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Liu Y, Sun D, Kong Q, Li D, Wang R, Yin J, Xie L, Dong Y, Zhang Y. Peripheral Neuropathy Symptoms and Ocular Surface Lesions in Patients with Type 2 Diabetes Mellitus and Dry Eye: A Clinical Correlational Study. Ophthalmol Ther 2025:10.1007/s40123-025-01150-x. [PMID: 40372617 DOI: 10.1007/s40123-025-01150-x] [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: 02/11/2025] [Accepted: 04/14/2025] [Indexed: 05/16/2025] Open
Abstract
INTRODUCTION Reduced corneal sensation in individuals with type 2 diabetes mellitus (T2DM) leads to a dissociation between dry eye disease (DED) signs and symptoms, thereby affecting diagnostic accuracy. This study aimed to investigate the correlation between ocular surface signs and diabetic peripheral neuropathy (DPN) symptoms in patients with T2DM-associated DED. METHODS The Michigan Neuropathy Screening Instrument Questionnaire (MNSIQ) was used to categorize patients with T2DM into MNSIQ-DPN and non-DPN groups. Ocular irritation symptoms were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. Ocular surface lesions were assessed via Cochet-Bonnet esthesiometry, corneal fluorescein staining (CFS), the Schirmer I tear test (SIT), tear meniscus height (TMH), noninvasive keratography break-up time (NIKf-BUT), and the meibomian gland loss (MGL) grade detected by OCULUS. Corneal nerve fiber parameters were evaluated using in vivo confocal microscopy (IVCM). RESULTS A total of 116 patients with T2DM, comprising 76 non-DPN patients and 40 MNSIQ-DPN patients, along with 51 age-matched participants without diabetes, were enrolled. Although OSDI scores were equivalent between MNSIQ-DPN patients and non-DPN patients, MNSIQ-DPN patients presented significantly more severe CFS (p < 0.001), meibomian gland dysfunction (MGD) (p < 0.001), corneal nerve fiber loss (p < 0.001), sensory dysfunction (p = 0.02), and corneal microneuromas (p < 0.001). The MNSIQ score was significantly positively correlated with CFS (p < 0.001); MGD (p < 0.01); corneal nerve fiber loss, including corneal nerve fiber density and length and branch density, in the paracentral (all p < 0.001) and inferior-whorl areas (p < 0.01, p < 0.05 and p < 0.01, respectively); and corneal microneuromas, characterized by increased microneuroma numbers (p < 0.001) and areas (p < 0.001) in these regions. CONCLUSION MNSIQ scores were significantly and robustly correlated with the presence of corneal epithelial defects, MGD, and nerve fiber loss in patients with T2DM. These findings suggest that DPN is a critical factor in diabetic ocular surface complications, highlighting the importance of the MNSIQ for assessing these conditions.
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Affiliation(s)
- Yanling Liu
- Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, 5 Yanerdao Road, Qingdao, 266071, China
- School of Ophthalmology, Shandong First Medical University, Jinan, China
| | - Dapeng Sun
- Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, 5 Yanerdao Road, Qingdao, 266071, China
| | - Qianqian Kong
- Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, 5 Yanerdao Road, Qingdao, 266071, China
| | - Dongfang Li
- Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, 5 Yanerdao Road, Qingdao, 266071, China
| | - Rui Wang
- Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, 5 Yanerdao Road, Qingdao, 266071, China
- School of Ophthalmology, Shandong First Medical University, Jinan, China
| | - Jia Yin
- Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, 5 Yanerdao Road, Qingdao, 266071, China
| | - Lixin Xie
- Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, 5 Yanerdao Road, Qingdao, 266071, China
- School of Ophthalmology, Shandong First Medical University, Jinan, China
| | - Yanling Dong
- Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, 5 Yanerdao Road, Qingdao, 266071, China.
- School of Ophthalmology, Shandong First Medical University, Jinan, China.
| | - Yangyang Zhang
- Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, 5 Yanerdao Road, Qingdao, 266071, China.
- School of Ophthalmology, Shandong First Medical University, Jinan, China.
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Brock C, Andersen H, Alibegovic AC, Andersen ST, Andreasen LJ, Charles MH, Christensen DH, Drewes AM, Gall MA, Gylfadottir SS, Hansen CS, Hecquet SK, Jensen TS, Karlsson P, Knudsen LB, Lobato CB, Kufaishi H, Maalmi H, Mizrak HI, Nilsen KB, Perkins BA, Røikjer J, Rossing P, Rungby J, Rømer J, Stouge A, Sulek K, Søfteland E, Tahrani AA, Terkelsen AJ, Tesfaye S, Wegeberg A, Åkerström T, Brock B, Pop-Busui R. Barriers and new opportunities in developing effective therapies for diabetic neuropathy: International expert consensus recommendations. Diabetes Res Clin Pract 2025; 221:112010. [PMID: 39855602 DOI: 10.1016/j.diabres.2025.112010] [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: 12/04/2024] [Revised: 01/08/2025] [Accepted: 01/19/2025] [Indexed: 01/27/2025]
Abstract
BACKGROUND Diabetic neuropathy (DN) affects up to half of individuals with type 1 and type 2 diabetes. Despite evidence that improving metabolic and cardiovascular health can slow its progression, DN remains a significant clinical challenge due to the lack of disease-modifying therapies and effective pain management strategies. This consensus aimed to identify gaps and recommend strategies to address these challenges. METHOD A workshop, initiated by Steno Diabetes Centre Copenhagen and the Danish Diabetes and Endocrinology Academy, conducted a gap analysis based on insights from clinical studies, observational cohorts, and clinical practice. Online invitations targeted experienced clinicians, researchers, and drug developers committed to improving DN treatment through innovative clinical trials. Thirty-five participants from six countries reached consensus via a Delphi process on key steps to advance DN therapy. RESULT Four critical barriers and needs were addressed: (1) Translating bench research to clinical practice, (2) Enhancing clinical trial design, (3) Improving outcome measures, and (4) Identifying effective treatments for painful DN. CONCLUSION Successful interventional trials require robust outcome measures to capture clinically meaningful changes in DN phenotypes, providing the basis for developing effective, disease-modifying treatments.
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Affiliation(s)
- C Brock
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark; Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - H Andersen
- Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
| | - A C Alibegovic
- Clinical Development and Project Leadership, Novo Nordisk A/S, Søborg, Denmark
| | - S T Andersen
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | | | - M H Charles
- Steno Diabetes Center Aarhus, Aarhus, Denmark
| | - D H Christensen
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Epidemiology, Aarhus University Hospital, Denmark
| | - A M Drewes
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark; Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - M-A Gall
- Clinical Development and Project Leadership, Novo Nordisk A/S, Søborg, Denmark
| | - S S Gylfadottir
- Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; Danish Pain Research Center, Health Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - C S Hansen
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - S K Hecquet
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - T S Jensen
- Danish Pain Research Center, Health Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - P Karlsson
- Danish Pain Research Center, Health Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Core Centre for Molecular Morphology, Section for Stereology for Microscopy, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - L B Knudsen
- Chief Scientific Advisor Office, Research & Early Development, Novo Nordisk A/S, Denmark
| | - C B Lobato
- Section of Endocrinology, Department of Medicine, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - H Kufaishi
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - H Maalmi
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - H I Mizrak
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - K B Nilsen
- Section for Clinical Neurophysiology, Department of Neurology, Oslo University Hospital, Oslo, Norway
| | - B A Perkins
- Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - J Røikjer
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark
| | - P Rossing
- Steno Diabetes Center Copenhagen, Herlev, Denmark and Department of Clinical Medicine, University of Copenhagen, Denmark
| | - J Rungby
- Steno Diabetes Center Copenhagen, Herlev, Denmark and Department of Clinical Medicine, University of Copenhagen, Denmark
| | - J Rømer
- Clinical Development and Project Leadership, Novo Nordisk A/S, Søborg, Denmark
| | - A Stouge
- Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
| | - K Sulek
- Steno Diabetes Center Copenhagen, Herlev, Denmark and Department of Clinical Medicine, University of Copenhagen, Denmark
| | - E Søfteland
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - A A Tahrani
- Clinical Development and Project Leadership, Novo Nordisk A/S, Søborg, Denmark; University of Birmingham, Department of Metabolism and Systems Science, Birmingham, UK
| | - A J Terkelsen
- Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - S Tesfaye
- Diabetes Research Unit, Sheffield Teaching Hospitals and the University of Sheffield, Sheffield, UK
| | - A Wegeberg
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - T Åkerström
- Diabetes Pharmacology, Novo Nordisk A/S, Denmark
| | - B Brock
- University of Birmingham, Department of Metabolism and Systems Science, Birmingham, UK.
| | - R Pop-Busui
- Department of Medicine, Division of Endocrinology, Diabetes and Clinical Nutrition, Oregon Health & Science University, Portland USA
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Malwanage KT, Liyanage E, Weerasinghe V, Antonypillai C, Nanayakkara I. A novel proprioceptive rehabilitation program: A pilot randomized controlled trail as an approach to address proprioceptive deficits in patients with diabetic polyneuropathy. PLoS One 2024; 19:e0305055. [PMID: 38968315 PMCID: PMC11226081 DOI: 10.1371/journal.pone.0305055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 05/22/2024] [Indexed: 07/07/2024] Open
Abstract
BACKGROUND Diabetic polyneuropathy (DPN) is a notable microvascular complication of DM, affecting 16%-66% globally. DPN often leads to proprioceptive deficits in the lower limbs (LL), leading to impaired functional performance. However, evidence supporting proprioceptive rehabilitation programs (PRP) for DPN remains scarce. AIMS This pilot study aims to evaluate the effectiveness of a novel 12-week PRP on LL static and dynamic proprioception and shed light on the potential benefits of PRP for DPN population. METHODS Randomized Controlled Trail was conducted among 30 DPN patients (age 53.25±7.72 years, BMI 24.01±1.41 and DM duration 9.48±6.45 years), randomly allocated to intervention (n = 15) or control (n = 15) groups. The intervention group received PRP 3 times/week for 12 weeks. The control group received no exercise. Both groups received regular diabetic care. Static and dynamic proprioception of both LL were assessed at baseline, 6 weeks and 12 weeks. Position-reposition test was used to assess ankle joint position sense by obtaining difference between target and reproduced angles. Error in detecting knee angle and speed were obtained by performing Lower Limb Matching and Sense of Movement tests respectively to assess dynamic proprioception. RESULTS Two-way ANOVA and paired comparisons revealed, no significant improvement in proprioceptive deficits at 6 weeks (p>0.05), but significant improvement was achieved at 12-weeks (p<0.05) in the intervention group. Mean errors in Pposition re-position(R:p<0.001, L;p<0.001) and Lower limb matching (R:p<0.001, L;p<0.001) tests reduced by 5° and 10° respectively, indicating a70% improvement in the intervention group. Error of detecting speed reduced only on right side by 0.041ms-1 accounting for a 42% improvement. No improvements were observed in the control group. CONCLUSIONS Novel 12-week PRP may yield a significant reduction in LL proprioceptive deficits among DPN patients. Future RCTs with larger samples should compare the effectiveness of this PRP compared with conventional rehabilitation programs.
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Affiliation(s)
- Kavinda T. Malwanage
- Department of Physiotherapy, Faculty of Allied Health Sciences, University of Peradeniya, Peradeniya, Sri Lanka
| | - Esther Liyanage
- Department of Physiotherapy, Faculty of Allied Health Sciences, University of Peradeniya, Peradeniya, Sri Lanka
| | - Vajira Weerasinghe
- Department of Physiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | | | - Indumathie Nanayakkara
- Department of Physiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
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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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Jasmin M, Yusuf S, Syahrul S, Abrar EA. Validity and Reliability of a Vibration-Based Cell Phone in Detecting Peripheral Neuropathy among Patients with a Risk of Diabetic Foot Ulcer. INT J LOW EXTR WOUND 2023; 22:687-694. [PMID: 34382442 DOI: 10.1177/15347346211037411] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The aim of this study was to determine the validity and reliability of a vibration-based cell phone in detecting peripheral neuropathy among individuals with a risk of diabetic foot ulcer (DFU). The current study consisted of 3 phases: a pilot study, concurrent validity study, and interreliability study. A 128 Hz tuning fork and vibration-based cell phone using the Vibrations-Test app was compared in the primary care setting. The pilot study confirmed that the vibration-based cell phone has an adequate reliability (r > 0.70, P < .001). The concurrent validity test involved 96 participants (aged 55.78 ± 8.32 years). The Pearson correlation test found the highest correlation in the fifth metatarsal heads (r = 0.741, right feet; 0.772, left feet; P < .001). In the 4 primary care settings, the interrater reliability between nurses of the vibration-based cell phone were k = 1.000, 1.000, 1.000, and 0.720. The concurrent validity test found moderate to strong correlation results and that the interrater reliability had a strong agreement that was almost perfect. Thus, vibration-based cell phone applications can be used as screening tools for detecting neuropathy among individuals with a risk of DFU.
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Affiliation(s)
- Muh Jasmin
- Nursing Study Program, College of Health Science Karya Kesehatan, Kendari, Indonesia
- Faculty of Nursing, Hasanuddin University, Makassar, Indonesia
| | - Saldy Yusuf
- Faculty of Nursing, Hasanuddin University, Makassar, Indonesia
| | - Syahrul Syahrul
- Faculty of Nursing, Hasanuddin University, Makassar, Indonesia
| | - Eva Arna Abrar
- Faculty of Nursing, Hasanuddin University, Makassar, Indonesia
- Stikes Nani Hasanuddin, Makassar, Indonesia
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Sher EK, Džidić-Krivić A, Karahmet A, Beća-Zećo M, Farhat EK, Softić A, Sher F. Novel therapeutical approaches based on neurobiological and genetic strategies for diabetic polyneuropathy - A review. Diabetes Metab Syndr 2023; 17:102901. [PMID: 37951098 DOI: 10.1016/j.dsx.2023.102901] [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: 07/28/2023] [Revised: 10/26/2023] [Accepted: 10/30/2023] [Indexed: 11/13/2023]
Abstract
BACKGROUND Neuropathy is among the most often reported consequences of diabetes and the biggest cause of morbidity and mortality in people suffering from this life-long disease. Although different therapeutic methods are available for diabetic neuropathy, it is still the leading cause of limb amputations, and it significantly decreases patients' quality of life. AIM This study investigates potential novel therapeutic options that could ameliorate symptoms of DN. METHODOLOGY Research and review papers from the last 10 years were taken into consideration. RESULTS There are various traditional drugs and non-pharmacological methods used to treat this health condition. However, the research in the area of pathogenic-oriented drugs in the treatment of DN showed no recent breakthroughs, mostly due to the limited evidence about their effectiveness and safety obtained through clinical trials. Consequently, there is an urgent demand for the development of novel therapeutic options for diabetic neuropathy. CONCLUSION Some of the latest novel diagnostic methods for diagnosing diabetic neuropathy are discussed as well as the new therapeutic approaches, such as the fusion of neuronal cells with stem cells, targeting gene delivery and novel drugs.
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Affiliation(s)
- Emina Karahmet Sher
- Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, United Kingdom.
| | - Amina Džidić-Krivić
- International Society of Engineering Science and Technology, Nottingham, United Kingdom; Department of Neurology, Clinical Hospital Zenica, Zenica, 72000, Bosnia and Herzegovina
| | - Alma Karahmet
- International Society of Engineering Science and Technology, Nottingham, United Kingdom
| | - Merima Beća-Zećo
- International Society of Engineering Science and Technology, Nottingham, United Kingdom; Department of Pharmacy, Faculty of Health Sciences, Victoria International University, Mostar, 88000, Bosnia and Herzegovina
| | - Esma Karahmet Farhat
- International Society of Engineering Science and Technology, Nottingham, United Kingdom; Faculty of Food Technology, Juraj Strossmayer University of Osijek, Osijek, 31000, Croatia
| | - Adaleta Softić
- Department of Biochemistry, Faculty of Pharmacy, University of Tuzla, Tuzla, 75000, Bosnia and Herzegovina
| | - Farooq Sher
- Department of Engineering, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, United Kingdom.
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Sher EK, Prnjavorac B, Farhat EK, Palić B, Ansar S, Sher F. Effect of Diabetic Neuropathy on Reparative Ability and Immune Response System. Mol Biotechnol 2023:10.1007/s12033-023-00813-z. [PMID: 37523019 DOI: 10.1007/s12033-023-00813-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 06/23/2023] [Indexed: 08/01/2023]
Abstract
The effects of diabetes can be divided into short, medium and long term and various human organ systems can be effected. The present study aimed to determine how much the duration of diabetes mellitus (DM) affect the reparative ability of the body, immune response and the development of DM complications. Interleukin 1-β (IL-1β) and Interleukin 6 (IL-6) were monitored as specific indicators of inflammatory reaction and C-reactive protein (CRP), leukocyte count (WBC) and sedimentation rate (ESR) as general markers of inflammatory reaction. Tumour necrosis factor α (TNF-α) and transforming growth factor β1 (TGF-β1) were observed as indicators of reparative ability and polyneuropathy. All interleukins were determined by ELISA and evaluated spectrophotometrically. Michigan Neuropathy Screening Instrument (MNSI) is performed for neuropathy examination. Patients with diabetes mellitus were divided into 3 groups, according to duration of diabetes mellitus. IL-6 levels correlated with clinical stage of diabetic polyneuropathy at p = 0.025 R = 0.402; with CRP at p = 0.0001, R = 0.784 as well as correlation of CRP and MNSI score (R = 0.500, p = 0.034) in a group of patients with DM lasting up to 10 years. The reparative ability of the body is reduced by physiological age and ages of DM duration. The immune response is weakened in DM additionally. The dual activity of cytokines IL-6 and TGF-β1 is present in long-duration Diabetes Mellitus.
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Affiliation(s)
- Emina Karahmet Sher
- Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK.
| | - Besim Prnjavorac
- Department of Pathophysiology, Faculty of Pharmacy, University of Sarajevo, Sarajevo, 71000, Bosnia and Herzegovina
| | - Esma Karahmet Farhat
- Department of Food and Nutrition Research, Faculty of Food Technology, University of Osijek Juraj Strossmayer, Osijek, 31000, Croatia
- International Society of Engineering Science and Technology, Nottingham, UK
| | - Benjamin Palić
- Department of Internal Medicine, University Clinical Hospital Mostar, Mostar, 88000, Bosnia and Herzegovina
| | - Sabah Ansar
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433, Saudi Arabia
| | - Farooq Sher
- Department of Engineering, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK.
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Chen T, Xing X, Huang L, Tu M, Lai X, Wen S, Cai J, Lin S, Zheng Y, Lin Y, Xu L, Qiu Y, Qiu L, Xu Y, Wu P. Efficacy and safety of high-dose intramuscular vitamin D 2 injection in type 2 diabetes mellitus with distal symmetric polyneuropathy combined with vitamin D insufficiency: study protocol for a multicenter, randomized, double-blinded, and placebo-controlled trial. Front Endocrinol (Lausanne) 2023; 14:1202917. [PMID: 37484958 PMCID: PMC10361572 DOI: 10.3389/fendo.2023.1202917] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Accepted: 06/19/2023] [Indexed: 07/25/2023] Open
Abstract
Background Distal symmetric polyneuropathy (DSPN) is the most common chronic complication of type 2 diabetes mellitus (T2DM). DSPN may lead to more serious complications, such as diabetic foot ulcer, amputation, and reduced life expectancy. Observational studies have suggested that vitamin D deficiency may be associated with the development of DSPN in T2DM. However, interventional studies have found that low-dose vitamin D supplementation does not significantly improve neuropathy in DSPN. This study aims to evaluate the efficacy and safety of intramuscular injection of high-dose vitamin D (HDVD) in T2DM with DSPN combined with vitamin D insufficiency. Methods and analysis We will conduct a multicenter, randomized, double-blinded, and placebo-controlled trial in four large hospitals. All eligible participants will be randomly assigned to either the vitamin D2 supplement or placebo control group and injected intramuscularly monthly for 3 months. Additionally, anthropometric measurements and clinical data will be collected at baseline and 3 months. Adverse events will be collected at 1, 2, and 3 months. The primary outcome measure is the change in the mean Michigan Neuropathy Screening Instrument (MNSI) score at baseline and 3 months post-intervention. We will use the gold-standard liquid chromatography-tandem mass spectrometry method to distinguish between 25(OH)D2 and 25(OH)D3 levels. The MNSN score before the intervention will be used as a covariate to compare the changes between both groups before and after the intervention, and the analysis of covariance will be used to analyze the change in the MNSI score after HDVD supplementation. Discussion Glycemic control alone does not prevent the progression of DSPN in T2DM. Some studies have suggested that vitamin D may improve DSPN; however, the exact dose, method, and duration of vitamin D supplementation are unknown. Additionally, neuropathy repair requires HDVD supplementation to sustain adequate vitamin D levels. This once-a-month intramuscular method avoids daily medication; therefore, compliance is high. This study will be the first randomized controlled trial in China to analyze the efficacy and safety of HDVD supplementation for patients with T2DM and DSPN and will provide new ideas for pharmacological research and clinical treatment of diabetic neuropathy. Clinical trial registration https://www.chictr.org.cn/, identifier ChiCTR2200062266.
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Affiliation(s)
- Tao Chen
- Department of Endocrinology, Clinical Research Center for Metabolic Diseases of Fujian Province, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Endocrinology and Metabolism, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Xiaoyan Xing
- Department of Endocrinology and Metabolism, China-Japan Friendship Hospital, Beijing, China
| | - Lihua Huang
- Department of Tumor Radiotherapy, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Mei Tu
- Department of Endocrinology and Metabolism, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Xiaoli Lai
- Department of Endocrinology and Metabolism, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Shidi Wen
- Department of Endocrinology and Metabolism, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Jin Cai
- Department of Endocrinology and Metabolism, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Shenglong Lin
- Department of Severe Liver Disease, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Youping Zheng
- Department of Ultrasound, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Yuehui Lin
- Department of Endocrinology and Metabolism, Longyan Traditional Chinese Medicine Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Longyan, China
| | - Lijuan Xu
- Department of Endocrinology and Metabolism, Longyan Traditional Chinese Medicine Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Longyan, China
| | - Yuwen Qiu
- Department of Endocrinology and Metabolism, Longyan Shanghang County Hospital, Longyan, China
| | - Lumin Qiu
- Department of Endocrinology and Metabolism, Longyan Shanghang County Hospital, Longyan, China
| | - Yuebo Xu
- Department of Diabetes, Longyan Boai Hospital, Longyan, China
| | - Peiwen Wu
- Department of Endocrinology, Clinical Research Center for Metabolic Diseases of Fujian Province, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
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Sutkowska E, Marciniak D, Koszewicz M, Dziadkowiak E, Budrewicz S, Biernat K, Kuciel N, Mazurek J, Hap K. Validity and reliability of the Polish version of the Michigan Neuropathy Screening Instrument. World J Diabetes 2023; 14:435-446. [PMID: 37122429 PMCID: PMC10130898 DOI: 10.4239/wjd.v14.i4.435] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 12/11/2022] [Accepted: 01/10/2023] [Indexed: 04/12/2023] Open
Abstract
BACKGROUND Diabetic sensorimotor polyneuropathy is an important risk factor for foot ulceration and amputation. Thus, patients with diabetes should be screened for this disorder according to local guidelines. An obstacle to the diagnosis of this disease may be the lack of unified diagnostic criteria due to the lack of properly validated scales used for assessment.
AIM To validate both sections (A and B) of the Michigan Neuropathy Screening Instrument (MNSI) in Polish (PL) patients with diabetes.
METHODS A cross-sectional study using a test (A1, B1) and re-test (A2, B2) formula was performed in 80 patients with diabetes. The gold standard used for neuropathy detection was a nerve conduction study (NCS) which was performed in all participants. Reliability of the MNSI-PL was assessed using the Cronbach’s alpha, Kuder-Richardson formula 20 (KR-20), split-half reliability, the Gottman split-half tests, and correlation between first and second half was accessed. Stability was assessed using an intraclass correlation coefficient (ICC). For external validation, we used simple linear correlation, binomial regression, and agreement between two different tools using a Bland-Altman plot analysis.
RESULTS The scale was internally consistent (Cronbach’s alpha for the full scale: 0.81 for A and 0.87 for B). MNSI-PL scores in test/retest showed high stability (ICC = 0.73 for A and ICC = 0.97 for B). The statistically important correlations between MNSI-PL and NCS were found for B1, B2, and A1 (P < 0.005). The cut-off points of ≥ 3 for section A (sensitivity of 90%-100%; specificity of 33%-40%) and ≥ 2 for section B (sensitivity of 81%-84%; specificity of 60%-70%) were obtained during neuropathy detection.
CONCLUSION The MNSI-PL is a reliable and valid instrument in screening for diabetic neuropathy.
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Affiliation(s)
- Edyta Sutkowska
- University Rehabilitation Centre, Wroclaw Medical University, Wroclaw 50-556, Poland
| | - Dominik Marciniak
- Department of Drugs Form Technology, Wroclaw Medical University, Wroclaw 50-556, Poland
| | | | - Edyta Dziadkowiak
- Department of Neurology, Wroclaw Medical University, Wroclaw 50-556, Poland
| | - Slawomir Budrewicz
- Department of Neurology, Wroclaw Medical University, Wroclaw 50-556, Poland
| | - Karolina Biernat
- University Rehabilitation Centre, Wroclaw Medical University, Wroclaw 50-556, Poland
| | - Natalia Kuciel
- University Rehabilitation Centre, Wroclaw Medical University, Wroclaw 50-556, Poland
| | - Justyna Mazurek
- University Rehabilitation Centre, Wroclaw Medical University, Wroclaw 50-556, Poland
| | - Katarzyna Hap
- University Rehabilitation Centre, Wroclaw Medical University, Wroclaw 50-556, Poland
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Viswanathan V, Ahmed Khan B, Nachimuthu S, Kumpatla S. Precision of Michigan Neuropathy Screening Instrument (MNSI) Tool for the Diagnosis of Diabetic Peripheral Neuropathy Among People with Type 2 Diabetes-A Study from South India. INT J LOW EXTR WOUND 2023:15347346231163209. [PMID: 36924005 DOI: 10.1177/15347346231163209] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
Diabetic peripheral neuropathy (DPN) is one of the risk factors for foot-related complications among people with type 2 diabetes mellitus (T2DM). Hence, we aimed to validate the Michigan Neuropathy Screening Instrument (MNSI) tool against biothesiometer with a cut-off value of ≥25 V and also to determine the cut-off point of MNSI score for the diagnosis of diabetic neuropathy among people with T2DM in India. A cross-sectional study was conducted among 357 people with T2DM in a tertiary care centre for diabetes in Chennai, South India. The eligible study participants underwent testing with a biothesiometer and the MNSI tool was administered. The patient version tool of MNSI was translated to the local language, Tamil. The MNSI scores (1, 1.5, 2, and 2.5) were compared with biothesiometer value. For the MNSI scores of less than 1, 1.5, 2, and 2.5, sensitivities were 97.6%, 97.6%, 96.8%, and 77.8% and specificities were 76.6%, 77.9%, 85.7%, and 88.3% respectively. The cut-off value of MNSI score was derived as two with AUC of 0.934. The sensitivity was 96.8% and the specificity was 85.7% with 89.6% accuracy. The high sensitivity indicates the positive cases are diagnosed correctly. There is no validated tool available for detection of DPN in Indian population. The Indian version of MNSI tool was found to be effective for screening diabetic neuropathy among people with T2DM. The MNSI tool was found to be reliable, convenient, and non-invasive for diagnosis of DPN and can be used in routine clinical settings.
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Affiliation(s)
- Vijay Viswanathan
- 58896MV Hospital for Diabetes and Prof M Viswanathan Diabetes Research Centre, Chennai, India
| | - Balkhiwala Ahmed Khan
- 58896MV Hospital for Diabetes and Prof M Viswanathan Diabetes Research Centre, Chennai, India
| | - Sukanya Nachimuthu
- Department of Epidemiology, 58896Prof M Viswanathan Diabetes Research Centre, Chennai, India
| | - Satyavani Kumpatla
- 58896MV Hospital for Diabetes and Prof M Viswanathan Diabetes Research Centre, Chennai, India
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11
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Potockova V, Mala S, Hoskovcova L, Capek V, Nedelka T, Riedlbauchova L, Baumgartner D, Mensova L, Mazanec R. Thermal quantitative sensory testing as a screening tool for cardiac autonomic neuropathy in patients with diabetes mellitus. Brain Behav 2022; 12:e2506. [PMID: 35212197 PMCID: PMC8933758 DOI: 10.1002/brb3.2506] [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: 08/03/2021] [Revised: 11/14/2021] [Accepted: 01/02/2022] [Indexed: 11/11/2022] Open
Abstract
INTRODUCTION Electrophysiological diagnosis of cardiac autonomic neuropathy (CAN) is based on the evaluation of cardiovascular autonomic reflex tests (CARTs). CARTs are relatively time consuming and must be performed under standardized conditions. This study aimed to determine whether thermal quantitative sensory testing (TQST) can be used as a screening tool to identify patients with diabetes at a higher risk of CAN. METHODS Eighty-five patients with diabetes and 49 healthy controls were included in the study. Neurological examination, CARTs, TQST, biochemical analyses, and neuropathy symptom questionnaires were performed. RESULTS CAN was diagnosed in 46 patients with diabetes (54%). CAN-positive patients with diabetes had significantly higher warm detection thresholds (WDT) and significantly lower cold detection thresholds (CDT) in all tested regions (thenar, tibia, and the dorsum of the foot). CDT on the dorsum < 21.8°C in combination with CDT on the tibia < 23.15°C showed the best diagnostic ability in CAN prediction, with 97.4 % specificity, 60.9% sensitivity, 96.6% positive predictive value, and 67.3% negative predictive value. CONCLUSION TQST can be used as a screening tool for CAN before CART.
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Affiliation(s)
- Veronika Potockova
- Second Faculty of Medicine, Department of Neurology, Motol University Hospital, Charles University, Prague, Czech Republic
| | - Sarka Mala
- Second Faculty of Medicine, Department of Internal Medicine, Motol University Hospital, Charles University, Prague, Czech Republic
| | - Lucie Hoskovcova
- Second Faculty of Medicine, Department of Internal Medicine, Motol University Hospital, Charles University, Prague, Czech Republic
| | - Vaclav Capek
- Second Faculty of Medicine, Department of Neurology, Motol University Hospital, Charles University, Prague, Czech Republic
| | - Tomas Nedelka
- Second Faculty of Medicine, Department of Neurology, Motol University Hospital, Charles University, Prague, Czech Republic.,Faculty of Biomedical Engineering, Czech Technical University in Prague, Prague, Czech Republic
| | - Lucie Riedlbauchova
- Second Faculty of Medicine, Department of Cardiology, Motol University Hospital, Charles University, Prague, Czech Republic
| | - Daniel Baumgartner
- Second Faculty of Medicine, Department of Neurology, Motol University Hospital, Charles University, Prague, Czech Republic
| | - Livie Mensova
- Second Faculty of Medicine, Department of Neurology, Motol University Hospital, Charles University, Prague, Czech Republic
| | - Radim Mazanec
- Second Faculty of Medicine, Department of Neurology, Motol University Hospital, Charles University, Prague, Czech Republic
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Abuzinadah AR, Alkully HS, Alanazy MH, Alrawaili MS, Milyani HA, AlAmri B, AlShareef AA, Bamaga AK. Translation, validation, and diagnostic accuracy of the Arabic version of the Michigan neuropathy screening instrument. Medicine (Baltimore) 2021; 100:e27627. [PMID: 34871227 PMCID: PMC8568465 DOI: 10.1097/md.0000000000027627] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 10/07/2021] [Indexed: 01/05/2023] Open
Abstract
The Michigan Neuropathy Screening Instrument (MNSI) is used to screen patients for diabetic neuropathy (DNP). We aimed to translate the MNSI questionnaire into Arabic (MNSIq-Ar) and to assess the validity and diagnostic performance of the MNSI Arabic version (MNSI-Ar).Cronbach alpha α and the interclass correlation coefficient were used to measure the reliability and reproducibility of the MNSIq-Ar. The instrument's validity was assessed by Spearman correlation with the Utah Early Neuropathy Scale (UENS), the Modified Toronto Neuropathy Score (mTCNS), diabetic neuropathy symptoms (DNS), and sural nerve amplitude (SNA). The construct validity of the MNSI-Ar was assessed by its ability to differentiate the severity of DNP (using the Kruskal-Wallis test). The diagnostic performance was assessed through the receiver operator curve area.We recruited 89 participants (mean [SD] age, 50.8 [12.3] years; 48% men). The MNSIq-Ar showed an α of 0.81 and intraclass correlation coefficient = 0.94, and the correlation coefficients with UENS, mTCNS, DNS, and sural nerve amplitude were 0.67, 0.83, 0.73, and -0.49, respectively (all P < .0001). The MNSI-Ar was able to differentiate the different severities of DNP. The receiver operator curve area was 0.93 with a high sensitivity of 95.9% and 100% for probable and confirmed DNP, respectively.MNSI-Ar is a reliable and valid tool to screen for diabetic neuropathy in the Arabic language with a good diagnostic performance and high sensitivity.
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Affiliation(s)
- Ahmad R. Abuzinadah
- King Abdulaziz University, Faculty of Medicine and King Abdulaziz University Hospital, Internal Medicine Department, Neurology Division, Neuroscience Unit, Jeddah, Saudi Arabia
- King Abdulaziz University, King Fahad Medical Research Center and King Abdulaziz University Hospital, Neuromuscular Medicine Unit, Jeddah, Saudi Arabia
| | - Hussien S. Alkully
- King Abdulaziz University, King Abdulaziz University Hospital, Internal Medicine Department, Neurology Division, Jeddah, Saudi Arabia
| | - Mohammed H. Alanazy
- Department of Internal Medicine, King Saud University Medical City and College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Moafaq S. Alrawaili
- King Abdulaziz University, King Abdulaziz University Hospital, Internal Medicine Department, Neurology Division, Jeddah, Saudi Arabia
| | - Haneen A. Milyani
- King Abdulaziz University, King Abdulaziz University Hospital, Internal Medicine Department, Neurology Division, Jeddah, Saudi Arabia
| | - Bashayr AlAmri
- King Abdulaziz University, King Abdulaziz University Hospital, Internal Medicine Department, Neurology Division, Jeddah, Saudi Arabia
| | - Aysha A. AlShareef
- King Abdulaziz University, Faculty of Medicine and King Abdulaziz University Hospital, Internal Medicine Department, Neurology Division, Neuroscience Unit, Jeddah, Saudi Arabia
- King Abdulaziz University, King Fahad Medical Research Center and King Abdulaziz University Hospital, Neuromuscular Medicine Unit, Jeddah, Saudi Arabia
| | - Ahmed K. Bamaga
- King Abdulaziz University, Faculty of Medicine and King Abdulaziz University Hospital, Pediatric Department, Pediatric Neurology Division, Jeddah, Saudi Arabia
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Silva Oggiam D, Vallim Jorgetto J, Chinini GL, Kusahara DM, Gamba MA. Distal Symmetric Polyneuropathy Pain in Diabetes Mellitus. AQUICHAN 2021. [DOI: 10.5294/aqui.2021.21.3.7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Objective: To evaluate neuropathic pain (NP), its intensity, and complications in people with type 2 diabetes mellitus (T2DM) in a city of eastern São Paulo.
Method: Cross-sectional study conducted with 96 individuals with T2DM served by primary health units in São João da Boa Vista-SP. The following instruments were used to screen NP: Michigan Neuropathy Screening Instrument, Leeds Assessment of Neuropathic Symptoms and Signs, Douleur Neuropathique 4, and Brief Pain Inventory. The data were analyzed using descriptive and inferential statistics, with a 5 % significance level.
Results: Of the 96 people with T2DM for longer than five years, 22.9 % had pain. NP was related to high levels of fasting blood glucose (mean = 214 ± 65.58 mg/dl; p = 0.0002), glycated hemoglobin (mean = 8.8 ± 0.11 %; p < 0.001), absence of a balanced diet (p = 0.0066), obesity (p = 0.023), and high blood pressure (p < 0.001).
Conclusion: Higher values of glycated hemoglobin rates increased three times the chance of NP. The screening and management of painful diabetic neuropathy is a challenge but adopting a screening protocol supports the secondary prevention of this manifestation.
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Kaymaz S, Alkan H, Karasu U, Çobankara V. Turkish version of the Michigan Neuropathy Screening Instrument in the assessment of diabetic peripheral neuropathy: a validity and reliability study. Diabetol Int 2020; 11:283-292. [PMID: 32802710 DOI: 10.1007/s13340-020-00427-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 02/11/2020] [Indexed: 01/19/2023]
Abstract
Background/aim Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus (DM). The Michigan Neuropathy Screening Instrument (MNSI) is a simple, brief, and useful screening tool that was designed to assess DPN. The aim of this study was to develop a Turkish version of the MNSI and assess its reliability and validity. Materials and methods Eighty-three patients with DM who were divided into two groups according the results of nerve conduction studies (NCS) as having DPN or without DPN were enrolled in this cross-sectional study. The Toronto clinical scoring system, pain detect questionnaire, and NCS were assessed along with the MNSI. Results Each section of the MNSI was internally consistent (Cronbach's alpha > 0.70), and the scores of both sections were positively correlated with total MNSI score (r = 0.938; r = 0.908, respectively, p < 0.001). The test-retest reliability of the Turkish version of the MNSI was determined as 0.99 for the total score (intraclass correlation coefficient = 0.996). Using the agreement between MNSI scores and DPN diagnosis by NCS as a gold standard, receiver-operating characteristic (ROC) curve values for section A and section B were estimated as 0.973 and 1.00, respectively. When a cut-off value ≥ 3.0 in section A and a cut-off value ≥ 2.0 in section B were used, we obtained a sensitivity of 97.6% and 100%; a specificity of 63.4% and 97.6%; a positive predictive value of 72.7% and 97.6%; and a negative predictive value of 96.3% and 100%, respectively. Conclusion The Turkish version of MNSI is a reliable and valid tool for screening DPN in Turkish patients.
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Affiliation(s)
- Serdar Kaymaz
- Department of Rheumatology, Faculty of Medicine, Pamukkale University, Kınıklı, 20070 Denizli, Turkey
| | - Hakan Alkan
- Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Pamukkale University, Denizli, Turkey
| | - Ugur Karasu
- Department of Rheumatology, Faculty of Medicine, Pamukkale University, Kınıklı, 20070 Denizli, Turkey
| | - Veli Çobankara
- Department of Rheumatology, Faculty of Medicine, Pamukkale University, Kınıklı, 20070 Denizli, Turkey
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Zhao J, Li Y, Xin L, Sun M, Yu C, Shi G, Bao T, Liu J, Ni Y, Lu R, Wu Y, Fang Z. Clinical Features and Rules of Chinese Herbal Medicine in Diabetic Peripheral Neuropathy Patients. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2020; 2020:5795264. [PMID: 32724325 PMCID: PMC7382735 DOI: 10.1155/2020/5795264] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 03/27/2020] [Accepted: 06/08/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To analyse the clinical features of diabetic peripheral neuropathy (DPN) and employ data mining technology to explore the rules of Chinese herbal medicine (CHM) therapy. METHODS The clinical data of 216 patients with DPN and qi-yin deficiency syndrome were obtained, and the clinical features of the patients were assessed by cluster analysis. Relevant information was entered into the clinical diagnosis and treatment collection system, and data mining techniques were used to analyse the drug frequency, core CHM, CHM pair, and so on. RESULTS In this study, glycated haemoglobin (HbA1c) and homocysteine (HCY) were closely related to the pathogenesis of DPN. Overall, 162 patients had typical DPN syndrome characteristics, and we analysed 216 prescriptions, including 182 CHM. The frequencies of prescription of Astragalus membranaceus, Ligusticum wallichii, Poria cocos, and Radix Rehmanniae were greater than 45%. A Bayesian network analysis diagram showed that the 9 most common core CHM included Astragalus membranaceus, Ligusticum wallichii, Poria cocos, atractylodes rhizome, and Salvia miltiorrhiza Bge. According to the association rules of CHM, Radix Ophiopogon is used for Codonopsis pilosula; Astragalus membranaceus and atractylodes rhizome for Rehmannia are also frequently used. Astragalus membranaceus and Cinnamomi Ramulus or Ligusticum wallichii and Moutan bark were highly related to a decreased Michigan Diabetic Neuropathy Score. CONCLUSION HbA1c and HCY are related risk factors for DPN. Numbness is a typical syndrome characteristic. Astragalus membranaceus is a monarch CHM and is used most frequently.
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Affiliation(s)
- Jindong Zhao
- Department of Endocrine Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
| | - Yan Li
- Department of Infectious Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
| | - Ling Xin
- Department of Information, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
| | - Min Sun
- School of Life Sciences, Anhui University, Hefei 230039, China
| | - Chanjuan Yu
- Department of Endocrine Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
| | - Guobin Shi
- Department of Endocrine Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
| | - Taotao Bao
- Department of Endocrine Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
| | - Jian Liu
- Department of Endocrine Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
| | - Yingqun Ni
- Department of Endocrine Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
| | - RuiMin Lu
- Department of Endocrine Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
| | - Yuanyuan Wu
- Department of Endocrine Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
| | - Zhaohui Fang
- Department of Endocrine Disease, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
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Aktar Reyhanioğlu D, Adiyaman SC, Bektaş M, Bulut O, Özgen Saydam B, Bayraktar F, Kara B. Validity and reliability of the Turkish version of the Michigan Neuropathy Screening Instrument. Turk J Med Sci 2020; 50:789-797. [PMID: 32178509 PMCID: PMC7379468 DOI: 10.3906/sag-1906-63] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 03/14/2020] [Indexed: 11/12/2022] Open
Abstract
Background/aim The aim of this study was to demonstrate the validity and reliability of the Turkish version of the Michigan Neuropathy Screening Instrument (MNSI-TR). Materials and methods The study included 127 patients aged 45–76 years who were previously diagnosed with type 1 or 2 diabetes. Stability of the instrument was assessed by intraclass correlation coefficient. Reliability of the MNSI-TR was assessed using the Kuder–Richardson formula 20 test, item-total correlations, and floor/ceiling effect. Validity was evaluated with receiver operating characteristic curve analysis. A logistic regression model was used to determine to what degree the MNSI-TR explain nerve conduction study (NCS) results in the prediction of neuropathy. Results With a cut-off value of 3.5 for the questionnaire, sensitivity and specificity of the MNSI-TR were 75.5% and 68.1%, respectively. A cut-off of 2.75 for the physical assessment part of the scale resulted in 87.5% sensitivity and 93.6% specificity. The scale was able to diagnose neuropathy in the rate of 71.5% of the patients diagnosed with neuropathy by NCS. Conclusion The MNSI-TR is a valid and reliable method for evaluating diabetic peripheral neuropathy in Turkish speaking societies. It must be obtained a minimum of 4 points from the questionnaire part and a minimum of 2.5 points from the physical assessment part for the diagnosis of neuropathy
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Affiliation(s)
- Duygu Aktar Reyhanioğlu
- Dokuz Eylül University, Graduate School of Health Sciences, Department of Physical Therapy and Rehabilitation, İzmir, Turkey
| | - Süleyman Cem Adiyaman
- Dokuz Eylül University, Faculty of Medicine, Department of Endocrinology and Metabolism, İzmir, Turkey
| | - Murat Bektaş
- Dokuz Eylül University, Faculty of Nursing, İzmir, Turkey
| | - Onur Bulut
- Dokuz Eylül University, Faculty of Medicine, Department of Neurology, İzmir, Turkey
| | - Başak Özgen Saydam
- Dokuz Eylül University, Faculty of Medicine, Department of Endocrinology and Metabolism, İzmir, Turkey
| | - Firat Bayraktar
- Dokuz Eylül University, Faculty of Medicine, Department of Endocrinology and Metabolism, İzmir, Turkey
| | - Bilge Kara
- Dokuz Eylül University, Department of Physical Therapy and Rehabilitation, İzmir, Turkey
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Rosenberger DC, Blechschmidt V, Timmerman H, Wolff A, Treede RD. Challenges of neuropathic pain: focus on diabetic neuropathy. J Neural Transm (Vienna) 2020; 127:589-624. [PMID: 32036431 PMCID: PMC7148276 DOI: 10.1007/s00702-020-02145-7] [Citation(s) in RCA: 167] [Impact Index Per Article: 33.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 01/19/2020] [Indexed: 02/07/2023]
Abstract
Neuropathic pain is a frequent condition caused by a lesion or disease of the central or peripheral somatosensory nervous system. A frequent cause of peripheral neuropathic pain is diabetic neuropathy. Its complex pathophysiology is not yet fully elucidated, which contributes to underassessment and undertreatment. A mechanism-based treatment of painful diabetic neuropathy is challenging but phenotype-based stratification might be a way to develop individualized therapeutic concepts. Our goal is to review current knowledge of the pathophysiology of peripheral neuropathic pain, particularly painful diabetic neuropathy. We discuss state-of-the-art clinical assessment, validity of diagnostic and screening tools, and recommendations for the management of diabetic neuropathic pain including approaches towards personalized pain management. We also propose a research agenda for translational research including patient stratification for clinical trials and improved preclinical models in relation to current knowledge of underlying mechanisms.
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Affiliation(s)
- Daniela C Rosenberger
- Department of Neurophysiology, Mannheim Center for Translational Neuroscience (MCTN), Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
| | - Vivian Blechschmidt
- Department of Neurophysiology, Mannheim Center for Translational Neuroscience (MCTN), Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
| | - Hans Timmerman
- Department of Anesthesiology, Pain Center, University Medical Center of Groningen (UMCG), University of Groningen, Groningen, The Netherlands
| | - André Wolff
- Department of Anesthesiology, Pain Center, University Medical Center of Groningen (UMCG), University of Groningen, Groningen, The Netherlands
| | - Rolf-Detlef Treede
- Department of Neurophysiology, Mannheim Center for Translational Neuroscience (MCTN), Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
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Barbosa M, Saavedra A, Oliveira S, Reis L, Rodrigues F, Severo M, Sittl R, Maier C, Carvalho DM. Prevalence and Determinants of Painful and Painless Neuropathy in Type 1 Diabetes Mellitus. Front Endocrinol (Lausanne) 2019; 10:402. [PMID: 31316463 PMCID: PMC6610998 DOI: 10.3389/fendo.2019.00402] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Accepted: 06/06/2019] [Indexed: 01/29/2023] Open
Abstract
Aims: To evaluate (1) the prevalence of diabetic distal symmetrical sensory-motor polyneuropathy (DSPN) and painful DSPN among patients with type 1 diabetes mellitus (DM1) aged over 18 years and (2) the determinant factors of neuropathy and pain in those patients. Materials and Methods: An epidemiological, cross-sectional, observational study was performed; 330,386 people were included, and a total of 444 people were diagnosed with DM1. After exclusion of possible confounders, 360 patients were assessed for painless and painful DSPNs using neurological examination and questionnaires for neuropathy and pain. Odds ratio (OR) and confidence intervals (95% CI) were estimated using multinomial logistic regression models. The analysis was based on a framework with four conceptual levels that consider feasible pathways between several risk factors: (1) socio-demographic factors and diabetes duration, (2) patient habits, (3) co-morbidities, and (4) metabolic factors and disease complications. Results: The prevalence of DSPN and painful DSPN were 42.8 and 18.9%, respectively. Diabetes duration was positively associated with painful (OR = 1.107, 95% CI: 1.107-1.139) and painless DSPN (OR = 1.069, 95% CI: 1.043-1.096). Education level was negatively associated with painful DSPN (OR = 0.889, 95% CI: 0.826-0.957). Sex (female) was positively associated only with painless DSPN (OR = 1.769, 95% CI: 1.007-3.107). Being a current or former smoker was positively associated only with painless DSPN (OR = 1.940, 95% CI: 1.069-3.518). Hypertension was positively associated with painful DSPN (OR = 2.474, 95% CI: 1.110-5.512) and painless DSPN (OR = 2.565, 95% CI: 1.252-5.256). Glycated hemoglobin (HbA1c) was positively associated only with painless DSPN (OR = 1.193, 95% CI: 1.018-1.399). Conclusions: Diabetes duration and hypertension have a direct impact on the development of painful and painless DSPN. However, female sex and HbA1c have a direct effect only on the development of painless DSPN, and education level has an indirect effect on the development of painful DSPN. Therefore, it can be concluded that different etiological factors have different contributions to the development of neuropathy and pain.
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Affiliation(s)
- Margarida Barbosa
- Department of Anesthesiology, Centro Hospitalar Universitário São João, Porto, Portugal
- Faculty of Medicine, Universidade do Porto, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- *Correspondence: Margarida Barbosa
| | - Ana Saavedra
- Faculty of Medicine, Universidade do Porto, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Sofia Oliveira
- Faculty of Medicine, Universidade do Porto, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Ligia Reis
- Department of Anesthesiology, Centro Hospitalar Universitário São João, Porto, Portugal
- Department of Anesthesiology of Hospital Espirito Santo, Évora, Portugal
| | - Filipa Rodrigues
- Department of Anesthesiology, Hospital do Divino Espírito Santo, Ponta Delgada, Portugal
| | - Milton Severo
- Epidemiology Research Unit, Public Health Institute, Universidade do Porto, Porto, Portugal
| | - Reinhard Sittl
- Hautklinik, Universitätsklinikum Erlangen, Erlangen, Germany
| | - Christoph Maier
- Department of Pain Medicine, BG University Hospital Bergmannsheil GmbH, Bochum, Germany
| | - Davide M. Carvalho
- Faculty of Medicine, Universidade do Porto, Porto, Portugal
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário São João, Porto, Portugal
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Sartor CD, Oliveira MD, Campos V, Ferreira JSSP, Sacco ICN. Cross-cultural adaptation and measurement properties of the Brazilian Version of the Michigan Neuropathy Screening Instrument. Braz J Phys Ther 2017; 22:222-230. [PMID: 29175181 DOI: 10.1016/j.bjpt.2017.10.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 10/23/2017] [Accepted: 10/24/2017] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND The Michigan Neuropathy Screening Instrument is an easy-to-use questionnaire aimed at screening and detecting diabetic polyneuropathy. OBJECTIVE To translate and cross-culturally adapt the MNSI to Brazilian Portuguese and evaluate its measurement properties. METHODS Two bilingual translators translated from English into Brazilian Portuguese and made a synthetic version. The synthetic version was back translated into English. A committee of specialists and the translator checked the cultural adaptations and developed a pre-final questionnaire in Brazilian Portuguese (prefinal version). In pretesting, the prefinal version was applied to a sample of 34 subjects in which each subject was interviewed to determine whether they understood each item. For the later assessment of measurement properties, 84 subjects were assessed. RESULTS A final Brazilian Portuguese version of the instrument was produced after obtaining 80% agreement (SEM<0.01%) among diabetic patients and specialists. We obtained excellent intra-rater reliability (ICC3,1=0.90), inter-rater reliability (ICC2,1=0.90) and within-subject reliability ICC3,1=0.80, excellent internal consistency (Cronbach's alpha>0.92), reasonable construct validity for the association between the MNSI and Neuropathy Symptom Score (r=0.46, p<0.05) and excellent association between the MNSI and Neuropathy Disability Score (r=0.79, p<0.05). We did not detect floor and ceiling effects (<9.5% of patients with maximum scores). CONCLUSIONS The Brazilian Portuguese version of the MNSI is suitable for application in the Brazilian diabetic population and is a reliable tool for the screening and detection of DPN. The MNSI can be used both in clinical practice and also for research purposes.
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Affiliation(s)
- Cristina D Sartor
- Universidade de Sao Paulo (USP), School of Medicine, Physical Therapy, Speech and Occupational Therapy Department, São Paulo, SP, Brazil; Universidade Ibirapuera, São Paulo, SP, Brazil.
| | - Mariana D Oliveira
- Universidade de Sao Paulo (USP), School of Medicine, Physical Therapy, Speech and Occupational Therapy Department, São Paulo, SP, Brazil
| | - Victoria Campos
- Universidade de Sao Paulo (USP), School of Medicine, Physical Therapy, Speech and Occupational Therapy Department, São Paulo, SP, Brazil
| | - Jane S S P Ferreira
- Universidade de Sao Paulo (USP), School of Medicine, Physical Therapy, Speech and Occupational Therapy Department, São Paulo, SP, Brazil
| | - Isabel C N Sacco
- Universidade de Sao Paulo (USP), School of Medicine, Physical Therapy, Speech and Occupational Therapy Department, São Paulo, SP, Brazil
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