Surabaya 60132, Indonesia
| | - Delvac Oceandy
- Division of Cardiovascular Sciences, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, United Kingdom
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26
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Qian Y, Zeng Y, Lin Q, Huang H, Zhang W, Yu H, Deng B. Association of platelet count and plateletcrit with nerve conduction function and peripheral neuropathy in patients with type 2 diabetes mellitus. J Diabetes Investig 2021; 12:1835-1844. [PMID: 33650778 PMCID: PMC8504918 DOI: 10.1111/jdi.13535] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 02/12/2021] [Accepted: 02/25/2021] [Indexed: 12/20/2022] Open
Abstract
AIMS/INTRODUCTION Diabetes has been considered as a 'pro-thrombotic state' with enhanced platelet reactivity. Abnormality in platelet aggregation has been found in patients with its most common chronic complication - diabetic peripheral neuropathy (DPN). The purpose of this study was to investigate the potential association of platelet indices with nerve conduction function and the presence of DPN in Chinese patients with type 2 diabetes mellitus. MATERIALS AND METHODS This study involved a total of 211 inpatients with type 2 diabetes mellitus and 55 healthy individuals for whom nerve conduction studies were carried out. DPN was diagnosed according to the American Diabetes Association recommendation. Clinical data were retrospectively collected. RESULTS Patients with diabetes in whom neuropathy developed had lower levels of platelet count (PLT) and plateletcrit (PCT) than healthy controls (P < 0.05). Statistically significant associations of low PLT and PCT levels with the reduction of summed amplitude/velocity Z-score, and the prolongation of F-wave minimum latency in nerve conduction studies were found. Furthermore, after multivariate adjustment, logistic regression analysis showed that low levels of PLT (odds ratio 2.268, 95% confidence interval 1.072-4.797; P < 0.05; PLT <226 vs PLT ≥226) and PCT (odds ratio 2.050, 95% confidence interval 1.001-4.201; P < 0.05; PCT <0.222 vs PCT ≥0.222) in type 2 diabetes mellitus patients were risk factors for the presence of DPN. CONCLUSIONS Lower PLT and PCT levels are closely associated with poorer peripheral nerve conduction functions and the presence of neuropathy in patients with type 2 diabetes mellitus, which suggests that PLT and PCT might be potential biomarkers for showing DPN.
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Affiliation(s)
- Yuqin Qian
- Department of NeurologyInstitute of NeurologyRuijin Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Yaying Zeng
- First School of Clinical MedicineWenzhou Medical UniversityWenzhouChina
| | - Qingxia Lin
- Department of PsychiatryThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Huanjie Huang
- Department of NeurologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Wanli Zhang
- Department of NeurologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Huan Yu
- Department of PediatricsTianjin Children's HospitalTianjinChina
| | - Binbin Deng
- Department of NeurologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
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27
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Ponirakis G, Abdul‐Ghani MA, Jayyousi A, Zirie MA, Qazi M, Almuhannadi H, Petropoulos IN, Khan A, Gad H, Migahid O, Megahed A, Al‐Mohannadi S, AlMarri F, Al‐Khayat F, Mahfoud Z, Al Hamad H, Ramadan M, DeFronzo R, Malik RA. Painful diabetic neuropathy is associated with increased nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control. J Diabetes Investig 2021; 12:1642-1650. [PMID: 33714226 PMCID: PMC8409832 DOI: 10.1111/jdi.13544] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Revised: 02/24/2021] [Accepted: 03/09/2021] [Indexed: 12/13/2022] Open
Abstract
AIMS/INTRODUCTION Painful diabetic peripheral neuropathy (pDPN) is associated with small nerve fiber degeneration and regeneration. This study investigated whether the presence of pDPN might influence nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control. MATERIALS AND METHODS This exploratory substudy of an open-label randomized controlled trial undertook the Douleur Neuropathique en 4 questionnaire and assessment of electrochemical skin conductance, vibration perception threshold and corneal nerve morphology using corneal confocal microscopy in participants with and without pDPN treated with exenatide and pioglitazone or basal-bolus insulin at baseline and 1-year follow up, and 18 controls at baseline only. RESULTS Participants with type 2 diabetes, with (n = 13) and without (n = 28) pDPN had comparable corneal nerve fiber measures, electrochemical skin conductance and vibration perception threshold at baseline, and pDPN was not associated with the severity of DPN. There was a significant glycated hemoglobin reduction (P < 0.0001) and weight gain (P < 0.005), irrespective of therapy. Participants with pDPN showed a significant increase in corneal nerve fiber density (P < 0.05), length (P < 0.0001) and branch density (P < 0.005), and a decrease in the Douleur Neuropathique en 4 score (P < 0.01), but no change in electrochemical skin conductance or vibration perception threshold. Participants without pDPN showed a significant increase in corneal nerve branch density (P < 0.01) and no change in any other neuropathy measures. A change in the severity of painful symptoms was not associated with corneal nerve regeneration and medication for pain. CONCLUSIONS This study showed that intensive glycemic control is associated with greater corneal nerve regeneration and an improvement in the severity of pain in patients with painful diabetic neuropathy.
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Affiliation(s)
- Georgios Ponirakis
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
- Faculty of Science and EngineeringManchester Metropolitan UniversityManchesterUK
| | - Muhammad A Abdul‐Ghani
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
- Division of DiabetesUniversity of Texas Health Science CenterSan AntonioTexasUSA
| | - Amin Jayyousi
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
| | - Mahmoud A Zirie
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
| | - Murtaza Qazi
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
| | | | | | - Adnan Khan
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
| | - Hoda Gad
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
| | - Osama Migahid
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
- Division of DiabetesUniversity of Texas Health Science CenterSan AntonioTexasUSA
| | - Ayman Megahed
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
| | | | - Fatema AlMarri
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
| | - Fatima Al‐Khayat
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
| | - Ziyad Mahfoud
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
| | | | | | - Ralph DeFronzo
- Division of DiabetesUniversity of Texas Health Science CenterSan AntonioTexasUSA
| | - Rayaz A Malik
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
- Faculty of Science and EngineeringManchester Metropolitan UniversityManchesterUK
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
- Institute of Cardiovascular ScienceUniversity of ManchesterManchesterUK
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28
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Uhelski ML, Li Y, Fonseca MM, Romero-Snadoval EA, Dougherty PM. Role of innate immunity in chemotherapy-induced peripheral neuropathy. Neurosci Lett 2021; 755:135941. [PMID: 33961945 DOI: 10.1016/j.neulet.2021.135941] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 04/28/2021] [Accepted: 04/30/2021] [Indexed: 01/18/2023]
Abstract
It has become increasingly clear that the innate immune system plays an essential role in the generation of many types of neuropathic pain including that which accompanies cancer treatment. In this article we review current findings of the role of the innate immune system in contributing to cancer treatment pain at the distal endings of peripheral nerve, in the nerve trunk, in the dorsal root ganglion and in the spinal dorsal horn.
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Affiliation(s)
- Megan L Uhelski
- The Department of Pain Medicine Research, The Division of Anesthesiology, Critical Care and Pain Medicine, The University of Texas M.D. Anderson Cancer Center, United States
| | - Yan Li
- The Department of Pain Medicine Research, The Division of Anesthesiology, Critical Care and Pain Medicine, The University of Texas M.D. Anderson Cancer Center, United States
| | - Miriam M Fonseca
- The Department of Anesthesiology, Wake Forest School of Medicine, United States
| | | | - Patrick M Dougherty
- The Department of Pain Medicine Research, The Division of Anesthesiology, Critical Care and Pain Medicine, The University of Texas M.D. Anderson Cancer Center, United States.
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Mohiuddin MS, Himeno T, Yamada Y, Morishita Y, Kondo M, Tsunekawa S, Kato Y, Nakamura J, Kamiya H. Glucagon Prevents Cytotoxicity Induced by Methylglyoxal in a Rat Neuronal Cell Line Model. Biomolecules 2021; 11:biom11020287. [PMID: 33672050 PMCID: PMC7919475 DOI: 10.3390/biom11020287] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 02/11/2021] [Accepted: 02/12/2021] [Indexed: 12/14/2022] Open
Abstract
Although diabetic polyneuropathy (DPN) is a frequent diabetic complication, no effective therapeutic approach has been established. Glucagon is a crucial hormone for glucose homeostasis but has pleiotropic effects, including neuroprotective effects in the central nervous system. However, the importance of glucagon in the peripheral nervous system (PNS) has not been clarified. Here, we hypothesized that glucagon might have a neuroprotective function in the PNS. The immortalized rat dorsal root ganglion (DRG) neuronal cell line 50B11 was treated with methylglyoxal (MG) to mimic an in vitro DPN model. The cells were cultured with or without glucagon or MG. Neurotoxicity, survival, apoptosis, neurite projection, cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) were examined. Glucagon had no cytotoxicity and rescued the cells from neurotoxicity. Cell survival was increased by glucagon. The ratio of apoptotic cells, which was increased by MG, was reduced by glucagon. Neurite outgrowth was accelerated in glucagon-treated cells. Cyclic AMP and PKA accumulated in the cells after glucagon stimulation. In conclusion, glucagon protected the DRG neuronal cells from MG-induced cellular stress. The cAMP/PKA pathway may have significant roles in those protective effects of glucagon. Glucagon may be a potential target for the treatment of DPN.
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Cai Q, Aimair G, Xu WX, Xiao PY, Liu LH, Liang YX, Wu C, Liao SJ. The Physiological Significance of A-Waves in Early Diabetic Neuropathy: Assessment of Motor Nerve Fibers by Neurophysiological Techniques. Front Syst Neurosci 2021; 15:633915. [PMID: 33584211 PMCID: PMC7876338 DOI: 10.3389/fnsys.2021.633915] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 01/05/2021] [Indexed: 01/19/2023] Open
Abstract
Objective: This study aimed to investigate how early A-waves could occur in type II diabetes, and what it implied functionally. Methods: We performed conduction velocity distribution (CVD) test in peroneal nerves of 37 type II diabetic patients with normal nerve conduction study (NCS) and 22 age-matched controls. The electrophysiological data and clinical information were analyzed. Results: A-waves were observed in 45.9% of diabetic patients and only in 1 person in healthy controls, all detected in the tibial nerves. The diabetic patients with A-waves showed faster conduction velocity in all quartiles in the motor peroneal nerves compared to the patients without A-waves, and their CVD histograms were shifted to the right side, consisting of a significantly larger percentage of fast conducting fibers. There was no significant difference in the CVD values of the upper extremity nerves among the patients with and without A-waves and the healthy controls. Conclusion: A-waves could occur in type II diabetes as early as when NCS showed normal, and represented as a sign of neuropathy as well as a sign of rescued motor nerve function.
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Affiliation(s)
- Qiong Cai
- Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
| | - Guliqiemu Aimair
- Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
| | - Wen-Xiao Xu
- Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
| | - Pei-Yao Xiao
- Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
| | - Lie-Hua Liu
- Department of Endocrinology and Diabetes Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yin-Xing Liang
- Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
| | - Chao Wu
- Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
| | - Song-Jie Liao
- Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China
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Grover A, Sharma K, Gautam S, Gautam S, Gulati M, Singh SK. Diabetes and Its Complications: Therapies Available, Anticipated and Aspired. Curr Diabetes Rev 2021; 17:397-420. [PMID: 33143627 DOI: 10.2174/1573399816666201103144231] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 08/26/2020] [Accepted: 09/12/2020] [Indexed: 11/22/2022]
Abstract
Worldwide, diabetes ranks among the ten leading causes of mortality. Prevalence of diabetes is growing rapidly in low and middle income countries. It is a progressive disease leading to serious co-morbidities, which results in increased cost of treatment and over-all health system of the country. Pathophysiological alterations in Type 2 Diabetes (T2D) progressed from a simple disturbance in the functioning of the pancreas to triumvirate to ominous octet to egregious eleven to dirty dozen model. Due to complex interplay of multiple hormones in T2D, there may be multifaceted approach in its management. The 'long-term secondary complications' in uncontrolled diabetes may affect almost every organ of the body, and finally may lead to multi-organ dysfunction. Available therapies are inconsistent in maintaining long term glycemic control and their long term use may be associated with adverse effects. There is need for newer drugs, not only for glycemic control but also for prevention or mitigation of secondary microvascular and macrovascular complications. Increased knowledge of the pathophysiology of diabetes has contributed to the development of novel treatments. Several new agents like Glucagon Like Peptide - 1 (GLP-1) agonists, Dipeptidyl Peptidase IV (DPP-4) inhibitors, amylin analogues, Sodium-Glucose transport -2 (SGLT- 2) inhibitors and dual Peroxisome Proliferator-Activated Receptor (PPAR) agonists are available or will be available soon, thus extending the range of therapy for T2D, thereby preventing its long term complications. The article discusses the pathophysiology of diabetes along with its comorbidities, with a focus on existing and novel upcoming antidiabetic drugs which are under investigation. It also dives deep to deliberate upon the novel therapies that are in various stages of development. Adding new options with new mechanisms of action to the treatment armamentarium of diabetes may eventually help improve outcomes and reduce its economic burden.
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Affiliation(s)
- Anu Grover
- Ipca Laboratories, Mumbai - 400063, India
| | - Komal Sharma
- Bhupal Nobles' Institute of Pharmaceutical Sciences, Udaipur, India
| | - Suresh Gautam
- Department of Biochemistry, Pacific Institute of Medical Sciences, Udaipur, India
| | - Srishti Gautam
- Ravinder Nath Tagore Medical College and Maharana Bhupal Govt. Hospital, Udaipur, India
| | - Monica Gulati
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab- 144411, India
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab- 144411, India
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32
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Lee KA, Park TS, Jin HY. Non-glucose risk factors in the pathogenesis of diabetic peripheral neuropathy. Endocrine 2020; 70:465-478. [PMID: 32895875 DOI: 10.1007/s12020-020-02473-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 08/23/2020] [Indexed: 11/29/2022]
Abstract
In this review, we consider the diverse risk factors in diabetes patients beyond hyperglycemia that are being recognized as contributors to diabetic peripheral neuropathy (DPN). Interest in such alternative mechanisms has been encouraged by the recognition that neuropathy occurs in subjects with metabolic syndrome and pre-diabetes and by the reporting of several large clinical studies that failed to show reduced prevalence of neuropathy after intensive glucose control in patients with type 2 diabetes. Animal models of obesity, dyslipidemia, hypertension, and other disorders common to both pre-diabetes and diabetes have been used to highlight a number of plausible pathogenic mechanisms that may either damage the nerve independent of hyperglycemia or augment the toxic potential of hyperglycemia. While pathogenic mechanisms stemming from hyperglycemia are likely to be significant contributors to DPN, future therapeutic strategies will require a more nuanced approach that considers a range of concurrent insults derived from the complex pathophysiology of diabetes beyond direct hyperglycemia.
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Affiliation(s)
- Kyung Ae Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Jeonbuk National University Hospital, Jeonbuk National University, Medical School, Jeonju, South Korea
| | - Tae Sun Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Jeonbuk National University Hospital, Jeonbuk National University, Medical School, Jeonju, South Korea
| | - Heung Yong Jin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Jeonbuk National University Hospital, Jeonbuk National University, Medical School, Jeonju, South Korea.
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33
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Mirazi N, Hosseini A. Attenuating properties of Rubus fruticosus L. on oxidative damage and inflammatory response following streptozotocin-induced diabetes in the male Wistar rats. J Diabetes Metab Disord 2020; 19:1311-1316. [PMID: 33520837 DOI: 10.1007/s40200-020-00649-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 09/10/2020] [Accepted: 09/28/2020] [Indexed: 12/16/2022]
Abstract
Purpose Diabetes mellitus is a prevalent metabolic disorder that entails numerous complications in various organs. In current era, different types of diseases are being treated by the applications of herbs. The present study is aimed at investigating the anti-inflammatory and antioxidant effects of the Rubus fruticosus hydroethanolic extracts (RFHE) in the streptozotocin (STZ)-induced diabetic rats. Methods At this experimental research, male Wistar rats with the weight of 220 ± 20 g, were categorized randomly into five groups of vehicles as control, STZ (60 mg kg- 1 of body weight, intraperitoneally (i.p.)) and RFHE (50, 100 and 200 mg kg- 1, i.p.). In the last stage (end of week 4) of the experiment, after being euthanized, the blood samples of the rats were collected for measuring malondialdehyde (MDA), glutathione (GSH), total antioxidant status (TAS) as well as inflammatory markers like tumor necrosis factor (TNF)-α, interleukin (IL)-6 and C-reactive protein (CRP). Results Data from this study was revealed that diabetes causes oxidative damage and consequently the serum level of inflammatory markers rises. RFHE was shown to be significantly correlated with lowering the level of MDA, TNF-α, IL-6 and CRP of diabetic rats. Moreover, RFHE significantly elevated the GSH and TAS serum levels in diabetic rats when compared with STZ group. Conclusions RFHE might have anti-diabetic properties; this outcome may be mediated by high antioxidant and anti-inflammatory effects.
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Affiliation(s)
- Naser Mirazi
- Department of Biology, Faculty of Basic Sciences, Bu-Ali Sina University, Hamedan, Iran
| | - Abdolkarim Hosseini
- Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
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34
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Influence of the complex drug Cocarnit on the sciatic nerve in the development of diabetic polyneuropathy in rats. CURRENT ISSUES IN PHARMACY AND MEDICAL SCIENCES 2020. [DOI: 10.2478/cipms-2020-0021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Abstract
Ulcers and slow wound healing are common in diabetic polyneuropathy (DP), as well as shooting or burning pain, sensitivity to touch or lack of sensitivity, low oxygenation of nerve tissue, conductivity disorders and various vascular disorders. The mechanisms of DP development are complex and have not been completely studied. To take into account the role of B group vitamins, we investigated histological structure of nerve tissue, the level of different growth factors and the qualitative composition of active proteolytic enzymes in rats with DP and after the use of the metabolic drug Cocarnit for 9 days. This drug composition include nicotinamide, cocarboxylase, cyanocobalamin, adenosine triphosphate disodium trihydrate. We used an histological study of sciatic nerve; enzyme-linked immunosorbent assay and enzyme electrophoresis methods. In rats with DP, fragmentation of nerve tissue and their necrosis was established. Moreover, degraded forms of plasmin that has a fully functional serine proteinase domain are evident, and, therefore, it exhibits proteolytic properties. DP led to a decrease of neuron growth factor (NGF), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). After treatment, the histological structure of nerve tissue was significantly improved, and the expression of growth factors NGF and bFGF was increased. Our study demonstrated that administration of Corcarnit brought about the complete restoration of the activation potential of plasmin and the almost disappearance of all degraded forms which were evident in the group with DP.
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35
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Escin alleviates peripheral neuropathy in streptozotocin induced diabetes in rats. Life Sci 2020; 254:117777. [DOI: 10.1016/j.lfs.2020.117777] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 05/05/2020] [Accepted: 05/08/2020] [Indexed: 02/02/2023]
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36
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Sahan A, Akbal C, Tavukcu HH, Cevik O, Cetinel S, Sekerci CA, Sener TE, Sener G, Tanidir Y. Melatonin prevents deterioration of erectile function in streptozotocin-induced diabetic rats via sirtuin-1 expression. Andrologia 2020; 52:e13639. [PMID: 32478903 DOI: 10.1111/and.13639] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 03/29/2020] [Accepted: 04/19/2020] [Indexed: 11/28/2022] Open
Abstract
A review of the literature indicated that sirtuin-1 expression, a regulator of nitric oxide bioavailability in erectile dysfunction (ED) after melatonin therapy, has not yet been investigated. The objective of this study was to evaluate the protective effects of melatonin for erectile function with sirtuin-1 protein expression in type 1 diabetic rat models. Fifty male Sprague Dawley rats were placed into five groups. Except for those in the control group (C), each animal received a single dose (60 mg/kg) of streptozotocin to induce diabetes. The animals were placed into the diabetes (D) group, insulin (I) group (6 U/kg/day), melatonin (Mel) group (10 mg kg-1 day-1 ) and combined treatment (I + Mel) group. Ten weeks later, the serum testosterone levels, intracavernosal pressure (ICP), mean arterial pressure (MAP), malondialdehyde (MDA), cyclic guanosine monophosphate (c-GMP), 8-hydroxydeoxyguanosine (8-OHdG), nitric oxide synthase (NOS), caspase-3 activity, sirtuin-1 and endothelial nitric oxide synthase (eNOS) protein expression and histological findings were assessed. The mean ICP/MAP ratio for the D group was lower than the mean ratios for the other groups. The treatment groups, particularly the I + Mel group, exhibited lower 8-OHdG and MDA levels and caspase-3 activity than the D group. The sirtuin-1 and eNOS expression and cavernosal tissue (CT) histology seemed to have been preserved by the melatonin and/or insulin therapy. These results were indicative of a profound protective effect of melatonin by the activation of sirtuin-1 protein expression against hyperglycemia-induced oxidative CT injury.
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Affiliation(s)
- Ahmet Sahan
- Department of Urology, Kartal Dr. Lutfi Kirdar Training and Research Hospital, Istanbul, Turkey
| | - Cem Akbal
- Department of Urology, School of Medicine, Acibadem University, Istanbul, Turkey
| | - Hasan Huseyin Tavukcu
- Department of Urology, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey
| | - Ozge Cevik
- Department of Biochemistry, School of Medicine, Adnan Menderes University, Aydın, Turkey
| | - Sule Cetinel
- Department of Histology and Embryology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Cagrı Akın Sekerci
- Department of Urology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Tarik Emre Sener
- Department of Urology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Goksel Sener
- Department of Pharmacology, School of Pharmacy, Marmara University, Istanbul, Turkey
| | - Yiloren Tanidir
- Department of Urology, School of Medicine, Marmara University, Istanbul, Turkey
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37
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Singh R, Rao HK, Singh TG. Neuropathic pain in diabetes mellitus: Challenges and future trends. ACTA ACUST UNITED AC 2020. [DOI: 10.1016/j.obmed.2020.100215] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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38
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Laddha AP, Kulkarni YA. NADPH oxidase: A membrane-bound enzyme and its inhibitors in diabetic complications. Eur J Pharmacol 2020; 881:173206. [PMID: 32442539 DOI: 10.1016/j.ejphar.2020.173206] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 05/08/2020] [Accepted: 05/14/2020] [Indexed: 12/20/2022]
Abstract
The human body has a mechanism for balancing the generation and neutralization of reactive oxygen species. The body is exposed to many agents that are responsible for the generation of reactive oxygen/nitrogen species, which leads to disruption of the balance between generation of these species and oxidative stress defence mechanisms. Diabetes is a chronic pathological condition associated with prolonged hyperglycaemia. Prolonged elevation of level of glucose in the blood leads to the generation of reactive oxygen species. This generation of reactive oxygen species is responsible for the development of diabetic vasculopathy, which includes micro- and macrovascular diabetic complications. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a membrane-bound enzyme responsible for the development of reactive oxygen species in hyperglycaemia. Phosphorylation of the cytosolic components of NOX, such as p47phox, p67phox, and RAC-1, in hyperglycaemia is one of the important causes of conversion of oxygen to reactive oxygen. Overexpression of NOX in pathological conditions is associated with activation of aldose reductase, advanced glycation end products, protein kinase C and the hexosamine pathway. In addition, NOX also promotes the activation of inflammatory cytokines, such as TGF-β, TNF-α, NF-kβ, IL-6, and IL-18, the activation of endothelial growth factors, such as VEGF and FGF, hyperlipidaemia, and the deposition of collagen. Thus, overexpression of NOX is linked to the development of diabetic complications. The present review focuses on the role of NOX, its associated pathways, and various NOX inhibitors in the management and treatment of diabetic complications, such as diabetic nephropathy, retinopathy, neuropathy and cardiomyopathy.
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Affiliation(s)
- Ankit P Laddha
- Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, V. L Mehta Road, Vile Parle (W), Mumbai, 400 056, India
| | - Yogesh A Kulkarni
- Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, V. L Mehta Road, Vile Parle (W), Mumbai, 400 056, India.
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Määttä LL, Charles M, Witte DR, Bjerg L, Jørgensen ME, Jensen TS, Andersen ST. Prospective Study of Neuropathic Symptoms Preceding Clinically Diagnosed Diabetic Polyneuropathy: ADDITION-Denmark. Diabetes Care 2019; 42:2282-2289. [PMID: 31558545 DOI: 10.2337/dc19-0869] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 09/09/2019] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To evaluate whether diabetic polyneuropathy (DPN) follows the hypothesis for the course of nerve fiber damage reflected by symptoms progressing from pure small through mixed to large nerve fiber symptoms with or without symptoms of loss of function of small nerve fibers. RESEARCH DESIGN AND METHODS Repeated assessments of nerve fiber-specific symptoms were obtained in 518 participants of the ADDITION-Denmark study from the time of a screening-based diagnosis of type 2 diabetes using specific items of the Michigan Neuropathy Screening Instrument questionnaire. DPN was clinically assessed 13 years after inclusion. The course of symptoms reflecting dysfunction of specific nerve fibers was evaluated, and the association between symptoms and DPN was estimated using logistic regression models. RESULTS An overall stable, yet heterogeneous course of symptoms was seen. According to the hypothesis of symptom progression, 205 (40%) participants remained free of symptoms and 56 (11%) had stable, 114 (23%) progressing, and 132 (26%) improving symptoms. Cross-sectional estimates showed a higher risk of DPN (odds ratios between 2.1 and 4.1) for participants with mixed or large nerve fiber symptoms with or without symptoms of loss of function of small nerve fibers compared with participants without symptoms. CONCLUSIONS There was no evidence for a progressive development of nerve fiber damage in DPN reflected by symptoms going from pure small through mixed to large nerve fiber symptoms with or without symptoms of loss of function of small nerve fibers. Yet overall, neuropathic symptoms were prospectively associated with a higher risk of DPN.
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Affiliation(s)
- Laura L Määttä
- Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Morten Charles
- Research Unit of General Practice, Aarhus University, Aarhus, Denmark.,Steno Diabetes Center Aarhus, Aarhus, Denmark
| | - Daniel R Witte
- Department of Public Health, Aarhus University, Aarhus, Denmark.,Danish Diabetes Academy, Odense, Denmark
| | - Lasse Bjerg
- Department of Public Health, Aarhus University, Aarhus, Denmark.,Danish Diabetes Academy, Odense, Denmark.,Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | - Marit E Jørgensen
- Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark.,National Institute of Public Health, University of Southern Denmark, Odense, Denmark
| | - Troels S Jensen
- Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
| | - Signe T Andersen
- Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark .,Department of Public Health, Aarhus University, Aarhus, Denmark
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40
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Simeoli R, Fierabracci A. Insights into the Role of MicroRNAs in the Onset and Development of Diabetic Neuropathy. Int J Mol Sci 2019; 20:ijms20184627. [PMID: 31540445 PMCID: PMC6770207 DOI: 10.3390/ijms20184627] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 08/30/2019] [Accepted: 09/11/2019] [Indexed: 12/18/2022] Open
Abstract
Diabetic neuropathy is a serious complication of chronic hyperglycemia in diabetes patients. This complication can involve both peripheral sensorimotor and autonomic nervous system. The precise nature of injury to the peripheral nerves mediated by chronic hyperglycemia is unknown; however, several mechanisms have been proposed including polyol pathway activation, enhanced glycation of proteins and lipids, increased oxidative stress, and cytokine release in the site of injury. MicroRNAs (miRNAs) are small non-coding RNAs that mediate RNA interference by post-transcriptionally modulating gene expression and protein synthesis. Therefore, they have been implicated in several developmental, physiological, and pathophysiological processes where they modulate the expression of different proteins. Recently, miRNAs gained an increasing attention also for their role as diagnostic test in many diseases due to their stability in serum and their easy detection. Furthermore, recent studies suggest that miRNAs may be involved in diabetic neuropathy although their role in the onset and the development of this complication is not fully understood. In this review, we discuss the most recent literature providing evidence for miRNAs role in diabetic neuropathy opening new pathways to improve both early diagnosis and treatment of this complication.
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Affiliation(s)
- Raffaele Simeoli
- Infectivology and Clinical Trials Area, Bambino Gesù Children's Hospital, IRCCS, Viale San Paolo 15, 00146 Rome, Italy.
| | - Alessandra Fierabracci
- Infectivology and Clinical Trials Area, Bambino Gesù Children's Hospital, IRCCS, Viale San Paolo 15, 00146 Rome, Italy.
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Sekiguchi K, Kohara N, Baba M, Komori T, Naito Y, Imai T, Satoh J, Yamaguchi Y, Hamatani T. Aldose reductase inhibitor ranirestat significantly improves nerve conduction velocity in diabetic polyneuropathy: A randomized double-blind placebo-controlled study in Japan. J Diabetes Investig 2019; 10:466-474. [PMID: 29975462 PMCID: PMC6400176 DOI: 10.1111/jdi.12890] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 06/20/2018] [Accepted: 07/02/2018] [Indexed: 01/01/2023] Open
Abstract
AIMS/INTRODUCTION Diabetic polyneuropathy is one of the most frequent diabetic complications, and impairs patients' quality of life. We evaluated the efficacy and safety of ranirestat (40 mg/day) in patients with diabetic polyneuropathy. MATERIALS AND METHODS This was a multicenter, placebo-controlled, randomized double-blind, parallel-group, phase III study in which 557 patients were randomly assigned to either the ranirestat or placebo group and assessed for 52 weeks. The co-primary end-points were the changes in tibial motor nerve conduction velocity and total modified Toronto Clinical Neuropathy Score as a measure of clinical symptoms. RESULTS There was a significant increase in tibial motor nerve conduction velocity in the ranirestat group compared with the placebo group. The difference between groups in the change at last observation was 0.52 m/s (P = 0.021). Increases in nerve conduction velocity in the ranirestat group were found not only in the tibial motor nerves, but also in the median motor nerves, proximal median sensory nerves and distal median sensory nerves. No significant differences in modified Toronto Clinical Neuropathy Score or safety parameters were found between the two groups. CONCLUSIONS Ranirestat (40 mg/day) was well tolerated and improved nerve conduction velocity. Regarding symptoms and signs, no detectable benefits over the placebo were observed in the ranirestat group during the 52 weeks of treatment.
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Affiliation(s)
- Kenji Sekiguchi
- Division of NeurologyKobe University Graduate School of MedicineKobeHyogoJapan
| | - Nobuo Kohara
- Department of NeurologyKobe City Medical Center General HospitalKobeHyogoJapan
| | - Masayuki Baba
- Department of NeurologyAomori Prefectural Central HospitalAomoriJapan
| | - Tetsuo Komori
- Department of NeurologyNational Hakone HospitalKanagawaJapan
| | - Yutaka Naito
- Department of NeurologyJapanese Red Cross Ise HospitalIseMieJapan
| | - Tomihiro Imai
- Department of Occupational TherapySapporo Medical University School of Health SciencesSapporoJapan
| | - Jo Satoh
- Tohoku Medical and Pharmaceutical University Wakabayashi HospitalSendaiMiyagiJapan
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Rajchgot T, Thomas SC, Wang JC, Ahmadi M, Balood M, Crosson T, Dias JP, Couture R, Claing A, Talbot S. Neurons and Microglia; A Sickly-Sweet Duo in Diabetic Pain Neuropathy. Front Neurosci 2019; 13:25. [PMID: 30766472 PMCID: PMC6365454 DOI: 10.3389/fnins.2019.00025] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2018] [Accepted: 01/11/2019] [Indexed: 12/11/2022] Open
Abstract
Diabetes is a common condition characterized by persistent hyperglycemia. High blood sugar primarily affects cells that have a limited capacity to regulate their glucose intake. These cells include capillary endothelial cells in the retina, mesangial cells in the renal glomerulus, Schwann cells, and neurons of the peripheral and central nervous systems. As a result, hyperglycemia leads to largely intractable complications such as retinopathy, nephropathy, hypertension, and neuropathy. Diabetic pain neuropathy is a complex and multifactorial disease that has been associated with poor glycemic control, longer diabetes duration, hypertension, advanced age, smoking status, hypoinsulinemia, and dyslipidemia. While many of the driving factors involved in diabetic pain are still being investigated, they can be broadly classified as either neuron -intrinsic or -extrinsic. In neurons, hyperglycemia impairs the polyol pathway, leading to an overproduction of reactive oxygen species and reactive nitrogen species, an enhanced formation of advanced glycation end products, and a disruption in Na+/K+ ATPase pump function. In terms of the extrinsic pathway, hyperglycemia leads to the generation of both overactive microglia and microangiopathy. The former incites a feed-forward inflammatory loop that hypersensitizes nociceptor neurons, as observed at the onset of diabetic pain neuropathy. The latter reduces neurons' access to oxygen, glucose and nutrients, prompting reductions in nociceptor terminal expression and losses in sensation, as observed in the later stages of diabetic pain neuropathy. Overall, microglia can be seen as potent and long-lasting amplifiers of nociceptor neuron activity, and may therefore constitute a potential therapeutic target in the treatment of diabetic pain neuropathy.
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Affiliation(s)
- Trevor Rajchgot
- Département de Pharmacologie et Physiologie, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada
| | - Sini Christine Thomas
- Département de Pharmacologie et Physiologie, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada
| | - Jo-Chiao Wang
- Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Maryam Ahmadi
- Département de Pharmacologie et Physiologie, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada
| | - Mohammad Balood
- Département de Pharmacologie et Physiologie, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada
| | - Théo Crosson
- Département de Pharmacologie et Physiologie, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada
| | - Jenny Pena Dias
- Johns Hopkins University School of Medicine, Division of Endocrinology, Diabetes and Metabolism, Baltimore, MD, United States
| | - Réjean Couture
- Département de Pharmacologie et Physiologie, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada
| | - Audrey Claing
- Département de Pharmacologie et Physiologie, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada
| | - Sébastien Talbot
- Département de Pharmacologie et Physiologie, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada
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Li K, Inam-u-llah, Shi X, Zhang M, Wu P, Li S, Suleman R, Nisar A, Piao F. Anti-apoptotic Effect of Taurine on Schwann Cells Exposed to High Glucose In Vitro. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1155:787-799. [DOI: 10.1007/978-981-13-8023-5_68] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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44
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Xu Y, Zhang Y, Yang Y, Liu L, Chen Y, Liu X. Prevalence and correlates of erectile dysfunction in type 2 diabetic men: a population-based cross-sectional study in Chinese men. Int J Impot Res 2018; 31:9-14. [DOI: 10.1038/s41443-018-0060-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2018] [Revised: 06/01/2018] [Accepted: 07/23/2018] [Indexed: 12/30/2022]
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Suarez-Mendez S, Tovilla-Zárate CA, Juárez-Rojop IE, Bermúdez-Ocaña DY. Erythropoietin: A potential drug in the management of diabetic neuropathy. Biomed Pharmacother 2018; 105:956-961. [PMID: 30021390 DOI: 10.1016/j.biopha.2018.06.068] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Revised: 06/06/2018] [Accepted: 06/13/2018] [Indexed: 12/28/2022] Open
Abstract
Erythropoietin (EPO) is required for promoting the progress of erythroid differentiation. However, the discovery of EPO and the EPO receptor (EPOR) in the nervous system may contribute to new treatment strategies for the use of EPO in neurodegenerative disorders. Diabetic neuropathy is a neurodegenerative disease that affects a large proportion of diabetic patients and results in alterations in functionality, mood and sleep. The pathogenic mechanisms generating diabetic neuropathy involve: Schwannopathy, polyol pathway activity, advanced glycation end-products (AGEs) accumulation, protein kinase C (PKC) activity, increased hexosamine pathway flux, oxidative stress, nitric oxide and inflammation. In this sense, evidence from both clinical and experimental studies indicates that EPO may reverse diabetic neuropathy through an antioxidant action by decreasing pro-inflammatory cytokines, restoring Na+/K+-ATPase activity, and blocking the generation of pro-apoptotic proteins. The aim of this review is to discuss the neuroprotector effect of EPO on pathogenic mechanisms of diabetic neuropathy.
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Affiliation(s)
- Samuel Suarez-Mendez
- División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Av. Gregorio Méndez 2838-A. Col. Tamulté, C.P. 86100, Villahermosa, Tabasco, Mexico
| | - Carlos Alfonso Tovilla-Zárate
- División Académica Multidisciplinaria de Comalcalco, Universidad Juárez Autónoma de Tabasco, Ranchería Sur, Cuarta Sección, C.P. 86650, Comalcalco, Tabasco, Mexico
| | - Isela E Juárez-Rojop
- División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Av. Gregorio Méndez 2838-A. Col. Tamulté, C.P. 86100, Villahermosa, Tabasco, Mexico.
| | - Deysi Y Bermúdez-Ocaña
- División Académica Multidisciplinaria de Comalcalco, Universidad Juárez Autónoma de Tabasco, Ranchería Sur, Cuarta Sección, C.P. 86650, Comalcalco, Tabasco, Mexico.
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Gregorio I, Braghetta P, Bonaldo P, Cescon M. Collagen VI in healthy and diseased nervous system. Dis Model Mech 2018; 11:dmm032946. [PMID: 29728408 PMCID: PMC6031366 DOI: 10.1242/dmm.032946] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Collagen VI is a major extracellular matrix protein exerting a number of functions in different tissues, spanning from biomechanical to regulatory signals in the cell survival processes, and playing key roles in maintaining the stemness or determining the differentiation of several types of cells. In the last couple of years, emerging findings on collagen VI have led to increased interest in its role in the nervous system. The role of this protein in the peripheral nervous system was intensely studied and characterized in detail. Collagen VI acts as a regulator of Schwann cell differentiation and is required for preserving peripheral nerve myelination, function and structure, as well as for orchestrating nerve regeneration after injury. Although the role and distribution of collagen VI in the peripheral nervous system is now well established, the role of this distinctive extracellular matrix component in the central nervous system, along with its links to human neurological and neurodegenerative disorders, remains an open field of investigation. In this Review, we summarize and discuss a number of recent findings related to collagen VI in the central and peripheral nervous systems. We further link these findings to different aspects of the protein that are relevant to human diseases in these compartments in order to provide a comprehensive overview of the roles of this key matrix component in the nervous system.
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Affiliation(s)
- Ilaria Gregorio
- Department of Molecular Medicine, University of Padova, 35131 Padova, Italy
| | - Paola Braghetta
- Department of Molecular Medicine, University of Padova, 35131 Padova, Italy
| | - Paolo Bonaldo
- Department of Molecular Medicine, University of Padova, 35131 Padova, Italy
| | - Matilde Cescon
- Department of Molecular Medicine, University of Padova, 35131 Padova, Italy
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Hiraoka Y, Akashi M, Wanifuchi S, Kusumoto J, Shigeoka M, Hasegawa T, Hashikawa K, Terashi H, Komori T. Association between pain severity and clinicohistopathologic findings in the mandibular canal and inferior alveolar nerve of patients with advanced mandibular osteoradionecrosis. Oral Surg Oral Med Oral Pathol Oral Radiol 2018; 126:264-271. [PMID: 29776771 DOI: 10.1016/j.oooo.2018.03.017] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Revised: 03/06/2018] [Accepted: 03/16/2018] [Indexed: 11/18/2022]
Abstract
OBJECTIVE Pain is one of the most problematic symptoms in patients with osteoradionecrosis of the jaws. This study investigated the associations between pain severity and morphologic alterations of the mandibular canal and inferior alveolar nerve, in respective computerized tomography images and resected specimens of mandibular osteoradionecrosis. STUDY DESIGN We assessed 14 lesions in 13 patients who underwent segmental mandibulectomy for surgical debridement and simultaneous reconstruction with free fibula flap (1 patient exhibited bilateral lesions). The extent of the mandibular canal bone defect on preoperative coronal computerized tomography images and the number of inferior alveolar nerve fascicles in resected specimens were evaluated. Comparisons were made between the slight pain and extreme pain groups. In most of the patients in the extreme pain group, either mandibular canal bone defects were absent or entire circumferential defects were present; inferior alveolar nerve fascicles were either distinguishable or completely absent in the resected specimens. RESULTS Although there was no statistically significant association between extreme pain and computerized tomography or histopathologic findings, the histopathologically indistinguishable inferior alveolar nerve fascicles was significantly associated with slight pain. CONCLUSIONS The degree of degeneration of mandibular canal and inferior alveolar nerve may be associated with pain severity in patients with mandibular osteoradionecrosis.
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Affiliation(s)
- Yujiro Hiraoka
- Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masaya Akashi
- Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
| | - Satoshi Wanifuchi
- Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Junya Kusumoto
- Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Manabu Shigeoka
- Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan; Division of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takumi Hasegawa
- Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kazunobu Hashikawa
- Department of Plastic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hiroto Terashi
- Department of Plastic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takahide Komori
- Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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Azzopardi K, Gatt A, Chockalingam N, Formosa C. Hidden dangers revealed by misdiagnosed diabetic neuropathy: A comparison of simple clinical tests for the screening of vibration perception threshold at primary care level. Prim Care Diabetes 2018; 12:111-115. [PMID: 29029862 DOI: 10.1016/j.pcd.2017.09.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Revised: 09/15/2017] [Accepted: 09/15/2017] [Indexed: 01/09/2023]
Abstract
AIM Diabetic peripheral neuropathy is an important complication and contributes to the morbidity of diabetes mellitus. Evidence indicates early detection of diabetic peripheral neuropathy results in fewer foot ulcers and amputations. The aim of this study was to compare different screening modalities in the detection of diabetic peripheral neuropathy in a primary care setting. METHOD A prospective non-experimental comparative multi-centre cross sectional study was conducted in various Primary Health Centres. One hundred participants living with Type 2 diabetes for at least 10 years were recruited using a convenience sampling method. The Vibratip, 128Hz tuning fork and neurothesiometer were compared in the detection of vibration perception. RESULTS This study showed different results of diabetic peripheral neuropathy screening tests, even in the same group of participants. This study has shown that the percentage of participants who did not perceive vibrations was highest when using the VibraTip (28.5%). This was followed by the neurothesiometer (21%) and the 128Hz tuning fork (12%) (p<0.001). CONCLUSION Correct diagnosis and treatment of neuropathy in patients with diabetes is crucial. This study demonstrates that some instruments are more sensitive to vibration perception than others. We recommend that different modalities should be used in patients with diabetes and when results do not concur, further neurological evaluation should be performed. This would significantly reduce the proportion of patients with diabetes who would be falsely identified as having no peripheral neuropathy and subsequently denied the benefit of beneficial and effective secondary risk factor control.
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Affiliation(s)
| | - Alfred Gatt
- Faculty of Health Sciences, University of Malta, Malta; Faculty of Health Sciences, Staffordshire University, United Kingdom.
| | - Nachiappan Chockalingam
- Faculty of Health Sciences, University of Malta, Malta; Faculty of Health Sciences, Staffordshire University, United Kingdom.
| | - Cynthia Formosa
- Faculty of Health Sciences, University of Malta, Malta; Faculty of Health Sciences, Staffordshire University, United Kingdom.
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Clinical Features of Idiopathic Parotid Pain Triggered by the First Bite in Japanese Patients with Type 2 Diabetes: A Case Study of Nine Patients. PAIN RESEARCH AND TREATMENT 2018; 2018:7861451. [PMID: 29796314 PMCID: PMC5896206 DOI: 10.1155/2018/7861451] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Accepted: 02/25/2018] [Indexed: 12/05/2022]
Abstract
Objective First bite syndrome, characterized by pain in the parotid region after the first bite of each meal, predominantly develops in patients who have had head and neck surgery. Idiopathic parotid pain (IPP) that mimics first bite syndrome may present in patients without a history of surgery or evidence of an underlying tumor, but its clinical features are unclear. This study characterized the clinical characteristics of IPP in patients with diabetes. Study Design A retrospective case review involving the clinical findings and pain characteristics of nine patients with IPP and diabetes who presented to our department between 2013 and 2016. Results All the patients were men diagnosed with type 2 diabetes (median age, 43 years). IPP developed unilaterally in seven patients and bilaterally in two. The median intensity of the first bite pain was 8 on a numerical rating scale of 0–10. The trigger factor was gustatory stimuli, and the trigger area was the posterior section of the tongue. Postprandial pain occurred within 1–10 min after meals in six patients. Conclusions IPP may be considered a separate disorder, in which the pain characteristics are similar to those of first bite syndrome but the clinical features and pathophysiology are different.
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50
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Tanshinone IIA Attenuates Diabetic Peripheral Neuropathic Pain in Experimental Rats via Inhibiting Inflammation. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:2789847. [PMID: 29713362 PMCID: PMC5866893 DOI: 10.1155/2018/2789847] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Accepted: 01/01/2018] [Indexed: 12/17/2022]
Abstract
Diabetic peripheral neuropathic pain (DPNP) is a common and intractable complication of diabetes. Conventional therapies are always not ideal; development of novel drugs is still needed to achieve better pain relief. Recent evidences have demonstrated that inflammation is involved in the onset and maintenance of DPNP. The anti-inflammatory property of Tanshinone IIA (TIIA) makes it a promising candidate to block or alter the pain perception. This study was conducted to investigate whether TIIA could attenuate DPNP in streptozotocin- (STZ-) induced rats model and its potential mechanisms. TIIA was administered to STZ-induced diabetic rats at the dose of 40 mg/kg once a day for 3 weeks. The effects of TIIA on thermal hyperalgesia and mechanical allodynia were investigated using behavioral tests. The mRNA level and expression of interleukin- (IL-) 1β, interleukin- (IL-) 6, tumor necrosis factor- (TNF-) α, and interleukin- (IL-) 10 in the fourth to sixth segments of the dorsal root ganglion (L4–6 DRG) were detected by quantitative real-time PCR (qPCR) and Western blot. TIIA treatment significantly attenuated mechanical allodynia and thermal hyperalgesia in diabetic rats. In addition, the expression of the proinflammatory cytokines IL-1β, IL-6, and TNF-α was inhibited, and the level of the anti-inflammatory cytokine IL-10 was increased by TIIA. This study demonstrated that TIIA has significant antiallodynic and antihyperalgesic effects in a rat model of STZ-induced DPNP, and the effect may be associated with its anti-inflammation property.
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