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Zaottini F, Pistoia F, Picasso R, Macciò M, Marcenaro G, Grandis M, Benedetti L, Martinoli C. Imaging for inflammatory neuropathies. Best Pract Res Clin Rheumatol 2025:102066. [PMID: 40319002 DOI: 10.1016/j.berh.2025.102066] [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: 03/10/2025] [Revised: 04/16/2025] [Accepted: 04/22/2025] [Indexed: 05/07/2025]
Abstract
Inflammatory neuropathies comprise a heterogeneous group of conditions united by inflammation-mediated damage to peripheral nerves and their vasa nervorum. Although classification, diagnosis and management are largely based on clinical features, electrodiagnostic and laboratory examinations, imaging studies play an important supporting role. Ultrasound and MRI are the two modalities used for imaging peripheral nerves. The two techniques differ in the clinical context of application, the information provided and the diagnostic performance. This narrative review aims to provide guidance on when and how to use ultrasound or MRI in patients with inflammatory neuropathies, highlighting their respective strengths and pitfalls, and how to combine these imaging modalities to enhance their usefulness in the diagnostic-therapeutic management of these far from rare conditions.
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Affiliation(s)
- Federico Zaottini
- IRCCS Ospedale Policlinico San Martino, Division of Radiology, Largo Rosanna Benzi 10, 16132, Genova, Italy; Department of Health Sciences (DISSAL), University of Genova, Via Antonio Pastore 1, 16132, Genova, Italy.
| | - Federico Pistoia
- Department of Health Sciences (DISSAL), University of Genova, Via Antonio Pastore 1, 16132, Genova, Italy.
| | - Riccardo Picasso
- Department of Health Sciences (DISSAL), University of Genova, Via Antonio Pastore 1, 16132, Genova, Italy.
| | - Marta Macciò
- IRCCS Ospedale Policlinico San Martino, Division of Radiology, Largo Rosanna Benzi 10, 16132, Genova, Italy.
| | - Giovanni Marcenaro
- IRCCS Ospedale Policlinico San Martino, Division of Radiology, Largo Rosanna Benzi 10, 16132, Genova, Italy.
| | - Marina Grandis
- IRCCS Ospedale Policlinico San Martino, Division of Neurology, Via Largo Rosanna Benzi 10, 16132, Genova, Italy; Department of Neuroscience (DINOGMI), University of Genova, Genoa, Italy.
| | - Luana Benedetti
- IRCCS Ospedale Policlinico San Martino, Division of Neurology, Via Largo Rosanna Benzi 10, 16132, Genova, Italy.
| | - Carlo Martinoli
- IRCCS Ospedale Policlinico San Martino, Division of Radiology, Largo Rosanna Benzi 10, 16132, Genova, Italy; Department of Health Sciences (DISSAL), University of Genova, Via Antonio Pastore 1, 16132, Genova, Italy.
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Toft-Hansen H, Aniol-Nielsen C, Elias D, Dahlbäck M, Rossing P, Sivalingam S, Hagopian WA, Schneider DA, Nielsen CH, Solberg H. Characterization of Anti-Insulin Antibodies in Type 1 and Type 2 Diabetes Mellitus: Clinical Relevance. Int J Mol Sci 2025; 26:1730. [PMID: 40004193 PMCID: PMC11854962 DOI: 10.3390/ijms26041730] [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] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 01/31/2025] [Accepted: 02/08/2025] [Indexed: 02/27/2025] Open
Abstract
The administration of insulin as a treatment for diabetes frequently leads to the formation of anti-insulin antibodies (IAs). The influence of these antibodies on the efficacy and safety of insulin therapy remains incompletely understood. This study presents a systematic, exploratory, cross-sectional analysis of the quantitative and qualitative properties of IAs in 101 patients with type 1 diabetes (T1D) and 101 patients with type 2 diabetes (T2D). The goal was to identify subpopulations of IAs that might impact glycemic control. We assessed the presence, titer, isotype, subclass, avidity, and in vitro neutralizing capacities of IAs, using glycated hemoglobin A1c (HbA1c) levels as an indicator of the clinical effectiveness of insulin. Our findings showed that 72% of individuals with T1D and 32% with T2D developed IAs, with IgG being the predominant isotype in both groups. Despite the presence of IAs, no in vitro neutralizing effect against insulin was observed, and there was no significant correlation between IA titer or avidity and HbA1c levels in either group. The results from this study demonstrate that while IAs are prevalent in both T1D and T2D, they do not have a significant clinical impact on the outcomes of insulin therapy in our study populations.
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Affiliation(s)
- Henrik Toft-Hansen
- Non-Clinical and Clinical Assay Sciences, Novo Nordisk A/S, DK-2760 Maaloev, Denmark
| | | | - Daniel Elias
- Non-Clinical and Clinical Assay Sciences, Novo Nordisk A/S, DK-2760 Maaloev, Denmark
| | - Madeleine Dahlbäck
- Centre for Functional Assays and Screening, Novo Nordisk A/S, DK-2760 Maaloev, Denmark
| | - Peter Rossing
- Steno Diabetes Center Copenhagen, DK-2730 Herlev, Denmark
- Department of Clinical Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark
| | | | | | | | - Claus H. Nielsen
- Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark
| | - Helene Solberg
- Non-Clinical and Clinical Assay Sciences, Novo Nordisk A/S, DK-2760 Maaloev, Denmark
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3
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Fan S, Qiu Y, Liu J, Zhu T, Wang C, Liu D, Yan L, Ren M. Effect of the glucagon-like peptide-1 receptor agonists on diabetic peripheral neuropathy: A meta-analysis. J Neurochem 2025; 169:e16242. [PMID: 39453834 DOI: 10.1111/jnc.16242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 08/31/2024] [Accepted: 09/23/2024] [Indexed: 10/27/2024]
Abstract
Previous researches found that glucagon-like peptide 1 receptor agonists (GLP-1RA) offer benefits beyond their anti-diabetic properties, including weight loss and cardiovascular disease prevention. However, the effects of GLP-1RA on diabetic peripheral neuropathy (DPN) remain unclear. This meta-analysis aims to assess the potential benefits of GLP-1RA treatment in DPN patients by evaluating peripheral neural function. Following the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a meta-analysis of the clinical trials investigating the impact of GLP-1RA treatment on peripheral neural function in patients with DPN. Outcomes were measured using electrophysiological tests, including nerve conduction velocity (NCV) and action potential amplitude. Our meta-analysis included six studies with 271 participants. Following GLP-1RA treatment, NCV significantly improved compared to the control group (MD 1.74; 95% CI 1.16 to 2.33; p < 0.001) and before treatment (MD 2.16; 95% CI 1.04 to 3.27; p < 0.001). Despite the improvement in NCV, blood glucose levels did not change significantly (MD -0.20 95% CI -0.87 to 0.46, p = 0.55) indicating that GLP-1RA enhances NCV through mechanisms other than glucose lowering. Nonetheless, as a result of the limited population studied, further research is needed to strengthen the reliability of these findings.
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Affiliation(s)
- Shujin Fan
- Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
- The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of Endocrinology and Metabolism, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai, China
- Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou, China
| | - Yue Qiu
- Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
- Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou, China
| | - Jing Liu
- Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
- Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou, China
| | - Tianxin Zhu
- Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
- Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou, China
| | - Chuan Wang
- Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
- Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou, China
| | - Dan Liu
- Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
- Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou, China
| | - Li Yan
- Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
- Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou, China
| | - Meng Ren
- Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
- Guangdong Clinical Research Center for Metabolic Diseases, Guangzhou Key Laboratory for Metabolic Diseases, Guangzhou, China
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Pantazopoulos D, Gouveri E, Papazoglou D, Papanas N. Ocular Motor Mononeuropathies in Diabetes Mellitus: A Brief Review. Exp Clin Endocrinol Diabetes 2025; 133:73-77. [PMID: 39510537 DOI: 10.1055/a-2463-7075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
Ocular motor mononeuropathies affect cranial nerves III, IV and VI and are more frequent in diabetes mellitus, with oculomotor nerve involvement being predominant. This narrative brief review discusses the clinical manifestations, diagnosis and management of ocular motor mononeuropathies in subjects with diabetes. Clinical manifestations often include ptosis, diplopia, and periorbital pain. Pupillary sparing is a characteristic of third nerve palsy. Differential diagnosis may be challenging due to overlapping symptoms with nerve palsies of other aetiologies. Treatment includes optimised glycaemic control and management of vascular risk factors. Neuroprotective agents, mainly alpha-lipoic acid and botulinum toxin A have been occasionally used, as well. Spontaneous recovery is seen in many cases.
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Affiliation(s)
- Dimitrios Pantazopoulos
- Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - Evanthia Gouveri
- Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - Dimitrios Papazoglou
- Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - Nikolaos Papanas
- Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece
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Gogan A, Potre O, Avram VF, Andor M, Caruntu F, Timar B. Cardiac Autonomic Neuropathy in Diabetes Mellitus: Pathogenesis, Epidemiology, Diagnosis and Clinical Implications: A Narrative Review. J Clin Med 2025; 14:671. [PMID: 39941342 PMCID: PMC11818907 DOI: 10.3390/jcm14030671] [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: 12/25/2024] [Revised: 01/12/2025] [Accepted: 01/17/2025] [Indexed: 02/16/2025] Open
Abstract
Background: Cardiac autonomic neuropathy (CAN) is a serious but sometimes underdiagnosed complications of Diabetes Mellitus (DM). Because of the subtle onset and non-specific symptoms that can be mistaken for other conditions, CAN is frequently underdiagnosed despite the serious consequences that can appear. Its significance as an independent risk factor for cardiovascular events, including arrhythmias, sudden cardiac death, and silent myocardial ischemia, is being demonstrated by recent studies. The objective of this review article is to highlight the reasons why CAN is underdiagnosed and its association with decreased cardiovascular risk and promote clinical awareness. This review article summarizes the epidemiology, influence on the cardiovascular system and diagnostic methods of CAN, and the clinical implications of diabetic neuropathy. This review analyzes available data from papers relevant to the topic of diabetic neuropathy, cardiac autonomic neuropathy, and cardiovascular system implications. Conclusions: CAN is still underdiagnosed despite its clinical impact because routine screening is lacking, and healthcare providers are not aware of it. To improve outcomes for people with DM, it is necessary to introduce standardized diagnostic procedures into clinical practice and increase the knowledge about CAN.
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Affiliation(s)
- Alexandra Gogan
- Doctoral School of Medicine, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania;
- First Department of Internal Medicine, Medical Semiology II, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania; (M.A.); (F.C.)
- Cardiology Clinic, Institute of Cardiovascular Disease, 300310 Timisoara, Romania
| | - Ovidiu Potre
- First Department of Internal Medicine, Hematology, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania
- Multidisciplinary Research Centre for Malignant Hematological Disease (CCMHM), “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Vlad-Florian Avram
- Department of Diabetes, “Pius Brinzeu” Emergency Hospital, 300723 Timisoara, Romania; (V.-F.A.); (B.T.)
- Centre for Molecular Research in Nephrology and Vascular Disease, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania
- Second Department of Internal Medicine, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania
| | - Minodora Andor
- First Department of Internal Medicine, Medical Semiology II, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania; (M.A.); (F.C.)
- Multidisciplinary Heart Research Center, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania
- Cardiology Clinic of Timisoara Municipal Clinical Emergency Hospital, 300040 Timisoara, Romania
| | - Florina Caruntu
- First Department of Internal Medicine, Medical Semiology II, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania; (M.A.); (F.C.)
- Multidisciplinary Heart Research Center, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania
- Cardiology Clinic of Timisoara Municipal Clinical Emergency Hospital, 300040 Timisoara, Romania
| | - Bogdan Timar
- Department of Diabetes, “Pius Brinzeu” Emergency Hospital, 300723 Timisoara, Romania; (V.-F.A.); (B.T.)
- Centre for Molecular Research in Nephrology and Vascular Disease, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania
- Second Department of Internal Medicine, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania
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Hermanns N, Ehrmann D, Kulzer B, Klinker L, Haak T, Schmitt A. Somatic and mental symptoms associated with dysglycaemia, diabetes-related complications and mental conditions in people with diabetes: Assessments in daily life using continuous glucose monitoring and ecological momentary assessment. Diabetes Obes Metab 2025; 27:61-70. [PMID: 39375863 PMCID: PMC11618240 DOI: 10.1111/dom.15983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 09/16/2024] [Accepted: 09/16/2024] [Indexed: 10/09/2024]
Abstract
AIM To analyse the potential drivers (glucose level, complications, diabetes type, gender, age and mental health) of diabetes symptoms using continuous glucose monitoring (CGM) and ecological momentary assessment. MATERIALS AND METHODS Participants used a smartphone application to rate 25 diabetes symptoms in their daily lives over 8 days. These symptoms were grouped into four blocks so that each symptom was rated six times on 2 days (noon, afternoon and evening). The symptom ratings were associated with the glucose levels for the previous 2 hours, measured with CGM. Linear mixed-effects models were used, allowing for nested random effects and the conduct of N = 1 analysis of individual associations. RESULTS In total, 192 individuals with type 1 diabetes and 179 with type 2 diabetes completed 6380 app check-ins. Four symptoms showed a significant negative association with glucose values, indicating higher ratings at lower glucose (speech difficulties, P = .003; coordination problems, P = .00005; confusion, P = .049; and food cravings, P = .0003). Four symptoms showed a significant positive association with glucose values, indicating higher scores at higher glucose (thirst, P = .0001; urination, P = .0003; taste disturbances, P = .021; and itching, P = .0120). There were also significant positive associations between microangiopathy and eight symptoms. Elevated depression and diabetes distress were associated with higher symptom scores. N = 1 analysis showed highly idiosyncratic associations between symptom reports and glucose levels. CONCLUSIONS The N = 1 analysis facilitated the creation of personalized symptom profiles related to glucose levels with consideration of factors such as complications, gender, body mass index, depression and diabetes distress. This approach can enhance precision monitoring for diabetes symptoms in precision medicine.
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Affiliation(s)
- Norbert Hermanns
- Research Institute of the Diabetes‐Academy Mergentheim (FIDAM)Bad MergentheimGermany
- Department of Clinical Psychology and PsychotherapyUniversity of BambergBambergGermany
- German Center for Diabetes Research (DZD)NeuherbergGermany
- Diabetes Center Mergentheim (DZM)Diabetes ClinicBad MergentheimGermany
| | - Dominic Ehrmann
- Research Institute of the Diabetes‐Academy Mergentheim (FIDAM)Bad MergentheimGermany
- Department of Clinical Psychology and PsychotherapyUniversity of BambergBambergGermany
- German Center for Diabetes Research (DZD)NeuherbergGermany
| | - Bernhard Kulzer
- Research Institute of the Diabetes‐Academy Mergentheim (FIDAM)Bad MergentheimGermany
- Department of Clinical Psychology and PsychotherapyUniversity of BambergBambergGermany
- German Center for Diabetes Research (DZD)NeuherbergGermany
- Diabetes Center Mergentheim (DZM)Diabetes ClinicBad MergentheimGermany
| | - Laura Klinker
- Research Institute of the Diabetes‐Academy Mergentheim (FIDAM)Bad MergentheimGermany
- German Center for Diabetes Research (DZD)NeuherbergGermany
- Diabetes Center Mergentheim (DZM)Diabetes ClinicBad MergentheimGermany
| | - Thomas Haak
- Diabetes Center Mergentheim (DZM)Diabetes ClinicBad MergentheimGermany
| | - Andreas Schmitt
- Research Institute of the Diabetes‐Academy Mergentheim (FIDAM)Bad MergentheimGermany
- German Center for Diabetes Research (DZD)NeuherbergGermany
- Diabetes Center Mergentheim (DZM)Diabetes ClinicBad MergentheimGermany
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Wang K, Zhao H, Zhao X, Zhang X, Zhang W, Cheng Y, Ge J. Photobiomodulation for diabetes and its complications: a review of general presentation, mechanisms and efficacy. Ann Med 2024; 56:2433684. [PMID: 39607829 PMCID: PMC11610354 DOI: 10.1080/07853890.2024.2433684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 06/12/2024] [Accepted: 08/01/2024] [Indexed: 11/30/2024] Open
Abstract
Diabetes mellitus is a metabolic disease that is marked by persistent hyperglycemia due to inadequate insulin secretion or insulin resistance. Its prevalence is increasing yearly. Diabetes mellitus can lead to serious health complications that are the primary cause of mortality and disability among diabetic patients, including diabetic retinopathy, diabetic foot ulcers, diabetic peripheral neuropathy, and diabetic periodontitis, and so on. Traditional treatments for diabetes and its complications still suffer from limited clinical efficacy and high therapeutic side effects. Photobiomodulation (PBM), which utilizes low levels of red or near-infrared laser to irradiate cells and tissues, has been shown to be efficacious for a wide range of organ damage. In this study, we focus on the application of PBM in diabetes and its complications and mechanisms, as well as the advantages, disadvantages with the aim of developing new ideas for the application of PBM.
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Affiliation(s)
- Keyan Wang
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, China
- Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun, China
- China Japan Union Hospital of Jilin University, Changchun, China
| | - Hongwei Zhao
- Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Xiaoqing Zhao
- China Japan Union Hospital of Jilin University, Changchun, China
| | - Xiaoyu Zhang
- China Japan Union Hospital of Jilin University, Changchun, China
| | - Wei Zhang
- Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Yan Cheng
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, China
| | - Jingyan Ge
- Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun, China
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Magony S, Nyiraty S, Tóth B, Pesei F, Orosz A, Ábrahám G, Kempler P, Lengyel C, Várkonyi T. Peripheral sensory nerve hyperesthesia in women with polycystic ovary syndrome. Minerva Endocrinol (Torino) 2024; 49:381-388. [PMID: 33880894 DOI: 10.23736/s2724-6507.21.03418-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Dysfunction of the nervous system is well-known in diabetes and among patients with prediabetes, obesity, and hypertension. However, there is only a limited amount of data available on the changes in neuronal function in polycystic ovary syndrome (PCOs), even though this condition is also accompanied by metabolic and vascular abnormalities. The aim of our study was to assess the cardiovascular autonomic and peripheral sensory function in patients with PCOs. METHODS The study involved 27 women with PCOs, and 24 healthy women as control subjects. Autonomic neuropathy (AN) was assessed using the four standard cardiovascular reflex tests. Peripheral sensory function was determined using the Neurometer (Neurotron Incorporated, Baltimore, MD, USA). Electric stimulation was applied transcutaneously and the current perception threshold (CPT) values were determined on the median and peroneal nerves. RESULTS No significant differences were found between the PCOs patients and the control group regarding the cardiovascular autonomic reflex tests and the AN scores. The CPT values of PCOs patients in the median and peroneal nerves were lower at all frequencies in comparison to controls. CONCLUSIONS The cardiovascular autonomic nerve function was normal in the patients with PCOs. The current perception thresholds were consequently lower in the PCOs patients both in the upper and lower extremities at all frequencies, which serves as an early sign of neuropathy. As a novel observation, our results suggest that early neuronal damage manifests in the form of sensory hyperesthesia in patients with PCOs.
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Affiliation(s)
- Sándor Magony
- Department of Medicine, University of Szeged, Szeged, Hungary -
| | | | - Bettina Tóth
- Department of Medicine, University of Szeged, Szeged, Hungary
| | - Fruzsina Pesei
- Department of Medicine, University of Szeged, Szeged, Hungary
| | - Andrea Orosz
- Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary
| | - György Ábrahám
- Department of Medicine, University of Szeged, Szeged, Hungary
| | - Peter Kempler
- Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary
| | - Csaba Lengyel
- Department of Medicine, University of Szeged, Szeged, Hungary
| | - Tamás Várkonyi
- Department of Medicine, University of Szeged, Szeged, Hungary
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Lin Z, Wang S, Cao Y, Lin J, Sun A, Huang W, Zhou J, Hong Q. Bioinformatics and validation reveal the potential target of curcumin in the treatment of diabetic peripheral neuropathy. Neuropharmacology 2024; 260:110131. [PMID: 39179172 DOI: 10.1016/j.neuropharm.2024.110131] [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: 07/15/2023] [Revised: 08/18/2024] [Accepted: 08/20/2024] [Indexed: 08/26/2024]
Abstract
Diabetic peripheral neuropathy (DPN) is a common nerve-damaging complication of diabetes mellitus. Effective treatments are needed to alleviate and reverse diabetes-associated damage to the peripheral nerves. Curcumin is an effective neuroprotectant that plays a protective role in DPN promoted by Schwann cells (SCs) lesions. However, the potential molecular mechanism of curcumin remains unclear. Therefore, our aim is to study the detailed molecular mechanism of curcumin-mediated SCs repair in order to improve the efficacy of curcumin in the clinical treatment of DPN. First, candidate target genes of curcumin in rat SC line RSC96 cells stimulated by high glucose were identified by RNA sequencing and bioinformatic analyses. Enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was carried out by Metascape, followed by 8 algorithms on Cytoscape to determine 4 hub genes, namly Hmox1, Pten, Vegfa and Myc. Next, gene set enrichment analysis (GSEA) and Pearson function showed that Hmox1 was significantly correlated with apoptosis. Subsequently, qRT-PCR, MTT assay, flow cytometry, caspase-3 activity detection and westernblot showed that curcumin treatment increased RSC96 cell viability, reduced cell apoptosis, increased Hmox1, Pten, Vegfa and Myc expression, and up-regulated Akt phosphorylation level under high glucose environment. Finally, molecular docking predicted the binding site of curcumin to Hmox1. These results suggest that curcumin can reduce the apoptosis of SCs induced by high glucose, and Hmox1 is a potential target for curcumin. Our findings provide new insights about the mechanism of action of curcumin on SC as a potential treatment in DPN.
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Affiliation(s)
- Ziqiang Lin
- Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, Guangdong, 510000, China; Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, No. 183 Zhongshan Avenue West, Tianhe District, Guangzhou, Guangdong, 510000, China
| | - Suo Wang
- Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, Guangdong, 510000, China
| | - Yu Cao
- Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, No. 183 Zhongshan Avenue West, Tianhe District, Guangzhou, Guangdong, 510000, China
| | - Jialing Lin
- Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, Guangdong, 510000, China
| | - Ailing Sun
- Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, Guangdong, 510000, China
| | - Wei Huang
- Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, Guangdong, 510000, China
| | - Jun Zhou
- Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University, No. 183 Zhongshan Avenue West, Tianhe District, Guangzhou, Guangdong, 510000, China.
| | - Qingxiong Hong
- Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, Guangdong, 510000, China.
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10
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Özdemir Sipahioğlu Ü, Boyraz Özkavak S. Evaluation of neuropathy in epidermal growth factor administered patients diagnosed with diabetic foot. J Tissue Viability 2024; 33:608-615. [PMID: 39396885 DOI: 10.1016/j.jtv.2024.09.008] [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: 02/03/2024] [Revised: 08/02/2024] [Accepted: 09/21/2024] [Indexed: 10/15/2024]
Abstract
AIM This study was conducted to evaluate the effect of epidermal growth factor administered to patients diagnosed with diabetic foot on neuropathy. Secondarily, the effect of EGF on foot ulcer and neuropathic pain has also been evaluated. MATERIALS AND METHODS The study is an analytical type study with a single-group pretest-posttest quasi-experimental design. It was conducted with 30 patients diagnosed with Type 1 and Type 2 Diabetes who applied to the wound care unit and cardiovascular surgery outpatient clinic at Pamukkale University Hospitals between March 2021 and November 2022. By not using the sampling method, all patients who received EGF in the units were reached. Data were collected by "structured patient information form", "SINBAD classification", and "LANSS pain scale." Data were obtained as a "pretest" before the administration of epidermal growth factor (EGF), and as a "posttest" applied one month after the completion of EGF administration. Data were analyzed with Wilcoxon, Mann-Whitney U, Kruskal-Wallis H, Spearman's Rank Correlation, Mc Nemar, and Chi-Square Tests. FINDINGS It was observed that the average age of individuals with diabetic foot ulcer was 60.1 ± 12.9, 40 % were obese/morbidly obese, 83.3 % were male, and 43.3 % were treated with insulin + oral antidiabetic. It was determined that the number of years with diabetes was 17.37 ± 10.93 years, and the duration of diabetic foot ulcer was 218.83 ± 279.04 days. 46.7 % of the participants were determined to have a previous foot wound, and 33.3 % had a history of amputation in the past. Neuropathy was present in 100 % of the participants in the pre-test, while it was found to be 56.7 % in the post-test. The participants with neuropathy were observed to have a significantly higher SINBAD classification and LANSS pain scale scores: (p = 0,01; p = .00). HbA1c, SINBAD, and LANSS scores decreased significantly after EGF (p = 0,00; p = .01; p = .01). EGF administration was observed to have a statistically significant positive effect on neuropathy (p < .01). RESULTS EGF administration was observed to have a positive effect on the healing of foot ulcers, the reduction of neuropathic pain, and on neuropathy in patients diagnosed with diabetic foot.
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Elzehery R, El-Hafez HA, Elsehely I, Barakat A, Foda EAE, Hendawy SR, Gameil MA, Nada HS, El-Sebaie A. Association of the E23K (rs5219) polymorphism in the potassium channel (KCNJ11) gene with diabetic neuropathy in type 2 diabetes. Gene 2024; 921:148525. [PMID: 38703869 DOI: 10.1016/j.gene.2024.148525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Revised: 04/14/2024] [Accepted: 05/01/2024] [Indexed: 05/06/2024]
Affiliation(s)
- Rasha Elzehery
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Dakahlia, Egypt.
| | - Hala Abd El-Hafez
- Internal Medicine Department, Endocrinology Unit, Faculty of Medicine, Mansoura University, Mansoura, Dakahlia, Egypt.
| | - Ibrahim Elsehely
- Internal Medicine Department, Endocrinology Unit, Faculty of Medicine, Mansoura University, Mansoura, Dakahlia, Egypt.
| | - Amira Barakat
- Internal Medicine Department, Endocrinology Unit, Faculty of Medicine, Mansoura University, Mansoura, Dakahlia, Egypt.
| | - Engy Ahmed Ebrahim Foda
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Dakahlia, Egypt.
| | - Shimaa Rabea Hendawy
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Dakahlia, Egypt.
| | - Mohammed Ali Gameil
- Internal Medicine Department, Endocrinology Unit, Faculty of Medicine, Mansoura University, Mansoura, Dakahlia, Egypt.
| | - Hyam Sameh Nada
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Dakahlia, Egypt.
| | - Ahmed El-Sebaie
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Dakahlia, Egypt.
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Costa YM, Herculiani CCF, Soares FFC, Azevedo MDCS, Conti PCR, Dionísio TJ, Oliveira GDM, Faria FACD, Santos CF, Garlet GP, Bonjardim LR. Impact of streptozotocin-induced diabetes on experimental masseter pain in rats. Braz Oral Res 2024; 38:e073. [PMID: 39109769 PMCID: PMC11376623 DOI: 10.1590/1807-3107bor-2024.vol38.0073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Accepted: 04/02/2024] [Indexed: 09/20/2024] Open
Abstract
This study aimed to assess the influence of streptozotocin (STZ)-induced diabetes on the nociceptive behavior evoked by the injection of hypertonic saline (HS) into the masseter muscle of rats. Forty male rats were equally divided into four groups: a) isotonic saline control, which received 0.9% isotonic saline (IS), (Ctrl-IS); b) hypertonic saline control, which received 5% HS (Ctrl-HS); c) STZ-induced diabetic, which received IS, (STZ-IS); d) STZ-induced diabetic, which received HS (STZ-HS). Experimental diabetes was induced by a single intraperitoneal injection of STZ at dose of 60 mg/kg dissolved in 0.1 M citrate buffer, and 100 μL of HS or IS were injected into the left masseter to measure the nociceptive behavior. Later on, muscle RNA was extracted to measure the relative expression of the following cytokines: cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and interleukins (IL)-1β, -2, -6, and -10. One-way analysis of variance (ANOVA) was applied to the data (p < 0.050). We observed a main effect of group on the nociceptive response (ANOVA: F = 11.60, p < 0.001), where the Ctrl-HS group presented the highest response (p < 0.001). However, nociceptive response was similar among the Ctrl-IS, STZ-IS, and STZ-HS group (p > 0.050). In addition, the highest relative gene expression of TNF-α and IL-6 was found in the masseter of control rats following experimental muscle pain (p < 0.050). In conclusion, the loss of somatosensory function can be observed in deep orofacial tissues of STZ-induced diabetic rats.
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Affiliation(s)
- Yuri Martins Costa
- Universidade Estadual de Campinas - Unicamp, Piracicaba Dental School, Department of Biosciences, Piracicaba, SP, Brazil
| | | | - Flávia Fonseca Carvalho Soares
- Universidade de São Paulo - USP, Bauru School of Dentistry, Department of Biological Sciences, Bauru, São Paulo, SP, Brazil
| | | | | | - Thiago José Dionísio
- Universidade de São Paulo - USP, Bauru School of Dentistry, Department of Biological Sciences, Bauru, São Paulo, SP, Brazil
| | | | | | - Carlos Ferreira Santos
- Universidade de São Paulo - USP, Bauru School of Dentistry, Department of Biological Sciences, Bauru, São Paulo, SP, Brazil
| | - Gustavo Pompermaier Garlet
- Universidade de São Paulo - USP, Bauru School of Dentistry, Department of Biological Sciences, Bauru, São Paulo, SP, Brazil
| | - Leonardo Rigoldi Bonjardim
- Universidade de São Paulo - USP, Bauru School of Dentistry, Department of Biological Sciences, Bauru, São Paulo, SP, Brazil
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13
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Zhou T, Dou Z, Cai Y, Zhu D, Fu Y. Tear Fluid Progranulin as a Noninvasive Biomarker for the Monitoring of Corneal Innervation Changes in Patients With Type 2 Diabetes Mellitus. Transl Vis Sci Technol 2024; 13:9. [PMID: 38984913 PMCID: PMC11238880 DOI: 10.1167/tvst.13.7.9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/11/2024] Open
Abstract
Purpose This study aimed to investigate the expression levels of progranulin (PGRN) in the tears of patients with diabetic retinopathy (DR) versus healthy controls. Additionally, we sought to explore the correlation between PGRN levels and the severity of ocular surface complications in patients with diabetes. Methods In this prospective, single-visit, cross-sectional study, patients with DR (n = 48) and age-matched healthy controls (n = 22) were included and underwent dry eye examinations. Tear fluid was collected, and its components were analyzed using the Luminex assay. The subbasal nerve plexus of all participants was evaluated by in vivo confocal microscopy. Results Patients with DR exhibited more severe dry eye symptoms, along with a reduction in nerve fiber density, length, and branch density within the subbasal nerve plexus, accompanied by an increase in the number of dendritic cells. Tear PGRN levels were also significantly lower in patients with diabetes than in normal controls, and the levels of some inflammatory factors (TNF-α, IL-6, and MMP-9) were higher in patients with DR. Remarkably, the PGRN level significantly correlated with nerve fiber density (R = 0.48, P < 0.001), nerve fiber length (R = 0.65, P < 0.001), and nerve branch density (R = 0.69, P < 0.001). Conclusions Tear PGRN levels might reflect morphological changes in the corneal nerve plexus under diabetic conditions, suggesting that PGRN itself is a reliable indicator for predicting the advancement of neurotrophic keratopathy in patients with diabetes. Translational Relevance PGRN insufficiency on the ocular surface under diabetic conditions was found to be closely associated with nerve impairment, providing a novel perspective to discover the pathogenesis of diabetic complications, which could help in developing innovative therapeutic strategies.
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Affiliation(s)
- Tianyi Zhou
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Zhiwei Dou
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Yuchen Cai
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Dongqing Zhu
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Yao Fu
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
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Hajdú N, Rácz R, Tordai DZ, Békeffy M, Vági OE, Istenes I, Körei AE, Kempler P, Putz Z. Genetic Variants Influence the Development of Diabetic Neuropathy. Int J Mol Sci 2024; 25:6429. [PMID: 38928135 PMCID: PMC11203776 DOI: 10.3390/ijms25126429] [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: 04/02/2024] [Revised: 05/22/2024] [Accepted: 06/06/2024] [Indexed: 06/28/2024] Open
Abstract
The exact mechanism by which diabetic neuropathy develops is still not fully known, despite our advances in medical knowledge. Progressing neuropathy may occur with a persistently favorable metabolic status in some patients with diabetes mellitus, while, in others, though seldom, a persistently unfavorable metabolic status is not associated with significant neuropathy. This might be significantly due to genetic differences. While recent years have brought compelling progress in the understanding of the pathogenetic background-in particular, accelerated progress is being made in understanding molecular biological mechanisms-some aspects are still not fully understood. A comparatively small amount of information is accessible on this matter; therefore, by summarizing the available data, in this review, we aim to provide a clearer picture of the current state of knowledge, identify gaps in the previous studies, and possibly suggest directions for future studies. This could help in developing more personalized approaches to the prevention and treatment of diabetic neuropathy, while also taking into account individual genetic profiles.
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Orlando G, Brown S, Jude E, Bowling FL, Boulton AJ, Reeves ND. Acute Effects of Vibrating Insoles on Dynamic Balance and Gait Quality in Individuals With Diabetic Peripheral Neuropathy: A Randomized Crossover Study. Diabetes Care 2024; 47:1004-1011. [PMID: 38536962 PMCID: PMC11116908 DOI: 10.2337/dc23-1858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Accepted: 03/07/2024] [Indexed: 05/22/2024]
Abstract
OBJECTIVE This study investigated the effects of vibrating insoles on dynamic balance and gait quality during level and stair walking and explored the influence of vibration type and frequency in individuals with diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS Twenty-two men with DPN were assessed for gait quality and postural and dynamic balance during walking and stair negotiation using a motion capture system and force plates across seven vibratory insole conditions (Vcs) versus a control (Ctrl) condition (insole without vibration). Vibration was applied during standing and walking tasks, and 15-min rest-stop periods without vibration were interposed between conditions. Repeated measures test conditions were randomized. The primary outcomes were gait speed and dynamic balance. RESULTS Gait speed during walking significantly improved in all Vcs compared with Ctrl (P < 0.005), with Vc2, Vc4, and Vc6 identified as the most effective. Gait speed increased (reflecting faster walking) during stair ascent and descent in Vc2 (Ctrl vs. Vc2 for ascent 0.447 ± 0.180 vs. 0.517 ± 0.127 m/s; P = 0.037 and descent 0.394 ± 0.170 vs. 0.487 ± 0.125 m/s; P = 0.016), Vc4 (Ctrl vs. Vc4 for ascent 0.447 ± 0.180 vs. 0.482 ± 0.197 m/s; P = 0.047 and descent 0.394 ± 0.170 vs. 0.438 ± 0.181 m/s; P = 0.017), and Vc6 (Ctrl vs. Vc6 for ascent 0.447 ± 0.180 vs. 0.506 ± 0.179 m/s; P = 0.043 and descent 0.394 ± 0.170 vs. 0.463 ± 0.159 m/s; P = 0.026). Postural balance improved during quiet standing with eyes closed in Vc2, Vc4, Vc6, and Vc7 (P < 0.005). CONCLUSIONS Vibrating insoles are an effective acute strategy for improving postural balance and gait quality during level walking and stair descent in individuals with DPN. These benefits are particularly evident when the entire plantar foot surface is stimulated.
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Affiliation(s)
- Giorgio Orlando
- Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, U.K
- Department of Sport and Exercise Sciences, Institute of Sport, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, U.K
| | - Steven Brown
- Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, U.K
- Department of Sport and Exercise Sciences, Institute of Sport, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, U.K
| | - Edward Jude
- Tameside and Glossop Integrated Care, National Health Service Foundation Trust, Ashton-under-Lyne, Manchester, U.K
| | - Frank L. Bowling
- Department of Medicine, Manchester Royal Infirmary, Manchester, U.K
| | - Andrew J.M. Boulton
- Department of Medicine, Manchester Royal Infirmary, Manchester, U.K
- Diabetes Research Institute, University of Miami, Miami, FL
| | - Neil D. Reeves
- Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, U.K
- Department of Sport and Exercise Sciences, Institute of Sport, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, U.K
- Lancaster Medical School, Faculty of Health and Medicine, Lancaster University, Lancaster, U.K
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Rodriguez-Saldana J, Mijangos JHS, Hancock CN, Ramsey DL, Weiser LK. Prevalence and disease burden of peripheral neuropathy in the general population in Mexico city: a cross-sectional epidemiological study. Curr Med Res Opin 2024:1-11. [PMID: 38822450 DOI: 10.1080/03007995.2024.2352852] [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: 03/19/2024] [Accepted: 05/05/2024] [Indexed: 06/03/2024]
Abstract
OBJECTIVE Peripheral neuropathy (PN) is one of the most common diseases of the peripheral nervous system. Symptoms range from mild sensory signs to severe neuropathic pain. Untreated PN is progressive and can lead to complications and impair quality of life (QoL). However, PN prevalence is underestimated in the general population and affected individuals often remain undiagnosed. This study aimed to contribute to the global generation of prevalence data and determine sociodemographic and disease-related characteristics of PN sufferers. METHODS This cross-sectional study collected information on PN prevalence and associated factors in the adult population (40-65 years) of the Mexico City area. Participants were recruited in public places and screened for PN using the Michigan Neuropathy Screening Instrument (MNSI). Subjects with PN answered the Neuropathy Total Symptom Score-6 (NTSS-6), the Short Form-36 Health Survey (SF-36), and the QoL Pharmacoeconomic Questionnaire. Statistical analysis included descriptive methods and calculation of PN prevalence with 95% confidence intervals. RESULTS Of 3066 participants, 448 had PN based on the MNSI physical examination. The overall PN prevalence was 14.6%, with the highest (18.9%) seen in subjects aged 61-65 years. PN was undiagnosed in 82.6%, and 62.9% had never heard of PN. Although half of all subjects had only mild PN symptoms, QoL was impacted in 91.8%. CONCLUSIONS The results confirm that PN prevalence in the general population is high. Despite the disease burden, most affected persons are undiagnosed and unaware of the disease. Almost all felt their QoL was impacted. The data highlight the need to raise awareness and identify undiagnosed individuals to prevent complications.
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Affiliation(s)
| | | | | | - David L Ramsey
- Procter & Gamble, Global Personal Health Care Division, Mason, OH, USA
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Saini T, Mazumder PM. Current advancement in the preclinical models used for the assessment of diabetic neuropathy. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:2727-2745. [PMID: 37987794 DOI: 10.1007/s00210-023-02802-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 10/17/2023] [Indexed: 11/22/2023]
Abstract
Diabetic neuropathy is one of the prevalent and debilitating microvascular complications of diabetes mellitus, affecting a significant portion of the global population. Relational preclinical animal models are essential to understand its pathophysiology and develop effective treatments. This abstract provides an overview of current knowledge and advancements in such models. Various animal models have been developed to mimic the multifaceted aspects of human diabetic neuropathy, including both type 1 and type 2 diabetes. These models involve rodents (rats and mice) and larger animals like rabbits and dogs. Induction of diabetic neuropathy in these models is achieved through chemical, genetic, or dietary interventions, such as diabetogenic agents, genetic modifications, or high-fat diets. Preclinical animal models have greatly contributed to studying the intricate molecular and cellular mechanisms underlying diabetic neuropathy. They have shed light on hyperglycemia-induced oxidative stress, neuroinflammation, mitochondrial dysfunction, and altered neurotrophic factor signaling. Additionally, these models have allowed for the investigation of morphological changes, functional alterations, and behavioral manifestations associated with diabetic neuropathy. These models have also been crucial for evaluating the efficacy and safety of potential therapeutic interventions. Novel pharmacological agents, gene therapies, stem cell-based approaches, exercise, dietary modifications, and neurostimulation techniques have been tested using these models. However, limitations and challenges remain, including physiological differences between humans and animals, complex neuropathy phenotypes, and the need for translational validation. In conclusion, preclinical animal models have played a vital role in advancing our understanding and management of diabetic neuropathy. They have enhanced our knowledge of disease mechanisms, facilitated the development of novel treatments, and provided a platform for translational research. Ongoing efforts to refine and validate these models are crucial for future treatment developments for this debilitating condition.
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Affiliation(s)
- Tanishk Saini
- Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology, Mesra, 835215, Ranchi, India
| | - Papiya Mitra Mazumder
- Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology, Mesra, 835215, Ranchi, India.
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18
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Ashoori M, Pourahmadi M, Hashemi SE, Dadgoo M, Hosseini MS. The effectiveness of neurodynamic techniques in patients with diabetic peripheral neuropathy: Study protocol for a randomized sham-controlled trial. Adv Biomed Res 2024; 13:6. [PMID: 38525394 PMCID: PMC10958726 DOI: 10.4103/abr.abr_180_23] [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: 05/26/2023] [Revised: 09/17/2023] [Accepted: 09/18/2023] [Indexed: 03/26/2024] Open
Abstract
Background Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus (DM). DPN is the primary risk factor for diabetic foot ulcers that can cause amputation. Although several observational studies have investigated the morphological and biomechanical characteristics of peripheral nerves in DPN, interventional studies regarding the effectiveness of neurodynamic techniques (NDT) in DPN patients are confined to a handful. The effects of NDT on neuropathy severity, nerve conduction parameters, quality of life (QoL), and mechanosensitivity have not been explored yet in this population. Materials and Methods Forty type 2 DPN (T2DPN) patients, diagnosed based on an electrodiagnosis study, will be recruited into two groups. The experimental group will receive the tibial nerve's real proximal and distal slider techniques in addition to DPN standard treatment as a basic treatment, and the control group will receive the tibial nerve's sham proximal and distal slider techniques along with the basic treatment for eight sessions twice a week. Baseline and post-intervention assessments will be based on the Michigan diabetic neuropathy score (MDNS) (primary outcome), tibial nerve conduction parameters, neuropathy-specific quality of life (Neuro QoL) questionnaire, and straight leg raising range of motion (SLR ROM) (secondary outcomes). Results This study is expected to last approximately seven months, depending on recruitment. The results of the study will be published in a peer-reviewed journal. Conclusions The present study will evaluate the efficacy of NDT on the primary and secondary outcome measurements in DPN patients.
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Affiliation(s)
- Mahdi Ashoori
- Iranian Center of Excellence in Physiotherapy, Rehabilitation Research Center, Department of Physiotherapy, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Pourahmadi
- Iranian Center of Excellence in Physiotherapy, Rehabilitation Research Center, Department of Physiotherapy, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Seyed Ebrahim Hashemi
- Exercise Physiology Research Center, Life Style Institute, Baqiyatallah al-Azam Hospital, Baqiyatallah University of Medical Science, Tehran, Islamic Republic of Iran
| | - Mehdi Dadgoo
- Iranian Center of Excellence in Physiotherapy, Rehabilitation Research Center, Department of Physiotherapy, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Mahboobeh Sadat Hosseini
- Health Research Center, Life Style Institute, Baqiyatallah al-Azam Hospital, Baqiyatallah University of Medical Science, Tehran, Islamic Republic of Iran
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Castater C, Bishop E, Santos A, Freedberg M, Kim P, Sciarretta C. Diabetic Soft Tissue Infections. Surg Clin North Am 2023; 103:1191-1216. [PMID: 37838463 DOI: 10.1016/j.suc.2023.06.002] [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] [Indexed: 10/16/2023]
Abstract
Diabetes is a systemic illness that can cause a broad range of physiologic effects. Infection rates and wound healing are both affected through multiple mechanisms. Other physiologic changes increase risk for wounds as well as complex soft tissue infections ranging from simple cellulitis to necrotizing soft tissue infections. Clinicians and surgeons need to have a low index of suspicion for severe infection in a patient presenting with diabetes, and even more so in patients with uncontrolled diabetes.
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Affiliation(s)
- Christine Castater
- Morehouse School of Medicine, Grady Memorial Hospital 1C-144, 80 Jesse Hill Jr Drive Southeast, Atlanta, GA 30303, USA.
| | - Elliot Bishop
- Emory University, Grady Memorial Hospital Glenn Building 69 Jesse Hill Jr Drive Southeast, Atlanta, GA 30303, USA
| | - Adora Santos
- Emory University, Grady Memorial Hospital Glenn Building 69 Jesse Hill Jr Drive Southeast, Atlanta, GA 30303, USA
| | - Mari Freedberg
- Emory University, Grady Memorial Hospital Glenn Building 69 Jesse Hill Jr Drive Southeast, Atlanta, GA 30303, USA
| | - Phillip Kim
- Emory University, Grady Memorial Hospital Glenn Building 69 Jesse Hill Jr Drive Southeast, Atlanta, GA 30303, USA
| | - Christopher Sciarretta
- University of Tennessee, University of Tennessee College of Medicine, 975 3rd Avenue, Chattanooga, TN 37403, USA
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Boulton AJM. A brief overview of the diabetic neuropathies. Diabetes Res Clin Pract 2023; 206 Suppl 1:110758. [PMID: 38245328 DOI: 10.1016/j.diabres.2023.110758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 05/30/2023] [Indexed: 01/22/2024]
Abstract
The diabetic neuropathies represent the commonest long-term complications of diabetes, and may be the presenting feature of Type 2 diabetes. In clinical practice, distal symmetrical polyneuropathy (DSPN) and the autonomic neuropathies are the most frequently seen forms of diabetic neuropathy. The 2017 American Diabetes Association classification system for the neuropathies of diabetes are in general use. Treatment challenges remain and the need for revised recommendations and further discussion of management of severely painful DSPN that does not fully respond to conventional medical management is clear, especially in light of the recent opioid crisis in the USA.
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Affiliation(s)
- Andrew J M Boulton
- Professor of Medicine, University of Manchester, Division of Diabetes, Endocrinology and Gastroenterology , Consultant Physician, Manchester Royal Infirmary, Visiting Professor of Medicine, University of Miami, Miami, FL, USA; President, Worldwide Initiative for Diabetes Education Immediate Past-President, International Diabetes Federation Past-President, European Association for the Study of Diabetes, United States.
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21
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Staehelin Jensen T. The pathogenesis of painful diabetic neuropathy and clinical presentation. Diabetes Res Clin Pract 2023; 206 Suppl 1:110753. [PMID: 38245319 DOI: 10.1016/j.diabres.2023.110753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 05/30/2023] [Indexed: 01/22/2024]
Abstract
Diabetic neuropathy is a common complication of diabetes that affects up to 50% of patients during the course of the disease; 20-30% of the patients also develop neuropathic pain. The mechanisms underlying neuropathy are not known in detail, but both metabolic and vascular factors may contribute to the development of neuropathy. The development of the most common type of neuropathy is insidious, often starting distally in the toes and feet and gradually ascending up the leg and later also involving fingers and hands. The symptoms are mainly sensory with either sensory loss or positive symptoms with different types of paresthesia or painful sensations. In more advanced cases motor dysfunction may occur, causing gait disturbances and falls. The diagnosis of neuropathy is based on history and a careful examination, which includes a sensory examination of both large and small sensory nerve fiber function, as well as an examination of motor function and deep tendon reflexes of the lower limbs. Attention needs to be paid to the feet including examination of the skin, joints, and vascular supply. Nerve conduction studies are rarely needed to make a diagnosis of neuropathy. In patients with clear motor deficit or with an asymmetrical presentation, additional electrophysiological examination may be necessary. Early detection of diabetic neuropathy is important to avoid further irreversible injury to the peripheral nerves.
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Affiliation(s)
- Troels Staehelin Jensen
- Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
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Wang LQ, Yue JH, Gao SL, Cao DN, Li A, Peng CL, Liu X, Han SW, Li XL, Zhang QH. Magnetic resonance imaging on brain structure and function changes in diabetic peripheral neuropathy. Front Neurol 2023; 14:1285312. [PMID: 38073636 PMCID: PMC10699301 DOI: 10.3389/fneur.2023.1285312] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 10/27/2023] [Indexed: 02/28/2025] Open
Abstract
With the significant increase in the global prevalence of diabetes mellitus (DM), the occurrence of diabetic peripheral neuropathy (DPN) has become increasingly common complication associated with DM. It is particularly in the peripheral nerves of the hands, legs, and feet. DPN can lead to various adverse consequences that greatly affect the quality of life for individuals with DM. Despite the profound impact of DPN, the specific mechanisms underlying its development and progression are still not well understood. Advancements in magnetic resonance imaging (MRI) technology have provided valuable tools for investigating the central mechanisms involved in DPN. Structural and functional MRI techniques have emerged as important methods for studying the brain structures and functions associated with DPN. Voxel-based morphometry allows researchers to assess changes in the volume and density of different brain regions, providing insights into potential structural alterations related to DPN. Functional MRI investigates brain activity patterns, helping elucidate the neural networks engaged during sensory processing and pain perception in DPN patients. Lastly, magnetic resonance spectroscopy provides information about the neurochemical composition of specific brain regions, shedding light on potential metabolic changes associated with DPN. By synthesizing available literature employing these MRI techniques, this study aims to enhance our understanding of the neural mechanisms underlying DPN and contribute to the improvement of clinical diagnosis.
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Affiliation(s)
- Li-qin Wang
- Department of Nursing Care, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jin-huan Yue
- Shenzhen Frontiers in Chinese Medicine Research Co., Ltd., Shenzhen, China
- Department of Acupuncture and Moxibustion, Vitality University, Hayward, CA, United States
| | - Sheng-lan Gao
- Graduate School of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Dan-na Cao
- Division of CT and MRI, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Ang Li
- Servier (Beijing) Pharmaceutical Research & Development Co. Ltd., Beijing, China
| | - Cai-liang Peng
- Third Ward of Cardiology Department, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xiao Liu
- Department of Pediatrics, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Sheng-wang Han
- Third Ward of Rehabilitation Department, Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xiao-ling Li
- Division of CT and MRI, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Qin-hong Zhang
- Shenzhen Frontiers in Chinese Medicine Research Co., Ltd., Shenzhen, China
- Heilongjiang University of Chinese Medicine, Harbin, China
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23
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Cohen CD, De Blasio MJ, Farrugia GE, Dona MS, Hsu I, Prakoso D, Kiriazis H, Krstevski C, Nash DM, Li M, Gaynor TL, Deo M, Drummond GR, Ritchie RH, Pinto AR. Mapping the cellular and molecular landscape of cardiac non-myocytes in murine diabetic cardiomyopathy. iScience 2023; 26:107759. [PMID: 37736052 PMCID: PMC10509303 DOI: 10.1016/j.isci.2023.107759] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 05/01/2023] [Accepted: 08/25/2023] [Indexed: 09/23/2023] Open
Abstract
Diabetes is associated with a significantly elevated risk of heart failure. However, despite extensive efforts to characterize the phenotype of the diabetic heart, the molecular and cellular protagonists that underpin cardiac pathological remodeling in diabetes remain unclear, with a notable paucity of data regarding the impact of diabetes on non-myocytes within the heart. Here we aimed to define key differences in cardiac non-myocytes between spontaneously type-2 diabetic (db/db) and healthy control (db/h) mouse hearts. Single-cell transcriptomic analysis revealed a concerted diabetes-induced cellular response contributing to cardiac remodeling. These included cell-specific activation of gene programs relating to fibroblast hyperplasia and cell migration, and dysregulation of pathways involving vascular homeostasis and protein folding. This work offers a new perspective for understanding the cellular mediators of diabetes-induced cardiac pathology, and pathways that may be targeted to address the cardiac complications associated with diabetes.
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Affiliation(s)
- Charles D. Cohen
- Cardiac Cellular Systems, Baker Heart and Diabetes Institute, Prahran, VIC, Australia
- Heart Failure Pharmacology, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia
- Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, VIC, Australia
- Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, VIC, Australia
| | - Miles J. De Blasio
- Heart Failure Pharmacology, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia
- Department of Pharmacology, Monash University, Clayton, VIC, Australia
| | - Gabriella E. Farrugia
- Cardiac Cellular Systems, Baker Heart and Diabetes Institute, Prahran, VIC, Australia
- Baker Department of Cardiovascular Research and Implementation, La Trobe University, Melbourne, VIC, Australia
| | - Malathi S.I. Dona
- Cardiac Cellular Systems, Baker Heart and Diabetes Institute, Prahran, VIC, Australia
| | - Ian Hsu
- Cardiac Cellular Systems, Baker Heart and Diabetes Institute, Prahran, VIC, Australia
| | - Darnel Prakoso
- Heart Failure Pharmacology, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia
| | - Helen Kiriazis
- Preclinical Cardiology, Microsurgery and Imaging Platform, Baker Heart and Diabetes Institute, Prahran, VIC, Australia
- Baker Department of Cardiometabolic Health, University of Melbourne, Parkville, VIC, Australia
| | - Crisdion Krstevski
- Cardiac Cellular Systems, Baker Heart and Diabetes Institute, Prahran, VIC, Australia
- Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, VIC, Australia
- Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, VIC, Australia
| | - David M. Nash
- Heart Failure Pharmacology, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia
| | - Mandy Li
- Heart Failure Pharmacology, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia
| | - Taylah L. Gaynor
- Cardiac Cellular Systems, Baker Heart and Diabetes Institute, Prahran, VIC, Australia
- Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, VIC, Australia
- Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, VIC, Australia
| | - Minh Deo
- Heart Failure Pharmacology, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia
| | - Grant R. Drummond
- Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, VIC, Australia
| | - Rebecca H. Ritchie
- Heart Failure Pharmacology, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia
- Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, VIC, Australia
- Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, VIC, Australia
| | - Alexander R. Pinto
- Cardiac Cellular Systems, Baker Heart and Diabetes Institute, Prahran, VIC, Australia
- Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, VIC, Australia
- Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, VIC, Australia
- Baker Department of Cardiometabolic Health, University of Melbourne, Parkville, VIC, Australia
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24
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Siddiqui AH, Tauheed N, Ashraf H, Ahmad J. Association of Sensory Nerve Action Potential Amplitude and Velocity With Type 2 Diabetic Peripheral Neuropathy. Cureus 2023; 15:e46501. [PMID: 37927653 PMCID: PMC10624771 DOI: 10.7759/cureus.46501] [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] [Accepted: 10/04/2023] [Indexed: 11/07/2023] Open
Abstract
BACKGROUND There is ongoing controversy regarding the predominant type of nerve injury in diabetic peripheral neuropathy, whether it is demyelination or axonal degeneration. OBJECTIVE This study aimed to investigate the association between nerve conduction study parameters, specifically nerve conduction velocity and the amplitude of the action potential, with diabetic peripheral neuropathy and determine their potential as early indicators of the condition. METHODS A cross-sectional study was conducted involving diagnosed type 2 diabetes mellitus patients, who were divided into two groups: Group I (n = 111) with symptomatic diabetic peripheral neuropathy and Group II (n = 109) without clinically detectable peripheral neuropathy. Age and sex-matched healthy controls (n = 100) were also included. Nerve conduction velocity measurements were performed on both upper and lower limbs, with motor nerve conduction study focusing on the dominant side using the median and posterior tibial nerves and sensory nerve conduction study using the median and sural nerves. RESULTS The nerve conduction studies revealed significantly lower sensory nerve action potential amplitudes and compound muscle action potential amplitudes in the median, posterior tibial, and sural nerves of the diabetic groups compared to the control subjects. Furthermore, these changes were more prominent in patients with peripheral neuropathy. Among the 220 diabetic patients analyzed, 135 (61.36%) exhibited nerve conduction abnormalities. The highest rate of abnormality was observed in the sural nerve, followed by the posterior tibial and median nerves. The most common abnormality detected in diabetic patients was a decrease in sensory nerve action potential, followed by a decrease in sensory nerve conduction velocity. CONCLUSION The study findings suggest an association between reduced sensory nerve action potential amplitude and diabetic peripheral neuropathy. These results highlight the potential of sensory nerve action potential and velocity as a sensitive indicator of peripheral neuropathy in diabetic patients.
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Affiliation(s)
- Anwar H Siddiqui
- Physiology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, IND
| | - Nazia Tauheed
- Anaesthesiology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, IND
| | - Hamid Ashraf
- Endocrinology and Diabetes, Rajiv Gandhi Centre for Diabetes and Endocrinology, Aligarh Muslim University, Aligarh, IND
| | - Jamal Ahmad
- Endocrinology and Diabetes, Rajiv Gandhi Centre for Diabetes and Endocrinology, Aligarh Muslim University, Aligarh, IND
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25
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Pappa A, Haeusler MG, Tittel SR, Boettcher C, Hilgard D, Knauer-Fischer S, Pavel M, Woelfle J, Holl RW. Neuropathy in paediatric type 1 diabetes mellitus - clinical characterization and analysis of risk factors in the diabetes prospective follow-up registry DPV (Diabetes-Patienten-Verlaufsdokumentation)-registry. J Pediatr Endocrinol Metab 2023; 0:jpem-2023-0074. [PMID: 37307302 DOI: 10.1515/jpem-2023-0074] [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: 02/20/2023] [Accepted: 05/21/2023] [Indexed: 06/14/2023]
Abstract
OBJECTIVES Data on the prevalence, clinical features and risk factors associated with paediatric diabetic neuropathy (DN) are scarce. METHODS We retrospectively analysed data from the DPV registry, including patients under 20 years of age, treated for type 1 diabetes mellitus (T1D) between 2005 and 2021. Patients with non-diabetic neuropathy were excluded. Data came from centres in Austria, Germany, Luxembourg and Switzerland. RESULTS 1,121 of the 84,390 patients included had been diagnosed with DN. Univariate analysis showed patients with DN to be older and predominantly female, with a longer duration of T1D, higher insulin dosages per kg and day, lower rates of insulin pump therapy, higher postprandial glucose-, higher HbA1c-and higher cholesterol levels, and higher diastolic and systolic blood pressure values. There was also a larger proportion of smokers and higher prevalence of diabetic retinopathy. Median duration of diabetes at diagnosis of DN was 8.3 years. Multivariable analysis, adjusted for demographics revealed an increased risk for DN among female patients and those who were older, underweight (BMI-SDS), smoked cigarettes or had a longer duration of T1D or higher levels of HbA1c and postprandial blood glucose. The presence of retinopathy and higher cholesterol levels were also linked to increased risk while not-using insulin pump therapy was not. CONCLUSIONS DN can develop after just a short duration of T1D. Prevention may be achieved by a lowering of HbA1c-and postprandial glucose levels through improved glycaemic control. This warrants further investigation. The slight female predominance suggests further hormonal and genetic etiological factors.
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Affiliation(s)
- Angeliki Pappa
- Department of Paediatrics, University Hospital RWTH Aachen, Aachen, Germany
| | - Martin G Haeusler
- Department of Paediatrics, Division of Neuropediatrics and Social Pediatrics, University Hospital RWTH Aachen, Aachen, Germany
| | - Sascha R Tittel
- Institute of Epidemiology and Medical Biometry, ZIBMT, Ulm University, Ulm, Germany
- German Centre for Diabetes Research (DZD), Munich-Neuherberg, Germany
| | - Claudia Boettcher
- Paediatric Endocrinology & Diabetology, University Children's Hospital, University of Berne, Berne, Switzerland
| | - Doerte Hilgard
- Kinder-und Jugenddiabetologische Praxis Witten, Herdecke, Germany
| | - Sabine Knauer-Fischer
- Klinik für Kinder-und Jugendmedizin, Universitätsmedizin Mannheim, Mannheim, Baden-Württemberg
| | - Marianne Pavel
- Medizinische Klinik 1, UK Erlangen-Nürnberg, Erlangen, Germany
| | - Joachim Woelfle
- Kinderklinik Universitätsklinikum Erlangen, Erlangen, Germany
| | - Reinhard W Holl
- Institute of Epidemiology and Medical Biometry, ZIBMT, Ulm University, Ulm, Germany
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26
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Syed O, Jancic P, Knezevic NN. A Review of Recent Pharmacological Advances in the Management of Diabetes-Associated Peripheral Neuropathy. Pharmaceuticals (Basel) 2023; 16:801. [PMID: 37375749 DOI: 10.3390/ph16060801] [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: 04/18/2023] [Revised: 05/14/2023] [Accepted: 05/18/2023] [Indexed: 06/29/2023] Open
Abstract
Diabetic peripheral neuropathy is a common complication of longstanding diabetes mellitus. These neuropathies can present in various forms, and with the increasing prevalence of diabetes mellitus, a subsequent increase in peripheral neuropathy cases has been noted. Peripheral neuropathy has a significant societal and economic burden, with patients requiring concomitant medication and often experiencing a decline in their quality of life. There is currently a wide variety of pharmacological interventions, including serotonin norepinephrine reuptake inhibitors, gapentanoids, sodium channel blockers, and tricyclic antidepressants. These medications will be discussed, as well as their respective efficacies. Recent advances in the treatment of diabetes mellitus with incretin system-modulating drugs, specifically glucagon-like peptide-1 agonists, have been promising, and their potential implication in the treatment of peripheral diabetic neuropathy is discussed in this review.
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Affiliation(s)
- Osman Syed
- Advocate Illinois Masonic Medical Center, Department of Anesthesiology, Chicago, IL 60657, USA
- Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA
| | - Predrag Jancic
- Advocate Illinois Masonic Medical Center, Department of Anesthesiology, Chicago, IL 60657, USA
| | - Nebojsa Nick Knezevic
- Advocate Illinois Masonic Medical Center, Department of Anesthesiology, Chicago, IL 60657, USA
- Department of Anesthesiology, University of Illinois, Chicago, IL 60612, USA
- Department of Surgery, University of Illinois, Chicago, IL 60612, USA
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27
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Shaphe MA, Alshehri MM, Alajam RA, Beg RA, Hamdi NIA, Nanjan S, Esht V, Aljahni MA, Ahmed H, Ahmad A, Khan A, Khan AR. Effectiveness of Epley-Canalith Repositioning Procedure versus Vestibular Rehabilitation Therapy in Diabetic Patients with Posterior Benign Paroxysmal Positional Vertigo: A Randomized Trial. Life (Basel) 2023; 13:life13051169. [PMID: 37240814 DOI: 10.3390/life13051169] [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: 03/30/2023] [Revised: 05/02/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
Benign paroxysmal positional vertigo (BPPV) is a common inner ear disorder, characterized by brief episodes of vertigo caused by changes in head position. The condition can cause significant functional impairment and reduced quality of life. BPPV is especially common among diabetic patients. The Epley-canalith repositioning procedure (CRP) and vestibular rehabilitation therapy (VRT) are two commonly used interventions for the treatment of BPPV. The objective of this study is to compare the effectiveness of Epley-canalith repositioning procedure (ECRP) and Vestibular Rehabilitation (VR) therapy in the management of vertigo among Type 2 Diabetes Mellitus patients. A total of 30 subjects with Type 2 diabetes mellitus, aged between 40 and 65 years, were randomly allocated to either the ECRP or VR therapy groups using a lottery method, and then underwent Epley-canalith repositioning procedure or vestibular rehabilitation therapy, respectively. The outcomes measured by the study were Vertigo Symptom Scale-Short Form (VSS-sf) score and Berg Balance Scale (BBS) score, assessed pre-treatment (pre) and 4 weeks post-treatment (post). The results demonstrated that both ECRP and VR therapy led to improvements in VSS-sf and BBS scores. However, VR therapy was found to be more effective, resulting in a 13.6% higher improvement in VSS-sf scores (p = 0.03) and a 5.1% higher improvement in BBS scores (p = 0.51) compared to ECRP. Both Epley-canalith repositioning procedure and vestibular rehabilitation therapy are effective in managing BPPV in diabetic patients. Although the differences in BBS scores are not statistically significant, VRT demonstrated a trend towards greater improvement. Vestibular rehabilitation therapy can be used by clinicians as another rehabilitation technique for improving vertigo, postural stability, and activity of daily living in diabetic patients with BPPV.
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Affiliation(s)
- Mohammad Abu Shaphe
- Department of Physical Therapy, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia
| | - Mohammed M Alshehri
- Department of Physical Therapy, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia
| | - Ramzi Abdu Alajam
- Department of Physical Therapy, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia
| | - Rashid Ali Beg
- Department of Physical Therapy, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia
| | - Najat Ibrahim A Hamdi
- Department of Physical Therapy, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia
| | - Saravanakumar Nanjan
- Department of Physical Therapy, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia
| | - Vandana Esht
- Department of Physical Therapy, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia
| | - Mohammed A Aljahni
- Physical Education Department, Jazan University, Jazan 45142, Saudi Arabia
| | - Hashim Ahmed
- Department of Medical Rehabilitation Science, College of Applied Medical Sciences, Najran University, Najran 66252, Saudi Arabia
| | - Ausaf Ahmad
- Department of Community Medicine, IIMS&R, Integral University, Lucknow 226026, India
| | - Ashfaque Khan
- Department of Physiotherapy, Integral University, Lucknow 226026, India
| | - Abdur Raheem Khan
- Department of Physiotherapy, Integral University, Lucknow 226026, India
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28
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Baskaran P, Mohandass A, Gustafson N, Bennis J, Louis S, Alexander B, Nemenov MI, Thyagarajan B, Premkumar LS. Evaluation of a polymer-coated nanoparticle cream formulation of resiniferatoxin for the treatment of painful diabetic peripheral neuropathy. Pain 2023; 164:782-790. [PMID: 36001079 PMCID: PMC9950295 DOI: 10.1097/j.pain.0000000000002765] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 08/10/2022] [Indexed: 02/02/2023]
Abstract
ABSTRACT Painful diabetic peripheral neuropathy (PDPN) is one of the major complications of diabetes. Currently, centrally acting drugs and topical analgesics are used for treating PDPN. These drugs have adverse effects; some are ineffective, and treatment with opioids is associated with use dependence and addiction. Recent research indicates that transient receptor potential vanilloid 1 (TRPV1) expressed in the peripheral sensory nerve terminals is an emerging target to treat pain associated with PDPN. Block of TRPV1 ion channel with specific antagonists, although effective as an analgesic, induced hyperthermia in clinical trials. However, TRPV1 agonists are useful to treat pain by virtue of their ability to cause Ca 2+ influx and subsequently leading to nerve terminal desensitization. Here, we report the effectiveness of an ultrapotent TRPV1 agonist, resiniferatoxin (RTX) nanoparticle, in a topical formulation (RTX-cream; RESINIZIN) that alleviates pain associated with DPN in animal models of diabetes. Resiniferatoxin causes nerve terminal depolarization block in the short term, which prevents pain during application and leading to nerve terminal desensitization/depletion in the long term resulting in long-lasting pain relief. Application of RTX cream to the hind limbs suppresses thermal hyperalgesia in streptozotocin-induced diabetic rats and mini pigs without any adverse effects as compared with capsaicin at therapeutic doses, which induces intense pain during application. Resiniferatoxin cream also decreases the expression of TRPV1 in the peripheral nerve endings and suppresses TRPV1-mediated calcitonin gene-related peptide release in the skin samples of diabetic rats and mini pigs. Our preclinical data confirm that RTX topical formulation is an effective treatment option for PDPN.
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Affiliation(s)
- Padmamalini Baskaran
- School of Pharmacy, University of Wyoming, Laramie, WY, USA
- Ion Channel, Pharmacology LLC, Springfield, IL, USA
| | | | - Noah Gustafson
- School of Pharmacy, University of Wyoming, Laramie, WY, USA
| | - Jane Bennis
- School of Pharmacy, University of Wyoming, Laramie, WY, USA
| | - Somaja Louis
- Department of Pharmacology, Southern Illinois University, Springfield, IL
| | | | - Mikhail I. Nemenov
- Department of Anesthesia, Stanford University, Palo Alto, CA, USA
- LasMed LLC, Mountain View, CA, USA
| | | | - Louis S. Premkumar
- Department of Pharmacology, Southern Illinois University, Springfield, IL
- Ion Channel, Pharmacology LLC, Springfield, IL, USA
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29
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Beigi S, Shabkhiz F, Kordi M, Haghi-Ashtiani B, Hashemi-Madani N, Zmijewski P. The Effects of a 10-Week Aerobic and Unilateral Lower Extremity Resistance Training Program on Amplitude and Nerve Conduction Velocity of Sensory and Motor Nerves in Diabetic Patients with Neuropathy. J Hum Kinet 2023; 87:93-103. [PMID: 37229418 PMCID: PMC10203839 DOI: 10.5114/jhk/161610] [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: 12/10/2022] [Accepted: 02/07/2023] [Indexed: 05/27/2023] Open
Abstract
This study aimed to investigate the effects of 10-week aerobic and unilateral lower extremity resistance training on nerve conduction velocity and amplitude of sensory and motor nerves in diabetic patients with neuropathy. This clinical trial was conducted on twenty women and men (aged 30-60 years old) with diabetic neuropathy. Participants were randomly assigned to one of the two groups: an exercise group (EG; n = 10) and a control group (CG; n = 10). The EG performed a 10-week programme with one session of aerobic exercises (40% to 70% of HR reserve), supplemented with one session of specific lower extremity resistance exercises (60-90 min/day) on the same day for four days per week. The CG subjects performed their regular daily activities. The nerve conduction velocity, amplitude of sensory and motor nerves and glycosylated haemoglobin A1c were measured before and after the intervention. The repeated-measures ANOVA showed a significant increase in the conduction velocity of the sural sensory nerve as well as the peroneal motor nerve (p < 0.01, p < 0.01). The changes in the conduction velocity of the tibial nerve were similar when compared to the control group (p > 0.05). A significantly greater decrease in glycosylated haemoglobin was also observed in the EG group (p < 0.01). Performing 10 weeks of aerobic and specific unilateral lower extremity exercises can improve the function of sensory and motor nerves and improve symptoms in diabetic patients with neuropathy. Given the limited studies in this area, the exact mechanisms of this performance improvement need further examination.
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Affiliation(s)
- Sharif Beigi
- Department of Exercise Physiology, Sport Sciences and Health Faculty, University of Tehran, Tehran, Iran
| | - Fatemeh Shabkhiz
- Department of Exercise Physiology, Sport Sciences and Health Faculty, University of Tehran, Tehran, Iran
| | - Mohammadreza Kordi
- Department of Exercise Physiology, Sport Sciences and Health Faculty, University of Tehran, Tehran, Iran
| | - Bahram Haghi-Ashtiani
- Department of Neurology, Firoozgar Hospital, Iran University of Medical Science, Tehran, Iran
| | - Nahid Hashemi-Madani
- Endocrinology and Metabolism Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Science, Iran
| | - Piotr Zmijewski
- Jozef Pilsudski University of Physical Education in Warsaw, Warsaw, Poland
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30
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Ma F, Wang G, Wu Y, Xie B, Zhang W. Improving Effects of Peripheral Nerve Decompression Microsurgery of Lower Limbs in Patients with Diabetic Peripheral Neuropathy. Brain Sci 2023; 13:brainsci13040558. [PMID: 37190523 DOI: 10.3390/brainsci13040558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 03/17/2023] [Accepted: 03/24/2023] [Indexed: 03/29/2023] Open
Abstract
Background: Peripheral nerve decompression microsurgery can relieve nerve entrapment and improve the symptoms of DPN. However, postoperative tissue adhesion will produce new pressure on the nerves, affecting the surgical efficacy. In this study, a nerve conduit was used in the peripheral nerve decompression microsurgery to prevent postoperative adhesions, and the role of the nerve conduit in surgical nerve decompression was explored. Methods: A total of 69 patients with DPN were recruited and randomly divided into three groups: the nerve conduit group, conventional surgery group, and control group. Two weeks before surgery and 6 months after surgery, patients in each group were clinically tested using the visual analog scale (VAS) score, neurophysiological test, Toronto clinical scoring system (TCSS) score, and two-point discrimination (2-PD) test. Results: The patients’ symptoms in the nerve conduit group were relieved to varying degrees, and the relief rate reached 90.9%; the treatment efficacy was higher than that in the other groups. The postoperative nerve conduction velocity (NCV) in the two surgical groups was significantly higher than that before the surgery, and the difference between the nerve conduit group and the conventional surgery group was statistically significant (p < 0.05). For the 2-PD test, there was a statistically significant difference between the two surgical groups (p < 0.05). The TCSS score in the two surgical groups was significantly higher than that in the control group (p < 0.01). There was a significant difference in the TCSS scores between the nerve conduit group and the conventional surgery group (p < 0.05). Conclusions: The nerve conduit could further improve the efficacy of peripheral nerve decompression microsurgery in the treatment of DPN.
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31
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Wu CS, Huang YJ, Ko YC, Lee CH. Efficacy and safety of duloxetine in painful diabetic peripheral neuropathy: a systematic review and meta-analysis of randomized controlled trials. Syst Rev 2023; 12:53. [PMID: 36945033 PMCID: PMC10031998 DOI: 10.1186/s13643-023-02185-6] [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: 05/31/2021] [Accepted: 02/02/2023] [Indexed: 03/23/2023] Open
Abstract
BACKGROUND Painful diabetic peripheral neuropathy (PDPN) is a key concern in clinical practice. In this systematic review and meta-analysis, we compared duloxetine and placebo treatments in terms of their efficacy and safety in patients with PDPN. METHODS Following the PRISMA guidelines, we searched the Cochrane Library, PubMed, and Embase databases for relevant English articles published before January 11, 2021. Treatment efficacy and safety were assessed in terms of pain improvement, patient-reported health-related performance, and patients' quality of life. RESULTS We reviewed a total of 7 randomized controlled trials. Regarding pain improvement, duloxetine was more efficacious than placebo (mean difference [MD] - 0.89; 95% confidence interval [CI] - 1.09 to - 0.69; P < .00001). Furthermore, duloxetine significantly improved the patients' quality of life, which was assessed using the Clinical Global Impression severity subscale (MD - 0.48; 95% CI - 0.61 to - 0.36; P < .00001), Patient Global Impression of Improvement scale (MD - 0.50; 95% CI - 0.64 to - 0.37; P < .00001), and European Quality of Life Instrument 5D version (MD 0.04; 95% CI 0.02 to 0.07; P = .0002). Severe adverse events were rare, whereas nausea, somnolence, dizziness, fatigue, constipation, and decreased appetite were common; approximately, 12.6% of all patients dropped out because of the common symptoms. CONCLUSIONS Duloxetine is more efficacious than placebo treatments in patients with PDPN. The rarity of severe adverse events indicates that duloxetine is safe. When a 60-mg dose is insufficient, 120 mg of duloxetine may improve PDPN symptoms. Our findings may help devise optimal treatment strategies for PDPN. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42021225451.
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Affiliation(s)
- Chung-Sheng Wu
- Department of Primary Care Medicine, Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
| | - Yu-Jui Huang
- Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan
| | - Yuan-Chun Ko
- Department of Primary Care Medicine, Wan-Fang Hospital, Taipei Medical University, Taipei City, Taiwan
| | - Che-Hsiung Lee
- Department of Plastic and Reconstructive Surgery, Division of Trauma Plastic Surgery, Chang Gung Memorial Hospital, No. 5, Fuxing St, Gueishan District 333, Linkou, Taiwan.
- Department of Plastic Reconstructive, Tucheng Hospital, Tucheng Dist, New Taipei City, Taiwan.
- Department of Biological Science and Technology, National Chiao Tung University, Hsinchu City, Taiwan.
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He W, Pang C, Chen L, Zeng Y, Gao L, Huang H, Zhang W, Wang X, Deng B. Low T3 syndrome is associated with peripheral neuropathy in patients with type 2 diabetes mellitus. Muscle Nerve 2022; 66:723-729. [PMID: 36089765 DOI: 10.1002/mus.27719] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 09/02/2022] [Accepted: 09/03/2022] [Indexed: 12/24/2022]
Abstract
INTRODUCTION/AIMS Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus. Diabetic patients often have thyroid dysfunction. The aim of this study was to investigate the association between low triiodothyronine (T3) syndrome and DPN in patients with type 2 diabetes mellitus (T2DM). METHODS A retrospective review was performed of 928 patients with T2DM for whom data was available for clinical manifestations and nerve conduction studies (NCS), and of 134 non-diabetic controls. The composite Z scores of conduction velocity and amplitude were calculated. Low T3 syndrome was defined as T3 levels below the lower limit of the reference interval. RESULTS Among the patients with T2DM, 632 (68.1%) had DPN, and a larger proportion of these patients presented with low T3 syndrome than patients without DPN. After adjusting for potential confounders, low T3 syndrome was independently associated with the occurrence of DPN (odds ratio [OR] = 2.049, 95% confidence interval [CI] 1.319-3.181, p = .001) and the severity of DPN (OR = 1.597, 95% CI 1.030-2.476, p = .036). Adding the criterion of low T3 syndrome improved the prognostic performance of the traditional model (age + gender + diabetic duration + glycated hemoglobin [HbA1c]) for predicting DPN. DISCUSSION Low T3 syndrome is associated with a higher risk and increased severity of DPN in patients with T2DM. These findings suggest that low T3 syndrome could be a predictor for risk stratification in patients with T2DM.
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Affiliation(s)
- Weilei He
- Department of Nuclear Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Chunyang Pang
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Luowei Chen
- Department of Neurology, The Second Affiliated Hospital of Zhejiang University, Hangzhou, China
| | - Yaying Zeng
- Department of Psychiatry, Zhejiang Traditional Chinese Medical Hospital, Hangzhou, China
| | - Lingfei Gao
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Huanjie Huang
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Wanli Zhang
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xun Wang
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Binbin Deng
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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33
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Zhao P, Ding C, Fu X, Zhang Y, Gu J, Hu J, Wang C, Yang M, Sheng Y, Zhang Y, Chen X, Mao P, Liu CF. Ultrasound exploration of muscle characteristic changes and diabetic peripheral neuropathy in diabetic patients. JOURNAL OF CLINICAL ULTRASOUND : JCU 2022; 50:1403-1411. [PMID: 36218110 DOI: 10.1002/jcu.23365] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 09/13/2022] [Accepted: 09/18/2022] [Indexed: 06/16/2023]
Abstract
PURPOSE Using brightness mode ultrasound combined with shear wave elastography, this study aims to detect structural and functional changes of the medial head of gastrocnemius (MG) in type 2 diabetes mellitus (T2DM) patients with or without diabetic peripheral neuropathy (DPN). METHODS 149 T2DM patients (DPN group and non-DPN group) and 60 healthy volunteers (control group) were enrolled. We measured the absolute difference of fascicle length (FL), pennation angle (PA), and shear wave velocity (SWV) of both MG in neutral position and maximal ankle joint's plantar flexion and calculated ΔFL, ΔPA, and ΔSWV. These three parameters, along with muscle thickness (MT), were compared among the three groups. RESULTS In the DPN group, the MG's MT, ΔPA, and ΔSWV were significantly lower than in the non-DPN group (p < 0.01); these parameters achieved the highest scores in the control group (p < 0.01). The area under the receiver operating characteristic curve of the combination of ΔSWV and ΔFL was the largest for predicting inpatients with or without DPN. CONCLUSIONS Decreased muscle mass (MT) and muscle contractibility (ΔFL and ΔSWV) were detected in patients with T2DM, with or without DPN. ΔSWV and ΔFL of the MG showed high-diagnostic accuracy for DPN warning signs.
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Affiliation(s)
- Ping Zhao
- Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Changwei Ding
- Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Xinxu Fu
- Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yingchun Zhang
- Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Jiarui Gu
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Ji Hu
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Caishan Wang
- Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Min Yang
- Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yujing Sheng
- Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Ying Zhang
- Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Xiaofang Chen
- Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Pan Mao
- Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Chun-Feng Liu
- Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China
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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: 4] [Impact Index Per Article: 1.3] [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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35
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Cardiac Autonomic Neuropathy in Type 1 and 2 Diabetes: Epidemiology, Pathophysiology, and Management. Clin Ther 2022; 44:1394-1416. [DOI: 10.1016/j.clinthera.2022.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 07/23/2022] [Accepted: 09/06/2022] [Indexed: 11/21/2022]
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36
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Cosmo E, Midena G, Frizziero L, Bruno M, Cecere M, Midena E. Corneal Confocal Microscopy as a Quantitative Imaging Biomarker of Diabetic Peripheral Neuropathy: A Review. J Clin Med 2022; 11:5130. [PMID: 36079060 PMCID: PMC9457345 DOI: 10.3390/jcm11175130] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/26/2022] [Accepted: 08/29/2022] [Indexed: 11/16/2022] Open
Abstract
Distal symmetric polyneuropathy (DPN), particularly chronic sensorimotor DPN, represents one of the most frequent complications of diabetes, affecting 50% of diabetic patients and causing an enormous financial burden. Whilst diagnostic methods exist to detect and monitor this condition, they have significant limitations, mainly due to their high subjectivity, invasiveness, and non-repeatability. Corneal confocal microscopy (CCM) is an in vivo, non-invasive, and reproducible diagnostic technique for the study of all corneal layers including the sub-basal nerve plexus, which represents part of the peripheral nervous system. We reviewed the current literature on the use of CCM as an instrument in the assessment of diabetic patients, particularly focusing on its role in the study of sub-basal nerve plexus alterations as a marker of DPN. CCM has been demonstrated to be a valid in vivo tool to detect early sub-basal nerve plexus damage in adult and pediatric diabetic patients, correlating with the severity of DPN. Despite its great potential, CCM has still limited application in daily clinical practice, and more efforts still need to be made to allow the dissemination of this technique among doctors taking care of diabetic patients.
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Affiliation(s)
| | | | - Luisa Frizziero
- Department of Neuroscience-Ophthalmology, University of Padova, 35128 Padova, Italy
| | | | | | - Edoardo Midena
- IRCCS—Fondazione Bietti, 00198 Rome, Italy
- Department of Neuroscience-Ophthalmology, University of Padova, 35128 Padova, Italy
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Sahba K, Berk L, Bussell M, Lohman E, Zamora F, Gharibvand L. Treating peripheral neuropathy in individuals with type 2 diabetes mellitus with intraneural facilitation: a single blind randomized control trial. J Int Med Res 2022; 50:3000605221109390. [PMID: 35922961 PMCID: PMC9358562 DOI: 10.1177/03000605221109390] [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] [Indexed: 11/16/2022] Open
Abstract
Objective To evaluate the effectiveness of intraneural facilitation (INF) for the treatment of diabetic peripheral neuropathy (DPN). Methods This single-blind, randomized clinical trial enrolled patients with type 2 diabetes mellitus and moderate-to-severe DPN symptoms below the ankle. Patients were randomly assigned to receive INF or sham treatment. In the INF group, trained INF physical therapists provided therapy for 50–60 min, three times a week for 3 weeks. Sham treatment consisted of patients believing they received anodyne therapy for 3 weeks. Pre- and post-treatment data were compared between the two groups for quality of life, balance, gait, protective sensory function and pain outcome measures. Results A total of 28 patients (17 males) were enrolled in the study (INF group n = 17; sham group n = 11). There was a significant decrease in the overall pain score in both the INF and sham groups over time, but the decrease was greater in the INF group (1.11 versus 0.82). Between-group comparisons demonstrated significant differences in unpleasant pain and protective sensory function. The INF group showed post-treatment improvements in protective sensory function and composite static balance score. Conclusions INF treatment improved pain perception, the composite static balance score and protective sensations in patients with DPN. Research Registry number: CNCT04025320
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Affiliation(s)
- Kyan Sahba
- Department of Allied Health Studies, School of Allied Health Professions, Loma Linda University, Loma Linda, CA, USA
| | - Lee Berk
- Department of Allied Health Studies, School of Allied Health Professions, Loma Linda University, Loma Linda, CA, USA.,Department of Pathology and Human Anatomy, School of Medicine, Loma Linda University, Loma Linda, CA, USA
| | - Mark Bussell
- Neuropathic Therapy Center, Loma Linda University Health, Loma Linda, CA, USA
| | - Everett Lohman
- Department of Physical Therapy, School of Allied Health Professions, Loma Linda University, Loma Linda, CA, USA
| | - Francis Zamora
- Department of Allied Health Studies, School of Allied Health Professions, Loma Linda University, Loma Linda, CA, USA
| | - Lida Gharibvand
- Department of Allied Health Studies, School of Allied Health Professions, Loma Linda University, Loma Linda, CA, USA
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38
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Yu FSX, Lee PSY, Yang L, Gao N, Zhang Y, Ljubimov AV, Yang E, Zhou Q, Xie L. The impact of sensory neuropathy and inflammation on epithelial wound healing in diabetic corneas. Prog Retin Eye Res 2022; 89:101039. [PMID: 34991965 PMCID: PMC9250553 DOI: 10.1016/j.preteyeres.2021.101039] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 12/10/2021] [Accepted: 12/20/2021] [Indexed: 02/08/2023]
Abstract
Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes, with several underlying pathophysiological mechanisms, some of which are still uncertain. The cornea is an avascular tissue and sensitive to hyperglycemia, resulting in several diabetic corneal complications including delayed epithelial wound healing, recurrent erosions, neuropathy, loss of sensitivity, and tear film changes. The manifestation of DPN in the cornea is referred to as diabetic neurotrophic keratopathy (DNK). Recent studies have revealed that disturbed epithelial-neural-immune cell interactions are a major cause of DNK. The epithelium is supplied by a dense network of sensory nerve endings and dendritic cell processes, and it secretes growth/neurotrophic factors and cytokines to nourish these neighboring cells. In turn, sensory nerve endings release neuropeptides to suppress inflammation and promote epithelial wound healing, while resident immune cells provide neurotrophic and growth factors to support neuronal and epithelial cells, respectively. Diabetes greatly perturbs these interdependencies, resulting in suppressed epithelial proliferation, sensory neuropathy, and a decreased density of dendritic cells. Clinically, this results in a markedly delayed wound healing and impaired sensory nerve regeneration in response to insult and injury. Current treatments for DPN and DNK largely focus on managing the severe complications of the disease. Cell-based therapies hold promise for providing more effective treatment for diabetic keratopathy and corneal ulcers.
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Affiliation(s)
- Fu-Shin X Yu
- Departments of Ophthalmology and Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
| | - Patrick S Y Lee
- Departments of Ophthalmology and Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, 48201, USA
| | - Lingling Yang
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China
| | - Nan Gao
- Departments of Ophthalmology and Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, 48201, USA
| | - Yangyang Zhang
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China
| | - Alexander V Ljubimov
- Departments of Biomedical Sciences and Neurosurgery, Cedars-Sinai Medical Center, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Ellen Yang
- Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, 60064, USA
| | - Qingjun Zhou
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China
| | - Lixin Xie
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China.
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El Hage R, Knippschild U, Arnold T, Hinterseher I. Stem Cell-Based Therapy: A Promising Treatment for Diabetic Foot Ulcer. Biomedicines 2022; 10:1507. [PMID: 35884812 PMCID: PMC9312797 DOI: 10.3390/biomedicines10071507] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/17/2022] [Accepted: 06/21/2022] [Indexed: 11/16/2022] Open
Abstract
Diabetic foot ulcer (DFU) is a severe complication of diabetes and a challenging medical condition. Conventional treatments for DFU have not been effective enough to reduce the amputation rates, which urges the need for additional treatment. Stem cell-based therapy for DFU has been investigated over the past years. Its therapeutic effect is through promoting angiogenesis, secreting paracrine factors, stimulating vascular differentiation, suppressing inflammation, improving collagen deposition, and immunomodulation. It is controversial which type and origin of stem cells, and which administration route would be the most optimal for therapy. We reviewed the different types and origins of stem cells and routes of administration used for the treatment of DFU in clinical and preclinical studies. Diabetes leads to the impairment of the stem cells in the diseased patients, which makes it less ideal to use autologous stem cells, and requires looking for a matching donor. Moreover, angioplasty could be complementary to stem cell therapy, and scaffolds have a positive impact on the healing process of DFU by stem cell-based therapy. In short, stem cell-based therapy is promising in the field of regenerative medicine, but more studies are still needed to determine the ideal type of stem cells required in therapy, their safety, proper dosing, and optimal administration route.
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Affiliation(s)
- Racha El Hage
- Department of Vascular Surgery, Universitätsklinikum Ruppin-Brandenburg, Medizinische Hochschule Branderburg Theodor Fontane, Fehrbelliner Str. 38, 16816 Neuruppin, Germany;
| | - Uwe Knippschild
- Department of General and Visceral Surgery, Surgery Center, Ulm University, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (U.K.); (T.A.)
| | - Tobias Arnold
- Department of General and Visceral Surgery, Surgery Center, Ulm University, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (U.K.); (T.A.)
| | - Irene Hinterseher
- Department of Vascular Surgery, Universitätsklinikum Ruppin-Brandenburg, Medizinische Hochschule Branderburg Theodor Fontane, Fehrbelliner Str. 38, 16816 Neuruppin, Germany;
- Berlin Institute of Health, Vascular Surgery Clinic, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
- Fakultät für Gesundheitswissenschaften Brandenburg, Gemeinsame Fakultät der Universität Potsdam, der Medizinischen Hochschule Brandenburg Theodor Fontane und der Brandenburgischen Technischen Universität Cottbus—Senftenberg, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany
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40
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Kender Z, Groener JB, Jende JME, Kurz FT, Fleming T, Sulaj A, Schuh-Hofer S, Treede RD, Bendszus M, Szendroedi J, Nawroth PP, Kopf S. Diabetic neuropathy is a generalized phenomenon with impact on hand functional performance and quality of life. Eur J Neurol 2022; 29:3081-3091. [PMID: 35700123 DOI: 10.1111/ene.15446] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 05/08/2022] [Accepted: 06/05/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND Diabetic sensorimotor peripheral neuropathy (DSPN) is usually considered to affect predominantly the lower limbs (LL-N), while the impact of upper limb neuropathy (UL-N) on hand functional performance and quality of life (QoL) has not been evaluated systematically. This study aims to investigate the prevalence and characteristics of UL-N and its functional and psychosocial consequences in type 2 diabetes. METHODS Individuals with type 2 diabetes (n=141) and an age- and sex-matched control group (n=73) underwent comprehensive assessment of neuropathy, hand functional performance and psychosocial status. RESULTS The prevalence of UL-N was 30.5% in patients with diabetes and that of LL-N 49.6%, with 25.5% exhibiting both. Patients with diabetes showed similar sensory phenotype regarding both large and small fiber functions in hands and feet. Patients with UL-N showed reduced manual dexterity, but normal hand grip force. Additionally, there was a correlation between reduced dexterity and sensory deficits. Patients with UL-N had reduced estimates of psychosocial health including health-related QoL compared to control subjects and patients without UL-N. UL-N correlated with the severity of LL-N, but not with duration of diabetes, glycaemia, age, or sex. CONCLUSIONS This study points to a substantial prevalence of UL-N in type 2 diabetes. The sensory phenotype of patients with UL-N was similar to LL-N and was characterized by loss of sensory function. Our study demonstrated an association of UL-N with impaired manual dexterity and reduced health-related QoL. Thus, upper limb sensorimotor functions should be assessed early in patients with diabetes.
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Affiliation(s)
- Zoltan Kender
- University Hospital of Heidelberg, Department of Internal Medicine 1 and Clinical Chemistry, Heidelberg, Germany.,German Center for Diabetes Research (DZD), Munich-, Neuherberg, Germany
| | - Jan B Groener
- University Hospital of Heidelberg, Department of Internal Medicine 1 and Clinical Chemistry, Heidelberg, Germany.,German Center for Diabetes Research (DZD), Munich-, Neuherberg, Germany.,Medicover Neuroendokrinologie, Munich, Germany
| | - Johann M E Jende
- University Hospital of Heidelberg, Department of Neuroradiology, Heidelberg, Germany
| | - Felix T Kurz
- University Hospital of Heidelberg, Department of Neuroradiology, Heidelberg, Germany.,German Cancer Research Center, Heidelberg, Germany
| | - Thomas Fleming
- University Hospital of Heidelberg, Department of Internal Medicine 1 and Clinical Chemistry, Heidelberg, Germany.,German Center for Diabetes Research (DZD), Munich-, Neuherberg, Germany
| | - Alba Sulaj
- University Hospital of Heidelberg, Department of Internal Medicine 1 and Clinical Chemistry, Heidelberg, Germany.,German Center for Diabetes Research (DZD), Munich-, Neuherberg, Germany
| | - Sigrid Schuh-Hofer
- Department of Neurophysiology, MCTN, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Rolf-Detlef Treede
- Department of Neurophysiology, MCTN, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Martin Bendszus
- University Hospital of Heidelberg, Department of Neuroradiology, Heidelberg, Germany
| | - Julia Szendroedi
- University Hospital of Heidelberg, Department of Internal Medicine 1 and Clinical Chemistry, Heidelberg, Germany.,German Center for Diabetes Research (DZD), Munich-, Neuherberg, Germany.,Joint Heidelberg-ICD Translational Diabetes Programme, Helmholtz-Zentrum, Munich, Germany
| | - Peter P Nawroth
- University Hospital of Heidelberg, Department of Internal Medicine 1 and Clinical Chemistry, Heidelberg, Germany.,German Center for Diabetes Research (DZD), Munich-, Neuherberg, Germany.,Joint Heidelberg-ICD Translational Diabetes Programme, Helmholtz-Zentrum, Munich, Germany
| | - Stefan Kopf
- University Hospital of Heidelberg, Department of Internal Medicine 1 and Clinical Chemistry, Heidelberg, Germany.,German Center for Diabetes Research (DZD), Munich-, Neuherberg, Germany
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Hagedorn JM, Engle AM, George TK, Karri J, Abdullah N, Ovrom E, Bocanegra-Becerra JE, D'Souza RS. An overview of painful diabetic peripheral neuropathy: Diagnosis and treatment advancements. Diabetes Res Clin Pract 2022; 188:109928. [PMID: 35580704 DOI: 10.1016/j.diabres.2022.109928] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 04/12/2022] [Accepted: 05/09/2022] [Indexed: 01/09/2023]
Abstract
Diabetes mellitus remains a public health problem, affecting 422 million people worldwide. Currently, there is no consensus around treating painful diabetic peripheral neuropathy in a step-wise manner. Among the non-pharmacological interventions, neuromodulation has become a promising alternative. Over the past decade, significant clinical trials have paved the way for prompt inclusion of high-frequency spinal cord stimulation within the painful diabetic peripheral neuropathy treatment algorithm. This article aims to provide an updated evidence-based approach for the management of painful diabetic peripheral neuropathy.
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Affiliation(s)
| | - Alyson M Engle
- Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | | | - Jay Karri
- Johns Hopkins University, Baltimore, MD, USA
| | - Newaj Abdullah
- Division of Pain Medicine, Department of Anesthesiology, University of Utah, Salt Lake City, UT, USA
| | - Erik Ovrom
- Mayo Clinic Alix School of Medicine, Rochester, MN, USA
| | | | - Ryan S D'Souza
- Department of Anesthesiology and Perioperative Medicine, Division of Pain Medicine, Mayo Clinic, Rochester, MN, USA
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Pathak R, Sachan N, Chandra P. Mechanistic approach towards diabetic neuropathy screening techniques and future challenges: A review. Biomed Pharmacother 2022; 150:113025. [PMID: 35658222 DOI: 10.1016/j.biopha.2022.113025] [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: 03/23/2022] [Revised: 04/16/2022] [Accepted: 04/20/2022] [Indexed: 11/24/2022] Open
Abstract
Diabetic neuropathy, also called peripheral diabetic neuropathy (PDN), is among the most significant diabetes health consequences, alongside diabetic nephropathy, diabetic cardiomyopathy and diabetic retinopathy. Diabetic neuropathy is the existence of signs and indications of peripheral nerve damage in patients with diabetes after other causes have been governed out. Diabetic neuropathy is a painful and severe complication of diabetes that affects roughly 20% of people. The development of diabetic neuropathy is regulated by blood arteries that nourish the peripheral nerves and metabolic problems such as increased stimulation of polyol pathway, loss of myo-inositol and enhanced non-enzymatic glycation. It's divided into four types based on where neurons are most affected: autonomic, peripheral, proximal, and focal, with each kind presenting different symptoms like numbing, gastrointestinal disorders, and heart concerns. Pharmacotherapy for neuropathic pain is complex and for many patients, effective treatment is lacking; as a result, scientific proof recommendations are crucial. As a result, the current demand is to give the most vital medications or combinations of drugs that work directly on the nerves to help diabetic neuropathy patients feel less pain without causing any adverse effects. In diabetic neuropathy research, animal models are ubiquitous, with rats and mice being the most typically chosen for various reasons. This review covers the epidemiology, clinical features, pathology, clinical symptom, mechanism of diabetic neuropathy development, diagnosis, screening models of animals, diabetic neuropathy pharmacotherapy.
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Affiliation(s)
- Rashmi Pathak
- School of Pharmaceutical Sciences, IFTM University, Lodhipur Rajput Delhi Road (NH-24), Moradabad, UP 244102, India
| | - Neetu Sachan
- School of Pharmaceutical Sciences, IFTM University, Lodhipur Rajput Delhi Road (NH-24), Moradabad, UP 244102, India
| | - Phool Chandra
- School of Pharmaceutical Sciences, IFTM University, Lodhipur Rajput Delhi Road (NH-24), Moradabad, UP 244102, India.
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Al-Bazz DY, Nelson AJ, Burgess J, Petropoulos IN, Nizza J, Marshall A, Brown E, Cuthbertson DJ, Marshall AG, Malik RA, Alam U. Is Nerve Electrophysiology a Robust Primary Endpoint in Clinical Trials of Treatments for Diabetic Peripheral Neuropathy? Diagnostics (Basel) 2022; 12:731. [PMID: 35328284 PMCID: PMC8947384 DOI: 10.3390/diagnostics12030731] [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: 02/04/2022] [Revised: 03/10/2022] [Accepted: 03/11/2022] [Indexed: 12/10/2022] Open
Abstract
There is currently no FDA-approved disease-modifying therapy for diabetic peripheral neuropathy (DPN). Nerve conduction velocity (NCV) is an established primary endpoint of disease-modifying therapies in DPN and clinical trials have been powered with an assumed decline of 0.5 m/s/year. This paper sought to establish the time-dependent change in NCV associated with a placebo, compared to that observed in the active intervention group. A literature search identified twenty-one double-blind, randomised controlled trials in DPN of ≥1 year duration conducted between 1971 and 2021. We evaluated changes in neurophysiology, with a focus on peroneal motor and sural sensory NCV and amplitude in the placebo and treatment groups. There was significant variability in the change and direction of change (reduction/increase) in NCV in the placebo arm, as well as variability influenced by the anatomical site of neurophysiological measurement within a given clinical trial. A critical re-evaluation of efficacy trials should consider placebo-adjusted effects and present the placebo-subtracted change in NCV rather than assume a universal annual decline of 0.5 m/s/year. Importantly, endpoints such as corneal confocal microscopy (CCM) have demonstrated early nerve repair, whilst symptoms and NCV have not changed, and should thus be considered as a viable alternative.
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Affiliation(s)
- Dalal Y. Al-Bazz
- Institute of Life Course and Medical Sciences and the Pain Research Institute, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool L9 7AL, UK; (A.J.N.); (J.B.); (J.N.); (A.M.); (A.G.M.)
| | - Andrew J. Nelson
- Institute of Life Course and Medical Sciences and the Pain Research Institute, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool L9 7AL, UK; (A.J.N.); (J.B.); (J.N.); (A.M.); (A.G.M.)
| | - Jamie Burgess
- Institute of Life Course and Medical Sciences and the Pain Research Institute, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool L9 7AL, UK; (A.J.N.); (J.B.); (J.N.); (A.M.); (A.G.M.)
| | - Ioannis N. Petropoulos
- Research Division, Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha 24144, Qatar; (I.N.P.); (R.A.M.)
| | - Jael Nizza
- Institute of Life Course and Medical Sciences and the Pain Research Institute, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool L9 7AL, UK; (A.J.N.); (J.B.); (J.N.); (A.M.); (A.G.M.)
| | - Anne Marshall
- Institute of Life Course and Medical Sciences and the Pain Research Institute, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool L9 7AL, UK; (A.J.N.); (J.B.); (J.N.); (A.M.); (A.G.M.)
| | - Emily Brown
- Obesity and Endocrinology Research Group, Institute of Life Course and Medical Sciences, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool L9 7AL, UK; (E.B.); (D.J.C.)
| | - Daniel J. Cuthbertson
- Obesity and Endocrinology Research Group, Institute of Life Course and Medical Sciences, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool L9 7AL, UK; (E.B.); (D.J.C.)
| | - Andrew G. Marshall
- Institute of Life Course and Medical Sciences and the Pain Research Institute, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool L9 7AL, UK; (A.J.N.); (J.B.); (J.N.); (A.M.); (A.G.M.)
- Institute of Cardiovascular Sciences, Cardiac Centre, Faculty of Medical and Human Sciences, University of Manchester and NIHR/Wellcome Trust Clinical Research Facility, Manchester M13 9WL, UK
| | - Rayaz A. Malik
- Research Division, Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha 24144, Qatar; (I.N.P.); (R.A.M.)
- Institute of Cardiovascular Sciences, Cardiac Centre, Faculty of Medical and Human Sciences, University of Manchester and NIHR/Wellcome Trust Clinical Research Facility, Manchester M13 9WL, UK
| | - Uazman Alam
- Institute of Life Course and Medical Sciences and the Pain Research Institute, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool L9 7AL, UK; (A.J.N.); (J.B.); (J.N.); (A.M.); (A.G.M.)
- Division of Diabetes, Endocrinology and Gastroenterology, Institute of Human Development, University of Manchester, Manchester M13 9PL, UK
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Correlation Analysis and Intervention Study on Disturbance of Lipid Metabolism and Diabetic Peripheral Neuropathy. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:2579692. [PMID: 35242203 PMCID: PMC8888052 DOI: 10.1155/2022/2579692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/18/2022] [Accepted: 01/26/2022] [Indexed: 11/18/2022]
Abstract
Objective To explore the significance and clinical value of dynamic monitoring of lipid metabolism indexes in patients with diabetic peridiabetic lesions. Methods A total of 192 patients with type 2 diabetes (T2DM) treated in our hospital from October 2019 to July 2021 were divided into two groups according to whether they were complicated with peripheral neuropathy (DPN). The patients in the observation group were randomly assigned into group A (n = 45) and group B (n = 45) according to the method of random number table. The patients were assigned into control group (n = 102) and observation group (n = 90), and the patients in the observation group were randomly divided into two groups (n = 45). All the patients in the three groups were given routine hypoglycemic treatment, and group B was observed to dynamically monitor the indexes of lipid metabolism and regulate blood lipids on the basis of routine hypoglycemic treatment. The indexes of lipid metabolism, including total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C)/low-density lipoprotein cholesterol (LDL-C), were detected before treatment. The receiver operating curve (ROC) was applied to elucidate the efficacy of TC, TG, and HDL-C and LDL-C in predicting peripheral neuropathy (DPN) in patients with T2DM. The indexes of lipid metabolism and neurological function of patients were determined after the treatment. The difference was considered to be statistically significant (P < 0.05). Results In contrast to the control, the serum levels of TG, TC, and LDL-C in the observation group were significantly higher, with HDL-C significantly lower. ROC curve analysis indicated that the area under the curve (AUC) of serum TG level to predict peripheral neuropathy in patients with T2DM was 0.753 (95% CI = 0.604 − 0.901, P = 0.007). When the Youden index reached the maximum (0.677), with corresponding sensitivity and specificity 77.18% and 82.58%, respectively, and the critical value was 2.31 mmol/L, the AUC of serum TC level for predicting peripheral neuropathy in patients with T2DM was 0.851 (95% CI = 0.735 ~ 0.967P < 0.001); when the Youden index reaches its maximum (0.750), with the sensitivity and specificity 84.44% and 92.06%, respectively, and the critical value is 4.52 mmol/L, the AUC of predicting peripheral neuropathy in patients with T2DM by serum LDL-C level was 0.799 (95% CI = 0.52 ~ 0.946, P = 0.001); when the Youden index reaches its maximum (0.706), with sensitivity and specificity 80.58% and 87.24%, respectively, and the critical value is 3.36 mmol/L, the AUC of serum HDL-C level for predicting DPN in patients with T2DM was 0.727 (95% CI = 0.568 ~ 0.886P = 0.014). When the Youden index reached the maximum (0.640), the sensitivity and specificity were 74.56% and 83.25%, respectively, the critical value is 1.51 mmol/L. The AUC in predicting DPN in patients with T2DM was 0.919 (95% CI = 0.839 ~ 0.978P < 0.001); when the Jordan index reached the maximum (0.786), the sensitivity and specificity were 91.75% and 95.82%, respectively. Compared with group A, the levels of serum TG, TC, and LDL-C in group B decreased significantly, while the level of HDL-C increased (P < 0.05). The motor nerve conduction velocity and sensory nerve conduction velocity of median nerve and peroneal nerve in group B were higher than those in group A (P < 0.05). Conclusion Diabetic patients with severe lipid metabolic disorders have a higher risk of DPN. Combined detection of lipid metabolism indexes such as TC, TG, and HDL-C and LDL-C is effective in predicting diabetic patients with DPN. In clinic, through dynamic monitoring of lipid metabolism indexes, we can actively regulate the level of blood lipids in patients with T2DM, which can delay the occurrence and development of DPN to a certain extent, as well as improving the prognosis of patients with diabetes.
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Afshar A, Tabrizi A. Interfascicular Gliding Dysfunction Relation with Focal Neuropathy in Diabetic Patients with Carpal Tunnel Syndrome. J Hand Microsurg 2022; 14:3-9. [PMID: 35256822 PMCID: PMC8898155 DOI: 10.1055/s-0040-1718236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Abstract
Carpal tunnel syndrome (CTS), a common neuropathy of the upper limb, is highly prevalent in diabetic patients. Recent findings indicate that changes in median nerve elasticity and its gliding characteristics may contribute to the development of CTS. Normally, each nerve should be able to adapt to the positional changes by passive movement relative to the surrounding tissues. This ability is provided by a gliding apparatus around the nerve trunk in the surrounding soft tissue. The fascicles of nerve trunks can also glide against each other (interfascicular gliding). Sonoelastography indicates that nerve elasticity is decreased in patients with CTS compared to healthy patients. Moreover, decreased nerve elasticity in diabetes mellitus type II is associated with increased neuropathy, especially in peripheral nerves. Biomechanical factors, oxidative stress, and microvascular defects are also observed in diabetic neuropathy and account for different complications. A reduction in the elasticity of peripheral nerves may be related to decreased interfascicular gliding because of the biomechanical changes that occur in neuropathy. Surgical treatments, including nerve release and reduction of carpal tunnel pressure, improve peripheral gliding but do not resolve disease symptoms completely. According to the evidence, interfascicular gliding dysfunction is the most important factor in the pathogenesis of CTS in diabetic patients. Available evidence suggests that biomechanical variations affect interfascicular gliding more than peripheral gliding in diabetic patients. Decreased nerve elasticity is strongly correlated with decreased interfascicular gliding. It is further hypothesized that the concurrent use of antioxidants and pharmacological treatment (neuroprotection) such as alpha lipoic acid with carpal tunnel release in diabetic patients may alleviate the interfascicular gliding dysfunction and improve median neve elasticity. Decreased nerve elasticity and interfascicular gliding dysfunction play significant roles in the pathogenesis of CTS in diabetic patients.
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Affiliation(s)
- Ahmadreza Afshar
- Department of Orthopedics, Imam Khomeini Hospital, Urmia University of Medical Sciences, Urmia, Iran
| | - Ali Tabrizi
- Department of Orthopedics, Imam Khomeini Hospital, Urmia University of Medical Sciences, Urmia, Iran
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Alshammari NA, Alodhayani AA, Joy SS, Isnani A, Mujammami M, Alfadda AA, Siddiqui K. Evaluation of Risk Factors for Diabetic Peripheral Neuropathy Among Saudi Type 2 Diabetic Patients with Longer Duration of Diabetes. Diabetes Metab Syndr Obes 2022; 15:3007-3014. [PMID: 36200063 PMCID: PMC9527617 DOI: 10.2147/dmso.s364933] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 09/14/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Neuropathy is the most common microvascular complications among diabetic patients. Diabetic peripheral neuropathy (DPN) is the predominant variety which may associate with increased in mortality and morbidity among type 2 diabetes mellitus (T2DM). OBJECTIVE To assess the prevalence of diabetic peripheral neuropathy and its correlation with risk factors among T2DM. METHODS This was a cross-sectional retrospective study, data was collected from a previous cohort study conducted at the University Diabetes Center, King Saud University Medical City (KSUMC), King Saud University, Riyadh, Saudi Arabia. The data of T2DM patients were collected from case report form, included demographic data, history of chronic diabetes neuropathy, and laboratory reports. Statistical analysis includes Student`s t test, chi square test, and Pearson correlation and logistic regression were performed. RESULTS A total of 430 patients with T2DM data was collected and analyzed, and of them 54% were females, with the mean age of 55.88 years. The prevalence of diabetic neuropathy among study participants were 40.2%, and 73.3% of them having the subtype polyneuropathy. The mean BMI; p = 0.006, FBS; p < 0.001, HbA1c; p < 0.001, cholesterol p = 0.001, LDL; p < 0.001, and triglyceride; p < 0.001 levels were a significantly higher among participants with diabetic neuropathy than without neuropathy. The male gender (Risk Ratio: 1.294, 95% CI:1.090, 1.536) p = 0.003, fasting blood glucose (Risk Ratio: 1.157, 95% CI:1.051, 1.273) p = 0.003 Cholesterol (Risk Ratio: 1.588, 95% CI:1.174, 2.147) p = 0.003, triglyceride (Risk Ratio: 1.290, 95% CI:1.086, 1.538), p = 0.004, and LDL (Risk Ratio: 1.299, 95% CI:1.073, 1.574), p = 0.007) were found to be significant risk factors for DPN. CONCLUSION DPN is highly prevalent among T2DM patients in Saudi Arabia. Poor glycemic control and hyperlipidemia were associated with significantly higher risk for DPN patients among T2DM.
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Affiliation(s)
- Nawaf A Alshammari
- University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
- King Salman Specialist Hospital, Diabetes and Endocrine Center, Hail Health Cluster, Hail, Hail Region, Saudi Arabia
| | - Abdulaziz A Alodhayani
- Department of Family and Community Medicine College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Salini S Joy
- Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Arthur Isnani
- Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Muhammad Mujammami
- University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
- Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Department of Medicine, College of Medicine, and King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Assim A Alfadda
- Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Department of Medicine, College of Medicine, and King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Khalid Siddiqui
- Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Correspondence: Khalid Siddiqui, Strategic Center for Diabetes Research, College of Medicine, King Saud University, P.O. Box 245, Riyadh, 11411, Saudi Arabia, Email
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Yorek M. Treatment for Diabetic Peripheral Neuropathy: What have we Learned from Animal Models? Curr Diabetes Rev 2022; 18:e040521193121. [PMID: 33949936 PMCID: PMC8965779 DOI: 10.2174/1573399817666210504101609] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 01/07/2021] [Accepted: 02/13/2021] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Animal models have been widely used to investigate the etiology and potential treatments for diabetic peripheral neuropathy. What we have learned from these studies and the extent to which this information has been adapted for the human condition will be the subject of this review article. METHODS A comprehensive search of the PubMed database was performed, and relevant articles on the topic were included in this review. RESULTS Extensive study of diabetic animal models has shown that the etiology of diabetic peripheral neuropathy is complex, with multiple mechanisms affecting neurons, Schwann cells, and the microvasculature, which contribute to the phenotypic nature of this most common complication of diabetes. Moreover, animal studies have demonstrated that the mechanisms related to peripheral neuropathy occurring in type 1 and type 2 diabetes are likely different, with hyperglycemia being the primary factor for neuropathology in type 1 diabetes, which contributes to a lesser extent in type 2 diabetes, whereas insulin resistance, hyperlipidemia, and other factors may have a greater role. Two of the earliest mechanisms described from animal studies as a cause for diabetic peripheral neuropathy were the activation of the aldose reductase pathway and increased non-enzymatic glycation. However, continuing research has identified numerous other potential factors that may contribute to diabetic peripheral neuropathy, including oxidative and inflammatory stress, dysregulation of protein kinase C and hexosamine pathways, and decreased neurotrophic support. In addition, recent studies have demonstrated that peripheral neuropathy-like symptoms are present in animal models, representing pre-diabetes in the absence of hyperglycemia. CONCLUSION This complexity complicates the successful treatment of diabetic peripheral neuropathy, and results in the poor outcome of translating successful treatments from animal studies to human clinical trials.
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Affiliation(s)
- Mark Yorek
- Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242 USA
- Department of Veterans Affairs Iowa City Health Care System, Iowa City, IA, 52246 USA
- Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, 52242 USA
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Zhou Q, Qian Z, Yang M, Liu J, Wu J, Ren L, Ren L. Alterations in plantar vessel blood flow in patients with mild diabetic peripheral neuropathy. BMJ Open Diabetes Res Care 2022; 10:10/1/e002492. [PMID: 35027366 PMCID: PMC8762148 DOI: 10.1136/bmjdrc-2021-002492] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 12/10/2021] [Indexed: 11/16/2022] Open
Abstract
INTRODUCTION Early identification and treatment of diabetic peripheral neuropathy (DPN) are crucial. Presently, the mechanism of DPN is not very clear, and there are inconclusive conclusions about the influencing factors of vascular dynamic characteristics in DPN. This study aims to detect and compare the hemodynamic characteristics of plantar blood vessels in patients with mild DPN and healthy participants to explore a simple and reliable new idea and a potential method for early assessment of DPN and to investigate the influence of gender and age on hemodynamic characteristics. RESEARCH DESIGN AND METHODS Sixty age-matched and gender-matched patients with mild DPN (30 men and 30 women) and 60 healthy participants were randomly recruited. Color Doppler ultrasound was used to measure and analyze the hemodynamic characteristics of plantar-related vessels. RESULTS Ultrasonic measurements had good test-retest reliability. There may be no statistically significant differences in the blood flow velocity and blood flow in the plantar-related blood vessels of participants, irrespective of their gender and age. For patients with mild DPN, color Doppler ultrasound may indicate early hemodynamic abnormalities when there are no obvious abnormalities in the large arteries of the lower limbs, which are specifically manifested as increased blood flow velocity and blood flow in the distal small vessels. CONCLUSIONS Our study provides in vivo data support for the dynamic characteristics of the plantar blood vessel biomechanical model and provides a new idea of in vivo and non-invasive early diagnosis of DPN.
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Affiliation(s)
- Qiang Zhou
- Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, China
- Cadre's Ward, The First Hospital of Jilin University, Changchun, China
| | - Zhihui Qian
- Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, China
| | - Maoguang Yang
- Department of Endocrinology, The Second Hospital of Jilin University, Changchun, China
| | - Jing Liu
- Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, China
| | - Jianan Wu
- Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, China
| | - Luquan Ren
- Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, China
| | - Lei Ren
- Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, China
- School of Mechanical, Aerospace and Civil Engineering, University of Manchester, Manchester, UK
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Abbas ZG, Boulton AJM. Diabetic foot ulcer disease in African continent: 'From clinical care to implementation' - Review of diabetic foot in last 60 years - 1960 to 2020. Diabetes Res Clin Pract 2022; 183:109155. [PMID: 34838640 DOI: 10.1016/j.diabres.2021.109155] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 11/22/2021] [Accepted: 11/22/2021] [Indexed: 12/22/2022]
Abstract
The prevalence of diabetes mellitus is increasing globally and the greatest potential increases in diabetes will occur in Africa. Data suggest that these increases is associated with rapid demographic, sociocultural and economic transitions. There will be a parallel increase in the complications of diabetes and among the various complications those related to diabetic foot disease are associated with the highest morbidity and mortality. Diabetic Peripheral neuropathy (DPN) is the most common cause of diabetic foot complications in African countries; however, peripheral arterial disease (PAD) appears to increase, possibly a result of rising urbanization. Search done for the past six decades (1960 to 2020) on all foot complications. Rates of complications of diabetic foot in last six decades varied by country as follow: DPN: 4-90%; PAD: 0-77%; foot ulcers: 4-61%; amputation rates: 3-61% and high mortality rates reaching to 55%, patients who presented late with infection and gangrene. Educational and prevention programmes are required to curb the growing complications of diabetic foot ulcers in Africa among patients and health care workers. Secondly, it is imperative that governments across the African continent recognise the clinical and public health implications of diabetic foot disease in persons with diabetes.
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Affiliation(s)
- Zulfiqarali G Abbas
- Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; Abbas Medical Centre, Dar es Salaam, Tanzania.
| | - Andrew J M Boulton
- Division of Diabetes, Endocrinology & Gastroenterology, School of Medical Sciences, Faculty of Biology(,) Medicine and Health, University of Manchester, Manchester, UK; Miller School of Medicine, University of Miami, FL, USA
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Nemenov MI, Singleton JR, Premkumar LS. Role of Mechanoinsensitive Nociceptors in Painful Diabetic Peripheral Neuropathy. Curr Diabetes Rev 2022; 18:e081221198649. [PMID: 34879806 DOI: 10.2174/1573399818666211208101555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 03/08/2021] [Accepted: 07/09/2021] [Indexed: 11/22/2022]
Abstract
The cutaneous mechanisms that trigger spontaneous neuropathic pain in diabetic peripheral neuropathy (PDPN) are far from clear. Two types of nociceptors are found within the epidermal and dermal skin layers. Small-diameter lightly myelinated Aδ and unmyelinated C cutaneous mechano and heat-sensitive (AMH and CMH) and C mechanoinsensitive (CMi) nociceptors transmit pain from the periphery to central nervous system. AMH and CMH fibers are mainly located in the epidermis, and CMi fibers are distributed in the dermis. In DPN, dying back intra-epidermal AMH and CMH fibers leads to reduced pain sensitivity, and the patients exhibit significantly increased pain thresholds to acute pain when tested using traditional methods. The role of CMi fibers in painful neuropathies has not been fully explored. Microneurography has been the only tool to access CMi fibers and differentiate AMH, CMH, and CMi fiber types. Due to the complexity, its use is impractical in clinical settings. In contrast, a newly developed diode laser fiber selective stimulation (DLss) technique allows to safely and selectively stimulate Aδ and C fibers in the superficial and deep skin layers. DLss data demonstrate that patients with painful DPN have increased Aδ fiber pain thresholds, while C-fiber thresholds are intact because, in these patients, CMi fibers are abnormally spontaneously active. It is also possible to determine the involvement of CMi fibers by measuring the area of DLss-induced neurogenic axon reflex flare. The differences in AMH, CMH, and CMi fibers identify patients with painful and painless neuropathy. In this review, we will discuss the role of CMi fibers in PDPN.
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Affiliation(s)
- Mikhail I Nemenov
- Department of Anesthesia, Stanford University, Palo Alto, CA, USA
- Lasmed LLC, Mountain View, CA, USA
| | | | - Louis S Premkumar
- Department of Pharmacology, SIU School of Medicine, Springfield, Illinois, USA and Ion Channel Pharmacology LLC, Springfield, IL, USA
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