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Sobhi N, Sadeghi-Bazargani Y, Mirzaei M, Abdollahi M, Jafarizadeh A, Pedrammehr S, Alizadehsani R, Tan RS, Islam SMS, Acharya UR. Artificial intelligence for early detection of diabetes mellitus complications via retinal imaging. J Diabetes Metab Disord 2025; 24:104. [PMID: 40224528 PMCID: PMC11993533 DOI: 10.1007/s40200-025-01596-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 02/23/2025] [Indexed: 04/15/2025]
Abstract
Background Diabetes mellitus (DM) increases the risk of vascular complications, and retinal vasculature imaging serves as a valuable indicator of both microvascular and macrovascular health. Moreover, artificial intelligence (AI)-enabled systems developed for high-throughput detection of diabetic retinopathy (DR) using digitized retinal images have become clinically adopted. This study reviews AI applications using retinal images for DM-related complications, highlighting advancements beyond DR screening, diagnosis, and prognosis, and addresses implementation challenges, such as ethics, data privacy, equitable access, and explainability. Methods We conducted a thorough literature search across several databases, including PubMed, Scopus, and Web of Science, focusing on studies involving diabetes, the retina, and artificial intelligence. We reviewed the original research based on their methodology, AI algorithms, data processing techniques, and validation procedures to ensure a detailed analysis of AI applications in diabetic retinal imaging. Results Retinal images can be used to diagnose DM complications including DR, neuropathy, nephropathy, and atherosclerotic cardiovascular disease, as well as to predict the risk of cardiovascular events. Beyond DR screening, AI integration also offers significant potential to address the challenges in the comprehensive care of patients with DM. Conclusion With the ability to evaluate the patient's health status in relation to DM complications as well as risk prognostication of future cardiovascular complications, AI-assisted retinal image analysis has the potential to become a central tool for modern personalized medicine in patients with DM.
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Affiliation(s)
- Navid Sobhi
- Nikookari Eye Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Majid Mirzaei
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mirsaeed Abdollahi
- Nikookari Eye Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Jafarizadeh
- Nikookari Eye Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Siamak Pedrammehr
- Institute for Intelligent Systems Research and Innovation (IISRI), Deakin University, 75 Pigdons Rd, Waurn Ponds, VIC 3216 Australia
- Faculty of Design, Tabriz Islamic Art University, Tabriz, Iran
| | - Roohallah Alizadehsani
- Institute for Intelligent Systems Research and Innovation (IISRI), Deakin University, 75 Pigdons Rd, Waurn Ponds, VIC 3216 Australia
| | - Ru-San Tan
- National Heart Centre Singapore, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - Sheikh Mohammed Shariful Islam
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Melbourne, VIC Australia
- Cardiovascular Division, The George Institute for Global Health, Newtown, Australia
- Sydney Medical School, University of Sydney, Camperdown, Australia
| | - U. Rajendra Acharya
- School of Mathematics, Physics, and Computing, University of Southern Queensland, Springfield, QLD 4300 Australia
- Centre for Health Research, University of Southern Queensland, Springfield, Australia
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Yu Y, Zhou T, Li L, Liu X, Yin Y, Yu R. Acupoint injection increases the efficacy of vitamin B12 for diabetic neuropathy: a meta-analysis and trial sequential analysis. Eur J Clin Nutr 2025:10.1038/s41430-025-01631-z. [PMID: 40410378 DOI: 10.1038/s41430-025-01631-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 05/09/2025] [Accepted: 05/12/2025] [Indexed: 05/25/2025]
Abstract
This study aims to systematically evaluate the efficacy and safety of vitamin B12 acupoint injections compared to other administration routes in treating diabetic neuropathy (DN). We included 20 randomized controlled trials published before March 1, 2024, sourced from eight public databases, involving 1688 participants. Subsequently, we recorded their basic data, investigated their risk of bias, and then carried out a meta-analysis and trial sequential analysis (TSA). The meta-analysis revealed that compared to other administration routes of vitamin B12, acupoint injection significantly improved the clinical effectiveness proportion by 28% (risk ratio [RR] 1.28, 95% confidence interval [CI] 1.22-1.35), peroneal nerve motor nerve conduction velocity (MNCV) by 4.43 m/s (MD 4.43, 95% CI 2.83-6.03), peroneal nerve sensory nerve conduction velocity (SNCV) by 3.82 m/s (MD 3.82, 95% CI 3.23-4.41), median nerve MNCV by 5.48 m/s (MD 5.48, 95% CI 4.71-6.24), and median nerve SNCV by 4.62 m/s (MD 4.62, 95% CI 3.84-5.39) in patients with DN, while having no significant impact on fasting blood glucose (FBG) (MD -0.18, 95% CI -0.44 to 0.08), 2-h postprandial blood glucose (2h-PBG) (MD -0.02, 95% CI -0.36 to 0.33), and the adverse event incidence (RR 1.44, 95% CI 0.44-4.70). TSA indicated that except for FBG, 2h-PBG, and adverse event incidence, the remaining meta-analysis results were conclusive. These findings indicate that compared to other administration routes of vitamin B12, acupoint injection improves neurological function in patients with DN without increasing adverse events and economic burden, suggesting that it may be the optimal administration route for vitamin B12.
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Affiliation(s)
- Yunfeng Yu
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
- The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Tongyi Zhou
- The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Liu Li
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Xiu Liu
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Yuman Yin
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Rong Yu
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China.
- The First Hospital of Hunan University of Chinese Medicine, Changsha, China.
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Bussell M, Sahba K, Jahromi H, Rashidian M, Hankins J. A Retrospective Assessment of Neuropathic Pain in Response to Intraneural Facilitation ® Therapy and Neurovascular Index-Guided Food Elimination. Biomedicines 2025; 13:688. [PMID: 40149665 PMCID: PMC11940592 DOI: 10.3390/biomedicines13030688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 02/27/2025] [Accepted: 03/10/2025] [Indexed: 03/29/2025] Open
Abstract
Background/Objectives: To evaluate the effectiveness of our dual approach in treating neural ischemia. Methods: Researchers were able to retrospectively audit patient data collected from January 2022-September 2024. Patients were included if they received intraneural facilitation® (INF®), participated in neurovascular index (NVI)-guided food elimination, and completed pre and post pain-quality assessment scale (PQAS) forms in its entirety. Results: Eighteen of the twenty PQAS descriptive pain variables were significantly different pre- vs. post treatment: intense (p = 0.000), sharp (p = 0.002), hot (p = 0.020), dull (p = 0.022), cold (p = 0.005), sensitive (p = 0.000), shooting (p = 0.000), numb (p = 0.000), electrical (p = 0.000), tingling (p = 0.000), cramping (p = 0.000), radiating (p = 0.000), throbbing (p = 0.000), aching (p = 0.000), heavy (p = 0.000), unpleasant (p = 0.000), deep pain (p = 0.000), and intense surface pain (p = 0.000). Itchy (p = 0.058) and tender (p = 0.062) were not found to be significant. There was also significance in pain decrease in the three mean domains: paroxysmal (p = 0.000), superficial (p = 0.000), and deep (p = 0.000). Conclusions: This study suggests that blending a mechanical intervention (INF®) with a lifestyle modification (NVI-guided food elimination) is effective in improving PQAS scores in patients with peripheral neuropathy, indicating a possible reversal of neural ischemia and maintenance of capillary patency.
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Affiliation(s)
- Mark Bussell
- Neuropathic Therapy Center, Loma Linda University Health, Loma Linda, CA 92354, USA; (M.B.); (H.J.)
| | - Kyan Sahba
- Neuropathic Therapy Center, Loma Linda University Health, Loma Linda, CA 92354, USA; (M.B.); (H.J.)
| | - Hailey Jahromi
- Neuropathic Therapy Center, Loma Linda University Health, Loma Linda, CA 92354, USA; (M.B.); (H.J.)
| | - Mitra Rashidian
- Department of Allied Health Studies, Loma Linda University, Loma Linda, CA 92354, USA;
| | - Jamie Hankins
- School of Nursing, Loma Linda University, Loma Linda, CA 92354, USA;
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Leo WZ, Ge L, Chandrasekar S, Tan E, Loh YB, Zhu X, Liew H, Yong E, Chew T, Hoe J, Law C, Lin J, Lim JA, Lingam P, Molina J, Ang G, Sun Y, Lo ZJ. Diabetic foot in primary and tertiary (DEFINITE) care: An efficacious, synergistic and cost-effective multidisciplinary team model for diabetic foot care in Singapore. Semin Vasc Surg 2025; 38:20-31. [PMID: 40086919 DOI: 10.1053/j.semvascsurg.2025.01.007] [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: 01/11/2025] [Revised: 01/19/2025] [Accepted: 01/20/2025] [Indexed: 03/16/2025]
Abstract
Diabetic foot ulcers (DFUs) and lower extremity amputations (LEAs) threaten survival and quality of life (QoL) of patients, contributing to healthcare and economic burden. Guidelines advocate for a multidisciplinary team (MDT) approach, but limited literature exists on cost-effectiveness and collaboration with primary care. We present the outcomes of the Diabetic Foot in Primary and Tertiary (DEFINITE) Care program, an MDT initiative in Singapore across primary and tertiary care. Patients with DFU from June 2020 to 2022 were enrolled. Clinical outcomes encompassed one-year minor and major LEAs, mortality and LEA-free survival rates. Healthcare utilization outcomes included number of admissions, length of stay, and primary care and hospital visits. QoL and Patient Reported Outcome Measures (PROMs) were respectively assessed using the EuroQol Five-Dimensional Questionnaire and Diabetic Foot Ulcer Scale-Short Form. Results from DEFINITE were propensity-score matched against a retrospective cohort. Cost-effectiveness analysis was performed using Markov simulation. Subgroup analyses focused on at-risk populations, including patients without access to MDT clinics or podiatry, appointment defaulters, octogenarians, patients with end-stage renal failure and different primary care locations. Total of 2,798 patients, with a mean age of 65.7 years and majority males (61.4%), were included for analysis. DEFINITE Care patients had higher minor LEA and improved LEA-free survival rates, fewer and shorter hospital admissions, and enhanced QoL and PROMs. DEFINITE Care demonstrated greater cost-effectiveness when compared to traditional care. Outcomes varied among subgroups. DEFINITE Care is an efficacious and cost-effective MDT model which fosters collaboration between primary and tertiary care for diabetic limb salvage.
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Affiliation(s)
- Wen Zhe Leo
- Vascular Surgery Service, Department of Surgery, Woodlands Health, Singapore
| | - Lixia Ge
- Health Services and Outcomes Research, National Healthcare Group, Singapore
| | | | - Elaine Tan
- National Healthcare Group Polyclinics, Singapore
| | - Yi Bing Loh
- National Healthcare Group Polyclinics, Singapore
| | - Xiaoli Zhu
- National Healthcare Group Polyclinics, Singapore
| | - Huiling Liew
- Department of Endocrinology, Tan Tock Seng Hospital, Singapore
| | - Enming Yong
- Vascular Surgery Service, Department of General Surgery, Tan Tock Seng Hospital, Singapore
| | - Tiffany Chew
- Department of Podiatry, Tan Tock Seng Hospital, Singapore
| | - Jeremy Hoe
- Department of General Medicine, Khoo Teck Puat Hospital, Singapore
| | - Chelsea Law
- Department of Podiatry, Khoo Teck Puat Hospital, Singapore
| | - Jaime Lin
- Department of Endocrinology, Woodlands Health, Singapore
| | - Jo Anne Lim
- Podiatry Service, Department of Rehabilitation, Woodlands Health, Singapore
| | - Pravin Lingam
- Vascular Surgery Service, Department of Surgery, Woodlands Health, Singapore
| | - Joseph Molina
- Health Services and Outcomes Research, National Healthcare Group, Singapore
| | - Gary Ang
- Health Services and Outcomes Research, National Healthcare Group, Singapore
| | - Yan Sun
- Health Services and Outcomes Research, National Healthcare Group, Singapore
| | - Zhiwen Joseph Lo
- Vascular Surgery Service, Department of Surgery, Woodlands Health, Singapore.
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Smithiseth K, Leurcharusmee P, Sawaddiruk P, Chattipakorn N, Chattipakorn S. Unraveling the link between magnesium and diabetic neuropathy: Evidence from in vitro to clinical studies. Nutr Res 2025; 135:13-31. [PMID: 39891959 DOI: 10.1016/j.nutres.2025.01.005] [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: 10/05/2024] [Revised: 01/07/2025] [Accepted: 01/07/2025] [Indexed: 02/03/2025]
Abstract
Diabetic neuropathy (DN) is one of the major complications of diabetes and the most common cause of neuropathic pain. Although the underlying pathological mechanisms remain unclear, several studies have produced conflicting results regarding the link between magnesium (Mg) concentration and DN. This ambiguity raises questions about the potential benefits of Mg supplementation in individuals with DN. Therefore, this comprehensive review summarizes and discusses the evidence from clinical, in vitro, and in vivo studies on the association between Mg and DN. Several findings indicate that Mg depletion is linked to the presence of neuropathy in diabetic patients. Additionally, low Mg concentration may contribute to the onset or worsening of DN by promoting axonal degeneration through various pathways. Furthermore, multiple studies have shown that Mg supplementation can have neuroprotective effects. These findings suggest potential as an alternative or complementary therapy for preventing and treating DN in the future.
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Affiliation(s)
- Kannika Smithiseth
- Department of Anesthesiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | - Passakorn Sawaddiruk
- Department of Anesthesiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Nipon Chattipakorn
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand; Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Siriporn Chattipakorn
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand; Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
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Eid SA, Townsend KL, Spallone V, Menichella DM, Koubek EJ, Feldman EL. A call to action for peripheral neuropathy research funding-Time to consolidate funding under one NIH initiative? J Peripher Nerv Syst 2025; 30:e12681. [PMID: 39801027 PMCID: PMC11725771 DOI: 10.1111/jns.12681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 11/11/2024] [Accepted: 12/04/2024] [Indexed: 01/16/2025]
Affiliation(s)
- Stéphanie A. Eid
- Department of NeurologyUniversity of MichiganAnn ArborMichiganUSA
| | - Kristy L. Townsend
- Department of Neurological SurgeryThe Ohio State UniversityColumbusOhioUSA
| | - Vincenza Spallone
- Department of Systems Medicine, Endocrinology SectionUniversity of Rome Tor VergataRomeItaly
| | - Daniela M. Menichella
- Department of NeurologyFeinberg School of MedicineChicagoIllinoisUSA
- Department of PharmacologyFeinberg School of MedicineChicagoIllinoisUSA
| | - Emily J. Koubek
- Department of NeurologyUniversity of MichiganAnn ArborMichiganUSA
| | - Eva L. Feldman
- Department of NeurologyUniversity of MichiganAnn ArborMichiganUSA
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Pal B, Ghosh R, Sarkar RD, Roy GS. The irreversible, towards fatalic neuropathy: from the genesis of diabetes. Acta Diabetol 2025; 62:139-156. [PMID: 39636401 DOI: 10.1007/s00592-024-02429-4] [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: 10/03/2024] [Accepted: 11/25/2024] [Indexed: 12/07/2024]
Abstract
Diabetic neuropathy is the most prevalent diabetes-associated complication that negatively impacts the quality of life of the patients. The extensive complications of diabetic peoples in the world are the leading cause of neuropathic pain, and over-activation of different biochemical signalling process induces the pathogenic progression and are also corresponding the epidemic painful symptom of diabetic neuropathy. The main prevalent abnormality is neuropathy, which further causing distal symmetric polyneuropathy and focal neuropathy. The exact pathological complication of diabetes associated neuropathic algesia is still unclear, but the alteration in micro-angiopathy associated nerve fibre loss, hyper polyol formation, MAPK signalling, WNT signalling, tau-derived insulin signalling processes are well known. Furthermore, the post-translational modification of different ion channels, oxidative and nitrosative stress, brain plasticity and microvascular changes can contributes the development of neuropathic pain. However, in the current review we discussed about these pathogenic development of neuropathic pain from the genesis of diabetes, and how diabetes affects the physiological and psychological health, and quality of life of the patients. Furthermore, the treatment of diabetic neuropathy with conventional monotherapy and emerging therapy are discussed. In addition, the treatment with phytochemical constituents their mechanisms and clinical evidences are also reported. The future investigation is required on pathological alteration occurs in neuropathic individuals, and on molecular mechanisms as well as the adverse effect of phytochemicals to determine all aspects of neuropathic algesia including effective treatments, which will prevents the sympathetic pain in patients.
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Affiliation(s)
- Bhaskar Pal
- Department of Pharmacology, Charaktala College of Pharmacy, Charaktala, Mothabari, Malda, West Bengal, India.
| | - Rashmi Ghosh
- Bengal College of Pharmaceutical Science & Research, Durgapur, West Bengal, India
| | - Raktimava Das Sarkar
- Department of Pharmaceutical Technology, Bengal School of Technology, Sugandha, Delhi Road, Chinsurah, Hooghly, West Bengal, India
| | - Gouranga Sundar Roy
- Department of Pharmaceutical Technology, Bengal School of Technology, Sugandha, Delhi Road, Chinsurah, Hooghly, West Bengal, India
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Saha P, Yarra SS, Arruri V, Mohan U, Kumar A. Exploring the role of miRNA in diabetic neuropathy: from diagnostics to therapeutics. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:1129-1144. [PMID: 39249503 DOI: 10.1007/s00210-024-03422-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 08/29/2024] [Indexed: 09/10/2024]
Abstract
Diabetic neuropathy (DN) is one of the major microvascular complications of diabetes mellitus affecting 50% of the diabetic population marred by various unmet clinical needs. There is a need to explore newer pathological mechanisms for designing futuristic regimens for the management of DN. There is a need for post-transcriptional regulation of gene expression by non-coding RNAs (ncRNAs) to finetune different cellular mechanisms with significant biological relevance. MicroRNAs (miRNAs) are a class of small ncRNAs (~ 20 to 24 nucleotide length) that are known to regulate the activity of ~ 50% protein-coding genes through repression of their target mRNAs. Differential expression of these miRNAs is associated with the pathophysiology of diabetic neuropathy via regulating various pathways such as neuronal hyperexcitability, inflammation, axonal growth, regeneration, and oxidative stress. Of note, the circulating and extracellular vesicular miRNAs serve as potential biomarkers underscoring their diagnostic potential. Recent pieces of evidence highlight the potential of miRNAs in modulating the initiation and progression of DN and the possibility of developing miRNAs as treatment options for DN. In this review, we have elaborated on the role of different miRNAs as potential biomarkers and emphasized their druggable aspects for promising future therapies for the clinical management of DN.
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Affiliation(s)
- Priya Saha
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER) SAS Nagar, Sec 67, Mohali, Punjab, 160062, India
| | - Sai Sumanjali Yarra
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER) Kolkata, Maniktala Main Road, Kolkata, West Bengal, India
| | - Vijay Arruri
- Department of Neurological Surgery, University of Wisconsin, Madison, USA
| | - Utpal Mohan
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER) Kolkata, Maniktala Main Road, Kolkata, West Bengal, India
| | - Ashutosh Kumar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER) SAS Nagar, Sec 67, Mohali, Punjab, 160062, India.
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Musial DC, Ajita ME, Bomfim GHS. Benefits of Cilostazol's Effect on Vascular and Neuropathic Complications Caused by Diabetes. Med Sci (Basel) 2024; 13:1. [PMID: 39846696 PMCID: PMC11755643 DOI: 10.3390/medsci13010001] [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: 10/15/2024] [Revised: 11/24/2024] [Accepted: 12/22/2024] [Indexed: 01/24/2025] Open
Abstract
Diabetes mellitus (DM) is a global health concern with a rising incidence, particularly in aging populations and those with a genetic predisposition. Over time, DM contributes to various complications, including nephropathy, retinopathy, peripheral arterial disease (PAD), and neuropathy. Among these, diabetic neuropathy and PAD stand out due to their high prevalence and significant impact on patients' quality of life. Diabetic distal symmetric polyneuropathy, the most common form of diabetic neuropathy, is driven by neuroinflammation stemming from prolonged hyperglycemia. Simultaneously, hyperglycemia significantly increases the risk of PAD, a condition further exacerbated by factors like smoking, age, and sedentary lifestyles. PAD frequently manifests as claudication, a debilitating symptom marked by pain and cramping during physical activity, which limits mobility and worsens patients' outcomes. Cilostazol, a phosphodiesterase-3 inhibitor, has proven effective in managing intermittent claudication in PAD by improving walking distances and enhancing blood flow. Recent studies have also explored its potential benefits for diabetic neuropathy. Cilostazol's mechanisms include vasodilation, platelet inhibition, and increased cyclic adenosine monophosphate (cAMP) levels, which may contribute to improved neurological outcomes. However, variability in the clinical evidence due to inconsistent treatment protocols highlights the need for further investigation. This review explores cilostazol's mechanisms of action and therapeutic applications for managing neuropathy and PAD in diabetic patients, aiming to provide insights into its potential as a dual-purpose pharmacological agent in this high-risk population.
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Affiliation(s)
| | - Maria Eduarda Ajita
- Department of Medicine, Pontifícia Universidade Católica do Paraná, Londrina 86067-000, PR, Brazil;
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Ge R, Liu R, He M, Wu J, Zhang F, Huang C. The efficacy of acupuncture for diabetic peripheral neuropathy: a systematic review and meta-analysis of randomized controlled trails. Front Neurol 2024; 15:1500709. [PMID: 39758782 PMCID: PMC11697586 DOI: 10.3389/fneur.2024.1500709] [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: 09/23/2024] [Accepted: 12/09/2024] [Indexed: 01/07/2025] Open
Abstract
Objective To systematically evaluate the clinical efficacy of acupuncture in the treatment of diabetic peripheral neuropathy (DPN). Methods Randomized controlled trial (RCT) of acupuncture for diabetic peripheral neuropathy in Chinese Knowledge Network (CNKI), Wanfang database, VIP database (VIP), PubMed, web of science, cochrane library, AMED and CINAHL were searched by computer since the establishment of the database. All publications in English and Chinese as of 30 December 2023 will be searched, without country or article type restrictions. Study selection, data extraction and evaluation were performed independently by two researchers. Risk of bias was assessed using the Cochrane risk assessment tool, and Meta-analysis was performed using RevMan5.3 software. Results DPN has good effective rate in acupuncture than conventional western medicine alone. However, the above conclusions need to be verified by larger samples and higher quality randomized controlled trials. ① Acupuncture treated DPN more effective than drug (RR = 1.38, 95%CI = 1.26 ~ 1.51, Z = 6.93, p < 0.00001), DPN of patients with acupuncture plus drug (RR = 1.38, 95%CI = 1.05 ~ 1.82, Z = 2.28, p = 0.02), There was no significant difference between acupuncture and usual care (RR = 2.41, 95%CI = 0.70 ~ 8.29, Z = 1.39, p = 0.16); ② Acupuncture treatment is superior to drug group in improving the SNCV of the median nerve (MD = 1.65, 95%CI = 0.74 ~ 2.57,Z = 3.55, p = 0.0004), sham needle treatment (MD = 0.50, 95%CI = 0.17 ~ 0.83, Z = 2.95, p = 0.003), Acupuncture plus drug was superior to drug in improving the SNCV of the median nerve (MD = 3.29, 95%CI = 2.55 ~ 4.03, Z = 8.70, p < 0.00001); ③ Acupuncture treatment is superior to drug group in improving the MNCV of the median nerve (MD = 2.24, 95%CI = 0.50 ~ 3.98, Z = 2.52, p = 0.01), and sham needle treatment (MD = 0.20, 95%CI = -0.03 ~ 0.43, Z = 1.69, p = 0.09), Acupuncture plus drug was superior to drug group in improving the MNCV of the median nerve (MD = 2.63, 95%CI = 1.83 ~ 3.42, Z = 6.46, p < 0.00001); ④ Acupuncture is better to drug group in improving SNCV of common peroneal nerve (MD = 1.67, 95%CI = 0.21 ~ 3.13, Z = 2.24, p = 0.02); ⑤ Acupuncture treatment is superior to drug group in improving the MNCV of the common peroneal nerve (MD = 2.03, 95%CI = 1.37 ~ 0.69, Z = 6.04, p < 0.00001), Acupuncture plus drug outperformed MNCV in improving the common peroneal nerve (MD = 4.23, 95%CI = -0.16 ~ 8.62, Z = 1, 89, p = 0.06); ⑥ Acupuncture treatment is superior to drug group in improving the SNCV of the tibial nerve (MD = 1.58, 95%CI = 0.85 ~ 2.30, Z = 4.26, p < 0.0001); ⑦ There was no significant difference between acupuncture treatment and drug group in improving the MNCV of the tibial nerve (MD =1.55, 95%CI = -0.59 ~ 3.68, Z = 1.42, p = 0.16); ⑧ Acupuncture plus drug is better than medication in reducing VAS (MD = -2.35, 95%CI = -3.78 ~ -0.93, Z = 3.23, p = 0.001), Acupuncture plus usual care is superior to usual caret (MD = -28.70, 95%CI = -39.50 ~ 17.90, Z = 5.21, p < 0.00001), There was no significant difference between acupuncture and sham needle treatment (MD = -4.00, 95%CI = -18.32 ~ 10.32, Z = 0.55, p = 0.58). Conclusion Compared with drug, usual care, and sham AT, AT has a better response rate and more favorable effect in improving nerve conduction velocity. The combination of AT and drug demonstrates a more significant improvement compared to drug alone. The combination of AT and usual care improves DPN symptoms more effectively than usual care. However, the above conclusions need to be verified by larger samples and higher quality randomized controlled trials. Systematic review registration [https://www.crd.york.ac.uk/], identifier [CRD42023451575].
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Affiliation(s)
| | | | | | | | | | - Chang Huang
- School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
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11
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Ferreira JSSP, Cruvinel-Júnior RH, da Silva EQ, Veríssimo JL, Monteiro RL, Duarte M, Giacomozzi C, Sacco ICN. Effectiveness of a web-based foot-ankle exercise program for treating ulcer risk factors in diabetic neuropathy in a randomized controlled trial. Sci Rep 2024; 14:27291. [PMID: 39516524 PMCID: PMC11549312 DOI: 10.1038/s41598-024-78188-7] [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: 05/13/2024] [Accepted: 10/29/2024] [Indexed: 11/16/2024] Open
Abstract
The need for strategies to prevent complications from diabetic neuropathy (DPN) is well recognized. However, foot-ankle exercise programs show weak to moderate evidence, and barriers to their implementation persist, including broad and facilitated access to exercise programs, which guarantee for equity. In this paper, we report for the first time the effectiveness of a web-based foot-ankle exercise program aiming to improve DPN-related outcomes, gait biomechanics and functional outcomes. Sixty-two participants with DPN were randomly allocated into the control group (CG; n = 31), which received the usual care, or the intervention group (IG; n = 31), which received the usual care plus a 12-week foot-ankle exercise program using a web-based software (the SOPeD software). The primary outcomes, DPN symptoms and severity, were assessed using the Brazilian version of the Michigan Neuropathy Screening Instrument and the Decision Support System for Classification of Diabetic Polyneuropathy, respectively. Secondary outcomes included tactile sensitivity (monofilaments) and vibration perception (tuning fork), functional outcomes, such as foot pain and function (Foot Health Status Questionnaire), foot muscle strength and plantar pressure during gait (emed plate), and foot-ankle kinematics and kinetics during gait. Outcomes were assessed at baseline, 12 and 24 weeks by an assessor blinded to group allocation. DPN symptoms and severity remained unchanged after the web-based foot-ankle program. However, IG showed improvements compared to CG, with greater functional reach at 12 weeks, better foot function, reduced foot pain and greater plantarflexion degree during push-off at 24 weeks. Regarding plantar loading during gait, the forefoot pressure reduced in the IG at 12 weeks compared to baseline, but at 24 weeks, forefoot load increased in the IG compared to CG. The 12-week web-based foot-ankle exercise program was feasible, acceptable, demonstrating safety with minimal adverse events, such as delayed onset muscle soreness and foot muscle cramping. While DPN-related outcomes were unaffected by the 12-week SOPeD program, modest improvements in foot pain and function, functional reach, and changes in plantar pressure and plantarflexion degree during gait were noted, mostly at 24 weeks.Trial registration: ClinicalTrials.gov, NCT04011267. Registered on 8 July 2019.
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Affiliation(s)
- Jane S S P Ferreira
- Departamento de Fisioterapia, Fonoaudiologia e Terapia Ocupacional da Faculdade de Medicina da Universidade de São Paulo, Rua Cipotânea, 51 - Cidade Universitária, São Paulo, São Paulo, 05360-160, Brazil
| | - Ronaldo H Cruvinel-Júnior
- Departamento de Fisioterapia, Fonoaudiologia e Terapia Ocupacional da Faculdade de Medicina da Universidade de São Paulo, Rua Cipotânea, 51 - Cidade Universitária, São Paulo, São Paulo, 05360-160, Brazil
| | - Erica Q da Silva
- Departamento de Fisioterapia, Fonoaudiologia e Terapia Ocupacional da Faculdade de Medicina da Universidade de São Paulo, Rua Cipotânea, 51 - Cidade Universitária, São Paulo, São Paulo, 05360-160, Brazil
| | - Jady L Veríssimo
- Departamento de Fisioterapia, Fonoaudiologia e Terapia Ocupacional da Faculdade de Medicina da Universidade de São Paulo, Rua Cipotânea, 51 - Cidade Universitária, São Paulo, São Paulo, 05360-160, Brazil
| | - Renan L Monteiro
- Department of Biological and Health Science, Universidade Federal do Amapá, Macapá, Amapá, Brazil
| | - Marcos Duarte
- Biomedical Engineering, Universidade Federal do ABC, São Bernardo do Campo, Brazil
| | - Claudia Giacomozzi
- Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome, Italy
| | - Isabel C N Sacco
- Departamento de Fisioterapia, Fonoaudiologia e Terapia Ocupacional da Faculdade de Medicina da Universidade de São Paulo, Rua Cipotânea, 51 - Cidade Universitária, São Paulo, São Paulo, 05360-160, Brazil.
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López Capdevilla L, Santamaría Fumas A, Sales Pérez JM, Domínguez Sevilla A, del Corral Cuervo J, Varela-Quintana C, Rabanal Rubio M, Roza Miguel P. Amputation versus circular external fixation in the treatment of diabetic foot with osteomyelitis: a cost and quality-of-life analysis. Ther Adv Endocrinol Metab 2024; 15:20420188241271795. [PMID: 39483172 PMCID: PMC11526285 DOI: 10.1177/20420188241271795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 06/12/2024] [Indexed: 11/03/2024] Open
Abstract
Background Charcot foot is a severe complication of diabetes mellitus. Amputation is associated with 5-year mortality rates as high as 70%, and the overall treatment cost for diabetic foot surpasses that of conditions such as cancer or depression. Objectives To compare clinical, quality-of-life, and cost outcomes related to Charcot foot management through two distinct treatments: amputation and resection with stabilization using circular external fixation (CEF). Methods This retrospective study included all adult patients treated at our unit between 2008 and 2022 for acute diabetic foot with infected ulcers. The allocation to treatment groups was based on the timing of patient enrollment. We gathered anthropometric, diagnostic, and surgical data, documenting individualized costs for preoperative, postoperative, and rehabilitation phases. Health status was assessed using the EQ-5D-3L questionnaire, and recorded data included mortality. Results A total of 31 patients (18 amputations; 13 CEF) were included. Amputees exhibited significantly higher mortality compared to those with a CEF (44.8% vs 7.7%, p = 0.045). The estimated 3-year survival was 60.8% for amputees and 90% for the CEF group (log-rank test, p = 0.096). In terms of quality of life (EQ-5D-3L), amputees reported a reduction of 14.67 points while CEF patients reported an increase of 40.39 points (p < 0.001). The EQ-5D-3L index improved by 1.8 points for amputees, as compared with 62.3 points in the CEF group (p < 0.001). The total mean cost of managing an amputated patient was €222,864, practically identical to the €224,438 incurred in the CEF group (p = 0.767). No statistically significant differences were found in the time distribution of costs. However, some specific expense items demonstrated statistical significance. Conclusion In treating infected diabetic foot ulcers, external fixation leads to a better quality of life compared to amputation. There's also a trend suggesting higher survival rates with external fixation, and both approaches have similar costs.
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Affiliation(s)
- Laia López Capdevilla
- Department of Orthopaedic Surgery, Hospital de la Santa Creu i Sant Pau, Carrer de Sant Quintí, 89, Barcelona 08025, Spain
| | | | | | | | - Julio del Corral Cuervo
- Department of Economic Analysis and Finance, University of Castilla–La Mancha, Ciudad Real, Spain
| | | | - María Rabanal Rubio
- MBA Institute, Gijón, Spain
- Cátedra MBA Institute de Investigación Médica y Biomecánica. University of Oviedo, Gijón, Spain
| | - Pablo Roza Miguel
- MBA Institute, Gijón, Spain
- Cátedra MBA Institute de Investigación Médica y Biomecánica, University of Oviedo, Gijón, Spain
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Hushmandi K, Einollahi B, Aow R, Suhairi SB, Klionsky DJ, Aref AR, Reiter RJ, Makvandi P, Rabiee N, Xu Y, Nabavi N, Saadat SH, Farahani N, Kumar AP. Investigating the interplay between mitophagy and diabetic neuropathy: Uncovering the hidden secrets of the disease pathology. Pharmacol Res 2024; 208:107394. [PMID: 39233055 PMCID: PMC11934918 DOI: 10.1016/j.phrs.2024.107394] [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: 05/12/2024] [Revised: 08/18/2024] [Accepted: 08/30/2024] [Indexed: 09/06/2024]
Abstract
Mitophagy, the cellular process of selectively eliminating damaged mitochondria, plays a crucial role in maintaining metabolic balance and preventing insulin resistance, both key factors in type 2 diabetes mellitus (T2DM) development. When mitophagy malfunctions in diabetic neuropathy, it triggers a cascade of metabolic disruptions, including reduced energy production, increased oxidative stress, and cell death, ultimately leading to various complications. Thus, targeting mitophagy to enhance the process may have emerged as a promising therapeutic strategy for T2DM and its complications. Notably, plant-derived compounds with β-cell protective and mitophagy-stimulating properties offer potential as novel therapeutic agents. This review highlights the intricate mechanisms linking mitophagy dysfunction to T2DM and its complications, particularly neuropathy, elucidating potential therapeutic interventions for this debilitating disease.
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Affiliation(s)
- Kiavash Hushmandi
- Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| | - Behzad Einollahi
- Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Rachel Aow
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Suhana Binte Suhairi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Daniel J Klionsky
- Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
| | - Amir Reza Aref
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Russel J Reiter
- Department of Cell Systems and Anatomy, UT Health San Antonio, Long School of Medicine, San Antonio, TX, USA
| | - Pooyan Makvandi
- Department of Biomaterials, Saveetha Dental College and Hospitals, SIMATS, Saveetha University, Chennai 600077, India; University Centre for Research & Development, Chandigarh University, Mohali, Punjab 140413, India
| | - Navid Rabiee
- Department of Biomaterials, Saveetha Dental College and Hospitals, SIMATS, Saveetha University, Chennai 600077, India
| | - Yi Xu
- Department of Science & Technology, Department of Urology, NanoBioMed Group, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China
| | - Noushin Nabavi
- Independent Researcher, Victoria, British Columbia V8V 1P7, Canada
| | - Seyed Hassan Saadat
- Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Najma Farahani
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Alan Prem Kumar
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
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Hajj J, Sizemore B, Singh K. Impact of Epigenetics, Diet, and Nutrition-Related Pathologies on Wound Healing. Int J Mol Sci 2024; 25:10474. [PMID: 39408801 PMCID: PMC11476922 DOI: 10.3390/ijms251910474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 09/20/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
Chronic wounds pose a significant challenge to healthcare. Stemming from impaired wound healing, the consequences can be severe, ranging from amputation to mortality. This comprehensive review explores the multifaceted impact of chronic wounds in medicine and the roles that diet and nutritional pathologies play in the wound-healing process. It has been well established that an adequate diet is crucial to proper wound healing. Nutrients such as vitamin D, zinc, and amino acids play significant roles in cellular regeneration, immune functioning, and collagen synthesis and processing. Additionally, this review discusses how patients with chronic conditions like diabetes, obesity, and nutritional deficiencies result in the formation of chronic wounds. By integrating current research findings, this review highlights the significant impact of the genetic make-up of an individual on the risk of developing chronic wounds and the necessity for adequate personalized dietary interventions. Addressing the nutritional needs of individuals, especially those with chronic conditions, is essential for improving wound outcomes and overall patient care. With new developments in the field of genomics, there are unprecedented opportunities to develop targeted interventions that can precisely address the unique metabolic needs of individuals suffering from chronic wounds, thereby enhancing treatment effectiveness and patient outcomes.
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Affiliation(s)
- John Hajj
- Indiana Center for Regenerative Medicine and Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; (J.H.); (B.S.)
| | - Brandon Sizemore
- Indiana Center for Regenerative Medicine and Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; (J.H.); (B.S.)
| | - Kanhaiya Singh
- Indiana Center for Regenerative Medicine and Engineering, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA; (J.H.); (B.S.)
- McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA
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Sendilraj V, Pilcher W, Choi D, Bhasin A, Bhadada A, Bhadadaa SK, Bhasin M. DFUCare: deep learning platform for diabetic foot ulcer detection, analysis, and monitoring. Front Endocrinol (Lausanne) 2024; 15:1386613. [PMID: 39381435 PMCID: PMC11460545 DOI: 10.3389/fendo.2024.1386613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 09/02/2024] [Indexed: 10/10/2024] Open
Abstract
Introduction Diabetic foot ulcers (DFUs) are a severe complication among diabetic patients, often leading to amputation or even death. Early detection of infection and ischemia is essential for improving healing outcomes, but current diagnostic methods are invasive, time-consuming, and costly. There is a need for non-invasive, efficient, and affordable solutions in diabetic foot care. Methods We developed DFUCare, a platform that leverages computer vision and deep learning (DL) algorithms to localize, classify, and analyze DFUs non-invasively. The platform combines CIELAB and YCbCr color space segmentation with a pre-trained YOLOv5s algorithm for wound localization. Additionally, deep-learning models were implemented to classify infection and ischemia in DFUs. The preliminary performance of the platform was tested on wound images acquired using a cell phone. Results DFUCare achieved an F1-score of 0.80 and a mean Average Precision (mAP) of 0.861 for wound localization. For infection classification, we obtained a binary accuracy of 79.76%, while ischemic classification reached 94.81% on the validation set. The system successfully measured wound size and performed tissue color and textural analysis for a comparative assessment of macroscopic wound features. In clinical testing, DFUCare localized wounds and predicted infected and ischemic with an error rate of less than 10%, underscoring the strong performance of the platform. Discussion DFUCare presents an innovative approach to wound care, offering a cost-effective, remote, and convenient healthcare solution. By enabling non-invasive and accurate analysis of wounds using mobile devices, this platform has the potential to revolutionize diabetic foot care and improve clinical outcomes through early detection of infection and ischemia.
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Affiliation(s)
- Varun Sendilraj
- Coulter Department of Biomedical Engineering Emory and Gatech, Atlanta, GA, United States
| | - William Pilcher
- Coulter Department of Biomedical Engineering Emory and Gatech, Atlanta, GA, United States
| | - Dahim Choi
- Coulter Department of Biomedical Engineering Emory and Gatech, Atlanta, GA, United States
| | - Aarav Bhasin
- Johns Creek High School, Johns Creek, GA, United States
| | | | - Sanjay Kumar Bhadadaa
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Manoj Bhasin
- Coulter Department of Biomedical Engineering Emory and Gatech, Atlanta, GA, United States
- Aflac Cancer and Blood Disorders Center, Children Healthcare of Atlanta, Atlanta, GA, United States
- Department of Pediatrics, Emory University, Atlanta, GA, United States
- Department of Biomedical Informatics, Emory University, Atlanta, GA, United States
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Alrashed FA, Iqbal M, Al-Regaiey KA, Ansari AA, Alderaa AA, Alhammad SA, Alsubiheen AM, Ahmad T. Evaluating diabetic foot care knowledge and practices at education level. Medicine (Baltimore) 2024; 103:e39449. [PMID: 39183414 PMCID: PMC11346884 DOI: 10.1097/md.0000000000039449] [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: 03/27/2024] [Revised: 08/04/2024] [Accepted: 08/05/2024] [Indexed: 08/27/2024] Open
Abstract
Diabetic foot is one of the complications in type 2 diabetes mellitus. Adequate knowledge and practice are an important aspect to control further deteriorating conditions such as ulcers and amputations. Thus, the objective of this cross-sectional study was to investigate the impact of the education levels of diabetic patients on diabetic foot care knowledge and practice. This cross-sectional study with a convenient sampling technique was conducted on 534 patients with diabetes mellitus from public and private care hospitals. The data was collected using a validated, pretested and structured bilingual (Arabic, English) questionnaire. There were 534 patients interviewed, 39.1% of whom were males and 60.9% of whom were females and 61.4% of the patients had had T2DM for over 10 years. There was a significant difference in education levels between the male and female patients (53.8% and 46.2%, P = .001). Furthermore, 83.9% patients were married. The difference in education between the married and the single, divorced, and widowed patients was significant (P = .007). Patients with uncontrolled HbA1c were 2.43 times more likely to have hypertension (RR = 2.43, P = .03), while patients with highly uncontrolled diabetes had 3.1 times more chances of hypertension (RR = 3.1, P = .009). Heart disease prevalence was 3.27 times higher in diabetes patients with uncontrolled HbA1c and 3.37 times higher in patients with highly uncontrolled HbA1c. Patients with diabetes who have been diabetic for more than 10 years have a greater risk of heart disease (RR = 2.1; P = .03). Patients with lower education levels exhibited more diabetic complications compared to patients with higher education levels (P < .05). The present study highlights the importance of education and awareness campaigns targeting diabetic patients, especially those with lower education levels, to improve diabetes control and prevent, or manage, comorbidities. Healthcare providers should also prioritize patient education and medication adherence to improve diabetes management and reduce the risk of complications.
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Affiliation(s)
- Fahad Abdulaziz Alrashed
- Department of Medical Education, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Muhammad Iqbal
- Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Khalid A. Al-Regaiey
- Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Asrar Ahmad Ansari
- Department of Medical Education, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Asma A. Alderaa
- Department of Health Rehabilitation Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Saad A. Alhammad
- Department of Health Rehabilitation Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Abdulrahman M. Alsubiheen
- Department of Health Rehabilitation Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Tauseef Ahmad
- Department of Medical Education, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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Xie L, Gan W, Cai G. The causal relationship between gut microbiota and diabetic neuropathy: a bi-directional two-sample Mendelian randomization study. Front Endocrinol (Lausanne) 2024; 15:1402014. [PMID: 39050567 PMCID: PMC11266094 DOI: 10.3389/fendo.2024.1402014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 06/26/2024] [Indexed: 07/27/2024] Open
Abstract
Background Many studies suggest a strong correlation between gut microbiota (GM) and diabetic neuropathy (DN). However, the precise causal relationship between GM and DN has yet to be fully elucidated. Hence, a bi-directional Mendelian randomization (MR) analysis was used to examine the association between GM and DN. Methods Widely known genome-wide association study (GWAS) of GM was collected from the MiBio Gen project. Summary-level datasets for DN were taken from the FinnGen project. Inverse variance weighted approach was used for evaluating the causal relationship between GM and DN. Subsequently, pleiotropy and heterogeneity tests were performed to verify the reliability of the data. Furthermore, a bidirectional two-sample MR analysis was done to investigate the directionality of the causal relationships. Gene Ontology analysis was conducted to identify the associations that could indicate biological functions. Results We identified potential causal associations between GM and DN (p< 0.05 in all three MR methods). Among them, we found increased levels of Christensenellaceae R-7 (Odds ratio, OR= 1.52; 95% confidence interval, CI = 1.03-2.23; p = 0.03), Ruminococcaceae UCG013 (OR =1.35; 95% CI = 1.00-1.85; p = 0.04), and Eggerthella groups (OR = 1.27; 95% CI = 1.05-1.55; p = 0.01), which may be associated with a higher risk of DN, while increased levels of Peptococcaceae (OR = 0.69; 95% CI = 0.54-0.90; p< 0.01) and Eubacterium coprostanoligenes groups (OR = 0.68; 95% CI = 0.49-0.93; p = 0.01) could be associated with a lower risk. Gene Ontology pathway analysis revealed enrichment of genes regulated by the associated single-nucleotide polymorphisms (SNPs) in the apical plasma membrane, glycosyltransferase activity, hexosyltransferase activity and membrane raft. Reverse MR analyses indicated that DN was associated with five microbial taxa in all three MR methods. Conclusion The results of our study validate the possible causative relationship between GM and DN. This discovery gives new perspectives into the mechanism on how GM influences DN, and establishes a theoretical foundation for future investigations into targeted preventive measures.
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Affiliation(s)
- Long Xie
- Department of Orthopedics, The Fourth Hospital of Changsha (The Changsha Affiliated Hospital of Hunan Normal University), Hunan Normal University, Changsha, China
| | - Wen Gan
- Department of Thoracic Surgery, Yuebei People’s Hospital, Shaoguan, Guangdong, China
| | - GuangRong Cai
- Trauma Department of Orthopaedics, Yuebei People’s Hospital, Shaoguan, Guangdong, China
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Baldimtsi E, Amezcua S, Ulander M, Hyllienmark L, Olausson H, Ludvigsson J, Wahlberg J. HbA 1c and the risk of developing peripheral neuropathy in childhood-onset type 1 diabetes: A follow-up study over 3 decades. Diabetes Metab Res Rev 2024; 40:e3825. [PMID: 38878301 DOI: 10.1002/dmrr.3825] [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: 01/09/2024] [Revised: 04/18/2024] [Accepted: 04/21/2024] [Indexed: 06/29/2024]
Abstract
AIMS We have evaluated long-term weighted mean HbA1c (wHbA1c), HbA1c variability, diabetes duration, and lipid profiles in relation to the development of diabetic peripheral neuropathy (DPN), nephropathy, and retinopathy in childhood-onset type 1 diabetes. MATERIALS AND METHODS In a longitudinal cohort study, 49 patients (21 women) with childhood-onset type 1 diabetes were investigated with neurophysiological measurements, blood tests, and clinical examinations after a diabetes duration of 7.7 (±3.3) years (baseline) and followed with repeated examinations for 30.6 (±5.2) years. We calculated wHbA1c by integrating the area under all HbA1c values since the diabetes diagnosis. Lipid profiles were analysed in relation to the presence of DPN. Long-term fluctuations of HbA1c variability were computed as the standard deviation of all HbA1c measurements. Data regarding the presence of other diabetes complications were retrieved from medical records. RESULTS In this follow-up study, 51% (25/49) of the patients fulfilled electrophysiological criteria for DPN. In nerve conduction studies, there was a deterioration in the amplitudes and conduction velocities for the median, peroneal, and sural nerves over time. Patients with DPN had a longer duration of diabetes, higher wHbA1c, and increased HbA1c variability. The lowest wHbA1c value associated with the development of DPN was 62 mmol/mol (7.8%). The presence of albuminuria and retinopathy was positively correlated with the presence of neuropathy. CONCLUSIONS More than half of the patients had developed DPN after 30 years. None of the patients who developed DPN had a wHbA1c of less than 62 mmol/mol (7.8%).
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Affiliation(s)
- Evangelia Baldimtsi
- Department of Acute Internal Medicine and Geriatrics in Linköping, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Salvador Amezcua
- Department of Biomedical and Clinical Medicine, Linköping University, Centre for Social and Affective Neuroscience, Linköping, Sweden
| | - Martin Ulander
- Department of Biomedical and Clinical Medicine, Linköping University, Centre for Social and Affective Neuroscience, Linköping, Sweden
| | - Lars Hyllienmark
- Clinical Neurophysiology, Karolinska University Hospital, and Karolinska Institute, Stockholm, Sweden
| | - Håkan Olausson
- Department of Biomedical and Clinical Medicine, Linköping University, Centre for Social and Affective Neuroscience, Linköping, Sweden
| | - Johnny Ludvigsson
- Department of Biomedical and Clinical Sciences, Crown Princess Victoria's Children Hospital and Division of Pediatrics, Linköping University, Linköping, Sweden
| | - Jeanette Wahlberg
- Department of Acute Internal Medicine and Geriatrics in Linköping, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Faculty of Medical Sciences, Örebro University, Örebro, Sweden
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Kim S, Sakorikar T, Huang H, Dickey MD, Liu M. Soft Variable Resistance Material for Pressure Sensing Platform. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2024; 2024:1-4. [PMID: 40040019 DOI: 10.1109/embc53108.2024.10781508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/06/2025]
Abstract
Herein, we present the mechanical response of two porous and conductive foams made of polydimethylsiloxane (PDMS) and polyurethane (PU). A coating of carbon nanotubes (CNTs) renders the foams with positive piezo-conductivity, which is useful for sensing mechanical loads. Such materials are useful as sensors to improve the fitting process of a prosthetic socket for lower limb amputees, PDMS and PU are used commonly in prosthetic liners; here, we modify them with CNTs to convert these soft foams to sensor elements. When PU foam was pressed 60 times, it could not recover its original shape, whereas PDMS foam could maintain its elastic properties. After selecting PDMS foam with CNT coating as the base material, we demonstrated that the localized mechanical load could reduce resistance, which led to a color change via Joule heating of a thermochromic dye.
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Tan L, Qu J, Wang J. Development of novel lysosome-related signatures and their potential target drugs based on bulk RNA-seq and scRNA-seq for diabetic foot ulcers. Hum Genomics 2024; 18:62. [PMID: 38862997 PMCID: PMC11165785 DOI: 10.1186/s40246-024-00629-1] [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: 02/23/2024] [Accepted: 05/27/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Diabetic foot ulcers (DFU) is the most serious complication of diabetes mellitus, which has become a global health problem due to its high morbidity and disability rates and the poor efficacy of conventional treatments. Thus, it is urgent to identify novel molecular targets to improve the prognosis and reduce disability rate in DFU patients. RESULTS In the present study, bulk RNA-seq and scRNA-seq associated with DFU were downloaded from the GEO database. We identified 1393 DFU-related DEGs by differential analysis and WGCNA analysis together, and GO/KEGG analysis showed that these genes were associated with lysosomal and immune/inflammatory responses. Immediately thereafter, we identified CLU, RABGEF1 and ENPEP as DLGs for DFU using three machine learning algorithms (Randomforest, SVM-RFE and LASSO) and validated their diagnostic performance in a validation cohort independent of this study. Subsequently, we constructed a novel artificial neural network model for molecular diagnosis of DFU based on DLGs, and the diagnostic performance in the training and validation cohorts was sound. In single-cell sequencing, the heterogeneous expression of DLGs also provided favorable evidence for them to be potential diagnostic targets. In addition, the results of immune infiltration analysis showed that the abundance of mainstream immune cells, including B/T cells, was down-regulated in DFUs and significantly correlated with the expression of DLGs. Finally, we found latamoxef, parthenolide, meclofenoxate, and lomustine to be promising anti-DFU drugs by targeting DLGs. CONCLUSIONS CLU, RABGEF1 and ENPEP can be used as novel lysosomal molecular signatures of DFU, and by targeting them, latamoxef, parthenolide, meclofenoxate and lomustine were identified as promising anti-DFU drugs. The present study provides new perspectives for the diagnosis and treatment of DFU and for improving the prognosis of DFU patients.
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Affiliation(s)
- Longhai Tan
- Department of Dermatology, Tianjin Beichen Hospital, Tianjin, 300400, China.
| | - Junjun Qu
- Zhu Xianyi Memorial Hospital of Tianjin Medical University, Tianjin, 300134, China
| | - Junxia Wang
- Department of Dermatology, Tianjin Beichen Hospital, Tianjin, 300400, China
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Das M, Chakraborty M, Das P, Santra S, Mukherjee A, Das S, Banyai K, Roy S, Choudhury L, Gupta R, Dey T, Das D, Bose A, Ganesh B, Banerjee R. System biology approaches for systemic diseases: Emphasis on type II diabetes mellitus and allied metabolism. BIOCATALYSIS AND AGRICULTURAL BIOTECHNOLOGY 2024; 58:103176. [DOI: 10.1016/j.bcab.2024.103176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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22
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Upshaw WC, Soileau LG, Storey NR, Perkinson KA, Luther PM, Spillers NJ, Robinson CL, Miller BC, Ahmadzadeh S, Viswanath O, Shekoohi S, Kaye AD. An extract of phase II and III trials on recent developments in managing neuropathic pain syndromes: diabetic peripheral neuropathy, trigeminal neuralgia, and postherpetic neuralgia. Expert Opin Emerg Drugs 2024; 29:103-112. [PMID: 38410863 DOI: 10.1080/14728214.2024.2323193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 02/21/2024] [Indexed: 02/28/2024]
Abstract
INTRODUCTION Neuropathic pain (NP) conditions involve lesions to the somatosensory nervous system leading to chronic and debilitating pain. Many patients suffering from NP utilize pharmacological treatments with various drugs that seek to reduce pathologic neuronal states. However, many of these drugs show poor efficacy as well as cause significant adverse effects. Because of this, there is a major need for the development of safer and more efficacious drugs to treat NP. AREAS COVERED In this review, we analyzed current treatments being developed for a variety of NP conditions. Specifically, we sought drugs in phase II/III clinical trials with indications for NP conditions. Various databases were searched including Google Scholar, PubMed, and clinicaltrials.gov. EXPERT OPINION All the mentioned targets for treatments of NP seem to be promising alternatives for existing treatments that often possess poor side effect profiles for patients. However, gene therapy potentially offers the unique ability to inject a plasmid containing growth factors leading to nerve growth and repair. Because of this, gene therapy appears to be the most intriguing new treatment for NP.
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Affiliation(s)
- William C Upshaw
- School of Medicine, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, USA
| | - Lenise G Soileau
- School of Medicine, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, USA
| | - Nicholas R Storey
- School of Medicine, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, USA
| | | | - Patrick M Luther
- School of Medicine, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, USA
| | - Noah J Spillers
- School of Medicine, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, USA
| | - Christopher L Robinson
- Beth Israel Deaconess Medical Center, Department of Anesthesiology, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA, USA
| | - Benjamin C Miller
- Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, USA
| | - Shahab Ahmadzadeh
- Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, USA
| | - Omar Viswanath
- Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, USA
- Creighton University School of Medicine, Phoenix, AZ, USA
| | - Sahar Shekoohi
- Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, USA
| | - Alan D Kaye
- Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, USA
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23
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Yang G, Hu Y, Guo W, Lei W, Liu W, Guo G, Geng C, Liu Y, Wu H. Tunable Hydrogel Electronics for Diagnosis of Peripheral Neuropathy. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2308831. [PMID: 37906182 DOI: 10.1002/adma.202308831] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 10/30/2023] [Indexed: 11/02/2023]
Abstract
Peripheral neuropathy characterized by rapidly increasing numbers of patients is commonly diagnosed via analyzing electromyography signals obtained from stimulation-recording devices. However, existing commercial electrodes have difficulty in implementing conformal contact with skin and gentle detachment, dramatically impairing stimulation/recording performances. Here, this work develops on-skin patches with polyaspartic acid-modified dopamine/ethyl-based ionic liquid hydrogel (PDEH) as stimulation/recording devices to capture electromyography signals for the diagnosis of peripheral neuropathy. Triggered by a one-step electric field treatment, the hydrogel achieves rapid and wide-range regulation of adhesion and substantially strengthened mechanical performances. Moreover, hydrogel patches assembled with a silver-liquid metal (SLM) layer exhibit superior charge injection and low contact impedance, capable of capturing high-fidelity electromyography. This work further verifies the feasibility of hydrogel devices for accurate diagnoses of peripheral neuropathy in sensory, motor, and mixed nerves. For various body parts, such as fingers, the elderly's loose skin, hairy skin, and children's fragile skin, this work regulates the adhesion of PDEH-SLM devices to establish intimate device/skin interfaces or ensure benign removal. Noticeably, hydrogel patches achieve precise diagnoses of nerve injuries in these clinical cases while providing extra advantages of more effective stimulation/recording performances. These patches offer a promising alternative for the diagnosis and rehabilitation of neuropathy in future.
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Affiliation(s)
- Ganguang Yang
- Flexible Electronics Research Center, State Key Laboratory of Intelligent Manufacturing Equipment and Technology, School of Mechanical Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
| | - Yijia Hu
- Flexible Electronics Research Center, State Key Laboratory of Intelligent Manufacturing Equipment and Technology, School of Mechanical Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
| | - Wei Guo
- Flexible Electronics Research Center, State Key Laboratory of Intelligent Manufacturing Equipment and Technology, School of Mechanical Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
| | - Wei Lei
- Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
| | - Wei Liu
- Department of Geriatrics, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China
| | - Guojun Guo
- Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
| | - ChaoFan Geng
- Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
| | - Yutian Liu
- Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
| | - Hao Wu
- Flexible Electronics Research Center, State Key Laboratory of Intelligent Manufacturing Equipment and Technology, School of Mechanical Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
- School of Integrated Circuits, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China
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24
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Wang CS, Pai YW, Lin CH, Lee IT, Chen HH, Chang MH. Diabetic peripheral neuropathy: age-stratified glycemic control. Front Endocrinol (Lausanne) 2024; 15:1377923. [PMID: 38694945 PMCID: PMC11061506 DOI: 10.3389/fendo.2024.1377923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 04/05/2024] [Indexed: 05/04/2024] Open
Abstract
Background We explore the effect of suboptimal glycemic control on the incidence of diabetic peripheral neuropathy (DPN) in both non-elderly and elderly patients with type 2 diabetes mellitus (T2DM). Methods A 6-year follow-up study (2013-2019) enrolled T2DM patients aged >20 without DPN. Participants were classified into two groups: those below 65 years (non-elderly) and those 65 years or older (elderly). Biochemical measurements, including glycated hemoglobin (HbA1C), were recorded regularly. DPN was diagnosed using the Michigan Neuropathy Screening Instrument examination. The outcome was DPN occurrence in 2019. Results In 552 enrollments (69% non-elderly), DPN occurred in 8.4% non-elderly and 24.0% elderly patients. A higher initial HbA1C level was significantly linked with a higher risk of future DPN in the non-elderly group (adjusted odds ratio [AOR] 1.46, 95% CI 1.13-1.89, p=0.004). In comparison, HbA1c at the end of the study period was not associated with DPN in the non-elderly group (AOR 1.17, 95% CI 0.72-1.90, p=0.526). In the elderly group, no statistical relationship was found between HbA1C levels and DPN, either in 2013 or in 2019. Conclusion Suboptimal glycemic control at baseline, rather than at the end of the study period, predicts an increased risk of future DPN in individuals with T2DM under age 65. This correlation is not seen in elderly patients. Therefore, we recommend implementing enhanced glycemic control early in middle-aged T2DM patients and propose individualized therapeutic strategies for diabetes in different age groups.
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Affiliation(s)
- Chi-Sheng Wang
- Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Yen-Wei Pai
- Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine and Brain and Neuroscience Research Center, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Ching-Heng Lin
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - I-Te Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Hsiao-Hui Chen
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Ming-Hong Chang
- Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine and Brain and Neuroscience Research Center, College of Medicine, National Chung Hsing University, Taichung, Taiwan
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Zhuang R, Xiong Z, Yan S, Zhang H, Dong Q, Liu W, Miao J, Zhuo Y, Fan X, Zhang W, Wang X, Liu L, Cao J, Zhang T, Hao C, Huang X, Jiang L. Efficacy of electro-acupuncture versus sham acupuncture for diabetic peripheral neuropathy: study protocol for a three-armed randomised controlled trial. BMJ Open 2024; 14:e079354. [PMID: 38569706 PMCID: PMC10989182 DOI: 10.1136/bmjopen-2023-079354] [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: 08/29/2023] [Accepted: 03/15/2024] [Indexed: 04/05/2024] Open
Abstract
INTRODUCTION Specific treatment for diabetic peripheral neuropathy (DPN) is still lacking, and acupuncture may relieve the symptoms. We intend to investigate the efficacy and safety of electro-acupuncture (EA) in alleviating symptoms associated with DPN in diabetes. METHODS AND ANALYSIS This multicentre, three-armed, participant- and assessor-blind, randomised, sham-controlled trial will recruit 240 eligible participants from four hospitals in China and will randomly assign (1:1:1) them to EA, sham acupuncture (SA) or usual care (UC) group. Participants in the EA and SA groups willl receive either 24-session EA or SA treatment over 8 weeks, followed by an 8-week follow-up period, while participants in the UC group will be followed up for 16 weeks. The primary outcome of this trial is the change in DPN symptoms from baseline to week 8, as rated by using the Total Symptom Score. The scale assesses four symptoms: pain, burning, paraesthesia and numbness, by evaluating the frequency and severity of each. All results will be analysed with the intention-to-treat population. ETHICS AND DISSEMINATION The protocol has been approved by the Ethics Committee of the Beijing University of Chinese Medicine (Identifier: 2022BZYLL0509). Every participant will be informed of detailed information about the study before signing informed consent. The results of this trial will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER ChiCTR2200061408.
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Affiliation(s)
- Rong Zhuang
- School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
| | - Zhiyi Xiong
- School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
| | - Shiyan Yan
- School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
| | - Haoran Zhang
- College of Preschool Education, Beijing Youth Politics College, Beijing, China
| | - Qi Dong
- Department of Metabolic Diseases, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan, Shanxi, China
| | - Weiai Liu
- Department of Acupuncture and Massage Rehabilitation, The Second Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Jinling Miao
- Acupuncture and Moxibustion Department, Shanxi Provincial Acupuncture and Moxibustion Hospital, Taiyuan, Shanxi, China
| | - Yuanyuan Zhuo
- Department of Acupuncture and Moxibustion, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
| | - Xiaohong Fan
- Department of Metabolic Diseases, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan, Shanxi, China
| | - Weiliang Zhang
- Department of Metabolic Diseases, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan, Shanxi, China
| | - Xiaomei Wang
- Department of Metabolic Diseases, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan, Shanxi, China
| | - Lian Liu
- Department of Acupuncture and Massage Rehabilitation, The Second Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Jianan Cao
- Department of Acupuncture and Massage Rehabilitation, The Second Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Tiansheng Zhang
- Acupuncture and Moxibustion Department, Shanxi Provincial Acupuncture and Moxibustion Hospital, Taiyuan, Shanxi, China
| | - Chongyao Hao
- Acupuncture and Moxibustion Department, Shanxi Provincial Acupuncture and Moxibustion Hospital, Taiyuan, Shanxi, China
| | - Xingxian Huang
- Department of Acupuncture and Moxibustion, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, China
| | - Lijiao Jiang
- The fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
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26
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Gholami F, Naderi A, Saeidpour A, Lefaucheur JP. Effect of exercise training on glycemic control in diabetic peripheral neuropathy: A GRADE assessed systematic review and meta-analysis of randomized-controlled trials. Prim Care Diabetes 2024; 18:109-118. [PMID: 38286719 DOI: 10.1016/j.pcd.2024.01.008] [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: 10/23/2023] [Revised: 01/03/2024] [Accepted: 01/20/2024] [Indexed: 01/31/2024]
Abstract
AIMS We conducted a systematic review and meta-analysis to investigate the effect of exercise training on HbA1c, and on fasting and postprandial plasma glucose concentrations in patients with diabetic peripheral neuropathy (DPN). METHODS Two independent researchers performed a systematic search in the electronic databases of PubMed, Web of Science and Scopus. Studies investigating the effect of exercise training on patients diagnosed with DPN using a randomized-controlled design were included in the meta-analysis. RESULTS Of 1254 retrieved studies, 68 studies were identified to undergo full-text review; out of these a total of 13 randomized trials met the inclusion criteria. Eleven studies assessed HbA1c, 8 fasting plasma-glucose concentration, and 3 postprandial plasma-glucose concentration. Overall, exercise training significantly decreased HbA1c [-0.54% (95% CI -0.78 to -0.31%)], fasting plasma glucose [-32.6 mg/dl [-1.8 mmol/L] (-44.2 to -20.9 mg/dl [-2.4 to -1.1 mmol/L])] and postprandial plasma glucose [-67.5 mg/dl [-3.7 mmol/L] (-129.5 to -5.4 mg/dl [-7.1 to -0.3 mmol/L])]. Studies with aerobic training intervention yielded the largest significant mean reduction in HbA1c (-0.75%) and fasting plasma glucose concertation (34.0 mg/dl). CONCLUSIONS aerobic training is the most effective modality to reduces HbA1c, fasting and postprandial plasma glucose concentration in patients with DPN. From a metabolic perspective, the magnitude precision range of the reduction in HbA1c is of clinical importance for patients with DPN. This area of research warrants further attention to investigate the impact of various exercise modalities on glycemic control. Registration number CRD42023413687.
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Affiliation(s)
- Farhad Gholami
- Department of Physical Education and Sport Sciences, Faculty of Physical Education, Shahrood University of Technology, Shahrood, Iran.
| | - Aynollah Naderi
- Department of Physical Education and Sport Sciences, Faculty of Physical Education, Shahrood University of Technology, Shahrood, Iran
| | - Asal Saeidpour
- Department of Physical Education and Sport Sciences, Faculty of Physical Education, Shahrood University of Technology, Shahrood, Iran
| | - Jean Pascal Lefaucheur
- ENT Team, EA4391, Faculty of Medicine, Paris Est Créteil University, Créteil, France; Clinical Neurophysiology Unit, Department of Physiology, Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris, Créteil, France
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27
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Miron RJ, Estrin NE, Sculean A, Zhang Y. Understanding exosomes: Part 2-Emerging leaders in regenerative medicine. Periodontol 2000 2024; 94:257-414. [PMID: 38591622 DOI: 10.1111/prd.12561] [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: 02/04/2024] [Revised: 02/16/2024] [Accepted: 02/21/2024] [Indexed: 04/10/2024]
Abstract
Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of diseases/conditions. Over 5000 publications are currently being published yearly on this topic, and this number is only expected to dramatically increase as novel therapeutic strategies continue to be developed. Today exosomes have been applied in numerous contexts including neurodegenerative disorders (Alzheimer's disease, central nervous system, depression, multiple sclerosis, Parkinson's disease, post-traumatic stress disorders, traumatic brain injury, peripheral nerve injury), damaged organs (heart, kidney, liver, stroke, myocardial infarctions, myocardial infarctions, ovaries), degenerative processes (atherosclerosis, diabetes, hematology disorders, musculoskeletal degeneration, osteoradionecrosis, respiratory disease), infectious diseases (COVID-19, hepatitis), regenerative procedures (antiaging, bone regeneration, cartilage/joint regeneration, osteoarthritis, cutaneous wounds, dental regeneration, dermatology/skin regeneration, erectile dysfunction, hair regrowth, intervertebral disc repair, spinal cord injury, vascular regeneration), and cancer therapy (breast, colorectal, gastric cancer and osteosarcomas), immune function (allergy, autoimmune disorders, immune regulation, inflammatory diseases, lupus, rheumatoid arthritis). This scoping review is a first of its kind aimed at summarizing the extensive regenerative potential of exosomes over a broad range of diseases and disorders.
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Affiliation(s)
- Richard J Miron
- Department of Periodontology, University of Bern, Bern, Switzerland
| | - Nathan E Estrin
- Advanced PRF Education, Venice, Florida, USA
- School of Dental Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Anton Sculean
- Department of Periodontology, University of Bern, Bern, Switzerland
| | - Yufeng Zhang
- Department of Oral Implantology, University of Wuhan, Wuhan, China
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28
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Mooshage CM, Tsilingiris D, Schimpfle L, Seebauer L, Eldesouky O, Aziz-Safaie T, Hohmann A, Herzig S, Szendroedi J, Nawroth P, Heiland S, Bendszus M, Kurz FT, Kopf S, Jende JME, Kender Z. A diminished sciatic nerve structural integrity is associated with distinct peripheral sensory phenotypes in individuals with type 2 diabetes. Diabetologia 2024; 67:275-289. [PMID: 38019287 PMCID: PMC10789832 DOI: 10.1007/s00125-023-06050-y] [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: 07/16/2023] [Accepted: 10/10/2023] [Indexed: 11/30/2023]
Abstract
AIMS/HYPOTHESIS Quantitative sensory testing (QST) allows the identification of individuals with rapid progression of diabetic sensorimotor polyneuropathy (DSPN) based on certain sensory phenotypes. Hence, the aim of this study was to investigate the relationship of these phenotypes with the structural integrity of the sciatic nerve among individuals with type 2 diabetes. METHODS Seventy-six individuals with type 2 diabetes took part in this cross-sectional study and underwent QST of the right foot and high-resolution magnetic resonance neurography including diffusion tensor imaging of the right distal sciatic nerve to determine the sciatic nerve fractional anisotropy (FA) and cross-sectional area (CSA), both of which serve as markers of structural integrity of peripheral nerves. Participants were then assigned to four sensory phenotypes (participants with type 2 diabetes and healthy sensory profile [HSP], thermal hyperalgesia [TH], mechanical hyperalgesia [MH], sensory loss [SL]) by a standardised sorting algorithm based on QST. RESULTS Objective neurological deficits showed a gradual increase across HSP, TH, MH and SL groups, being higher in MH compared with HSP and in SL compared with HSP and TH. The number of participants categorised as HSP, TH, MH and SL was 16, 24, 17 and 19, respectively. There was a gradual decrease of the sciatic nerve's FA (HSP 0.444, TH 0.437, MH 0.395, SL 0.382; p=0.005) and increase of CSA (HSP 21.7, TH 21.5, MH 25.9, SL 25.8 mm2; p=0.011) across the four phenotypes. Further, MH and SL were associated with a lower sciatic FA (MH unstandardised regression coefficient [B]=-0.048 [95% CI -0.091, -0.006], p=0.027; SL B=-0.062 [95% CI -0.103, -0.020], p=0.004) and CSA (MH β=4.3 [95% CI 0.5, 8.0], p=0.028; SL B=4.0 [95% CI 0.4, 7.7], p=0.032) in a multivariable regression analysis. The sciatic FA correlated negatively with the sciatic CSA (r=-0.35, p=0.002) and markers of microvascular damage (high-sensitivity troponin T, urine albumin/creatinine ratio). CONCLUSIONS/INTERPRETATION The most severe sensory phenotypes of DSPN (MH and SL) showed diminishing sciatic nerve structural integrity indexed by lower FA, likely representing progressive axonal loss, as well as increasing CSA of the sciatic nerve, which cannot be detected in individuals with TH. Individuals with type 2 diabetes may experience a predefined cascade of nerve fibre damage in the course of the disease, from healthy to TH, to MH and finally SL, while structural changes in the proximal nerve seem to precede the sensory loss of peripheral nerves and indicate potential targets for the prevention of end-stage DSPN. TRIAL REGISTRATION ClinicalTrials.gov NCT03022721.
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Affiliation(s)
- Christoph M Mooshage
- Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Dimitrios Tsilingiris
- Department of Endocrinology, Diabetology, Metabolism and Clinical Chemistry (Internal Medicine 1), Heidelberg University Hospital, Heidelberg, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece
| | - Lukas Schimpfle
- Department of Endocrinology, Diabetology, Metabolism and Clinical Chemistry (Internal Medicine 1), Heidelberg University Hospital, Heidelberg, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Lukas Seebauer
- Department of Endocrinology, Diabetology, Metabolism and Clinical Chemistry (Internal Medicine 1), Heidelberg University Hospital, Heidelberg, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Omar Eldesouky
- Department of Endocrinology, Diabetology, Metabolism and Clinical Chemistry (Internal Medicine 1), Heidelberg University Hospital, Heidelberg, Germany
| | - Taraneh Aziz-Safaie
- Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Anja Hohmann
- Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany
| | - Stephan Herzig
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Institute for Diabetes and Cancer (IDC), Helmholtz Diabetes Center, Helmholtz Center, Munich, Neuherberg, Germany
- Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany
| | - Julia Szendroedi
- Department of Endocrinology, Diabetology, Metabolism and Clinical Chemistry (Internal Medicine 1), Heidelberg University Hospital, Heidelberg, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany
| | - Peter Nawroth
- Department of Endocrinology, Diabetology, Metabolism and Clinical Chemistry (Internal Medicine 1), Heidelberg University Hospital, Heidelberg, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany
| | - Sabine Heiland
- Division of Experimental Radiology, Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Martin Bendszus
- Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Felix T Kurz
- Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany
- German Cancer Research Center, Heidelberg, Germany
| | - Stefan Kopf
- Department of Endocrinology, Diabetology, Metabolism and Clinical Chemistry (Internal Medicine 1), Heidelberg University Hospital, Heidelberg, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Johann M E Jende
- Department of Neuroradiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Zoltan Kender
- Department of Endocrinology, Diabetology, Metabolism and Clinical Chemistry (Internal Medicine 1), Heidelberg University Hospital, Heidelberg, Germany.
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
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Abstract
Diabetic neuropathy is a highly prevalent complication of diabetes. It consists of a broad range of neuropathic conditions, such as distal symmetric polyneuropathy and various forms of autonomic neuropathies involving the cardiovascular, gastrointestinal, and urogenital systems. Prevention or diagnosis in early stages of disease is crucial to prevent symptomatic onset and progression, particularly in the absence of current disease-modifying therapies. In this review, we describe the four main types of diabetic neuropathy. We review current understanding with respect to diagnosis and treatment while highlighting knowledge gaps and future directions.
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Affiliation(s)
- Brendan R Dillon
- Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA;
| | - Lynn Ang
- Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA; ,
| | - Rodica Pop-Busui
- Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA; ,
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Zhu J, Hu Z, Luo Y, Liu Y, Luo W, Du X, Luo Z, Hu J, Peng S. Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment. Front Endocrinol (Lausanne) 2024; 14:1265372. [PMID: 38264279 PMCID: PMC10803883 DOI: 10.3389/fendo.2023.1265372] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Accepted: 12/14/2023] [Indexed: 01/25/2024] Open
Abstract
Diabetic peripheral neuropathy (DPN) refers to the development of peripheral nerve dysfunction in patients with diabetes when other causes are excluded. Diabetic distal symmetric polyneuropathy (DSPN) is the most representative form of DPN. As one of the most common complications of diabetes, its prevalence increases with the duration of diabetes. 10-15% of newly diagnosed T2DM patients have DSPN, and the prevalence can exceed 50% in patients with diabetes for more than 10 years. Bilateral limb pain, numbness, and paresthesia are the most common clinical manifestations in patients with DPN, and in severe cases, foot ulcers can occur, even leading to amputation. The etiology and pathogenesis of diabetic neuropathy are not yet completely clarified, but hyperglycemia, disorders of lipid metabolism, and abnormalities in insulin signaling pathways are currently considered to be the initiating factors for a range of pathophysiological changes in DPN. In the presence of abnormal metabolic factors, the normal structure and function of the entire peripheral nervous system are disrupted, including myelinated and unmyelinated nerve axons, perikaryon, neurovascular, and glial cells. In addition, abnormalities in the insulin signaling pathway will inhibit neural axon repair and promote apoptosis of damaged cells. Here, we will discuss recent advances in the study of DPN mechanisms, including oxidative stress pathways, mechanisms of microvascular damage, mechanisms of damage to insulin receptor signaling pathways, and other potential mechanisms associated with neuroinflammation, mitochondrial dysfunction, and cellular oxidative damage. Identifying the contributions from each pathway to neuropathy and the associations between them may help us to further explore more targeted screening and treatment interventions.
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Affiliation(s)
- Jinxi Zhu
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Ziyan Hu
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yifan Luo
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yinuo Liu
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Wei Luo
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Xiaohong Du
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Zhenzhong Luo
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Jialing Hu
- Department of Emergency Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Shengliang Peng
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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Aziz N, Dash B, Wal P, Kumari P, Joshi P, Wal A. New Horizons in Diabetic Neuropathies: An Updated Review on their Pathology, Diagnosis, Mechanism, Screening Techniques, Pharmacological, and Future Approaches. Curr Diabetes Rev 2024; 20:e201023222416. [PMID: 37867268 DOI: 10.2174/0115733998242299231011181615] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 07/16/2023] [Accepted: 08/25/2023] [Indexed: 10/24/2023]
Abstract
BACKGROUND One of the largest problems for global public health is diabetes mellitus (DM) and its micro and macrovascular consequences. Although prevention, diagnosis, and treatment have generally improved, its incidence is predicted to keep rising over the coming years. Due to the intricacy of the molecular mechanisms, which include inflammation, oxidative stress, and angiogenesis, among others, discovering treatments to stop or slow the course of diabetic complications is still a current unmet need. METHODS The pathogenesis and development of diabetic neuropathies may be explained by a wide variety of molecular pathways, hexosamine pathways, such as MAPK pathway, PARP pathway, oxidative stress pathway polyol (sorbitol) pathway, cyclooxygenase pathway, and lipoxygenase pathway. Although diabetic neuropathies can be treated symptomatically, there are limited options for treating the underlying cause. RESULT Various pathways and screening models involved in diabetic neuropathies are discussed, along with their possible outcomes. Moreover, both medicinal and non-medical approaches to therapy are also explored. CONCLUSION This study highlights the probable involvement of several processes and pathways in the establishment of diabetic neuropathies and presents in-depth knowledge of new therapeutic approaches intended to stop, delay, or reverse different types of diabetic complications.
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Affiliation(s)
- Namra Aziz
- Pranveer Singh Institute of Technology (Pharmacy), Bhauti, Kanpur 209305, UP, India
| | - Biswajit Dash
- Department of Pharmaceutical Technology, School of Medical Sciences, ADAMAS University, Kolkata 700 126, West Bengal, India
| | - Pranay Wal
- Pranveer Singh Institute of Technology (Pharmacy), Bhauti, Kanpur 209305, UP, India
| | - Prachi Kumari
- Pranveer Singh Institute of Technology (Pharmacy), Bhauti, Kanpur 209305, UP, India
| | - Poonam Joshi
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun 248007, Uttarakhand, India
| | - Ankita Wal
- Pranveer Singh Institute of Technology (Pharmacy), Bhauti, Kanpur 209305, UP, India
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Yeung AM, Huang J, Nguyen KT, Xu NY, Hughes LT, Agrawal BK, Ejskjaer N, Klonoff DC. Painful Diabetic Neuropathy: The Need for New Approaches. J Diabetes Sci Technol 2024; 18:159-167. [PMID: 36305521 PMCID: PMC10899841 DOI: 10.1177/19322968221132252] [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] [Indexed: 11/16/2022]
Abstract
Painful diabetic neuropathy is a common vexing problem for people with diabetes and a costly problem for society. The pathophysiology is not well understood, and no safe and effective mechanistically-based treatment has been identified. Poor glycemic control is a risk factor for painful diabetic neuropathy. Excessive intraneuronal glucose in people with diabetes can be shunted away from physiological glycolysis into multiple pathological pathways associated with neuropathy and pain. The first three treatments that are traditionally offered consist of risk factor reduction, lifestyle modifications, and pharmacological therapy, which includes only three drugs that are approved for this indication by the United States Food and Drug Administration. All of these traditional treatments are often inadequate for relieving neuropathic pain, and thus, new approaches are needed. Modern devices based on neuromodulation technology, which act directly on the nervous system, have been recently cleared by the United States Food and Drug Administration for painful diabetic neuropathy and offer promise as next-in-line therapy when traditional therapies fail.
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Affiliation(s)
| | | | | | - Nicole Y. Xu
- Diabetes Technology Society, Burlingame, CA, USA
| | - Lorenzo T. Hughes
- Balance Health, San Francisco, CA, USA
- Mills-Peninsula Medical Center, Burlingame, CA, USA
| | | | - Niels Ejskjaer
- Steno Diabetes Center North Denmark and Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - David C. Klonoff
- Diabetes Technology Society, Burlingame, CA, USA
- Diabetes Research Institute, Mills-Peninsula Medical Center, San Mateo, CA, USA
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Chen T, Xiao S, Chen Z, Yang Y, Yang B, Liu N. Risk factors for peripheral artery disease and diabetic peripheral neuropathy among patients with type 2 diabetes. Diabetes Res Clin Pract 2024; 207:111079. [PMID: 38154538 DOI: 10.1016/j.diabres.2023.111079] [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: 11/14/2023] [Revised: 12/14/2023] [Accepted: 12/20/2023] [Indexed: 12/30/2023]
Abstract
AIMS To investigate the prevalence of peripheral artery disease (PAD) and diabetic peripheral neuropathy (DPN) and the associated risk factors among Chinese patients with type 2 diabetes mellitus. METHODS A cross-sectional study was conducted using data between November 1, 2018, and December 31, 2022. PAD was defined as ABI ≤ 0.9. DPN diagnosis involved specialized physician assessments using questionnaires and vibration perception threshold tests. Logistic regression analysis was used to identify related factors. We also evaluated the association between the clustering of risk factors and disease incidence. RESULTS The study population comprised 13,315 patients (mean age: 63.3 years). 4.9 % of the patients had PAD and 43.9 % had DPN. Multivariate regression analysis revealed advanced age, smoking, hypertension, coronary heart disease, dyslipidemia, elevated HbA1c, and uric acid levels as independent risk factors for PAD. For DPN, independent risk factors included advanced age, female gender, hypertension, coronary heart disease, elevated total cholesterol, triglycerides, lipoprotein(a), fasting plasma glucose, HbA1c, alkaline phosphatase, cystatin C, albumin-to-creatinine ratio, and elevated homocysteine levels, whereas apolipoprotein A was a protective factor. The clustering of risk factors was prevalent and associated with higher disease risk. CONCLUSIONS Our study contributed to identifying high-risk individuals and improving lower limb health among diabetic individuals.
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Affiliation(s)
- Tian Chen
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China
| | - Shengjue Xiao
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China
| | - Zhengdong Chen
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China
| | - Yiqing Yang
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China
| | - Bingquan Yang
- Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
| | - Naifeng Liu
- Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
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Hashim M, Badruddeen, Akhtar J, Khan MI, Ahmad M, Islam A, Ahmad A. Diabetic Neuropathy: An Overview of Molecular Pathways and Protective Mechanisms of Phytobioactives. Endocr Metab Immune Disord Drug Targets 2024; 24:758-776. [PMID: 37867264 DOI: 10.2174/0118715303266444231008143430] [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: 06/09/2023] [Revised: 07/31/2023] [Accepted: 08/25/2023] [Indexed: 10/24/2023]
Abstract
Diabetic neuropathy (DN) is a common and debilitating complication of diabetes mellitus that affects the peripheral nerves and causes pain, numbness, and impaired function. The pathogenesis of DN involves multiple molecular mechanisms, such as oxidative stress, inflammation, and pathways of advanced glycation end products, polyol, hexosamine, and protein kinase C. Phytochemicals are natural compounds derived from plants that have various biological activities and therapeutic potential. Flavonoids, terpenes, alkaloids, stilbenes, and tannins are some of the phytochemicals that have been identified as having protective potential for diabetic neuropathy. These compounds can modulate various cellular pathways involved in the development and progression of neuropathy, including reducing oxidative stress and inflammation and promoting nerve growth and repair. In this review, the current evidence on the effects of phytochemicals on DN by focusing on five major classes, flavonoids, terpenes, alkaloids, stilbenes, and tannins, are summarized. This compilation also discusses the possible molecular targets of numerous pathways of DN that these phytochemicals modulate. These phytochemicals may offer a promising alternative or complementary approach to conventional drugs for DN management by modulating multiple pathological pathways and restoring nerve function.
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Affiliation(s)
- Mohd Hashim
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | - Badruddeen
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | - Juber Akhtar
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | | | - Mohammad Ahmad
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | - Anas Islam
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | - Asad Ahmad
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
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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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Dunker Ø, Uglem M, Bu Kvaløy M, Løseth S, Hjelland IE, Allen SM, Dehli Vigeland M, Kleggetveit IP, Sand T, Nilsen KB. Diagnostic accuracy of the 5.07 monofilament test for diabetes polyneuropathy: influence of age, sex, neuropathic pain and neuropathy severity. BMJ Open Diabetes Res Care 2023; 11:e003545. [PMID: 37989346 PMCID: PMC10660161 DOI: 10.1136/bmjdrc-2023-003545] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 09/13/2023] [Indexed: 11/23/2023] Open
Abstract
INTRODUCTION There is a need for simple and cheap diagnostic tools for diabetic polyneuropathy (DPN). We aimed to assess the diagnostic accuracy of the 5.07/10 g monofilament test in patients referred to polyneuropathy assessments, as well as to examine how disease severity, age, sex and neuropathic pain (NP) impact diagnostic accuracy. RESEARCH DESIGN AND METHODS Five Norwegian university hospitals recruited patients with diabetes aged 18-70 referred to neurological outpatient clinics for polyneuropathy assessments. The 5.07/10 g Semmes-Weinstein monofilament examination (SWME) was validated against the Toronto consensus for diagnosing diabetic neuropathies; the results were stratified by age, sex and NP. Disease severity was graded by a combined nerve conduction study (NCS) Z-score, and logistic regression was applied to assess whether disease severity was a predictor of diagnostic accuracy. RESULTS In total, 506 patients were included in the study. Global sensitivity was 0.60 (95% CI 0.55, 0.66), specificity 0.82 (95% CI 0.75, 0.87), positive and negative predictive values were 0.86 (95% CI 0.81, 0.90) and 0.52 (95% CI 0.46, 0.58), respectively, positive and negative likelihood ratios were 3.28 (95% CI 2.37, 4.53) and 0.49 (95% CI 0.42, 0.57), respectively. The SWME was less sensitive in females (0.43), had lower specificity in patients with NP (0.56), and performed worse in patients ≥50 years. NCS-based disease severity did not affect diagnostic accuracy (OR 1.15, 95% CI 0.95, 1.40). CONCLUSIONS This multicenter study demonstrates poor diagnostic performance for the 5.07/10 g SWME in patients with diabetes referred to polyneuropathy assessments; it is particularly unsuited for female patients and those with NP. The diagnostic accuracy of the SWME was not influenced by NCS-based disease severity, demonstrating that it does not perform better in patients with later stages of DPN. We do not recommend the use of the 5.07/10 g monofilament in the evaluation of patients with diabetes referred to polyneuropathy assessments.
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Affiliation(s)
- Øystein Dunker
- Department of Research and Innovation, Oslo University Hospital, Oslo, Norway
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Neurology and Clinical Neurophysiology, Oslo University Hospital, Oslo, Norway
| | - Martin Uglem
- Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology Faculty of Medicine and Health Sciences, Trondheim, Norway
- Department of Neurology and Clinical Neurophysiology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Marie Bu Kvaløy
- Department of Neurology, Section of Clinical Neurophysiology, Stavanger University Hospital, Stavanger, Norway
| | - Sissel Løseth
- Department of Neurology and Clinical Neurophysiology, University Hospital of North Norway, Tromsø, Norway
- Department of Clinical Medicine, The Artic University of Norway, Tromsø, Norway
| | - Ina Elen Hjelland
- Department of Clinical Neurophysiology, Haukeland University Hospital, Bergen, Norway
| | - Sara Maria Allen
- Department of Neurology and Clinical Neurophysiology, Oslo University Hospital, Oslo, Norway
| | | | - Inge Petter Kleggetveit
- Department of Neurology and Clinical Neurophysiology, Oslo University Hospital, Oslo, Norway
| | - Trond Sand
- Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology Faculty of Medicine and Health Sciences, Trondheim, Norway
- Department of Neurology and Clinical Neurophysiology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Kristian Bernhard Nilsen
- Department of Research and Innovation, Oslo University Hospital, Oslo, Norway
- Department of Neurology and Clinical Neurophysiology, Oslo University Hospital, Oslo, Norway
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Elafros MA, Callaghan BC. Diabetic Neuropathies. Continuum (Minneap Minn) 2023; 29:1401-1417. [PMID: 37851036 PMCID: PMC11088946 DOI: 10.1212/con.0000000000001291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2023]
Abstract
OBJECTIVE This article provides an up-to-date review of the diagnosis and management of the most common neuropathies that occur in patients with diabetes. LATEST DEVELOPMENTS The prevalence of diabetes continues to grow worldwide and, as a result, the burden of diabetic neuropathies is also increasing. Most diabetic neuropathies are caused by hyperglycemic effects on small and large fiber nerves, and glycemic control in individuals with type 1 diabetes reduces neuropathy prevalence. However, among people with type 2 diabetes, additional factors, particularly metabolic syndrome components, play a role and should be addressed. Although length-dependent distal symmetric polyneuropathy is the most common form of neuropathy, autonomic syndromes, particularly cardiovascular autonomic neuropathy, are associated with increased mortality, whereas lumbosacral radiculoplexus neuropathy and treatment-induced neuropathy cause substantial morbidity. Recent evidence-based guidelines have updated the recommended treatment options to manage pain associated with distal symmetric polyneuropathy of diabetes. ESSENTIAL POINTS Identifying and appropriately diagnosing the neuropathies of diabetes is key to preventing progression. Until better disease-modifying therapies are identified, management remains focused on diabetes and metabolic risk factor control and pain management.
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Tsilingiris D, Schimpfle L, von Rauchhaupt E, Sulaj A, Seebauer L, Bartl H, Herzig S, Szendroedi J, Kopf S, Kender Z. Dysmetabolism-related Early Sensory Deficits and Their Relationship With Peripheral Neuropathy Development. J Clin Endocrinol Metab 2023; 108:e979-e988. [PMID: 37139855 PMCID: PMC10505541 DOI: 10.1210/clinem/dgad248] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 04/03/2023] [Accepted: 05/02/2023] [Indexed: 05/05/2023]
Abstract
AIM To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development. METHODS A total of 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as "healthy" and those with EPSD based on a standardized QST protocol. A total of 196 were followed-up over a mean of 2.64 years for PN occurrence. RESULTS Among those without T2DM, apart from male sex, height, and higher fat and lower lean mass, only higher insulin resistance (IR; homeostatic model assessment for IR: odds ratio [OR], 1.70; P = .009; McAuley index OR, 0.62, P = .008), was independently associated with EPSD. In T2DM, metabolic syndrome (OR, 18.32; P < .001) and skin advanced glycation end-products (AGEs; OR, 5.66; P = .003) were independent predictors of EPSD. In longitudinal analysis, T2DM (hazard ratio [HR], 3.32 vs no diabetes mellitus; P < .001), EPSD (adjusted HR, 1.88 vs healthy; P = .049 adjusted for diabetes mellitus and sex), higher IR and AGEs predicted PN development. Among the 3 EPSD-associated sensory phenotypes, "sensory loss" was most strongly associated with PN development (adjusted HR, 4.35; P = .011). CONCLUSION We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, metabolic syndrome, and higher AGEs, which in turn are shown to influence PN development.
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Affiliation(s)
- Dimitrios Tsilingiris
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
| | - Lukas Schimpfle
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Ekaterina von Rauchhaupt
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
| | - Alba Sulaj
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
| | - Lukas Seebauer
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Hannelore Bartl
- Department of General, Visceral and Transplant Surgery, University of Heidelberg, 69120 Heidelberg, Germany
| | - Stephan Herzig
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
- Joint Heidelberg-IDC Translational Diabetes Program, Helmholtz Center Munich, 85764 Neuherberg, Germany
- Helmholtz Center Munich, Institute for Diabetes and Cancer, 85764 Munich-Neuherberg, Germany
| | - Julia Szendroedi
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
- Joint Heidelberg-IDC Translational Diabetes Program, Helmholtz Center Munich, 85764 Neuherberg, Germany
| | - Stefan Kopf
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
| | - Zoltan Kender
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
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Walz ID, Waibel S, Lippi V, Kammermeier S, Gollhofer A, Maurer C. "PNP slows down" - linearly-reduced whole body joint velocities and altered gait patterns in polyneuropathy. Front Hum Neurosci 2023; 17:1229440. [PMID: 37780958 PMCID: PMC10534044 DOI: 10.3389/fnhum.2023.1229440] [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: 05/26/2023] [Accepted: 08/28/2023] [Indexed: 10/03/2023] Open
Abstract
Introduction Gait disturbances are a common consequence of polyneuropathy (PNP) and a major factor in patients' reduced quality of life. Less is known about the underlying mechanisms of PNP-related altered motor behavior and its distribution across the body. We aimed to capture whole body movements in PNP during a clinically relevant mobility test, i.e., the Timed Up and Go (TUG). We hypothesize that joint velocity profiles across the entire body would enable a deeper understanding of PNP-related movement alterations. This may yield insights into motor control mechanisms responsible for altered gait in PNP. Methods 20 PNP patients (61 ± 14 years) and a matched healthy control group (CG, 60 ± 15 years) performed TUG at (i) preferred and (ii) fast movement speed, and (iii) while counting backward (dual-task). We recorded TUG duration (s) and extracted gait-related parameters [step time (s), step length (cm), and width (cm)] during the walking sequences of TUG and calculated center of mass (COM) velocity [represents gait speed (cm/s)] and joint velocities (cm/s) (ankles, knees, hips, shoulders, elbows, wrists) with respect to body coordinates during walking; we then derived mean joint velocities and ratios between groups. Results Across all TUG conditions, PNP patients moved significantly slower (TUG time, gait speed) with prolonged step time and shorter steps compared to CG. Velocity profiles depend significantly on group designation, TUG condition, and joint. Correlation analysis revealed that joint velocities and gait speed are closely interrelated in individual subjects, with a 0.87 mean velocity ratio between groups. Discussion We confirmed a PNP-related slowed gait pattern. Interestingly, joint velocities in the rest of the body measured in body coordinates were in a linear relationship to each other and to COM velocity in space coordinates, despite PNP. Across the whole body, PNP patients reduce, on average, their joint velocities with a factor of 0.87 compared to CG and thus maintain movement patterns in terms of velocity distributions across joints similarly to healthy individuals. This down-scaling of mean absolute joint velocities may be the main source for the altered motor behavior of PNP patients during gait and is due to the poorer quality of their somatosensory information. Clinical Trial Registration https://drks.de/search/de, identifier DRKS00016999.
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Affiliation(s)
- Isabelle D. Walz
- Department of Neurology and Neuroscience, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany
- Department of Sport and Sport Science, University of Freiburg, Freiburg, Germany
| | - Sarah Waibel
- Department of Neurology and Neuroscience, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany
| | - Vittorio Lippi
- Department of Neurology and Neuroscience, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany
- Faculty of Medicine Freiburg, Institute of Digitalization in Medicine, Medical Center, University of Freiburg, Freiburg, Germany
| | | | - Albert Gollhofer
- Department of Sport and Sport Science, University of Freiburg, Freiburg, Germany
| | - Christoph Maurer
- Department of Neurology and Neuroscience, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany
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Monteiro RL, Drechsel TJ, Ferreira JSSP, Zippenfennig C, Sacco ICN. Potential predictive effect of mechanical properties of the plantar skin and superficial soft tissue, and vibration perception on plantar loading during gait in individuals with diabetes. BMC Musculoskelet Disord 2023; 24:712. [PMID: 37674163 PMCID: PMC10483699 DOI: 10.1186/s12891-023-06851-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 09/02/2023] [Indexed: 09/08/2023] Open
Abstract
BACKGROUND This exploratory study aimed to investigate the extent to which mechanical properties of the plantar skin and superficial soft tissue (hardness, stiffness, and thickness) and vibration perception thresholds (VPTs) predict plantar pressure loading during gait in people with diabetes compared to healthy controls. METHODS Mechanical properties, VPTs, and plantar loadings during gait at the heel and first metatarsal head (MTH) of 20 subjects with diabetes, 13 with DPN, and 33 healthy controls were acquired. Multiple regression analyses were used to predict plantar pressure peaks and pressure-time integrals at both locations based on the mechanical properties of the skin and superficial soft tissues and VPTs. RESULTS In the diabetes group at the MTH, skin hardness associated with 30-Hz (R2 = 0.343) and 200-Hz (R2 = 0.314) VPTs predicted peak pressure at the forefoot. In the controls at the heel, peak pressure was predicted by the skin thickness, hardness, and stiffness associated with 30-Hz (R2 = 0.269, 0.268, and 0.267, respectively) and 200-Hz (R2 = 0.214, 0.247, and 0.265, respectively) VPTs. CONCLUSION The forefoot loading of people with diabetes can be predicted by the hardness of the skin when combined with loss of vibration perception at low (30-Hz) and high (200-Hz) frequencies. Further data from larger sample sizes are needed to confirm the current findings.
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Affiliation(s)
- Renan L Monteiro
- Department of Physical Therapy, Speech, and Occupational Therapy, School of Medicine, University of São Paulo, São Paulo, Brazil
- Department of Health and Biological Science, Federal University of Amapá, Macapá, Brazil
| | - Tina J Drechsel
- Department of Human Locomotion, Institute of Human Movement Science and Health, Chemnitz University of Technology, Chemnitz, Germany
| | - Jane Suelen S P Ferreira
- Department of Physical Therapy, Speech, and Occupational Therapy, School of Medicine, University of São Paulo, São Paulo, Brazil
| | - Claudio Zippenfennig
- Department of Human Locomotion, Institute of Human Movement Science and Health, Chemnitz University of Technology, Chemnitz, Germany
| | - Isabel C N Sacco
- Department of Physical Therapy, Speech, and Occupational Therapy, School of Medicine, University of São Paulo, São Paulo, Brazil.
- Departamento de Fisioterapia, Fonoaudiologia e Terapia Ocupacional da Faculdade de Medicina da Universidade de São Paulo, Rua Cipotânea, 51 - Cidade Universitária, São Paulo, 05360-160, Brazil.
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Stephens S, Jaffri A, Saliba S. Local microvascular tissue oxygenation of the intrinsic foot muscles in patients with diabetes: A cross-sectional case-comparison study. Foot (Edinb) 2023; 56:102035. [PMID: 37167703 DOI: 10.1016/j.foot.2023.102035] [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: 03/22/2022] [Revised: 04/03/2023] [Accepted: 05/06/2023] [Indexed: 05/13/2023]
Abstract
BACKGROUND Foot-related complications including impaired peripheral circulation and lower limb ulceration are severe consequences for those with diabetes mellitus. This study aimed to assess differences in tissue oxygenation and oxygen utilization of the plantar surface intrinsic foot muscles between diabetic participants and healthy comparisons following short foot exercise and a standard walking protocol. METHODS Eighteen participants, 9 with diabetes and 9 healthy age- and sex-matched comparisons, completed two interventions in a randomized order. For the short foot exercise intervention, participants completed 5 sets of 15 intrinsic foot muscle contractions. For the walking intervention, participants completed a modified six-minute walk test. Tissue oxygenation variables including oxygenated hemoglobin, deoxygenated hemoglobin, and tissue saturation index were measured using near-infrared spectroscopy in quiet stance and during intrinsic foot muscle contraction cycles following each intervention. Means, standard deviations, 95 % confidence intervals, mean differences, and Cohen's d effect sizes were calculated for each tissue oxygenation variable. RESULTS The results of this study indicated no significant group differences in quiet standing tissue oxygenation measures at baseline and following each intervention. Participants in the diabetic group had significantly less change in tissue saturation index during intrinsic foot muscle contractions compared to healthy participants after the short foot exercise intervention (ES= 4.00, P = .0002) and walking intervention (ES= 1.33, P = .015). CONCLUSIONS By utilizing wireless NIRS and novel research methodology, this study was able to explore changes in plantar surface tissue oxygenation of the intrinsic foot muscles following a targeted short foot exercise intervention as well as a standard walking protocol in patients diagnosed with diabetes compared to age- and sex- matched individuals without diabetes. We identified that diabetic participants presented with less oxygen utilization during intrinsic foot muscle contractions performed following both exercise interventions compared to their healthy age- and sex- matched comparisons.
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Affiliation(s)
- Stephanie Stephens
- University of Virginia, Department of Kinesiology, Charlottesville, VA, United States.
| | - Abbis Jaffri
- Creighton University, School of Pharmacy and Health Professions, Omaha, NE, United States
| | - Susan Saliba
- University of Virginia, Department of Kinesiology, Charlottesville, VA, United States
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Xu J, Chen Q, Cai M, Han X, Lu H. Ultra-high performance liquid chromatography coupled to tandem mass spectrometry-based metabolomics study of diabetic distal symmetric polyneuropathy. J Diabetes Investig 2023; 14:1110-1120. [PMID: 37347226 PMCID: PMC10445193 DOI: 10.1111/jdi.14041] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 05/17/2023] [Accepted: 05/29/2023] [Indexed: 06/23/2023] Open
Abstract
AIMS/INTRODUCTION Distal symmetric polyneuropathy (DSPN) is a common complication of type 2 diabetes mellitus, but the underlining mechanisms have not yet been elucidated. The current study was designed to screen the feature metabolites classified as potential biomarkers, and to provide deeper insights into the underlying distinctive metabolic changes during disease progression. MATERIALS AND METHODS Plasma metabolite profiles were obtained by the ultra-high liquid chromatography coupled to tandem mass spectrometry method from healthy control participants, patients with type 2 diabetes mellitus and patients with DSPN. Potential biomarkers were selected through comprehensive analysis of statistically significant differences between groups. RESULTS Overall, 938 metabolites were identified. Among them, 12 metabolites (dimethylarginine, N6-acetyllysine, N-acetylhistidine, N,N,N-trimethyl-alanylproline betaine, cysteine, 7-methylguanine, N6-carbamoylthreonyladenosine, pseudouridine, 5-methylthioadenosine, N2,N2-dimethylguanosine, aconitate and C-glycosyl tryptophan) were identified as the specific biomarkers. The content of 12 metabolites were significantly higher in the DSPN group compared with the other two groups. Additionally, they showed good performance to discriminate the DSPN state. Correlation analyses showed that the levels of 12 metabolites might be more closely related to the glucose metabolic changes, followed by the levels of lipid metabolism. CONCLUSIONS The finding of the 12 signature metabolites might provide a novel perspective for the pathogenesis of DSPN. Future studies are required to test this observation further.
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Affiliation(s)
- Jiahui Xu
- Department of EndocrinologyShuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina
| | - Qingguang Chen
- Department of EndocrinologyShuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina
| | - Mengjie Cai
- Department of EndocrinologyShuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina
| | - Xu Han
- Department of EndocrinologyShuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina
| | - Hao Lu
- Department of EndocrinologyShuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina
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Cheng MK, Guo YY, Kang XN, Zhang L, Wang D, Ren HH, Yuan G. Advances in cardiovascular-related biomarkers to predict diabetic peripheral neuropathy. World J Diabetes 2023; 14:1226-1233. [PMID: 37664477 PMCID: PMC10473952 DOI: 10.4239/wjd.v14.i8.1226] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/24/2023] [Accepted: 07/07/2023] [Indexed: 08/11/2023] Open
Abstract
Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes mellitus. One of the most common types is distal symmetric poly-neuropathy, which begins as bilateral symmetry pain and hyperesthesia and gradually progresses into hypoesthesia with nerve fibre disorder and is frequently accompanied by depression and anxiety. Notably, more than half of patients with DPN can be asymptomatic, which tends to delay early detection. Furthermore, the study of adverse outcomes showed that DPN is a prominent risk factor for foot ulceration, gangrene and nontraumatic amputation, which decreases quality of life. Thus, it is essential to develop convenient diagnostic biomarkers with high sensitivity for screening and early intervention. It has been reported that there may be common pathways for microvascular and macrovascular complications of diabetes. The pathogenesis of both disorders involves vascular endothelial dys-function. Emerging evidence indicates that traditional and novel cardiovascular-related biomarkers have the potential to characterize patients by subclinical disease status and improve risk prediction. Additionally, beyond traditional cardiovascular-related biomarkers, novel cardiovascular-related biomarkers have been linked to diabetes and its complications. In this review, we evaluate the association between major traditional and nontraditional car-diovascular-related biomarkers of DPN, such as cardiac troponin T, B-type natriuretic peptide, C-reactive protein, myeloperoxidase, and homocysteine, and assess the evidence for early risk factor-based management strategies to reduce the incidence and slow the progression of DPN.
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Affiliation(s)
- Meng-Ke Cheng
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei Province, China
| | - Yao-Yao Guo
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei Province, China
| | - Xiao-Nan Kang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei Province, China
| | - Lu Zhang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei Province, China
| | - Dan Wang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei Province, China
| | - Hui-Hui Ren
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei Province, China
| | - Gang Yuan
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, Hubei Province, China
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Li J, Chongpison Y, Amornvit J, Chaikittisilpa S, Santibenchakul S, Jaisamrarn U. Association of reproductive factors and exogenous hormone use with distal sensory polyneuropathy among postmenopausal women in the United States: results from 1999 to 2004 NHANES. Sci Rep 2023; 13:9274. [PMID: 37286578 DOI: 10.1038/s41598-023-35934-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 05/25/2023] [Indexed: 06/09/2023] Open
Abstract
Postmenopausal status is a risk factor for distal sensory polyneuropathy-the most common type of peripheral neuropathy. We aimed to investigate associations between reproductive factors and history of exogenous hormone use with distal sensory polyneuropathy among postmenopausal women in the United States using data from the National Health and Nutrition Examination Survey 1999-2004, and to explore the modifying effects of ethnicity on these associations. We conducted a cross-sectional study among postmenopausal women aged ≥ 40 years. Women with a history of diabetes, stroke, cancer, cardiovascular disease, thyroid disease, liver disease, weak or failing kidneys, or amputation were excluded. Distal sensory polyneuropathy was measured using a 10-g monofilament test, and a questionnaire was used to collect data on reproductive history. Multivariable survey logistic regression was used to test the association between reproductive history variables and distal sensory polyneuropathy. In total, 1144 postmenopausal women aged ≥ 40 years were included. The adjusted odds ratios were 8.13 [95% confidence interval (CI) 1.24-53.28] and 3.18 (95% CI 1.32-7.68) for age at menarche < 11 years and time since menopause > 20 years, respectively, which were positively associated with distal sensory polyneuropathy; adjusted odds ratios were 0.45 for the history of breastfeeding (95% CI 0.21-0.99) and 0.41 for exogenous hormone use (95% CI 0.19-0.87) were negatively associated. Subgroup analysis revealed ethnicity-based heterogeneity in these associations. Age at menarche, time since menopause, breastfeeding, and exogenous hormone use were associated with distal sensory polyneuropathy. Ethnicity significantly modified these associations.
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Affiliation(s)
- Jiayu Li
- Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Yuda Chongpison
- Center of Excellence in Biostatistics, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
- The Skin and Allergy Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
| | - Jakkrit Amornvit
- Division of Neurology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Sukanya Chaikittisilpa
- Menopause Research Group, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Somsook Santibenchakul
- Family Planning and Reproductive Health Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Rama 4 Road, Bangkok, 10330, Thailand.
| | - Unnop Jaisamrarn
- Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Matheson BT, Osofsky RB, Friedrichsen DM, Brooks BJ, Giacolone J, Khotan M, Shekarriz R, Pankratz VS, Lew EJ, Clark RM, Kanagy NL. A novel, microvascular evaluation method and device for early diagnosis of peripheral artery disease and chronic limb-threatening ischemia in individuals with diabetes. J Vasc Surg Cases Innov Tech 2023; 9:101101. [PMID: 37152916 PMCID: PMC10160786 DOI: 10.1016/j.jvscit.2023.101101] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 12/22/2022] [Indexed: 05/09/2023] Open
Abstract
Objective A novel transdermal arterial gasotransmitter sensor (TAGS) has been tested as a diagnostic tool for lower limb microvascular disease in individuals with and without diabetes mellitus (DM). Methods The TAGS system noninvasively measures hydrogen sulfide (H2S) emitted from the skin. Measurements were made on the forearm and lower limbs of individuals from three cohorts, including subjects with DM and chronic limb-threatening ischemia, to evaluate skin microvascular integrity. These measurements were compared with diagnosis of peripheral artery disease (PAD) using the standard approach of the toe brachial index. Other measures of vascular health were made in some subjects including fasting blood glucose, hemoglobin A1c, plasma lipids, blood pressure, estimated glomerular filtration, and body mass index. Results The leg:arm ratio of H2S emissions correlated with risk factors for microvascular disease (ie, high-density lipoprotein levels, estimated glomerular filtration rate, systolic blood pressure, and hemoglobin A1c). The ratios were significantly lower in symptomatic DM subjects being treated for chronic limb-threatening ischemia (n = 8, 0.48 ± 0.21) compared with healthy controls (n = 5, 1.08 ± 0.30; P = .0001) and with asymptomatic DM subjects (n = 4, 0.79 ± 0.08; P = .0086). The asymptomatic DM group ratios were also significantly lower than the healthy controls (P = .0194). Using ratios of leg:arm transdermal H2S measurement (17 subjects, 34 ratios), the overall accuracy to identify limbs with severe PAD had an area under the curve of the receiver operating curve of 0.93. Conclusions Ratios of transdermal H2S measurements are lower in legs with impaired microvascular function, and the decrease in ratio precedes clinically apparent severe microvascular disease and diabetic ulcers. The TAGS instrument is a novel, sensitive tool that may aid in the early detection and monitoring of PAD complications and efforts for limb salvage.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Eric J. Lew
- School of Medicine, University of New Mexico, Albuquerque, NM
| | - Ross M. Clark
- School of Medicine, University of New Mexico, Albuquerque, NM
| | - Nancy L. Kanagy
- School of Medicine, University of New Mexico, Albuquerque, NM
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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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Sacco ICN, Trombini-Souza F, Suda EY. Impact of biomechanics on therapeutic interventions and rehabilitation for major chronic musculoskeletal conditions: A 50-year perspective. J Biomech 2023; 154:111604. [PMID: 37159980 DOI: 10.1016/j.jbiomech.2023.111604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 04/12/2023] [Accepted: 04/25/2023] [Indexed: 05/11/2023]
Abstract
The pivotal role of biomechanics in the past 50 years in consolidating the basic knowledge that underpins prevention and rehabilitation measures has made this area a great spotlight for health practitioners. In clinical practice, biomechanics analysis of spatiotemporal, kinematic, kinetic, and electromyographic data in various chronic conditions serves to directly enhance deeper understanding of locomotion and the consequences of musculoskeletal dysfunctions in terms of motion and motor control. It also serves to propose straightforward and tailored interventions. The importance of this approach is supported by myriad biomechanical outcomes in clinical trials and by the development of new interventions clearly grounded on biomechanical principles. Over the past five decades, therapeutic interventions have been transformed from fundamentally passive in essence, such as orthoses and footwear, to emphasizing active prevention, including exercise approaches, such as bottom-up and top-down strengthening programs for runners and people with osteoarthritis. These approaches may be far more effective inreducing pain, dysfunction, and, ideally, incidence if they are based on the biomechanical status of the affected person. In this review, we demonstrate evidence of the impact of biomechanics and motion analysis as a foundation for physical therapy/rehabilitation and preventive strategies for three chronic conditions of high worldwide prevalence: diabetes and peripheral neuropathy, knee osteoarthritis, and running-related injuries. We conclude with a summary of recommendations for future studies needed to address current research gaps.
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Affiliation(s)
- Isabel C N Sacco
- Physical Therapy, Speech and Occupational Therapy, School of Medicine, University of São Paulo, São Paulo, Brazil.
| | - Francis Trombini-Souza
- Department of Physical Therapy, University of Pernambuco, Petrolina, Pernambuco, Brazil; Master's and Doctoral Programs in Rehabilitation and Functional Performance, University of Pernambuco, Petrolina, Pernambuco, Brazil
| | - Eneida Yuri Suda
- Postgraduate Program in Physiotherapy, Universidade Ibirapuera, São Paulo, Brazil
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Kang SM, Hong JH, Ku BJ. A randomized, active-controlled, parallel, open-label, multicenter, phase 4 study to compare the efficacy and safety of pregabalin sustained release tablet and pregabalin immediate release capsule in type II diabetic patients with peripheral neuropathic pain. Medicine (Baltimore) 2023; 102:e33701. [PMID: 37115054 PMCID: PMC10145715 DOI: 10.1097/md.0000000000033701] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 04/14/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND Diabetic peripheral polyneuropathy is the most common chronic complication of type 2 diabetes. Neuropathic pain is challenging to manage, and various drugs are required to control it, decreasing treatment adherence. Pregabalin, a ligand that binds to alpha-2-delta subunits of the presynaptic calcium channel, has been approved by the Food and Drug Administration for the treatment of diabetic neuropathic pain. In this study, we will compare the efficacy, safety, treatment satisfaction, and compliance between pregabalin sustained-release (SR) tablets and pregabalin immediate-release (IR) capsules in type 2 diabetic patients with peripheral neuropathic pain. METHODS This study is a randomized, active-controlled, parallel, open-label, multicenter, phase 4 clinical trial (trial registration NCT05624853). Type 2 diabetic patients with glycosylated hemoglobin below 10% and peripheral neuropathic pain who have been taking pregabalin 150 mg/d or more for more than 4 weeks will be randomly assigned to pregabalin SR tablet (150 mg once a day, n = 65) or pregabalin IR capsule (75 mg twice a day, n = 65) therapy for 8 weeks. The primary outcome will be the efficacy of SR pregabalin after 8 weeks of treatment, which will be assessed by visual analog scale measurements. The secondary outcomes will include changes in several parameters, such as quality of life, treatment satisfaction, quality of sleep, and drug compliance. DISCUSSION In thus study, we aim to demonstrate that pregabalin SR tablets are associated with better compliance and satisfaction compared with pregabalin IR capsules, despite similar efficacy.
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Affiliation(s)
- Seon Mee Kang
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, South Korea
| | - Jun Hwa Hong
- Department of Internal Medicine, Eulji University Hospital, Eulji University School of Medicine, Daejeon, South Korea
| | - Bon Jeong Ku
- Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, South Korea
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Sethi Y, Uniyal N, Vora V, Agarwal P, Murli H, Joshi A, Patel N, Chopra H, Hasabo EA, Kaka N. Hypertension the 'Missed Modifiable Risk Factor' for Diabetic Neuropathy: a Systematic Review. Curr Probl Cardiol 2023; 48:101581. [PMID: 36584725 DOI: 10.1016/j.cpcardiol.2022.101581] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 12/23/2022] [Indexed: 12/29/2022]
Abstract
Diabetes and hypertension stand as the major non-infectious diseases affecting 34.2 million and 1.28 billion people respectively. The literature on the impact of diabetes on hypertension and vice versa is evolving. The major objectives of this review were to compile the evolving literature establishing the role of hypertension in diabetic neuropathy, derive the exact mechanisms for its pathogenesis, and describe evidence-based precise individualized management of diabetic neuropathy in patients having diabetes complicated by hypertension. A systematic review was conducted by searching databases of PubMed, Embase, and Scopus covering the literature from inception to 2022. We included all observational and experimental studies, including both human and animal studies looking into the correlation between diabetic neuropathy and hypertension. Hypertension poses to be the leading modifiable risk factor for the development of diabetic neuropathy, especially distal symmetrical polyneuropathy, producing abnormal nerve conduction parameters and increased vibration perception threshold in patients with diabetes mellitus. Thus, we advocate that good glycemic control in patients with diabetes needs to be supported with strict blood pressure control for preventing and delaying the onset of diabetic neuropathy.
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Affiliation(s)
- Yashendra Sethi
- PearResearch, Dehradun, Uttarakhand, India; Department of Medicine, Government Doon Medical College, Dehradun, Uttarakhand, India.
| | - Nidhi Uniyal
- PearResearch, Dehradun, Uttarakhand, India; Department of Medicine, Gautam Buddha Chikitsa Mahavidyalaya, Ras Bihari Bose Subharti University, Dehradun, Uttarakhand, India
| | - Vidhi Vora
- PearResearch, Dehradun, Uttarakhand, India; Department of Medicine, Lokmanya Tilak Municipal Medical College, Sion, Mumbai, India
| | - Pratik Agarwal
- PearResearch, Dehradun, Uttarakhand, India; Department of Medicine, Lokmanya Tilak Municipal Medical College, Sion, Mumbai, India
| | - Hamsa Murli
- PearResearch, Dehradun, Uttarakhand, India; Department of Medicine, Lokmanya Tilak Municipal Medical College, Sion, Mumbai, India
| | - Archi Joshi
- PearResearch, Dehradun, Uttarakhand, India; Department of Medicine, Government Medical College, Haldwani, Uttarakhand, India
| | - Neil Patel
- PearResearch, Dehradun, Uttarakhand, India; Department of Medicine, GMERS Medical College, Himmatnagar, Gujarat, India
| | - Hitesh Chopra
- Department of Pharmaceutics, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Elfatih A Hasabo
- Faculty of Medicine, University of Khartoum, Khartoum, Khartoum State, Sudan
| | - Nirja Kaka
- PearResearch, Dehradun, Uttarakhand, India; Department of Medicine, GMERS Medical College, Himmatnagar, Gujarat, India
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50
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Huang W, Gu L, Wang J, Wang Y, Cao F, Jin T, Cheng Y. Causal association between vitamin D and diabetic neuropathy: a Mendelian randomization analysis. Endocrine 2023; 80:328-335. [PMID: 36754931 DOI: 10.1007/s12020-023-03315-9] [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: 12/18/2022] [Accepted: 01/13/2023] [Indexed: 02/10/2023]
Abstract
OBJECTIVES Vitamin D has been linked to diabetic neuropathy (DN) in previous epidemiological observational studies, however, their findings are inconsistent. The causal relationship between vitamin D and DN remains unknown. In this study we aim to investigate the causal association of serum 25-hydroxyvitamin D (25OHD) and DN. METHODS Based on summary statistics from publicly available genome-wide association studies (GWAS) database, we detected the genetic correlation between serum 25OHD levels and DN by a two-sample Mendelian randomization (MR) analysis. The inverse-variance weighted (IVW) method was used as the primary analysis, weighted median and MR-Egger were applied as complementary methods for MR estimates. In addition, we took sensitivity analyses including Cochran's Q test, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) and leave-one-out analysis to ensure that we obtained stable and reliable results. RESULTS Our MR study showed no significant genetic association between serum 25OHD levels and DN (OR = 1.13, 95% CI = 0.81-1.57, P = 0.46). Furthermore, in the reverse direction analysis, we did not find a significant causal effect of DN and serum 25OHD levels (OR = 0.99, 95% CI = 0.98-1.00, P = 0.09). Results of MR-Egger, Weighted Median were consistent with those of the IVW method. The sensitivity analysis suggesting that no significant heterogeneity and genetic pleiotropy was observed. CONCLUSIONS Our results provided no evidence to support the causal association of serum 25OHD levels with DN.
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Affiliation(s)
- Wei Huang
- Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 310014, Hangzhou, China
- Rheumatism and Immunity Research Institute, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 310014, Hangzhou, China
| | - Lei Gu
- Department of Rehabilitation, Ningbo Medical Treatment Center Lihuili Hospital, 315000, Ningbo, China
| | - Jingwen Wang
- Department of Neurology, Tiantai People's Hospital Of Zhejiang Province, 317200, Tiantai, China
| | - Yiqi Wang
- Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 310014, Hangzhou, China
| | - Fangzheng Cao
- Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 310014, Hangzhou, China
- Department of Neurology, The Second Clinical Medical College, Zhejiang Chinese Medical University, 310014, Hangzhou, China
| | - Tianyu Jin
- Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 310014, Hangzhou, China.
- Department of Neurology, The Second Clinical Medical College, Zhejiang Chinese Medical University, 310014, Hangzhou, China.
| | - Yifan Cheng
- Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 310014, Hangzhou, China.
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